@article{4157, abstract = {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.}, author = {Papusheva, Ekaterina and Heisenberg, Carl-Philipp J}, journal = {EMBO Journal}, number = {16}, pages = {2753 -- 2768}, publisher = {Wiley-Blackwell}, title = {{Spatial organization of adhesion: force-dependent regulation and function in tissue morphogenesis}}, doi = {10.1038/emboj.2010.182}, volume = {29}, year = {2010}, } @article{4243, abstract = {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).}, author = {Barton, Nicholas H and Etheridge, Alison and Véber, Amandine}, journal = {Electronic Journal of Probability}, number = {7}, pages = {162 -- 216}, publisher = {Institute of Mathematical Statistics}, title = {{A new model for evolution in a spatial continuum}}, doi = {10.1214/EJP.v15-741}, volume = {15}, year = {2010}, } @article{3867, abstract = {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.}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Henzinger, Thomas A}, journal = {Logical Methods in Computer Science}, number = {3}, pages = {1 -- 23}, publisher = {International Federation for Computational Logic}, title = {{Expressiveness and closure properties for quantitative languages}}, doi = {10.2168/LMCS-6(3:10)2010}, volume = {6}, year = {2010}, } @article{3868, abstract = {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}, author = {Chatterjee, Krishnendu and De Alfaro, Luca and Majumdar, Ritankar and Raman, Vishwanath}, journal = {Logical Methods in Computer Science}, number = {3}, pages = {1 -- 27}, publisher = {International Federation for Computational Logic}, title = {{Algorithms for game metrics}}, doi = {10.2168/LMCS-6(3:13)2010}, volume = {6}, year = {2010}, } @inproceedings{3782, abstract = {In cortex surface segmentation, the extracted surface is required to have a particular topology, namely, a two-sphere. We present a new method for removing topology noise of a curve or surface within the level set framework, and thus produce a cortical surface with correct topology. We define a new energy term which quantifies topology noise. We then show how to minimize this term by computing its functional derivative with respect to the level set function. This method differs from existing methods in that it is inherently continuous and not digital; and in the way that our energy directly relates to the topology of the underlying curve or surface, versus existing knot-based measures which are related in a more indirect fashion. The proposed flow is validated empirically.}, author = {Chen, Chao and Freedman, Daniel}, booktitle = {Conference proceedings MCV 2010}, location = {Beijing, China}, pages = {31 -- 42}, publisher = {Springer}, title = {{Topology noise removal for curve and surface evolution}}, doi = {10.1007/978-3-642-18421-5_4}, volume = {6533}, year = {2010}, } @article{3789, abstract = {The development of multicellular organisms is dependent on the tight coordination between tissue growth and morphogenesis. The stereotypical orientation of cell divisions has been proposed to be a fundamental mechanism by which proliferating and growing tissues take shape. However, the actual contribution of stereotypical division orientation (SDO) to tissue morphogenesis is unclear. In zebrafish, cell divisions with stereotypical orientation have been implicated in both body-axis elongation and neural rod formation [1, 2], although there is little direct evidence for a critical function of SDO in either of these processes. Here we show that SDO is required for formation of the neural rod midline during neurulation but dispensable for elongation of the body axis during gastrulation. Our data indicate that SDO during both gastrulation and neurulation is dependent on the noncanonical Wnt receptor Frizzled 7 (Fz7) and that interfering with cell division orientation leads to severe defects in neural rod midline formation but not body-axis elongation. These findings suggest a novel function for Fz7-controlled cell division orientation in neural rod midline formation during neurulation. }, author = {Quesada-Hernández, Elena and Caneparo, Luca and Schneider, Sylvia and Winkler, Sylke and Liebling, Michael and Fraser, Scott and Heisenberg, Carl-Philipp J}, journal = {Current Biology}, number = {21}, pages = {1966 -- 1972}, publisher = {Cell Press}, title = {{Stereotypical cell division orientation controls neural rod midline formation in zebrafish}}, doi = {10.1016/j.cub.2010.10.009}, volume = {20}, year = {2010}, } @inproceedings{4542, abstract = {Weighted automata are finite automata with numerical weights on transitions. Nondeterministic weighted automata define quantitative languages L that assign to each word w a real number L(w) computed as the maximal value of all runs over w, and the value of a run r is a function of the sequence of weights that appear along r. There are several natural functions to consider such as Sup, LimSup, LimInf, limit average, and discounted sum of transition weights. We introduce alternating weighted automata in which the transitions of the runs are chosen by two players in a turn-based fashion. Each word is assigned the maximal value of a run that the first player can enforce regardless of the choices made by the second player. We survey the results about closure properties, expressiveness, and decision problems for nondeterministic weighted automata, and we extend these results to alternating weighted automata. For quantitative languages L 1 and L 2, we consider the pointwise operations max(L 1,L 2), min(L 1,L 2), 1 − L 1, and the sum L 1 + L 2. We establish the closure properties of all classes of alternating weighted automata with respect to these four operations. We next compare the expressive power of the various classes of alternating and nondeterministic weighted automata over infinite words. In particular, for limit average and discounted sum, we show that alternation brings more expressive power than nondeterminism. Finally, we present decidability results and open questions for the quantitative extension of the classical decision problems in automata theory: emptiness, universality, language inclusion, and language equivalence.