TY - CONF
AB - Recent progress in per-pixel object class labeling of natural images can be attributed to the use of multiple types of image features and sound statistical learning approaches. Within the latter, Conditional Random Fields (CRF) are prominently used for their ability to represent interactions between random variables. Despite their popularity in computer vision, parameter learning for CRFs has remained difficult, popular approaches being cross-validation and piecewise training.
In this work, we propose a simple yet expressive tree-structured CRF based on a recent hierarchical image segmentation method. Our model combines and weights multiple image features within a hierarchical representation and allows simple and efficient globally-optimal learning of ≈ 105 parameters. The tractability of our model allows us to pose and answer some of the open questions regarding parameter learning applying to CRF-based approaches. The key findings for learning CRF models are, from the obvious to the surprising, i) multiple image features always help, ii) the limiting dimension with respect to current models is the amount of training data, iii) piecewise training is competitive, iv) current methods for max-margin training fail for models with many parameters.
AU - Nowozin, Sebastian
AU - Gehler, Peter
AU - Lampert, Christoph
ID - 3793
TI - On parameter learning in CRF-based approaches to object class image segmentation
VL - 6316
ER -
TY - CONF
AB - We study the problem of multimodal dimensionality reduction assuming that data samples can be missing at training time, and not all data modalities may be present at application time. Maximum covariance analysis, as a generalization of PCA, has many desirable properties, but its application to practical problems is limited by its need for perfectly paired data. We overcome this limitation by a latent variable approach that allows working with weakly paired data and is still able to efficiently process large datasets using standard numerical routines. The resulting weakly paired maximum covariance analysis often finds better representations than alternative methods, as we show in two exemplary tasks: texture discrimination and transfer learning.
AU - Lampert, Christoph
AU - Krömer, Oliver
ID - 3794
TI - Weakly-paired maximum covariance analysis for multimodal dimensionality reduction and transfer learning
VL - 6312
ER -
TY - CHAP
AB - The (apparent) contour of a smooth mapping from a 2-manifold to the plane, f: M → R2 , is the set of critical values, that is, the image of the points at which the gradients of the two component functions are linearly dependent. Assuming M is compact and orientable and measuring difference with the erosion distance, we prove that the contour is stable.
AU - Edelsbrunner, Herbert
AU - Morozov, Dmitriy
AU - Patel, Amit
ID - 3795
T2 - Topological Data Analysis and Visualization: Theory, Algorithms and Applications
TI - The stability of the apparent contour of an orientable 2-manifold
ER -
TY - JOUR
AB - To determine the number of open Ca(2+) channels necessary for transmitter release at the inhibitory basket cell-granule cell synapse in rat hippocampus, we combined presynaptic Ca(2+) imaging, recording of postsynaptic currents and modeling. We found that that the opening of three or fewer Ca(2+) channels triggered transmitter release. Furthermore, a small number of Ca(2+) channels were able to evoke release with high temporal precision, despite stochastic Ca(2+) channel opening.
AU - Bucurenciu, Iancu
AU - Bischofberger, Josef
AU - Peter Jonas
ID - 3829
IS - 1
JF - Nature Neuroscience
TI - A small number of open Ca(2+) channels trigger transmitter release at a central GABAergic synapse
VL - 13
ER -
TY - JOUR
AB - Fast-spiking, parvalbumin-expressing basket cells (BCs) are important for feedforward and feedback inhibition. During network activity, BCs respond with short latency and high temporal precision. It is thought that the specific properties of input synapses are responsible for rapid recruitment. However, a potential contribution of active dendritic conductances has not been addressed. We combined confocal imaging and patch-clamp techniques to obtain simultaneous somatodendritic recordings from BCs. Action potentials were initiated in the BC axon and backpropagated into the dendrites with reduced amplitude and little activity dependence. These properties were explained by a high K+ to Na+ conductance ratio in BC dendrites. Computational analysis indicated that dendritic K+ channels convey unique integration properties to BCs, leading to the rapid and temporally precise activation by excitatory inputs.
AU - Hua Hu
AU - Martina, Marco
AU - Peter Jonas
ID - 3830
IS - 5961
JF - Science
TI - Dendritic mechanisms underlying rapid synaptic activation of fast-spiking hippocampal interneurons
VL - 327
ER -
TY - JOUR
AB - Fast-spiking, parvalbumin-expressing basket cells (BCs) play a key role in feedforward and feedback inhibition in the hippocampus. However, the dendritic mechanisms underlying rapid interneuron recruitment have remained unclear. To quantitatively address this question, we developed detailed passive cable models of BCs in the dentate gyrus based on dual somatic or somatodendritic recordings and complete morphologic reconstructions. Both specific membrane capacitance and axial resistivity were comparable to those of pyramidal neurons, but the average somatodendritic specific membrane resistance (R(m)) was substantially lower in BCs. Furthermore, R(m) was markedly nonuniform, being lowest in soma and proximal dendrites, intermediate in distal dendrites, and highest in the axon. Thus, the somatodendritic gradient of R(m) was the reverse of that in pyramidal neurons. Further computational analysis revealed that these unique cable properties accelerate the time course of synaptic potentials at the soma in response to fast inputs, while boosting the efficacy of slow distal inputs. These properties will facilitate both rapid phasic and efficient tonic activation of BCs in hippocampal microcircuits.
AU - Norenberg, Anja
AU - Hua Hu
AU - Vida, Imre
AU - Bartos, Marlene
AU - Peter Jonas
ID - 3831
IS - 2
JF - PNAS
TI - Distinct nonuniform cable properties optimize rapid and efficient activation of fast-spiking GABAergic interneurons
VL - 107
ER -
TY - JOUR
AB - A recent paper by von Engelhardt et al. identifies a novel auxiliary subunit of native AMPARs, termedCKAMP44. Unlike other auxiliary subunits, CKAMP44 accelerates desensitization and prolongs recovery from desensitization. CKAMP44 is highly expressed in hippocampal dentate gyrus granule cells and decreases the paired-pulse ratio at perforant path input synapses. Thus, both principal and auxiliary AMPAR subunits control the time course of signaling at glutamatergic synapses.
AU - Guzmán, José
AU - Jonas, Peter M
ID - 3832
IS - 1
JF - Neuron
TI - Beyond TARPs: The growing list of auxiliary AMPAR subunits
VL - 66
ER -
TY - JOUR
AU - Jonas, Peter M
AU - Hefft, Stefan
ID - 3833
IS - 7
JF - The European Journal of Neuroscience
TI - GABA release at terminals of CCK-interneurons: synchrony, asynchrony and modulation by cannabinoid receptors (commentary on Ali & Todorova)
VL - 31
ER -
TY - JOUR
AB - Background
The chemical master equation (CME) is a system of ordinary differential equations that describes the evolution of a network of chemical reactions as a stochastic process. Its solution yields the probability density vector of the system at each point in time. Solving the CME numerically is in many cases computationally expensive or even infeasible as the number of reachable states can be very large or infinite. We introduce the sliding window method, which computes an approximate solution of the CME by performing a sequence of local analysis steps. In each step, only a manageable subset of states is considered, representing a "window" into the state space. In subsequent steps, the window follows the direction in which the probability mass moves, until the time period of interest has elapsed. We construct the window based on a deterministic approximation of the future behavior of the system by estimating upper and lower bounds on the populations of the chemical species.
Results
In order to show the effectiveness of our approach, we apply it to several examples previously described in the literature. The experimental results show that the proposed method speeds up the analysis considerably, compared to a global analysis, while still providing high accuracy.
Conclusions
The sliding window method is a novel approach to address the performance problems of numerical algorithms for the solution of the chemical master equation. The method efficiently approximates the probability distributions at the time points of interest for a variety of chemically reacting systems, including systems for which no upper bound on the population sizes of the chemical species is known a priori.
AU - Wolf, Verena
AU - Goel, Rushil
AU - Mateescu, Maria
AU - Henzinger, Thomas A
ID - 3834
IS - 42
JF - BMC Systems Biology
TI - Solving the chemical master equation using sliding windows
VL - 4
ER -
TY - CONF
AB - We present a numerical approximation technique for the analysis of continuous-time Markov chains that describe net- works of biochemical reactions and play an important role in the stochastic modeling of biological systems. Our approach is based on the construction of a stochastic hybrid model in which certain discrete random variables of the original Markov chain are approximated by continuous deterministic variables. We compute the solution of the stochastic hybrid model using a numerical algorithm that discretizes time and in each step performs a mutual update of the transient prob- ability distribution of the discrete stochastic variables and the values of the continuous deterministic variables. We im- plemented the algorithm and we demonstrate its usefulness and efficiency on several case studies from systems biology.
AU - Henzinger, Thomas A
AU - Mateescu, Maria
AU - Mikeev, Linar
AU - Wolf, Verena
ID - 3838
TI - Hybrid numerical solution of the chemical master equation
ER -
TY - CONF
AB - We present a loop property generation method for loops iterating over multi-dimensional arrays. When used on matrices, our method is able to infer their shapes (also called types), such as upper-triangular, diagonal, etc. To gen- erate loop properties, we first transform a nested loop iterating over a multi- dimensional array into an equivalent collection of unnested loops. Then, we in- fer quantified loop invariants for each unnested loop using a generalization of a recurrence-based invariant generation technique. These loop invariants give us conditions on matrices from which we can derive matrix types automatically us- ing theorem provers. Invariant generation is implemented in the software package Aligator and types are derived by theorem provers and SMT solvers, including Vampire and Z3. When run on the Java matrix package JAMA, our tool was able to infer automatically all matrix types describing the matrix shapes guaranteed by JAMA’s API.
AU - Henzinger, Thomas A
AU - Hottelier, Thibaud
AU - Kovács, Laura
AU - Voronkov, Andrei
ID - 3839
TI - Invariant and type inference for matrices
VL - 5944
ER -
TY - CONF
AB - Classical formalizations of systems and properties are boolean: given a system and a property, the property is either true or false of the system. Correspondingly, classical methods for system analysis determine the truth value of a property, preferably giving a proof if the property is true, and a counterexample if the property is false; classical methods for system synthesis construct a system for which a property is true; classical methods for system transformation, composition, and abstraction aim to preserve the truth of properties. The boolean view is prevalent even if the system, the property, or both refer to numerical quantities, such as the times or probabilities of events. For example, a timed automaton either satisfies or violates a formula of a real-time logic; a stochastic process either satisfies or violates a formula of a probabilistic logic. The classical black-and-white view partitions the world into "correct" and "incorrect" systems, offering few nuances. In reality, of several systems that satisfy a property in the boolean sense, often some are more desirable than others, and of the many systems that violate a property, usually some are less objectionable than others. For instance, among the systems that satisfy the response property that every request be granted, we may prefer systems that grant requests quickly (the quicker, the better), or we may prefer systems that issue few unnecessary grants (the fewer, the better); and among the systems that violate the response property, we may prefer systems that serve many initial requests (the more, the better), or we may prefer systems that serve many requests in the long run (the greater the fraction of served to unserved requests, the better). Formally, while a boolean notion of correctness is given by a preorder on systems and properties, a quantitative notion of correctness is defined by a directed metric on systems and properties, where the distance between a system and a property provides a measure of "fit" or "desirability." There are many ways how such distances can be defined. In a linear-time framework, one assigns numerical values to individual behaviors before assigning values to systems and properties, which are sets of behaviors. For example, the value of a single behavior may be a discounted value, which is largely determined by a prefix of the behavior, e.g., by the number of requests that are granted before the first request that is not granted; or a limit value, which is independent of any finite prefix. A limit value may be an average, such as the average response time over an infinite sequence of requests and grants, or a supremum, such as the worst-case response time. Similarly, the value of a set of behaviors may be an extremum or an average across the values of all behaviors in the set: in this way one can measure the worst of all possible average-case response times, or the average of all possible worst-case response times, etc. Accordingly, the distance between two sets of behaviors may be defined as the worst or average difference between the values of corresponding behaviors. In summary, we propagate replacing boolean specifications for the correctness of systems with quantitative measures for the desirability of systems. In quantitative analysis, the aim is to compute the distance between a system and a property (or between two systems, or two properties); in quantitative synthesis, the objective is to construct a system that has minimal distance from a given property. Multiple quantitative measures can be prioritized (e.g., combined lexicographically into a single measure) or studied along the Pareto curve. Quantitative transformations, compositions, and abstractions of systems are useful if they allow us to bound the induced change in distance from a property. We present some initial results in some of these directions. We also give some potential applications, which not only generalize tradiditional correctness concerns in the functional, timed, and probabilistic domains, but also capture such system measures as resource use, performance, cost, reliability, and robustness.