}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Henzinger, Thomas A}, location = {Wroclaw, Poland}, pages = {3 -- 13}, publisher = {Springer}, title = {{Alternating weighted automata}}, doi = {10.1007/978-3-642-03409-1_2}, volume = {5699}, year = {2009}, } @inproceedings{4543, abstract = {The synthesis of a reactive system with respect to all omega-regular specification requires the solution of a graph game. Such games have been extended in two natural ways. First, a game graph can be equipped with probabilistic choices between alternative transitions, thus allowing the, modeling of uncertain behaviour. These are called stochastic games. Second, a liveness specification can he strengthened to require satisfaction within all unknown but bounded amount of time. These are called finitary objectives. We study. for the first time, the, combination of Stochastic games and finitary objectives. We characterize the requirements on optimal strategies and provide algorithms for Computing the maximal achievable probability of winning stochastic games with finitary parity or Street, objectives. Most notably the set of state's from which a player can win with probability . for a finitary parity objective can he computed in polynomial time even though no polynomial-time algorithm is known in the nonfinitary case.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Horn, Florian}, location = {High Tatras, Slovakia}, pages = {34 -- 54}, publisher = {Springer}, title = {{Stochastic games with finitary objectives}}, doi = {10.1007/978-3-642-03816-7_4}, volume = {5734}, year = {2009}, } @inproceedings{4545, abstract = {A stochastic game is a two-player game played oil a graph, where in each state the successor is chosen either by One of the players, or according to a probability distribution. We Survey Stochastic games with limsup and liminf objectives. A real-valued re-ward is assigned to each state, and the value of all infinite path is the limsup (resp. liminf) of all rewards along the path. The value of a stochastic game is the maximal expected value of an infinite path that call he achieved by resolving the decisions of the first player. We present the complexity of computing values of Stochastic games and their subclasses, and the complexity, of optimal strategies in such games. }, author = {Chatterjee, Krishnendu and Doyen, Laurent and Henzinger, Thomas A}, location = {Rhodos, Greece}, pages = {1 -- 15}, publisher = {Springer}, title = {{A survey of stochastic games with limsup and liminf objectives}}, doi = {10.1007/978-3-642-02930-1_1}, volume = {5556}, year = {2009}, } @inproceedings{4569, abstract = {Most specification languages express only qualitative constraints. However, among two implementations that satisfy a given specification, one may be preferred to another. For example, if a specification asks that every request is followed by a response, one may prefer an implementation that generates responses quickly but does not generate unnecessary responses. We use quantitative properties to measure the “goodness” of an implementation. Using games with corresponding quantitative objectives, we can synthesize “optimal” implementations, which are preferred among the set of possible implementations that satisfy a given specification. In particular, we show how automata with lexicographic mean-payoff conditions can be used to express many interesting quantitative properties for reactive systems. In this framework, the synthesis of optimal implementations requires the solution of lexicographic mean-payoff games (for safety requirements), and the solution of games with both lexicographic mean-payoff and parity objectives (for liveness requirements). We present algorithms for solving both kinds of novel graph games.}, author = {Bloem, Roderick and Chatterjee, Krishnendu and Henzinger, Thomas A and Jobstmann, Barbara}, location = {Grenoble, France}, pages = {140 -- 156}, publisher = {Springer}, title = {{Better quality in synthesis through quantitative objectives}}, doi = {10.1007/978-3-642-02658-4_14}, volume = {5643}, year = {2009}, } @misc{5392, abstract = {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 of [GO09] and present a precise characterization of the decidability and undecidability frontier of the quantitative and qualitative decision problems.}, author = {Chatterjee, Krishnendu}, issn = {2664-1690}, pages = {17}, publisher = {IST Austria}, title = {{Probabilistic automata on infinite words: Decidability and undecidability results}}, doi = {10.15479/AT:IST-2009-0004}, year = {2009}, } @misc{5393, abstract = {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 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.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Jobstmann, Barbara and Radhakrishna, Arjun}, issn = {2664-1690}, pages = {12}, publisher = {IST Austria}, title = {{Gist: A solver for probabilistic games}}, doi = {10.15479/AT:IST-2009-0003}, year = {2009}, } @misc{5394, abstract = {We consider two-player games played on graphs with request-response and finitary Streett objectives. We show these games are PSPACE-hard, improving the previous known NP-hardness. We also improve the lower bounds on memory required by the winning strategies for the players.