AU - Henzinger, Thomas A
ID - 3840
IS - 1
TI - From boolean to quantitative notions of correctness
VL - 45
ER -
TY - JOUR
AB - Within systems biology there is an increasing interest in the stochastic behavior of biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous-time Markov chain (CTMC). The uniformization technique is an efficient method to compute probability distributions of a CTMC if the number of states is manageable. However, the size of a CTMC that represents a biochemical reaction network is usually far beyond what is feasible. In this paper we present an on-the-fly variant of uniformization, where we improve the original algorithm at the cost of a small approximation error. By means of several examples, we show that our approach is particularly well-suited for biochemical reaction networks.
AU - Didier, Frédéric
AU - Henzinger, Thomas A
AU - Mateescu, Maria
AU - Wolf, Verena
ID - 3842
IS - 6
JF - IET Systems Biology
TI - Fast adaptive uniformization of the chemical master equation
VL - 4
ER -
TY - CONF
AB - This paper presents Aligators, a tool for the generation of universally quantified array invariants. Aligators leverages recurrence solving and algebraic techniques to carry out inductive reasoning over array content. The Aligators’ loop extraction module allows treatment of multi-path loops by exploiting their commutativity and serializability properties. Our experience in applying Aligators on a collection of loops from open source software projects indicates the applicability of recurrence and algebraic solving techniques for reasoning about arrays.
AU - Henzinger, Thomas A
AU - Hottelier, Thibaud
AU - Kovács, Laura
AU - Rybalchenko, Andrey
ID - 3845
TI - Aligators for arrays
VL - 6397
ER -
TY - CONF
AB - The importance of stochasticity within biological systems has been shown repeatedly during the last years and has raised the need for efficient stochastic tools. We present SABRE, a tool for stochastic analysis of biochemical reaction networks. SABRE implements fast adaptive uniformization (FAU), a direct numerical approximation algorithm for computing transient solutions of biochemical reaction networks. Biochemical reactions networks represent biological systems studied at a molecular level and these reactions can be modeled as transitions of a Markov chain. SABRE accepts as input the formalism of guarded commands, which it interprets either as continuous-time or as discrete-time Markov chains. Besides operating in a stochastic mode, SABRE may also perform a deterministic analysis by directly computing a mean-field approximation of the system under study. We illustrate the different functionalities of SABRE by means of biological case studies.
AU - Didier, Frédéric
AU - Henzinger, Thomas A
AU - Mateescu, Maria
AU - Wolf, Verena
ID - 3847
TI - SABRE: A tool for the stochastic analysis of biochemical reaction networks
ER -
TY - CONF
AB - We define the robustness of a level set homology class of a function f:XR as the magnitude of a perturbation necessary to kill the class. Casting this notion into a group theoretic framework, we compute the robustness for each class, using a connection to extended persistent homology. The special case X=R3 has ramifications in medical imaging and scientific visualization.
AU - Bendich, Paul
AU - Edelsbrunner, Herbert
AU - Morozov, Dmitriy
AU - Patel, Amit
ID - 3848
TI - The robustness of level sets
VL - 6346
ER -
TY - CONF
AB - Using ideas from persistent homology, the robustness of a level set of a real-valued function is defined in terms of the magnitude of the perturbation necessary to kill the classes. Prior work has shown that the homology and robustness information can be read off the extended persistence diagram of the function. This paper extends these results to a non-uniform error model in which perturbations vary in their magnitude across the domain.
AU - Bendich, Paul
AU - Edelsbrunner, Herbert
AU - Kerber, Michael
AU - Patel, Amit
ID - 3849
TI - Persistent homology under non-uniform error
VL - 6281
ER -
TY - JOUR
AB - Scanning tunneling spectroscopy studies on high-quality Bi2Te3 crystals exhibit perfect correspondence to angle-resolved photoemission spectroscopy data, hence enabling identification of different regimes measured in the local density of states (LDOS). Oscillations of LDOS near a step are analyzed. Within the main part of the surface band oscillations are strongly damped, supporting the hypothesis of topological protection. At higher energies, as the surface band becomes concave, oscillations appear, dispersing with a wave vector that may result from a hexagonal warping term.
AU - Alpichshev, Zhanybek
AU - Analytis, James
AU - Chu, Jiunhaw
AU - Fisher, Ian
AU - Chen, Yulin
AU - Shen, Zhixun
AU - Fang, Aiping
AU - Kapitulnik, Aharon
ID - 385
IS - 1
JF - Physical Review Letters
TI - STM imaging of electronic waves on the surface of Bi2Te3 Topologically protected surface states and hexagonal warping effects
VL - 104
ER -
TY - CONF
AB - Given a polygonal shape Q with n vertices, can it be expressed, up to a tolerance ε in Hausdorff distance, as the Minkowski sum of another polygonal shape with a disk of fixed radius? If it does, we also seek a preferably simple solution shape P;P’s offset constitutes an accurate, vertex-reduced, and smoothened approximation of Q. We give a decision algorithm for fixed radius in O(nlogn) time that handles any polygonal shape. For convex shapes, the complexity 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.
AU - Berberich, Eric
AU - Halperin, Dan
AU - Kerber, Michael
AU - Pogalnikova, Roza
ID - 3850
TI - Polygonal reconstruction from approximate offsets
ER -
TY - CONF
AB - Energy parity games are infinite two-player turn-based games played on weighted graphs. The objective of the game combines a (qualitative) parity condition with the (quantitative) requirement that the sum of the weights (i.e., the level of energy in the game) must remain positive. Beside their own interest in the design and synthesis of resource-constrained omega-regular specifications, energy parity games provide one of the simplest model of games with combined qualitative and quantitative objective. Our main results are as follows: (a) exponential memory is sufficient and may be necessary for winning strategies in energy parity games; (b) the problem of deciding the winner in energy parity games can be solved in NP ∩ coNP; and (c) we give an algorithm to solve energy parity by reduction to energy games. We also show that the problem of deciding the winner in energy parity games is polynomially equivalent to the problem of deciding the winner in mean-payoff parity games, which can thus be solved in NP ∩ coNP. As a consequence we also obtain a conceptually simple algorithm to solve mean-payoff parity games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 3851
TI - Energy parity games
VL - 6199
ER -
TY - CONF
AB - We introduce two-level discounted games played by two players on a perfect-information stochastic game graph. The upper level game is a discounted game and the lower level game is an undiscounted reachability game. Two-level games model hierarchical and sequential decision making under uncertainty across different time scales. We show the existence of pure memoryless optimal strategies for both players and an ordered field property for such games. We show that if there is only one player (Markov decision processes), then the values can be computed in polynomial time. It follows that whether the value of a player is equal to a given rational constant in two-level discounted games can be decided in NP intersected coNP. We also give an alternate strategy improvement algorithm to compute the value.
AU - Chatterjee, Krishnendu
AU - Majumdar, Ritankar
ID - 3852
TI - Discounting in games across time scales
VL - 25
ER -
TY - CONF
AB - Quantitative languages are an extension of boolean languages that assign to each word a real number. Mean-payoff automata are finite automata with numerical weights on transitions that assign to each infinite path the long-run average of the transition weights. When the mode of branching of the automaton is deterministic, nondeterministic, or alternating, the corresponding class of quantitative languages is not robust as it is not closed under the pointwise operations of max, min, sum, and numerical complement. Nondeterministic and alternating mean-payoff automata are not decidable either, as the quantitative generalization of the problems of universality and language inclusion is undecidable. We introduce a new class of quantitative languages, defined by mean-payoff automaton expressions, which is robust and decidable: it is closed under the four pointwise operations, and we show that all decision problems are decidable for this class. Mean-payoff automaton expressions subsume deterministic meanpayoff automata, and we show that they have expressive power incomparable to nondeterministic and alternating mean-payoff automata. We also present for the first time an algorithm to compute distance between two quantitative languages, and in our case the quantitative languages are given as mean-payoff automaton expressions.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Edelsbrunner, Herbert
AU - Henzinger, Thomas A
AU - Rannou, Philippe
ID - 3853
TI - Mean-payoff automaton expressions
VL - 6269
ER -
TY - CONF
AB - Graph games of infinite length provide a natural model for open reactive systems: one player (Eve) represents the controller and the other player (Adam) represents the environment. The evolution of the system depends on the decisions of both players. The specification for the system is usually given as an ω-regular language L over paths and Eve’s goal is to ensure that the play belongs to L irrespective of Adam’s behaviour. The classical notion of winning strategies fails to capture several interesting scenarios. For example, strong fairness (Streett) conditions are specified by a number of request-grant pairs and require every pair that is requested infinitely often to be granted infinitely often: Eve might win just by preventing Adam from making any new request, but a “better” strategy would allow Adam to make as many requests as possible and still ensure fairness. To address such questions, we introduce the notion of obliging games, where Eve has to ensure a strong condition Φ, while always allowing Adam to satisfy a weak condition Ψ. We present a linear time reduction of obliging games with two Muller conditions Φ and Ψ to classical Muller games. We consider obliging Streett games and show they are co-NP complete, and show a natural quantitative optimisation problem for obliging Streett games is in FNP. We also show how obliging games can provide new and interesting semantics for multi-player games.
AU - Chatterjee, Krishnendu
AU - Horn, Florian
AU - Löding, Christof
ID - 3854
TI - Obliging games
VL - 6269
ER -
TY - CONF
AB - We study observation-based strategies for partially-observable Markov decision processes (POMDPs) with parity objectives. An observation-based strategy relies on partial information about the history of a play, namely, on the past sequence of observations. We consider qualitative analysis problems: given a POMDP with a parity objective, decide whether there exists an observation-based strategy to achieve the objective with probability 1 (almost-sure winning), or with positive probability (positive winning). Our main results are twofold. First, we present a complete picture of the computational complexity of the qualitative analysis problem for POMDPs with parity objectives and its subclasses: safety, reachability, Büchi, and coBüchi objectives. We establish several upper and lower bounds that were not known in the literature. Second, we give optimal bounds (matching upper and lower bounds) for the memory required by pure and randomized observation-based strategies for each class of objectives.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ID - 3855
TI - Qualitative analysis of partially-observable Markov Decision Processes
VL - 6281
ER -
TY - CONF
AB - We consider two-player zero-sum games on graphs. These games can be classified on the basis of the information of the players and on the mode of interaction between them. On the basis of information the classification is as follows: (a) partial-observation (both players have partial view of the game); (b) one-sided complete-observation (one player has complete observation); and (c) complete-observation (both players have complete view of the game). On the basis of mode of interaction we have the following classification: (a) concurrent (players interact simultaneously); and (b) turn-based (players interact in turn). The two sources of randomness in these games are randomness in transition function and randomness in strategies. In general, randomized strategies are more powerful than deterministic strategies, and randomness in transitions gives more general classes of games. We present a complete characterization for the classes of games where randomness is not helpful in: (a) the transition function (probabilistic transition can be simulated by deterministic transition); and (b) strategies (pure strategies are as powerful as randomized strategies). As consequence of our characterization we obtain new undecidability results for these games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Gimbert, Hugo
AU - Henzinger, Thomas A
ID - 3856
TI - Randomness for free
VL - 6281
ER -
TY - CONF
AB - We consider probabilistic automata on infinite words with acceptance defined by safety, reachability, Büchi, coBüchi, and limit-average conditions. We consider quantitative and qualitative decision problems. We present extensions and adaptations of proofs for probabilistic finite automata and present an almost complete characterization of the decidability and undecidability frontier of the quantitative and qualitative decision problems for probabilistic automata on infinite words.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
ID - 3857
TI - Probabilistic Automata on infinite words: decidability and undecidability results
VL - 6252
ER -
TY - CONF
AB - We consider two-player zero-sum games on graphs. On the basis of the information available to the players these games can be classified as follows: (a) partial-observation (both players have partial view of the game); (b) one-sided partial-observation (one player has partial-observation and the other player has complete-observation); and (c) complete-observation (both players have com- plete view of the game). We survey the complexity results for the problem of de- ciding the winner in various classes of partial-observation games with ω-regular winning conditions specified as parity objectives. We present a reduction from the class of parity objectives that depend on sequence of states of the game to the sub-class of parity objectives that only depend on the sequence of observations. We also establish that partial-observation acyclic games are PSPACE-complete.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 3858
TI - The complexity of partial-observation parity games
VL - 6397
ER -
TY - GEN
AB - This book constitutes the proceedings of the 8th International Conference on Formal Modeling and Analysis of Timed Systems, FORMATS 2010, held in Klosterneuburg, Austria in September 2010. The 14 papers presented were carefully reviewed and selected from 31 submissions. In addition, the volume contains 3 invited talks and 2 invited tutorials.The aim of FORMATS is to promote the study of fundamental and practical aspects of timed systems, and to bring together researchers from different disciplines that share an interest in the modeling and analysis of timed systems. Typical topics include foundations and semantics, methods and tools, and applications.
ED - Chatterjee, Krishnendu
ED - Henzinger, Thomas A
ID - 3859
TI - Formal modeling and analysis of timed systems
VL - 6246
ER -
TY - CONF
AB - In mean-payoff games, the objective of the protagonist is to ensure that the limit average of an infinite sequence of numeric weights is nonnegative. In energy games, the objective is to ensure that the running sum of weights is always nonnegative. Generalized mean-payoff and energy games replace individual weights by tuples, and the limit average (resp. running sum) of each coordinate must be (resp. remain) nonnegative. These games have applications in the synthesis of resource-bounded processes with multiple resources. We prove the finite-memory determinacy of generalized energy games and show the inter- reducibility of generalized mean-payoff and energy games for finite-memory strategies. We also improve the computational complexity for solving both classes of games with finite-memory strategies: while the previously best known upper bound was EXPSPACE, and no lower bound was known, we give an optimal coNP-complete bound. For memoryless strategies, we show that the problem of deciding the existence of a winning strategy for the protagonist is NP-complete.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
AU - Raskin, Jean
ID - 3860
TI - Generalized mean-payoff and energy games
VL - 8
ER -
TY - JOUR
AB - We introduce strategy logic, a logic that treats strategies in two-player games as explicit first-order objects. The explicit treatment of strategies allows us to specify properties of nonzero-sum games in a simple and natural way. We show that the one-alternation fragment of strategy logic is strong enough to express the existence of Nash equilibria and secure equilibria, and subsumes other logics that were introduced to reason about games, such as ATL, ATL*, and game logic. We show that strategy logic is decidable, by constructing tree automata that recognize sets of strategies. While for the general logic, our decision procedure is nonelementary, for the simple fragment that is used above we show that the complexity is polynomial in the size of the game graph and optimal in the size of the formula (ranging from polynomial to 2EXPTIME depending on the form of the formula).
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Piterman, Nir
ID - 3861
IS - 6
JF - Information and Computation
TI - Strategy logic
VL - 208
ER -
TY - JOUR
AB - Quantitative generalizations of classical languages, which assign to each word a real number instead of a Boolean value, have applications in modeling resource-constrained computation. We use weighted automata (finite automata with transition weights) to define several natural classes of quantitative languages over finite and infinite words; in particular, the real value of an infinite run is computed as the maximum, limsup, liminf, limit average, or discounted sum of the transition weights. We define the classical decision problems of automata theory (emptiness, universality, language inclusion, and language equivalence) in the quantitative setting and study their computational complexity. As the decidability of the language-inclusion problem remains open for some classes of weighted automata, we introduce a notion of quantitative simulation that is decidable and implies language inclusion. We also give a complete characterization of the expressive power of the various classes of weighted automata. In particular, we show that most classes of weighted automata cannot be determinized.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ID - 3862
IS - 4
JF - ACM Transactions on Computational Logic (TOCL)
TI - Quantitative languages
VL - 11
ER -
TY - JOUR
AB - We consider two-player parity games with imperfect information in which strategies rely on observations that provide imperfect information about the history of a play. To solve such games, i.e., to determine the winning regions of players and corresponding winning strategies, one can use the subset construction to build an equivalent perfect-information game. Recently, an algorithm that avoids the inefficient subset construction has been proposed. The algorithm performs a fixed-point computation in a lattice of antichains, thus maintaining a succinct representation of state sets. However, this representation does not allow to recover winning strategies. In this paper, we build on the antichain approach to develop an algorithm for constructing the winning strategies in parity games of imperfect information. One major obstacle in adapting the classical procedure is that the complementation of attractor sets would break the invariant of downward-closedness on which the antichain representation relies. We overcome this difficulty by decomposing problem instances recursively into games with a combination of reachability, safety, and simpler parity conditions. We also report on an experimental implementation of our algorithm: to our knowledge, this is the first implementation of a procedure for solving imperfect-information parity games on graphs.
AU - Berwanger, Dietmar
AU - Chatterjee, Krishnendu
AU - De Wulf, Martin
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ID - 3863
IS - 10
JF - Information and Computation
TI - Strategy construction for parity games with imperfect information
VL - 208
ER -
TY - CONF
AB - Often one has a preference order among the different systems that satisfy a given specification. Under a probabilistic assumption about the possible inputs, such a preference order is naturally expressed by a weighted automaton, which assigns to each word a value, such that a system is preferred if it generates a higher expected value. We solve the following optimal-synthesis problem: given an omega-regular specification, a Markov chain that describes the distribution of inputs, and a weighted automaton that measures how well a system satisfies the given specification tinder the given input assumption, synthesize a system that optimizes the measured value. For safety specifications and measures that are defined by mean-payoff automata, the optimal-synthesis problem amounts to finding a strategy in a Markov decision process (MDP) that is optimal for a long-run average reward objective, which can be done in polynomial time. For general omega-regular specifications, the solution rests on a new, polynomial-time algorithm for computing optimal strategies in MDPs with mean-payoff parity objectives. We present some experimental results showing optimal systems that were automatically generated in this way.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Jobstmann, Barbara
AU - Singh, Rohit
ID - 3864
TI - Measuring and synthesizing systems in probabilistic environments
VL - 6174
ER -
TY - CONF
AB - We introduce a technique for debugging multi-threaded C programs and analyzing the impact of source code changes, and its implementation in the prototype tool DIRECT. Our approach uses a combination of source code instrumentation and runtime management. The source code along with a test harness is instrumented to monitor Operating System (OS) and user defined function calls. DIRECT tracks all concurrency control primitives and, optionally, data from the program. DIRECT maintains an abstract global state that combines information from every thread, including the sequence of function calls and concurrency primitives executed. The runtime manager can insert delays, provoking thread inter-leavings that may exhibit bugs that are difficult to reach otherwise. The runtime manager collects an approximation of the reachable state space and uses this approximation to assess the impact of change in a new version of the program.
AU - Chatterjee, Krishnendu
AU - De Alfaro, Luca
AU - Raman, Vishwanath
AU - Sánchez, César
ED - Rosenblum, David
ED - Taenzer, Gabriele
ID - 3865
TI - Analyzing the impact of change in multi-threaded programs
VL - 6013
ER -
TY - CONF
AB - Systems ought to behave reasonably even in circumstances that are not anticipated in their specifications. We propose a definition of robustness for liveness specifications which prescribes, for any number of environment assumptions that are violated, a minimal number of system guarantees that must still be fulfilled. This notion of robustness can be formulated and realized using a Generalized Reactivity formula. We present an algorithm for synthesizing robust systems from such formulas. For the important special case of Generalized Reactivity formulas of rank 1, our algorithm improves the complexity of [PPS06] for large specifications with a small number of assumptions and guarantees.
AU - Bloem, Roderick
AU - Chatterjee, Krishnendu
AU - Greimel, Karin
AU - Henzinger, Thomas A
AU - Jobstmann, Barbara
ED - Touili, Tayssir
ED - Cook, Byron
ED - Jackson, Paul
ID - 3866
TI - Robustness in the presence of liveness
VL - 6174
ER -
TY - JOUR
AB - Weighted automata are nondeterministic automata with numerical weights on transitions. They can define quantitative languages L that assign to each word w a real number L(w). In the case of infinite words, the value of a run is naturally computed as the maximum, limsup, liminf, limit-average, or discounted-sum of the transition weights. The value of a word w is the supremum of the values of the runs over w. We study expressiveness and closure questions about these quantitative languages. We first show that the set of words with value greater than a threshold can be omega-regular for deterministic limit-average and discounted-sum automata, while this set is always omega-regular when the threshold is isolated (i.e., some neighborhood around the threshold contains no word). In the latter case, we prove that the omega-regular language is robust against small perturbations of the transition weights. We next consider automata with transition weights 0 or 1 and show that they are as expressive as general weighted automata in the limit-average case, but not in the discounted-sum case. Third, for quantitative languages L-1 and L-2, we consider the operations max(L-1, L-2), min(L-1, L-2), and 1 - L-1, which generalize the boolean operations on languages, as well as the sum L-1 + L-2. We establish the closure properties of all classes of quantitative languages with respect to these four operations.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ID - 3867
IS - 3
JF - Logical Methods in Computer Science
TI - Expressiveness and closure properties for quantitative languages
VL - 6
ER -
TY - JOUR
AB - Simulation and bisimulation metrics for stochastic systems provide a quantitative generalization of the classical simulation and bisimulation relations. These metrics capture the similarity of states with respect to quantitative specifications written in the quantitative mu-calculus and related probabilistic logics. We first show that the metrics provide a bound for the difference in long-run average and discounted average behavior across states, indicating that the metrics can be used both in system verification, and in performance evaluation. For turn-based games and MDPs, we provide a polynomial-time algorithm for the computation of the one-step metric distance between states. The algorithm is based on linear programming; it improves on the previous known exponential-time algorithm based on a reduction to the theory of reals. We then present PSPACE algorithms for both the decision problem and the problem of approximating the metric distance between two states, matching the best known algorithms for Markov chains. For the bisimulation kernel of the metric our algorithm works in time O(n(4)) for both turn-based games and MDPs; improving the previously best known O(n(9).log(n)) time algorithm for MDPs. For a concurrent game G, we show that computing the exact distance be tween states is at least as hard as computing the value of concurrent reachability games and the square-root-sum problem in computational geometry. We show that checking whether the metric distance is bounded by a rational r, can be done via a reduction to the theory of real closed fields, involving a formula with three quantifier alternations, yielding O(vertical bar G vertical bar(O(vertical bar G vertical bar 5))) time complexity, improving the previously known reduction, which yielded O(vertical bar G vertical bar(O(vertical bar G vertical bar 7))) time complexity. These algorithms can be iterated to approximate the metrics using binary search
AU - Chatterjee, Krishnendu
AU - De Alfaro, Luca
AU - Majumdar, Ritankar
AU - Raman, Vishwanath
ID - 3868
IS - 3
JF - Logical Methods in Computer Science
TI - Algorithms for game metrics
VL - 6
ER -
TY - BOOK
AB - Combining concepts from topology and algorithms, this book delivers what its title promises: an introduction to the field of computational topology. Starting with motivating problems in both mathematics and computer science and building up from classic topics in geometric and algebraic topology, the third part of the text advances to persistent homology. This point of view is critically important in turning a mostly theoretical field of mathematics into one that is relevant to a multitude of disciplines in the sciences and engineering. The main approach is the discovery of topology through algorithms. The book is ideal for teaching a graduate or advanced undergraduate course in computational topology, as it develops all the background of both the mathematical and algorithmic aspects of the subject from first principles. Thus the text could serve equally well in a course taught in a mathematics department or computer science department.
AU - Edelsbrunner, Herbert
AU - Harer, John
ID - 3899
SN - 978-0-8218-4925-5
TI - Computational Topology: An Introduction
VL - 69
ER -
TY - JOUR
AB - We are interested in 3-dimensional images given as arrays of voxels with intensity values. Extending these values to acontinuous function, we study the robustness of homology classes in its level and interlevel sets, that is, the amount of perturbationneeded to destroy these classes. The structure of the homology classes and their robustness, over all level and interlevel sets, can bevisualized by a triangular diagram of dots obtained by computing the extended persistence of the function. We give a fast hierarchicalalgorithm using the dual complexes of oct-tree approximations of the function. In addition, we show that for balanced oct-trees, thedual complexes are geometrically realized in $R^3$ and can thus be used to construct level and interlevel sets. We apply these tools tostudy 3-dimensional images of plant root systems.
AU - Bendich, Paul
AU - Edelsbrunner, Herbert
AU - Kerber, Michael
ID - 3901
IS - 6
JF - IEEE Transactions of Visualization and Computer Graphics
TI - Computing robustness and persistence for images
VL - 16
ER -
TY - JOUR
AB - Social organisms are constantly exposed to infectious agents via physical contact with conspecifics. While previous work has shown that disease susceptibility at the individual and group level is influenced by gen- etic diversity within and between group members, it remains poorly understood how group-level resistance to pathogens relates directly to individual physiology, defence behaviour and social interactions. We investigated the effects of high versus low genetic diversity on both the individual and collective disease defences in the ant Cardiocondyla obscurior. We compared the antiseptic behaviours (grooming and hygienic behaviour) of workers from genetically homogeneous and diverse colonies after exposure of their brood to the entomopathogenic fungus Metarhizium anisopliae. While workers from diverse colonies performed intensive allogrooming and quickly removed larvae covered with live fungal spores from the nest, workers from homogeneous colonies only removed sick larvae late after infection. This difference was not caused by a reduced repertoire of antiseptic behaviours or a generally decreased brood care activity in ants from homogeneous colonies. Our data instead suggest that reduced genetic diversity compromises the ability of Cardiocondyla colonies to quickly detect or react to the presence of pathogenic fungal spores before an infection is established, thereby affecting the dynamics of social immunity in the colony.
AU - Ugelvig, Line V
AU - Kronauer, Daniel
AU - Schrempf, Alexandra
AU - Heinze, Jürgen
AU - Cremer, Sylvia
ID - 3904
IS - 1695
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Rapid anti-pathogen response in ant societies relies on high genetic diversity
VL - 277
ER -
TY - JOUR
AB - The shuttling of leukocytes between the bloodstream and interstitial tissues involves different locomotion strategies that are governed by locally presented soluble and cell-bound signals. Recent studies have furthered our understanding of the rapidly advancing field of leukocyte migration, particularly regarding cellular and subcellular events at the level of the venular wall. Furthermore, emerging cellular models are now addressing the transition from an adherent mode to a non-adherent state, incorporating mechanisms that support an efficient migratory profile of leukocytes in the interstitial tissue beyond the venular wall.