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Horn, Florian}, issn = {2664-1690}, pages = {11}, publisher = {IST Austria}, title = {{Improved lower bounds for request-response and finitary Streett games}}, doi = {10.15479/AT:IST-2009-0002}, year = {2009}, } @misc{5395, abstract = {We study observation-based strategies for partially-observable Markov decision processes (POMDPs) with omega-regular objectives. An observation-based strategy relies on partial information about the history of a play, namely, on the past sequence of observa- tions. We consider the qualitative analysis problem: given a POMDP with an omega-regular objective, whether there is 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 of POMDPs with parity objectives (a canonical form to express omega-regular objectives) and its subclasses. Our contribution consists in establishing several upper and lower bounds that were not known in literature. Second, we present optimal bounds (matching upper and lower bounds) on the memory required by pure and randomized observation-based strategies for the qualitative analysis of POMDPs with parity objectives and its subclasses.}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Henzinger, Thomas A}, issn = {2664-1690}, pages = {20}, publisher = {IST Austria}, title = {{Qualitative analysis of partially-observable Markov decision processes}}, doi = {10.15479/AT:IST-2009-0001}, year = {2009}, } @article{9453, abstract = {Parent-of-origin-specific (imprinted) gene expression is regulated in Arabidopsis thaliana endosperm by cytosine demethylation of the maternal genome mediated by the DNA glycosylase DEMETER, but the extent of the methylation changes is not known. Here, we show that virtually the entire endosperm genome is demethylated, coupled with extensive local non-CG hypermethylation of small interfering RNA–targeted sequences. Mutation of DEMETER partially restores endosperm CG methylation to levels found in other tissues, indicating that CG demethylation is specific to maternal sequences. Endosperm demethylation is accompanied by CHH hypermethylation of embryo transposable elements. Our findings demonstrate extensive reconfiguration of the endosperm methylation landscape that likely reinforces transposon silencing in the embryo.}, author = {Hsieh, Tzung-Fu and Ibarra, Christian A. and Silva, Pedro and Zemach, Assaf and Eshed-Williams, Leor and Fischer, Robert L. and Zilberman, Daniel}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {5933}, pages = {1451--1454}, publisher = {American Association for the Advancement of Science}, title = {{Genome-wide demethylation of Arabidopsis endosperm}}, doi = {10.1126/science.1172417}, volume = {324}, year = {2009}, } @inbook{3675, abstract = {Sex and recombination have long been seen as adaptations that facilitate natural selection by generating favorable variations. If recombination is to aid selection, there must be negative linkage disequilibria—favorable alleles must be found together less often than expected by chance. These negative linkage disequilibria can be generated directly by selection, but this must involve negative epistasis of just the right strength, which is not expected, from either experiment or theory. Random drift provides a more general source of negative associations: Favorable mutations almost always arise on different genomes, and negative associations tend to persist, precisely because they shield variation from selection. We can understand how recombination aids adaptation by determining the maximum possible rate of adaptation. With unlinked loci, this rate increases only logarithmically with the influx of favorable mutations. With a linear genome, a scaling argument shows that in a large population, the rate of adaptive substitution depends only on the expected rate in the absence of interference, divided by the total rate of recombination. A two-locus approximation predicts an upper bound on the rate of substitution, proportional to recombination rate. If associations between linked loci do impede adaptation, there can be substantial selection for modifiers that increase recombination. Whether this can account for the maintenance of high rates of sex and recombination depends on the extent of selection. It is clear that the rate of species-wide substitutions is typically far too low to generate appreciable selection for recombination. However, local sweeps within a subdivided population may be effective.}, author = {Barton, Nicholas H}, booktitle = {Cold Spring Harbor Symposia on Quantitative Biology}, pages = {187 -- 195}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{Why sex and recombination?