AU - Nourshargh, Sussan
AU - Hordijk, Peter L
AU - Michael Sixt
ID - 3956
IS - 5
JF - Nature Reviews Molecular Cell Biology
TI - Breaching multiple barriers: leukocyte motility through venular walls and the interstitium
VL - 11
ER -
TY - JOUR
AU - Riedl, Julia
AU - Flynn, Kevin C
AU - Raducanu, Aurelia
AU - Florian Gärtner
AU - Beck, Gisela
AU - Bosl, Michael
AU - Bradke, Frank
AU - Massberg, Steffen
AU - Aszodi, Attila
AU - Michael Sixt
AU - Wedlich-Söldner, Roland
ID - 3957
IS - 3
JF - Nature Methods
TI - Lifeact mice for studying F-actin dynamics
VL - 7
ER -
TY - JOUR
AB - Extracellular matrix (ECM) proteins can modify immune reactions, e.g. by sequestering or displaying growth factors and by interacting with immune and glial cells. Here we quantified by quantitative polymerase chain reaction (qPCR) expression of 50 ECM components and 34 ECM degrading enzymes in multiple sclerosis (MS) active and inactive white matter lesions. COL1A1, COL3A1, COL5A1 and COL5A2 chains were induced strongly in active lesions and even more in inactive lesions. These chains interact to form collagen types I, III and V, which are fibrillar collagens. Biglycan and decorin, which can decorate fibrillar collagens, were also induced strongly. The fibrillar collagens, biglycan and decorin were largely found between the endothelium and astrocytic glia limitans in the perivascular space where they formed a meshwork which was closely associated with infiltrating immune cells. In active lesions collagen V was also seen in the heavily infiltrated parenchyma. Fibrillar collagens I and III inhibited in vitro human monocyte production of CCL2 (MCP-1), an inflammatory chemokine involved in recruitment of immune cells. Together, ECM changes in lesions with different activities were quantified and proteins forming a perivascular fibrosis were identified. Induced fibrillar collagens may contribute to limiting enlargement of MS lesions by inhibiting the production of CCL2 by monocytes.
AU - Mohan, Hema
AU - Krumbholz, Markus
AU - Sharma, Rakhi
AU - Eisele, Sylvia
AU - Junker, Andreas
AU - Michael Sixt
AU - Newcombe, Jia
AU - Wekerle, Hartmut
AU - Hohlfeld, Reinhard
AU - Lassmann, Hans
AU - Meinl, Edgar
ID - 3958
IS - 5
JF - Brain Pathology
TI - Extracellular matrix in multiple sclerosis lesions: fibrillar collagens, biglycan and decorin are upregulated and associated with infiltrating immune cells
VL - 20
ER -
TY - JOUR
AB - Chemokines orchestrate immune cell trafficking by eliciting either directed or random migration and by activating integrins in order to induce cell adhesion. Analyzing dendritic cell (DC) migration, we showed that these distinct cellular responses depended on the mode of chemokine presentation within tissues. The surface-immobilized form of the chemokine CCL21, the heparan sulfate-anchoring ligand of the CC-chemokine receptor 7 (CCR7), caused random movement of DCs that was confined to the chemokine-presenting surface because it triggered integrin-mediated adhesion. Upon direct contact with CCL21, DCs truncated the anchoring residues of CCL21, thereby releasing it from the solid phase. Soluble CCL21 functionally resembles the second CCR7 ligand, CCL19, which lacks anchoring residues and forms soluble gradients. Both soluble CCR7 ligands triggered chemotactic movement, but not surface adhesion. Adhesive random migration and directional steering cooperate to produce dynamic but spatially restricted locomotion patterns closely resembling the cellular dynamics observed in secondary lymphoid organs.
AU - Schumann, Kathrin
AU - Lämmermann, Tim
AU - Bruckner, Markus
AU - Legler, Daniel
AU - Polleux, Julien
AU - Spatz, Joachim
AU - Schuler, Gerold
AU - Förster, Reinhold
AU - Lutz, Manfred
AU - Sorokin, Lydia
AU - Sixt, Michael K
ID - 3959
IS - 5
JF - Immunity
TI - Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells
VL - 32
ER -
TY - JOUR
AB - When lymphocytes follow chemotactic cues, they can adopt different migratory modes depending on the geometry and molecular composition of their extracellular environment. In this issue of The EMBO Journal, Klemke et al (2010) describe a novel Ras-dependent chemokine receptor signalling pathway that leads to activation of cofilin, which in turn amplifies actin turnover. This signalling module is exclusively required for lymphocyte migration in three-dimensional (3D) environments, but not for locomotion on two-dimensional (2D) surfaces.
AU - Michele Weber
AU - Michael Sixt
ID - 3960
IS - 17
JF - EMBO Journal
TI - MEK signalling tunes actin treadmilling for interstitial lymphocyte migration
VL - 29
ER -
TY - JOUR
AB - For innate and adaptive immune responses it is essential that inflammatory cells use quick and flexible locomotion strategies. Accordingly, most leukocytes can efficiently infiltrate and traverse almost every physiological or artificial environment. Here, we review how leukocytes might achieve this task mechanistically, and summarize recent findings on the principles of cytoskeletal force generation and transduction at the leading edge of leukocytes. We propose a model in which the cells switch between adhesion-receptor-mediated force transmission and locomotion modes that are based on cellular deformations, but independent of adhesion receptors. This plasticity in migration strategies allows leukocytes to adapt to the geometry and molecular composition of their environment.
AU - Jörg Renkawitz
AU - Michael Sixt
ID - 3961
IS - 10
JF - EMBO Reports
TI - Mechanisms of force generation and force transmission during interstitial leukocyte migration
VL - 11
ER -
TY - THES
AU - Pflicke, Holger
ID - 3962
TI - Dendritic cell migration across basement membranes in the skin
ER -
TY - JOUR
AB - Almost all species of the orchid genus Ophrys are pollinated by sexual deception. The orchids mimic the sex pheromone of receptive female insects, mainly hymenopterans, in order to attract males seeking to copulate. Most Ophrys species have achromatic flowers, but some exhibit a coloured perianth and a bright, conspicuous labellum pattern. We recently showed that the pink perianth of Ophrys heldreichii flowers increases detectability by its pollinator, males of the long-horned bee Eucera berlandi. Here we tested the hypothesis that the bright, complex labellum pattern mimics the female of the pollinator to increase attractiveness toward males. In a dual-choice test we offered E. berlandi males an O. heldreichii flower and a flower from O. dictynnae, which also exhibits a pinkish perianth but no conspicuous labellum pattern. Both flowers were housed in UV-transmitting acrylic glass boxes to exclude olfactory signals. Males significantly preferred O. heldreichii to O. dictynnae flowers. In a second experiment, we replaced the perianth of both flowers with identical artificial perianths made from pink card, so that only the labellum differed between the two flower stimuli. Males then chose between both stimuli at random, suggesting that the presence of a labellum pattern does not affect their choice. Spectral measurements revealed higher colour contrast with the background of the perianth of O. heldreichii compared to O. dictynnae, but no difference in green receptor-specific contrast or brightness. Our results show that male choice is guided by the chromatic contrast of the perianth during the initial flower approach but is not affected by the presence of a labellum pattern. Instead, we hypothesise that the labellum pattern is involved in aversive learning during post-copulatory behaviour and used by the orchid as a strategy to increase outcrossing.
AU - Streinzer, M.
AU - Ellis, Thomas
AU - Paulus, H.
AU - Spaethe, J.
ID - 3963
IS - 3
JF - Arthropod-Plant Interactions
TI - Visual discrimination between two sexually deceptive Ophrys species by a bee pollinator
VL - 4
ER -
TY - JOUR
AB - We prove two stability results for Lipschitz functions on triangulable, compact metric spaces and consider applications of both to problems in systems biology. Given two functions, the first result is formulated in terms of the Wasserstein distance between their persistence diagrams and the second in terms of their total persistence.
AU - Cohen-Steiner, David
AU - Herbert Edelsbrunner
AU - Harer, John
AU - Mileyko, Yuriy
ID - 3964
IS - 2
JF - Foundations of Computational Mathematics
TI - Lipschitz functions have L_p-stable persistence
VL - 10
ER -
TY - JOUR
AB - All species are restricted in their distribution. Currently, ecological models can only explain such limits if patches vary in quality, leading to asymmetrical dispersal, or if genetic variation is too low at the margins for adaptation. However, population genetic models suggest that the increase in genetic variance resulting from dispersal should allow adaptation to almost any ecological gradient. Clearly therefore, these models miss something that prevents evolution in natural populations. We developed an individual-based simulation to explore stochastic effects in these models. At high carrying capacities, our simulations largely agree with deterministic predictions. However, when carrying capacity is low, the population fails to establish for a wide range of parameter values where adaptation was expected from previous models. Stochastic or transient effects appear critical around the boundaries in parameter space between simulation behaviours. Dispersal, gradient steepness, and population density emerge as key factors determining adaptation on an ecological gradient.
AU - Bridle, Jon
AU - Polechova, Jitka
AU - Kawata, Masakado
AU - Butlin, Roger
ID - 4134
IS - 4
JF - Ecology Letters
TI - Why is adaptation prevented at ecological margins? New insights from individual-based simulations
VL - 13
ER -
TY - JOUR
AB - Integrin- and cadherin-mediated adhesion is central for cell and tissue morphogenesis, allowing cells and tissues to change shape without loosing integrity. Studies predominantly in cell culture showed that mechanosensation through adhesion structures is achieved by force-mediated modulation of their molecular composition. The specific molecular composition of adhesion sites in turn determines their signalling activity and dynamic reorganization. Here, we will review how adhesion sites respond to mecanical stimuli, and how spatially and temporally regulated signalling from different adhesion sites controls cell migration and tissue morphogenesis.
AU - Papusheva, Ekaterina
AU - Heisenberg, Carl-Philipp J
ID - 4157
IS - 16
JF - EMBO Journal
TI - Spatial organization of adhesion: force-dependent regulation and function in tissue morphogenesis
VL - 29
ER -
TY - JOUR
AB - Organ formation requires the precise assembly of progenitor cells into a functional multicellular structure. Mechanical forces probably participate in this process but how they influence organ morphogenesis is still unclear. Here, we show that Wnt11- and Prickle1a-mediated planar cell polarity (PCP) signalling coordinates the formation of the zebrafish ciliated laterality organ (Kupffer's vesicle) by regulating adhesion properties between organ progenitor cells (the dorsal forerunner cells, DFCs). Combined inhibition of Wnt11 and Prickle1a reduces DFC cell-cell adhesion and impairs their compaction and arrangement during vesicle lumen formation. This leads to the formation of a mis-shapen vesicle with small fragmented lumina and shortened cilia, resulting in severely impaired organ function and, as a consequence, randomised laterality of both molecular and visceral asymmetries. Our results reveal a novel role for PCP-dependent cell adhesion in coordinating the supracellular organisation of progenitor cells during vertebrate laterality organ formation.
AU - Oteíza, Pablo
AU - Koeppen, Mathias
AU - Krieg, Michael
AU - Pulgar, Eduardo
AU - Farias, Cecilia
AU - Melo, Cristina
AU - Preibisch, Steffen
AU - Mueller, Daniel
AU - Tada, Masazumi
AU - Hartel, Steffen
AU - Heisenberg, Carl-Philipp J
AU - Concha, Miguel
ID - 4163
IS - 20
JF - Development
TI - Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ
VL - 137
ER -
TY - JOUR
AB - Cell migration is central to embryonic development, homeostasis and disease(1), processes in which cells move as part of a group or individually. Whereas the mechanisms controlling single-cell migration in vitro are relatively well understood(2-4), less is known about the mechanisms promoting the motility of individual cells in vivo. In particular, it is not clear how cells that form blebs in their migration use those protrusions to bring about movement in the context of the three-dimensional cellular environment(5,6). Here we show that the motility of chemokine-guided germ cells within the zebrafish embryo requires the function of the small Rho GTPases Rac1 and RhoA, as well as E-cadherin-mediated cell-cell adhesion. Using fluorescence resonance energy transfer we demonstrate that Rac1 and RhoA are activated in the cell front. At this location, Rac1 is responsible for the formation of actin-rich structures, and RhoA promotes retrograde actin flow. We propose that these actin-rich structures undergoing retrograde flow are essential for the generation of E-cadherin-mediated traction forces between the germ cells and the surrounding tissue and are therefore crucial for cell motility in vivo.
AU - Kardash, Elena
AU - Reichman-Fried, Michal
AU - Maître, Jean-Léon
AU - Boldajipour, Bijan
AU - Ekaterina Papusheva
AU - Messerschmidt, Esther-Maria
AU - Heisenberg, Carl-Philipp
AU - Raz, Erez
ID - 4187
IS - 1
JF - Nature Cell Biology
TI - A role for Rho GTPases and cell-cell adhesion in single-cell motility in vivo
VL - 12
ER -
TY - JOUR
AB - Collective cell migration, the simultaneous movement of multiple cells that are connected by cell-cell adhesion, is ubiquitous in development, tissue repair, and tumor metastasis [1, 2]. It has been hypothesized that the directionality of cell movement during collective migration emerges as a collective property [3, 4]. Here we determine how movement directionality is established in collective mesendoderm migration during zebrafish gastrulation. By interfering with two key features of collective migration, (1) having neighboring cells and (2) adhering to them, we show that individual mesendoderm cells are capable of normal directed migration when moving as single cells but require cell-cell adhesion to participate in coordinated and directed migration when moving as part of a group. We conclude that movement directionality is not a de novo collective property of mesendoderm cells but rather a property of single mesendoderm cells that requires cell-cell adhesion during collective migration.
AU - Arboleda Estudillo, Yohanna
AU - Krieg, Michael
AU - Stuehmer, Jan
AU - Licata, Nicholas
AU - Mueller, Daniel
AU - Heisenberg, Carl-Philipp J
ID - 4221
IS - 2
JF - Current Biology
TI - Movement directionality in collective migration of germ layer progenitors
VL - 20
ER -
TY - JOUR
AB - We investigate a new model for populations evolving in a spatial continuum. This model can be thought of as a spatial version of the Lambda-Fleming-Viot process. It explicitly incorporates both small scale reproduction events and large scale extinction-recolonisation events. The lineages ancestral to a sample from a population evolving according to this model can be described in terms of a spatial version of the Lambda-coalescent. Using a technique of Evans (1997), we prove existence and uniqueness in law for the model. We then investigate the asymptotic behaviour of the genealogy of a finite number of individuals sampled uniformly at random (or more generally `far enough apart') from a two-dimensional torus of sidelength L as L tends to infinity. Under appropriate conditions (and on a suitable timescale) we can obtain as limiting genealogical processes a Kingman coalescent, a more general Lambda-coalescent or a system of coalescing Brownian motions (with a non-local coalescence mechanism).
AU - Barton, Nicholas H
AU - Etheridge, Alison
AU - Véber, Amandine
ID - 4243
IS - 7
JF - Electronic Journal of Probability
TI - A new model for evolution in a spatial continuum
VL - 15
ER -
TY - CHAP
AB - Mit diesem Buch möchten wir einen Überblick der aktuellen Diskussion zum Thema Bibliothek 2.0 geben und den Stand der tatsächlichen Umsetzung der Web 2.0-Ansätze in deutschsprachigen Bibliotheken beleuchten. An dieser Stelle ist die Frage erlaubt, warum es zu einer Zeit, in der es bereits die ersten "Web 3.0"- Konferenzen gibt, eines Handbuches der Bibliothek 2.0 noch bedarf. Und warum es überhaupt ein deutschsprachiges Handbuch zur Bibliothek 2.0 braucht, wo es doch bereits verschiedenste Publikationen zu diesem Thema aus anderen Ländern, insbesondere des angloamerikanischen Raums gibt. Ist dazu nicht bereits alles gesagt?
AU - Bergmann, Julia
AU - Danowski, Patrick
ED - Bergmann, Julia
ED - Danowski, Patrick
ID - 4339
T2 - Handbuch Bibliothek 2.0
TI - Ist Bibliothek 2.0 überhaupt noch relevant? – Eine Einleitung in das Handbuch
ER -
TY - GEN
AB - More and more libraries starting semantic web projects. The question about the license of the data
is not discussed or the discussion is deferred to the end of project. in this paper is discussed why
the question of the license is so important in context of the semantic web that is should be one of the
first aspects in a semantic web project. Also it will be shown why a public domain weaver is the
only solution that fulfill the the special requirements of the semantic web and that guaranties the
reuseablitly of semantic library data for a sustainability of the projects.
AU - Danowski, Patrick
ID - 4340
T2 - European Library Automation Group (ELAG) 2010
TI - Open bibliographic data
ER -
TY - CONF
AB - More and more libraries starting semantic web projects. The question about the license of the data is not discussed or the discussion is deferred to the end of project. in this paper is discussed why the question of the license is so important in context of the semantic web that is should be one of the first aspects in a semantic web project. Also it will be shown why a public domain weaver is the only solution that fulfill the the special requirements of the semantic web and that guaranties the reuseablitly of semantic library data for a sustainability of the projects.
AU - Patrick Danowski
ID - 4341
TI - Step one: blow up the silo! - Open bibliographic data, the first step towards Linked Open Data
ER -
TY - BOOK
AB - With the term "Library 2.0" the editors mean an institution which applies the principles of the Web 2.0 such as openness, re-use, collaboration and interaction in the entire organization. Libraries are extending their service offerings and work processes to include the potential of Web 2.0 technologies. This changes the job description and self-image of librarians. The collective volume offers a complete overview of the topic Library 2.0 and the current state of developments from a technological, sociological, information theoretical and practice-oriented perspective.
ED - Danowski, Patrick
ED - Bergmann, Julia
ID - 4346
SN - 9-783-1102-3209-7
TI - Handbuch Bibliothek 2.0
VL - 41
ER -
TY - JOUR
AB - Phenotypic biotyping has traditionally been used to differentiate bacteria occupying distinct ecological niches such as host species. For example, the capacity of Staphylococcus aureus from sheep to coagulate ruminant plasma, reported over 60 years ago, led to the description of small ruminant and bovine S. aureus ecovars. The great majority of small ruminant isolates are represented by a single, widespread clonal complex (CC133) of S. aureus, but its evolutionary origin and the molecular basis for its host tropism remain unknown. Here, we provide evidence that the CC133 clone evolved as the result of a human to ruminant host jump followed by adaptive genome diversification. Comparative whole-genome sequencing revealed molecular evidence for host adaptation including gene decay and diversification of proteins involved in host-pathogen interactions. Importantly, several novel mobile genetic elements encoding virulence proteins with attenuated or enhanced activity in ruminants were widely distributed in CC133 isolates, suggesting a key role in its host-specific interactions. To investigate this further, we examined the activity of a novel staphylococcal pathogenicity island (SaPIov2) found in the great majority of CC133 isolates which encodes a variant of the chromosomally encoded von Willebrand-binding protein (vWbp(Sov2)), previously demonstrated to have coagulase activity for human plasma. Remarkably, we discovered that SaPIov2 confers the ability to coagulate ruminant plasma suggesting an important role in ruminant disease pathogenesis and revealing the origin of a defining phenotype of the classical S. aureus biotyping scheme. Taken together, these data provide broad new insights into the origin and molecular basis of S. aureus ruminant host specificity.
AU - Guinane, Caitriona M
AU - Ben Zakour, Nouri L
AU - Tormo-Mas, Maria A
AU - Weinert, Lucy A
AU - Lowder, Bethan V
AU - Cartwright, Robyn A
AU - Smyth, Davida S
AU - Smyth, Cyril J
AU - Lindsay, Jodi A
AU - Gould, Katherine A
AU - Witney, Adam
AU - Hinds, Jason
AU - Jonathan Bollback
AU - Rambaut, Andrew
AU - Penades, Jose R
AU - Fitzgerald, J Ross
ID - 4358
JF - Genome Biology and Evolution
TI - Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation
VL - 2
ER -
TY - CONF
AB - Depth-bounded processes form the most expressive known fragment of the π-calculus for which interesting verification problems are still decidable. In this paper we develop an adequate domain of limits for the well-structured transition systems that are induced by depth-bounded processes. An immediate consequence of our result is that there exists a forward algorithm that decides the covering problem for this class. Unlike backward algorithms, the forward algorithm terminates even if the depth of the process is not known a priori. More importantly, our result suggests a whole spectrum of forward algorithms that enable the effective verification of a large class of mobile systems.
AU - Wies, Thomas
AU - Zufferey, Damien
AU - Henzinger, Thomas A
ED - Ong, Luke
ID - 4361
TI - Forward analysis of depth-bounded processes
VL - 6014
ER -
TY - CONF
AB - Software transactional memories (STMs) promise simple and efficient concurrent programming. Several correctness properties have been proposed for STMs. Based on a bounded conflict graph algorithm for verifying correctness of STMs, we develop TRACER, a tool for runtime verification of STM implementations. The novelty of TRACER lies in the way it combines coarse and precise runtime analyses to guarantee sound and complete verification in an efficient manner. We implement TRACER in the TL2 STM implementation. We evaluate the performance of TRACER on STAMP benchmarks. While a precise runtime verification technique based on conflict graphs results in an average slowdown of 60x, the two-level approach of TRACER performs complete verification with an average slowdown of around 25x across different benchmarks.
AU - Singh, Vasu
ED - Sokolsky, Oleg
ED - Rosu, Grigore
ED - Tilmann, Nikolai
ED - Barringer, Howard
ED - Falcone, Ylies
ED - Finkbeiner, Bernd
ED - Havelund, Klaus
ED - Lee, Insup
ED - Pace, Gordon
ID - 4362
TI - Runtime verification for software transactional memories
VL - 6418
ER -
TY - CONF
AU - Podelski,Andreas
AU - Thomas Wies
ID - 4364
TI - Counterexample-guided focus
ER -
TY - CONF
AB - In this paper we propose a novel technique for constructing timed automata from properties expressed in the logic mtl, under bounded-variability assumptions. We handle full mtl and include all future operators. Our construction is based on separation of the continuous time monitoring of the input sequence and discrete predictions regarding the future. The separation of the continuous from the discrete allows us to determinize our automata in an exponential construction that does not increase the number of clocks. This leads to a doubly exponential construction from mtl to deterministic timed automata, compared with triply exponential using existing approaches. We offer an alternative to the existing approach to linear real-time model checking, which has never been implemented. It further offers a unified framework for model checking, runtime monitoring, and synthesis, in an approach that can reuse tools, implementations, and insights from the discrete setting.
AU - Nickovic, Dejan
AU - Piterman, Nir
ED - Henzinger, Thomas A.
ED - Chatterjee, Krishnendu
ID - 4369
TI - From MTL to deterministic timed automata
VL - 6246
ER -
TY - CONF
AB - Techniques such as verification condition generation, predicate abstraction, and expressive type systems reduce software verification to proving formulas in expressive logics. Programs and their specifications often make use of data structures such as sets, multisets, algebraic data types, or graphs. Consequently, formulas generated from verification also involve such data structures. To automate the proofs of such formulas we propose a logic (a “calculus”) of such data structures. We build the calculus by starting from decidable logics of individual data structures, and connecting them through functions and sets, in ways that go beyond the frameworks such as Nelson-Oppen. The result are new decidable logics that can simultaneously specify properties of different kinds of data structures and overcome the limitations of the individual logics. Several of our decidable logics include abstraction functions that map a data structure into its more abstract view (a tree into a multiset, a multiset into a set), into a numerical quantity (the size or the height), or into the truth value of a candidate data structure invariant (sortedness, or the heap property). For algebraic data types, we identify an asymptotic many-to-one condition on the abstraction function that guarantees the existence of a decision procedure. In addition to the combination based on abstraction functions, we can combine multiple data structure theories if they all reduce to the same data structure logic. As an instance of this approach, we describe a decidable logic whose formulas are propositional combinations of formulas in: weak monadic second-order logic of two successors, two-variable logic with counting, multiset algebra with Presburger arithmetic, the Bernays-Schönfinkel-Ramsey class of first-order logic, and the logic of algebraic data types with the set content function. The subformulas in this combination can share common variables that refer to sets of objects along with the common set algebra operations. Such sound and complete combination is possible because the relations on sets definable in the component logics are all expressible in Boolean Algebra with Presburger Arithmetic. Presburger arithmetic and its new extensions play an important role in our decidability results. In several cases, when we combine logics that belong to NP, we can prove the satisfiability for the combined logic is still in NP.
AU - Kuncak, Viktor
AU - Piskac, Ruzica
AU - Suter, Philippe
AU - Wies, Thomas
ED - Barthe, Gilles
ED - Hermenegildo, Manuel
ID - 4378
TI - Building a calculus of data structures
VL - 5944
ER -
TY - JOUR
AB - The formal specification component of verification can be exported to simulation through the idea of property checkers. The essence of this approach is the automatic construction of an observer from the specification in the form of a program that can be interfaced with a simulator and alert the user if the property is violated by a simulation trace. Although not complete, this lighter approach to formal verification has been effectively used in software and digital hardware to detect errors. Recently, the idea of property checkers has been extended to analog and mixed-signal systems.