}}, doi = {10.1101/sqb.2009.74.030}, volume = {74}, year = {2009}, } @article{3775, abstract = {There is a close analogy between statistical thermodynamics and the evolution of allele frequencies under mutation, selection and random drift. Wright's formula for the stationary distribution of allele frequencies is analogous to the Boltzmann distribution in statistical physics. Population size, 2N, plays the role of the inverse temperature, 1/kT, and determines the magnitude of random fluctuations. Log mean fitness, View the MathML source, tends to increase under selection, and is analogous to a (negative) energy; a potential function, U, increases under mutation in a similar way. An entropy, SH, can be defined which measures the deviation from the distribution of allele frequencies expected under random drift alone; the sum View the MathML source gives a free fitness that increases as the population evolves towards its stationary distribution. Usually, we observe the distribution of a few quantitative traits that depend on the frequencies of very many alleles. The mean and variance of such traits are analogous to observable quantities in statistical thermodynamics. Thus, we can define an entropy, SΩ, which measures the volume of allele frequency space that is consistent with the observed trait distribution. The stationary distribution of the traits is View the MathML source; this applies with arbitrary epistasis and dominance. The entropies SΩ, SH are distinct, but converge when there are so many alleles that traits fluctuate close to their expectations. Populations tend to evolve towards states that can be realised in many ways (i.e., large SΩ), which may lead to a substantial drop below the adaptive peak; we illustrate this point with a simple model of genetic redundancy. This analogy with statistical thermodynamics brings together previous ideas in a general framework, and justifies a maximum entropy approximation to the dynamics of quantitative traits.}, author = {Barton, Nicholas H and Coe, Jason}, journal = {Journal of Theoretical Biology}, number = {2}, pages = {317 -- 324}, publisher = {Elsevier}, title = {{On the application of statistical physics to evolutionary biology}}, doi = {10.1016/j.jtbi.2009.03.019}, volume = {259}, year = {2009}, } @article{3780, abstract = {Why are sinistral snails so rare? Two main hypotheses are that selection acts against the establishment of new coiling morphs, because dextral and sinistral snails have trouble mating, or else a developmental constraint prevents the establishment of sinistrals. We therefore used an isolate of the snail Lymnaea stagnalis, in which sinistrals are rare, and populations of Partula suturalis, in which sinistrals are common, as well as a mathematical model, to understand the circumstances by which new morphs evolve. The main finding is that the sinistral genotype is associated with reduced egg viability in L. stagnalis, but in P. suturalis individuals of sinistral and dextral genotype appear equally fecund, implying a lack of a constraint. As positive frequency-dependent selection against the rare chiral morph in P. suturalis also operates over a narrow range (< 3%), the results suggest a model for chiral evolution in snails in which weak positive frequency-dependent selection may be overcome by a negative frequency-dependent selection, such as reproductive character displacement. In snails, there is not always a developmental constraint. As the direction of cleavage, and thus the directional asymmetry of the entire body, does not generally vary in other Spiralia (annelids, echiurans, vestimentiferans, sipunculids and nemerteans), it remains an open question as to whether this is because of a constraint and/or because most taxa do not have a conspicuous external asymmetry (like a shell) upon which selection can act.}, author = {Davison, Angus and Barton, Nicholas H and Clarke, Bryan}, journal = {Journal of Evolutionary Biology}, number = {8}, pages = {1624 -- 1635}, publisher = {Wiley}, title = {{The effect of chirality phenotype and genotype on the fecundity and viability of Partula suturalis and Lymnaea stagnalis: Implications for the evolution of sinistral snails}}, doi = {10.1111/j.1420-9101.2009.01770.x}, volume = {22}, year = {2009}, } @inproceedings{3837, abstract = {In this paper we extend the work of Alfaro, Henzinger et al. on interface theories for component-based design. Existing interface theories often fail to capture functional relations between the inputs and outputs of an interface. For example, a simple synchronous interface that takes as input a number n ≥ 0 and returns, at the same time, as output n + 1, cannot be expressed in existing theories. In this paper we provide a theory of relational interfaces, where such input-output relations can be captured. Our theory supports synchronous interfaces, both stateless and stateful. It includes explicit notions of environments and pluggability, and satisfies fundamental properties such as preservation of refinement by composition, and characterization of pluggability by refinement. We achieve these properties by making reasonable restrictions on feedback loops in interface compositions.}, author = {Tripakis, Stavros and Lickly, Ben and Henzinger, Thomas A and Lee, Edward}, booktitle = {EMSOFT '09 Proceedings of the seventh ACM international conference on Embedded software}, location = {Grenoble, France}, pages = {67 -- 76}, publisher = {ACM}, title = {{On relational interfaces}}, doi = {10.1145/1629335.1629346}, year = {2009}, } @inproceedings{3841, abstract = {We compare several languages for specifying Markovian population models such as queuing networks and chemical reaction networks. These languages —matrix descriptions, stochastic Petri nets, stoichiometric equations, stochastic process algebras, and guarded command models— all describe continuous-time Markov chains, but they differ according to important properties, such as compositionality, expressiveness and succinctness, executability, ease of use, and the support they provide for checking the well-formedness of a model and for analyzing a model. }, author = {Henzinger, Thomas A and Jobstmann, Barbara and Wolf, Verena}, location = {Palaiseau, France}, pages = {3 -- 23}, publisher = {Springer}, title = {{Formalisms for specifying Markovian population models}}, doi = {10.1007/978-3-642-04420-5_2}, volume = {5797}, year = {2009}, }