In this paper, we apply the property-based checking methodology to an industrial and realistic example of a DDR2 memory interface. The properties describing the DDR2 analog behavior are expressed in the formal specification language stl/psl in form of assertions. The simulation traces generated from an actual DDR2 interface design are checked with respect to the stl/psl assertions using the amt tool. The focus of this paper is on the translation of the official (informal and descriptive) specification of two non-trivial DDR2 properties into stl/psl assertions. We study both the benefits and the current limits of such approach.
AU - Jones, Kevin D
AU - Konrad,Victor
AU - Dejan Nickovic
ID - 4379
IS - 2
JF - Formal Methods in System Design
TI - Analog property checkers: a DDR2 case study
VL - 36
ER -
TY - CONF
AB - Cloud computing is an emerging paradigm aimed to offer users pay-per-use computing resources, while leaving the burden of managing the computing infrastructure to the cloud provider. We present a new programming and pricing model that gives the cloud user the flexibility of trading execution speed and price on a per-job basis. We discuss the scheduling and resource management challenges for the cloud provider that arise in the implementation of this model. We argue that techniques from real-time and embedded software can be useful in this context.
AU - Henzinger, Thomas A
AU - Tomar, Anmol
AU - Singh, Vasu
AU - Wies, Thomas
AU - Zufferey, Damien
ID - 4380
TI - A marketplace for cloud resources
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 claim that, in order to realize the full potential of cloud computing, the user must be presented with a pricing model that offers flexibility at the requirements level, such as a choice between different degrees of execution speed and the cloud provider must be presented with a programming model that offers flexibility at the execution level, such as a choice between different scheduling policies. In such a flexible framework, with each job, the user purchases a virtual computer with the desired speed and cost characteristics, and the cloud provider can optimize the utilization of resources across a stream of jobs from different users. We designed a flexible framework to test our hypothesis, which is called FlexPRICE (Flexible Provisioning of Resources in a Cloud Environment) and works as follows. A user presents a job to the cloud. The cloud finds different schedules to execute the job and presents a set of quotes to the user in terms of price and duration for the execution. The user then chooses a particular quote and the cloud is obliged to execute the job according to the chosen quote. FlexPRICE thus hides the complexity of the actual scheduling decisions from the user, but still provides enough flexibility to meet the users actual demands. We implemented FlexPRICE in a simulator called PRICES that allows us to experiment with our framework. We observe that FlexPRICE provides a wide range of execution options-from fast and expensive to slow and cheap-- for the whole spectrum of data-intensive and computation-intensive jobs. We also observe that the set of quotes computed by FlexPRICE do not vary as the number of simultaneous jobs increases.
AU - Henzinger, Thomas A
AU - Tomar, Anmol
AU - Singh, Vasu
AU - Wies, Thomas
AU - Zufferey, Damien
ID - 4381
TI - FlexPRICE: Flexible provisioning of resources in a cloud environment
ER -
TY - CONF
AB - Transactional memory (TM) has shown potential to simplify the task of writing concurrent programs. Inspired by classical work on databases, formal definitions of the semantics of TM executions have been proposed. Many of these definitions assumed that accesses to shared data are solely performed through transactions. In practice, due to legacy code and concurrency libraries, transactions in a TM have to share data with non-transactional operations. The semantics of such interaction, while widely discussed by practitioners, lacks a clear formal specification. Those interactions can vary, sometimes in subtle ways, between TM implementations and underlying memory models. We propose a correctness condition for TMs, parametrized opacity, to formally capture the now folklore notion of strong atomicity by stipulating the two following intuitive requirements: first, every transaction appears as if it is executed instantaneously with respect to other transactions and non-transactional operations, and second, non-transactional operations conform to the given underlying memory model. We investigate the inherent cost of implementing parametrized opacity. We first prove that parametrized opacity requires either instrumenting non-transactional operations (for most memory models) or writing to memory by transactions using potentially expensive read-modify-write instructions (such as compare-and-swap). Then, we show that for a class of practical relaxed memory models, parametrized opacity can indeed be implemented with constant-time instrumentation of non-transactional writes and no instrumentation of non-transactional reads. We show that, in practice, parametrizing the notion of correctness allows developing more efficient TM implementations.
AU - Guerraoui, Rachid
AU - Henzinger, Thomas A
AU - Kapalka, Michal
AU - Singh, Vasu
ID - 4382
TI - Transactions in the jungle
ER -
TY - CONF
AB - GIST is a tool that (a) solves the qualitative analysis problem of turn-based probabilistic games with ω-regular objectives; and (b) synthesizes reasonable environment assumptions for synthesis of unrealizable specifications. Our tool provides the first and efficient implementations of several reduction-based techniques to solve turn-based probabilistic games, and uses the analysis of turn-based probabilistic games for synthesizing environment assumptions for unrealizable specifications.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Jobstmann, Barbara
AU - Radhakrishna, Arjun
ID - 4388
TI - GIST: A solver for probabilistic games
VL - 6174
ER -
TY - CONF
AB - Digital components play a central role in the design of complex embedded systems. These components are interconnected with other, possibly analog, devices and the physical environment. This environment cannot be entirely captured and can provide inaccurate input data to the component. It is thus important for digital components to have a robust behavior, i.e. the presence of a small change in the input sequences should not result in a drastic change in the output sequences. In this paper, we study a notion of robustness for sequential circuits. However, since sequential circuits may have parts that are naturally discontinuous (e.g., digital controllers with switching behavior), we need a flexible framework that accommodates this fact and leaves discontinuous parts of the circuit out from the robustness analysis. As a consequence, we consider sequential circuits that have their input variables partitioned into two disjoint sets: control and disturbance variables. Our contributions are (1) a definition of robustness for sequential circuits as a form of continuity with respect to disturbance variables, (2) the characterization of the exact class of sequential circuits that are robust according to our definition, (3) an algorithm to decide whether a sequential circuit is robust or not.
AU - Doyen, Laurent
AU - Henzinger, Thomas A
AU - Legay, Axel
AU - Nickovic, Dejan
ID - 4389
TI - Robustness of sequential circuits
ER -
TY - CONF
AB - Concurrent data structures with fine-grained synchronization are notoriously difficult to implement correctly. The difficulty of reasoning about these implementations does not stem from the number of variables or the program size, but rather from the large number of possible interleavings. These implementations are therefore prime candidates for model checking. We introduce an algorithm for verifying linearizability of singly-linked heap-based concurrent data structures. We consider a model consisting of an unbounded heap where each vertex stores an element from an unbounded data domain, with a restricted set of operations for testing and updating pointers and data elements. Our main result is that linearizability is decidable for programs that invoke a fixed number of methods, possibly in parallel. This decidable fragment covers many of the common implementation techniques — fine-grained locking, lazy synchronization, and lock-free synchronization. We also show how the technique can be used to verify optimistic implementations with the help of programmer annotations. We developed a verification tool CoLT and evaluated it on a representative sample of Java implementations of the concurrent set data structure. The tool verified linearizability of a number of implementations, found a known error in a lock-free implementation and proved that the corrected version is linearizable.
AU - Cerny, Pavol
AU - Radhakrishna, Arjun
AU - Zufferey, Damien
AU - Chaudhuri, Swarat
AU - Alur, Rajeev
ID - 4390
TI - Model checking of linearizability of concurrent list implementations
VL - 6174
ER -
TY - CHAP
AB - While a boolean notion of correctness is given by a preorder on systems and properties, a quantitative notion of correctness is defined by a distance function on systems and properties, where the distance between a system and a property provides a measure of “fit” or “desirability.” In this article, we explore several ways how the simulation preorder can be generalized to a distance function. This is done by equipping the classical simulation game between a system and a property with quantitative objectives. In particular, for systems that satisfy a property, a quantitative simulation game can measure the “robustness” of the satisfaction, that is, how much the system can deviate from its nominal behavior while still satisfying the property. For systems that violate a property, a quantitative simulation game can measure the “seriousness” of the violation, that is, how much the property has to be modified so that it is satisfied by the system. These distances can be computed in polynomial time, since the computation reduces to the value problem in limit average games with constant weights. Finally, we demonstrate how the robustness distance can be used to measure how many transmission errors are tolerated by error correcting codes.
AU - Cerny, Pavol
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ED - Manna, Zohar
ED - Peled, Doron
ID - 4392
T2 - Time For Verification: Essays in Memory of Amir Pnueli
TI - Quantitative Simulation Games
VL - 6200
ER -
TY - CONF
AB - Boolean notions of correctness are formalized by preorders on systems. Quantitative measures of correctness can be formalized by real-valued distance functions between systems, where the distance between implementation and specification provides a measure of “fit” or “desirability.” We extend the simulation preorder to the quantitative setting, by making each player of a simulation game pay a certain price for her choices. We use the resulting games with quantitative objectives to define three different simulation distances. The correctness distance measures how much the specification must be changed in order to be satisfied by the implementation. The coverage distance measures how much the implementation restricts the degrees of freedom offered by the specification. The robustness distance measures how much a system can deviate from the implementation description without violating the specification. We consider these distances for safety as well as liveness specifications. The distances can be computed in polynomial time for safety specifications, and for liveness specifications given by weak fairness constraints. We show that the distance functions satisfy the triangle inequality, that the distance between two systems does not increase under parallel composition with a third system, and that the distance between two systems can be bounded from above and below by distances between abstractions of the two systems. These properties suggest that our simulation distances provide an appropriate basis for a quantitative theory of discrete systems. We also demonstrate how the robustness distance can be used to measure how many transmission errors are tolerated by error correcting codes.
AU - Cerny, Pavol
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 4393
TI - Simulation distances
VL - 6269
ER -
TY - CONF
AB - The problem of locally transforming or translating programs without altering their semantics is central to the construction of correct compilers. For concurrent shared-memory programs this task is challenging because (1) concurrent threads can observe transformations that would be undetectable in a sequential program, and (2) contemporary multiprocessors commonly use relaxed memory models that complicate the reasoning. In this paper, we present a novel proof methodology for verifying that a local program transformation is sound with respect to a specific hardware memory model, in the sense that it is not observable in any context. The methodology is based on a structural induction and relies on a novel compositional denotational semantics for relaxed memory models that formalizes (1) the behaviors of program fragments as a set of traces, and (2) the effect of memory model relaxations as local trace rewrite operations. To apply this methodology in practice, we implemented a semi- automated tool called Traver and used it to verify/falsify several compiler transformations for a number of different hardware memory models.
AU - Burckhardt, Sebastian
AU - Musuvathi, Madanlal
AU - Singh, Vasu
ED - Gupta, Rajiv
ID - 4395
TI - Verifying local transformations on relaxed memory models
VL - 6011
ER -
TY - CONF
AB - Shape analysis is a promising technique to prove program properties about recursive data structures. The challenge is to automatically determine the data-structure type, and to supply the shape analysis with the necessary information about the data structure. We present a stepwise approach to the selection of instrumentation predicates for a TVLA-based shape analysis, which takes us a step closer towards the fully automatic verification of data structures. The approach uses two techniques to guide the refinement of shape abstractions: (1) during program exploration, an explicit heap analysis collects sample instances of the heap structures, which are used to identify the data structures that are manipulated by the program; and (2) during abstraction refinement along an infeasible error path, we consider different possible heap abstractions and choose the coarsest one that eliminates the infeasible path. We have implemented this combined approach for automatic shape refinement as an extension of the software model checker BLAST. Example programs from a data-structure library that manipulate doubly-linked lists and trees were successfully verified by our tool.
AU - Beyer, Dirk
AU - Henzinger, Thomas A
AU - Théoduloz, Grégory
AU - Zufferey, Damien
ED - Rosenblum, David
ED - Taenzer, Gabriele
ID - 4396
TI - Shape refinement through explicit heap analysis
VL - 6013
ER -
TY - CONF
AB - We address the problem of localizing homology classes, namely, finding the cycle representing a given class with the most concise geometric measure. We focus on the volume measure, that is, the 1-norm of a cycle. Two main results are presented. First, we prove the problem is NP-hard to approximate within any constant factor. Second, we prove that for homology of dimension two or higher, the problem is NP-hard to approximate even when the Betti number is O(1). A side effect is the inapproximability of the problem of computing the nonbounding cycle with the smallest volume, and computing cycles representing a homology basis with the minimal total volume. We also discuss other geometric measures (diameter and radius) and show their disadvantages in homology localization. Our work is restricted to homology over the ℤ2 field.
AU - Chen, Chao
AU - Freedman, Daniel
ID - 10909
T2 - Proceedings of the 2010 Annual ACM-SIAM Symposium on Discrete Algorithms
TI - Hardness results for homology localization
ER -
TY - CONF
AB - We present ABC, a software tool for automatically computing symbolic upper bounds on the number of iterations of nested program loops. The system combines static analysis of programs with symbolic summation techniques to derive loop invariant relations between program variables. Iteration bounds are obtained from the inferred invariants, by replacing variables with bounds on their greatest values. We have successfully applied ABC to a large number of examples. The derived symbolic bounds express non-trivial polynomial relations over loop variables. We also report on results to automatically infer symbolic expressions over harmonic numbers as upper bounds on loop iteration counts.
AU - Blanc, Régis
AU - Henzinger, Thomas A
AU - Hottelier, Thibaud
AU - Kovács, Laura
ED - Clarke, Edmund M
ED - Voronkov, Andrei
ID - 10908
SN - 0302-9743
T2 - Logic for Programming, Artificial Intelligence, and Reasoning
TI - ABC: Algebraic Bound Computation for loops
VL - 6355
ER -
TY - JOUR
AB - Nuclear pore complexes (NPCs) serve as transport channels across the nuclear membrane, a double lipid bilayer that physically separates the nucleoplasm and cytoplasm of eukaryotic cells. New evidence suggests that the multiprotein nuclear pores also play a role in chromatin organization and gene expression. Given the importance of NPC function, it is not surprising that a growing list of human diseases and developmental defects have been linked to its malfunction. In order to fully understand the functional repertoire of NPCs and their essential role for nuclear organization, it is critical to determine the sequence of events that lead to the formation of nuclear pores. This is particularly relevant since NPC number, and possibly composition, are tightly linked to metabolic activity. Most of our knowledge is derived from NPC formation that occurs in dividing cells at the end of mitosis when the nuclear envelope (NE) and NPCs reform from disassembled precursors. However, NPC assembly also takes place during interphase into an intact NE. Importantly, this process is not restricted to dividing cells but also occurs during cell differentiation. Here, we will review aspects unique to this process, namely the regulation of nuclear expansion and the mechanisms of fusion between the outer and inner nuclear membranes. We will then discuss conserved and diverging mechanisms between post-mitotic and interphase assembly of the proteinaceous structure in light of recently published data.
AU - Doucet, Christine M.
AU - HETZER, Martin W
ID - 11099
JF - Chromosoma
KW - Genetics (clinical)
KW - Genetics
SN - 0009-5915
TI - Nuclear pore biogenesis into an intact nuclear envelope
VL - 119
ER -
TY - JOUR
AB - Nuclear pore complexes have recently been shown to play roles in gene activation; however their potential involvement in metazoan transcription remains unclear. Here we show that the nucleoporins Sec13, Nup98, and Nup88, as well as a group of FG-repeat nucleoporins, bind to the Drosophila genome at functionally distinct loci that often do not represent nuclear envelope contact sites. Whereas Nup88 localizes to silent loci, Sec13, Nup98, and a subset of FG-repeat nucleoporins bind to developmentally regulated genes undergoing transcription induction. Strikingly, RNAi-mediated knockdown of intranuclear Sec13 and Nup98 specifically inhibits transcription of their target genes and prevents efficient reactivation of transcription after heat shock, suggesting an essential role of NPC components in regulating complex gene expression programs of multicellular organisms.
AU - Capelson, Maya
AU - Liang, Yun
AU - Schulte, Roberta
AU - Mair, William
AU - Wagner, Ulrich
AU - HETZER, Martin W
ID - 11102
IS - 3
JF - Cell
KW - General Biochemistry
KW - Genetics and Molecular Biology
SN - 0092-8674
TI - Chromatin-bound nuclear pore components regulate gene expression in higher eukaryotes
VL - 140
ER -
TY - JOUR
AB - In metazoa, nuclear pore complexes (NPCs) assemble from disassembled precursors into a reforming nuclear envelope (NE) at the end of mitosis and into growing intact NEs during interphase. Here, we show via RNAi-mediated knockdown that ELYS, a nucleoporin critical for the recruitment of the essential Nup107/160 complex to chromatin, is required for NPC assembly at the end of mitosis but not during interphase. Conversely, the transmembrane nucleoporin POM121 is critical for the incorporation of the Nup107/160 complex into new assembly sites specifically during interphase. Strikingly, recruitment of the Nup107/160 complex to an intact NE involves a membrane curvature-sensing domain of its constituent Nup133, which is not required for postmitotic NPC formation. Our results suggest that in organisms with open mitosis, NPCs assemble via two distinct mechanisms to accommodate cell cycle-dependent differences in NE topology.
AU - Doucet, Christine M.
AU - Talamas, Jessica A.
AU - HETZER, Martin W
ID - 11101
IS - 6
JF - Cell
KW - General Biochemistry
KW - Genetics and Molecular Biology
SN - 0092-8674
TI - Cell cycle-dependent differences in nuclear pore complex assembly in metazoa
VL - 141
ER -
TY - JOUR
AB - The nuclear envelope (NE) is a highly regulated membrane barrier that separates the nucleus from the cytoplasm in eukaryotic cells. It contains a large number of different proteins that have been implicated in chromatin organization and gene regulation. Although the nuclear membrane enables complex levels of gene expression, it also poses a challenge when it comes to cell division. To allow access of the mitotic spindle to chromatin, the nucleus of metazoans must completely disassemble during mitosis, generating the need to re-establish the nuclear compartment at the end of each cell division. Here, I summarize our current understanding of the dynamic remodeling of the NE during the cell cycle.
AU - HETZER, Martin W
ID - 11097
IS - 3
JF - Cold Spring Harbor Perspectives in Biology
KW - General Biochemistry
KW - Genetics and Molecular Biology
SN - 1943-0264
TI - The nuclear envelope
VL - 2
ER -
TY - JOUR
AU - HETZER, Martin W
ID - 11098
IS - 2
JF - Aging
KW - Cell Biology
KW - Aging
SN - 1945-4589
TI - The role of the nuclear pore complex in aging of post-mitotic cells
VL - 2
ER -
TY - CONF
AB - Ferroelectric ceramic materials have a wide range of applications because of their piezoelectric and pyroelectric properties. One of their most important physical properties is the specific heat. In this study, the specific heats of a series of lead-zirconate-titanate (PZT) compositions in the vicinity of the morphotropic phase boundary (MPB) were measured. The temperature range was from 1.8 to 300 K. It is believed that these are the lowest temperature measurements ever made on PZT. Differences between the specific heats of the different compositions were very small. However, the calculated Debye temperatures were slightly different. The results are useful in computing design parameters for technical devices.
AU - Lang, S. B.
AU - Lashley, J. C.
AU - Modic, Kimberly A
AU - Fisher, R. A.
AU - Zhu, W. M.
AU - Ye, Z. G.
ID - 11753
SN - 1553-5282
T2 - Proceedings of the 2010 IEEE International Conference on Solid Dielectrics
TI - Specific heat of a ferroelectric PZT ceramic at the morphotropic phase boundary
ER -
TY - CONF
AB - Ferroelectric ceramic materials have a wide range of applications because of their piezoelectric and pyroelectric properties. One of their most important physical properties is the specific heat. In this study, the specific heats of a series of lead-zirconate-titanate (PZT) compositions in the vicinity of the morphotropic phase boundary (MPB) were measured. The temperature range was from 1.8 to 300 K. It is believed that these are the lowest temperature measurements ever made on PZT. Differences between the specific heats of the different compositions were very small. However, the calculated Debye temperatures were slightly different. The results are useful in computing design parameters for technical devices.
AU - Lang, S.B.
AU - Lashley, J.C.
AU - Modic, Kimberly A
AU - Fisher, R.A.
AU - Zhu, W.M.
AU - Ye, Z.G.
ID - 11754
SN - 978-142445795-3
T2 - 15th IEEE Mediterranean Electrotechnical Conference
TI - Specific heat of a ferroelectric PZT ceramic at the morphotropic phase boundary
ER -
TY - JOUR
AB - As reported in a number of recent studies, turbulence in pipe flow is transient for Re<2000 and the flow eventually always returns to the laminar state. Generally, the lifetime of turbulence has been observed to increase rapidly with Reynolds number but there is currently no accord on the exact scaling behaviour. In particular, it is not clear whether a critical point exists where turbulence becomes sustained or if it remains transient. We here aim to clarify if these conflicting results may have been caused by the different experimental and numerical protocols used to trigger turbulence in these studies.
AU - de Lózar, Alberto
AU - Björn Hof
ID - 2796
IS - 1888
JF - Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences
TI - An experimental study of the decay of turbulent puffs in pipe flow
VL - 367
ER -
TY - CONF
AB - In pipe flow at low Reynolds number, decay of localized disturbances is observed. As the Reynolds number is increased, the question emerges whether the life time of these disturbances diverges at a finite Reynolds number or remains transient. In the current investigation we determine their life time quantitatively from pressure measurements, while in previous investigations the distance over which a structure survives has been determined. The obtained results confirm that the life time of localized disturbances does not diverge in the range of Reynolds numbers covered in the current experiment.
AU - Kuik, Dirk J
AU - Poelma, Christian
AU - Björn Hof
AU - Westerweel, Jerry
ID - 2797
TI - Quantitative measurement of the life time of turbulence in pipe flow
VL - 132
ER -
TY - JOUR
AB - Plants exhibit an amazing developmental flexibility. Plant embryogenesis results in the establishment of a simple apical-basal axis represented by apical shoot and basal root meristems. Later, during postembryonic growth, shaping of the plant body continues by the formation and activation of numerous adjacent meristems that give rise to lateral shoot branches, leaves, flowers, or lateral roots. This developmental plasticity reflects an important feature of the plant's life strategy based on the rapid reaction to different environmental stimuli, such as temperature fluctuations, availability of nutrients, light or water and response resulting in modulation of developmental programs. Plant hormones are important endogenous factors for the integration of these environmental inputs and regulation of plant development. After a period of studies focused primarily on single hormonal pathways that enabled us to understand the hormone perception and signal transduction mechanisms, it became obvious that the developmental output mediated by a single hormonal pathway is largely modified through a whole network of interactions with other hormonal pathways. In this review, we will summarize recent knowledge on hormonal networks that regulate the development and growth of root with focus on the hormonal interactions that shape the root apical meristem.
AU - Eva Benková
AU - Hejátko, Jan
ID - 2868
IS - 4
JF - Plant Molecular Biology
TI - Hormone interactions at the root apical meristem
VL - 69
ER -
TY - JOUR
AB - Lateral root formation is a major determinant of root systems architecture. The degree of root branching impacts the efficiency of water uptake, acquisition of nutrients and anchorage by plants. Understanding the regulation of lateral root development is therefore of vital agronomic importance. The molecular and cellular basis of lateral root formation has been most extensively studied in the plant model Arabidopsis thaliana (Arabidopsis). Significant progress has recently been made in identifying many new Arabidopsis genes that regulate lateral root initiation, patterning and emergence processes. We review how these studies have revealed that the plant hormone auxin represents a common signal that integrates these distinct yet interconnected developmental processes.
AU - Péret, Benjamin
AU - De Rybel, Bert
AU - Casimiro, Ilda
AU - Eva Benková
AU - Swarup, Ranjan
AU - Laplaze, Laurent
AU - Beeckman, Tom
AU - Bennett, Malcolm J
ID - 2869
IS - 7
JF - Trends in Plant Science
TI - Arabidopsis lateral root development: an emerging story
VL - 14
ER -
TY - JOUR
AB - We describe a new implementation of the Edmonds’s algorithm for computing a perfect matching of minimum cost, to which we refer as Blossom V. A key feature of our implementation is a combination of two ideas that were shown to be effective for this problem: the “variable dual updates” approach of Cook and Rohe (INFORMS J Comput 11(2):138–148, 1999) and the use of priority queues. We achieve this by maintaining an auxiliary graph whose nodes correspond to alternating trees in the Edmonds’s algorithm. While our use of priority queues does not improve the worst-case complexity, it appears to lead to an efficient technique. In the majority of our tests Blossom V outperformed previous implementations of Cook and Rohe (INFORMS J Comput 11(2):138–148, 1999) and Mehlhorn and Schäfer (J Algorithmics Exp (JEA) 7:4, 2002), sometimes by an order of magnitude. We also show that for large VLSI instances it is beneficial to update duals by solving a linear program, contrary to a conjecture by Cook and Rohe.
AU - Vladimir Kolmogorov
ID - 2932
IS - 1
JF - Mathematical Programming Computation
TI - Blossom V: A new implementation of a minimum cost perfect matching algorithm
VL - 1
ER -
TY - JOUR
AB - Plant-parasitic nematodes are destructive plant pathogens that cause significant yield losses. They induce highly specialized feeding sites (NFS) in infected plant roots from which they withdraw nutrients. In order to establish these NFS, it is thought that the nematodes manipulate the molecular and physiological pathways of their hosts. Evidence is accumulating that the plant signalling molecule auxin is involved in the initiation and development of the feeding sites of sedentary plant-parasitic nematodes. Intercellular transport of auxin is essential for various aspects of plant growth and development. Here, we analysed the spatial and temporal expression of PIN auxin transporters during the early events of NFS establishment using promoter-GUS/GFP fusion lines. Additionally, single and double pin mutants were used in infection studies to analyse the role of the different PIN proteins during cyst nematode infection. Based on our results, we postulate a model in which PIN1-mediated auxin transport is needed to deliver auxin to the initial syncytial cell, whereas PIN3 and PIN4 distribute the accumulated auxin laterally and are involved in the radial expansion of the NFS. Our data demonstrate that cyst nematodes are able to hijack the auxin distribution network in order to facilitate the infection process. © 2009 Grunewald et al
AU - Grunewald, Wim
AU - Cannoot, Bernard
AU - Jirí Friml
AU - Gheysen, Godelieve
ID - 3046
IS - 1
JF - PLoS Pathogens
TI - Parasitic nematodes modulate PIN mediated auxin transport to facilitate infection
VL - 5
ER -
TY - JOUR
AB -
Auxin transport is mediated at the cellular level by three independent mechanisms that are characterised by the PIN-formed (PIN), P-glycoprotein (ABCB/PGP) and AUX/LAX transport proteins. The PIN and ABCB transport proteins, best represented by PIN1 and ABCB19 (PGP19), have been shown to coordinately regulate auxin efflux. When PIN1 and ABCB19 coincide on the plasma membrane, their interaction enhances the rate and specificity of auxin efflux and the dynamic cycling of PIN1 is reduced. However, ABCB19 function is not regulated by the dynamic cellular trafficking mechanisms that regulate PIN1 in apical tissues, as localisation of ABCB19 on the plasma membrane was not inhibited by short-term treatments with latrunculin B, oryzalin, brefeldin A (BFA) or wortmannin - all of which have been shown to alter PIN1 and/or PIN2 plasma membrane localisation. When taken up by endocytosis, the styryl dye FM4-64 labels diffuse rather than punctuate intracellular bodies in abcb19 (pgp19), and some aggregations of PIN1 induced by short-term BFA treatment did not disperse after BFA washout in abcb19. Although the subcellular localisations of ABCB19 and PIN1 in the reciprocal mutant backgrounds were like those in wild type, PIN1 plasma membrane localisation in abcb19 roots was more easily perturbed by the detergent Triton X-100, but not other non-ionic detergents. ABCB19 is stably associated with sterol/sphingolipid-enriched membrane fractions containing BIG/TIR3 and partitions into Triton X-100 detergent-resistant membrane (DRM) fractions. In the wild type, PIN1 was also present in DRMs, but was less abundant in abcb19 DRMs. These observations suggested a rationale for the observed lack of auxin transport activity when PIN1 is expressed in a non-plant heterologous system. PIN1 was therefore expressed in Schizosaccharomyces pombe, which has plant-like sterol-enriched microdomains, and catalysed auxin transport in these cells. These data suggest that ABCB19 stabilises PIN1 localisation at the plasma membrane in discrete cellular subdomains where PIN1 and ABCB19 expression overlaps.
AU - Titapiwatanakun, Boosaree
AU - Blakeslee, Joshua
AU - Bandyopadhyay, Anindita
AU - Yang, Haibing
AU - Mravec, Jozef
AU - Sauer, Michael
AU - Cheng, Yan
AU - Adamec, Jiří
AU - Nagashima, Akitomo
AU - Geisler, Markus
AU - Sakai, Tatsuya
AU - Jirí Friml
AU - Peer, Wendy A
AU - Murphy, Angus S
ID - 3047
IS - 1
JF - Plant Journal
TI - ABCB19 PGP19 stabilises PIN1 in membrane microdomains in Arabidopsis
VL - 57
ER -
TY - JOUR
AB - Endocytic vesicle trafficking is crucial for regulating activity and localization of plasma membrane components, but the process is still poorly genetically defined in plants. Membrane proteins of the PIN-FORMED (PIN) family exhibit polar localization in plant cells and facilitate cellular efflux of the plant hormone auxin, thereby regulating multiple developmental processes [1, 2]. PIN proteins undergo constitutive endocytosis and GNOM ARF GEF-dependent recycling [3-5], and their localization is under extensive regulation by developmental and environmental cues [6-9]. We designed a fluorescence imaging-based screen to identify Arabidopsis thaliana mutants defective in internalization of proteins including PINs from the plasma membrane. We identified three mutant loci, BFA-visualized endocytic trafficking defective1 (ben1) through ben3 that do not efficiently accumulate PIN1-GFP in intracellular compartments after inhibition of recycling and secretion by fungal toxin brefeldin A (BFA). Fine mapping revealed that BEN1 encodes an ARF GEF vesicle trafficking regulator from the functionally uncharacterized BIG class. ben1 mutant has been previously implicated in pathogen response [10] and shows cell polarity, BFA sensitivity, and growth defects. BEN1 is involved in endocytosis of plasma membrane proteins and localizes to early endocytic compartments distinct from GNOM-positive endosomes. Our results identify BEN1 as the ARF GEF mediating early endosomal traffic.
AU - Tanaka, Hirokazu
AU - Kitakura, Saeko
AU - De Rycke, Riet M
AU - De Groodt, Ruth
AU - Jirí Friml
ID - 3048
IS - 5
JF - Current Biology
TI - Fluorescence imaging based screen identifies ARF GEF component of early endosomal trafficking
VL - 19
ER -
TY - JOUR
AB - Postembryonic de novo organogenesis represents an important competence evolved in plants that allows their physiological and developmental adaptation to changing environmental conditions. The phytohormones auxin and cytokinin (CK) are important regulators of the developmental fate of pluripotent plant cells. However, the molecular nature of their interaction(s) in control of plant organogenesis is largely unknown. Here, we show that CK modulates auxin-induced organogenesis (AIO) via regulation of the efflux-dependent intercellular auxin distribution. We used the hypocotyl explants-based in vitro system to study the mechanism underlying de novo organogenesis. We show that auxin, but not CK, is capable of triggering organogenesis in hypocotyl explants. The AIO is accompanied by endogenous CK production and tissue-specific activation of CK signaling. CK affects differential auxin distribution, and the CK-mediated modulation of organogenesis is simulated by inhibition of polar auxin transport. CK reduces auxin efflux from cultured tobacco cells and regulates expression of auxin efflux carriers from the PIN family in hypocotyl explants. Moreover, endogenous CK levels influence PIN transcription and are necessary to maintain intercellular auxin distribution in planta. Based on these findings, we propose a model in which auxin acts as a trigger of the organogenic processes, whose output is modulated by the endogenously produced CKs. We propose that an important mechanism of this CK action is its effect on auxin distribution via regulation of expression of auxin efflux carriers.
AU - Pernisová, Markéta
AU - Klíma, Petr
AU - Horák, Jakub
AU - Válková, Martina
AU - Malbeck, Jiří
AU - Souček, Přemysl
AU - Reichman, Pavel
AU - Hoyerová, Klára
AU - Dubová, Jaroslava
AU - Jirí Friml
AU - Zažímalová, Eva
AU - Hejátko, Jan
ID - 3049
IS - 9
JF - PNAS
TI - Cytokinins modulate auxin induced organogenesis in plants via regulation of the auxin efflux
VL - 106
ER -
TY - JOUR
AB - Plant development is governed by signaling molecules called phytohormones. Typically, in certain developmental processes more than 1 hormone is implicated and, thus, coordination of their overlapping activities is crucial for correct plant development. However, molecular mechanisms underlying the hormonal crosstalk are only poorly understood. Multiple hormones including cytokinin and auxin have been implicated in the regulation of root development. Here we dissect the roles of cytokinin in modulating growth of the primary root. We show that cytokinin effect on root elongation occurs through ethylene signaling whereas cytokinin effect on the root meristem size involves ethylene-independent modulation of transport-dependent asymmetric auxin distribution. Exogenous or endogenous modification of cytokinin levels and cytokinin signaling lead to specific changes in transcription of several auxin efflux carrier genes from the PIN family having a direct impact on auxin efflux from cultured cells and on auxin distribution in the root apex. We propose a novel model for cytokinin action in regulating root growth: Cytokinin influences cell-to-cell auxin transport by modification of expression of several auxin transport components and thus modulates auxin distribution important for regulation of activity and size of the root meristem.
AU - Růžička, Kamil
AU - Šimášková, Mária
AU - Duclercq, Jérôme
AU - Petrášek, Jan
AU - Zažímalová, Eva
AU - Sibu Simon
AU - Jirí Friml
AU - Van Montagu, Marc C
AU - Eva Benková
ID - 3050
IS - 11
JF - PNAS
TI - Cytokinin regulates root meristem activity via modulation of the polar auxin transport
VL - 106
ER -
TY - JOUR
AU - Weijers, Dolf
AU - Friml, Jirí
ID - 3051
IS - 6
JF - Cell
TI - SnapShot: Auxin signaling and transport
VL - 136
ER -
TY - JOUR
AB - The dynamic, differential distribution of the hormone auxin within plant tissues controls an impressive variety of developmental processes, which tailor plant growth and morphology to environmental conditions. Various environmental and endogenous signals can be integrated into changes in auxin distribution through their effects on local auxin biosynthesis and intercellular auxin transport. Individual cells interpret auxin largely by a nuclear signaling pathway that involves the F box protein TIR1 acting as an auxin receptor. Auxin-dependent TIR1 activity leads to ubiquitination-based degradation of transcriptional repressors and complex transcriptional reprogramming. Thus, auxin appears to be a versatile trigger of preprogrammed developmental changes in plant cells.
AU - Vanneste, Steffen
AU - Friml, Jirí
ID - 3052
IS - 6
JF - Cell
TI - Auxin: A trigger for change in plant development
VL - 136
ER -
TY - JOUR
AU - Benková, Eva
AU - Ivanchenko, Maria
AU - Friml, Jirí
AU - Shishkova, Svetlana
AU - Dubrovsky, Joseph
ID - 3053
IS - 4
JF - Trends in Plant Science
TI - A morphogenetic trigger: Is there an emerging concept in plant developmental biology?
VL - 14
ER -
TY - JOUR
AB - As multicellular organisms, plants, like animals, use endogenous signaling molecules to coordinate their own physiology and development. To compensate for the absence of a cardiovascular system, plants have evolved specialized transport pathways to distribute signals and nutrients. The main transport streams include the xylem flow of the nutrients from the root to the shoot and the phloem flow of materials from the photosynthetic active tissues. These long-distance transport processes are complemented by several intercellular transport mechanisms (apoplastic, symplastic and transcellular transport). A prominent example of transcellular flow is transport of the phytohormone auxin within tissues. The process is mediated by influx and efflux carriers, whose polar localization in the plasma membrane determines the directionality of the flow. This polar auxin transport generates auxin maxima and gradients within tissues that are instrumental in the diverse regulation of various plant developmental processes, including embryogenesis, organogenesis, vascular tissue formation and tropisms.
AU - Robert, Hélène
AU - Friml, Jirí
ID - 3054
IS - 5
JF - Nature Chemical Biology
TI - Auxin and other signals on the move in plants
VL - 5
ER -
TY - JOUR
AB - ACAP-type ARF GTPase activating proteins (ARF-GAPs) regulate multiple cellular processes, including endocytosis, secretion, phagocytosis, cell adhesion and cell migration. However, the regulation of ACAP functions by other cellular proteins is poorly understood. We have reported previously that a plant ACAP, VAN3, plays a pivotal role in plant venation continuity. Here, we report on newly identified VAN3 regulators: the CVP2 (cotyledon vascular pattern 2) 5 PTase, which is considered to degrade IP3 and also to produce PtdIns(4)P from PtdIns(4,5)P2; and a PH domain-containing protein, VAB (VAN3 binding protein). Combinational mutations of both CVP2 and its closest homologue CVL1 (CVP2 like 1) phenocopied the strong allele of van3 mutants, showing severe vascular continuity. The phenotype of double mutants between van3, cvp2 and vab suggested that VAN3, CVP2 and VAB function in vascular pattern formation in the same pathway. Localization analysis revealed that both CVP2 and VAB colocalize with VAN3 in the trans- Golgi network (TGN), supporting their functions in the same pathway. The subcellular localization of VAN3 was dependent on its PH domain, and mislocalization of VAN3 was induced in cvp2 or vab mutants. These results suggest that CVP2 and VAB cooperatively regulate the subcellular localization of VAN3 through the interaction between its PH domain and phosphoinositides and/or inositol phosphates. In addition, PtdIns(4)P, to which VAN3 binds preferentially, enhanced the ARF-GAP activity of VAN3, whereas IP3 inhibited it. These results suggest the existence of PtdIns(4)P and/or IP3-dependent subcellular targeting and regulation of VAN3 ACAP activity that governs plant vascular tissue continuity.
AU - Naramoto, Satoshi
AU - Sawa, Shinichiro
AU - Koizumi, Koji
AU - Uemura, Tomohiro
AU - Ueda, Takashi
AU - Jirí Friml
AU - Nakano, Akihiko
AU - Fukuda, Hiroo
ID - 3055
IS - 9
JF - Development
TI - Phosphoinositide-dependent regulation of VAN3 ARF-GAP localization and activity essential for vascular tissue continuity in plants
VL - 136
ER -