TY - JOUR
AB - How cells orchestrate their behavior during collective migration is a long-standing question. Using magnetic tweezers to apply mechanical stimuli to Xenopus mesendoderm cells, Weber etal. (2012) now reveal, in this issue of Developmental Cell, a cadherin-mediated mechanosensitive response that promotes cell polarization and movement persistence during the collective mesendoderm migration in gastrulation.
AU - Behrndt, Martin
AU - Heisenberg, Carl-Philipp J
ID - 3245
IS - 1
JF - Developmental Cell
TI - Spurred by resistance mechanosensation in collective migration
VL - 22
ER -
TY - JOUR
AB - Visualizing and analyzing shape changes at various scales, ranging from single molecules to whole organisms, are essential for understanding complex morphogenetic processes, such as early embryonic development. Embryo morphogenesis relies on the interplay between different tissues, the properties of which are again determined by the interaction between their constituent cells. Cell interactions, on the other hand, are controlled by various molecules, such as signaling and adhesion molecules, which in order to exert their functions need to be spatiotemporally organized within and between the interacting cells. In this review, we will focus on the role of cell adhesion functioning at different scales to organize cell, tissue and embryo morphogenesis. We will specifically ask how the subcellular distribution of adhesion molecules controls the formation of cell-cell contacts, how cell-cell contacts determine tissue shape, and how tissue interactions regulate embryo morphogenesis.
AU - Barone, Vanessa
AU - Heisenberg, Carl-Philipp J
ID - 3246
IS - 1
JF - Current Opinion in Cell Biology
TI - Cell adhesion in embryo morphogenesis
VL - 24
ER -
TY - JOUR
AB - The Brazilian Merganser is a very rare and threatened species that nowadays inhabits only a few protected areas and their surroundings in the Brazilian territory. In order to estimate the remaining genetic diversity and population structure in this species, two mitochondrial genes were sequenced in 39 individuals belonging to two populations and in one individual collected in Argentina in 1950. We found a highly significant divergence between two major remaining populations of Mergus octosetaceus, which suggests a historical population structure in this species. Furthermore, two deeply divergent lineages were found in a single location, which could due to current or historical secondary contact. Based on the available genetic data, we point out future directions which would contribute to design strategies for conservation and management of this threatened species.
AU - Vilaça, Sibelle
AU - Fernandes Redondo, Rodrigo A
AU - Lins, Lívia
AU - Santos, Fabrício
ID - 3247
IS - 1
JF - Conservation Genetics
TI - Remaining genetic diversity in Brazilian Merganser (Mergus octosetaceus)
VL - 13
ER -
TY - JOUR
AB - We describe RTblob, a high speed vision system that detects objects in cluttered scenes based on their color and shape at a speed of over 800 frames/s. Because the system is available as open-source software and relies only on off-the-shelf PC hardware components, it can provide the basis for multiple application scenarios. As an illustrative example, we show how RTblob can be used in a robotic table tennis scenario to estimate ball trajectories through 3D space simultaneously from four cameras images at a speed of 200 Hz.
AU - Lampert, Christoph
AU - Peters, Jan
ID - 3248
IS - 1
JF - Journal of Real-Time Image Processing
TI - Real-time detection of colored objects in multiple camera streams with off-the-shelf hardware components
VL - 7
ER -
TY - JOUR
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 - 3249
IS - 1
JF - Theoretical Computer Science
TI - Simulation distances
VL - 413
ER -
TY - CONF
AB - The Learning Parity with Noise (LPN) problem has recently found many applications in cryptography as the hardness assumption underlying the constructions of "provably secure" cryptographic schemes like encryption or authentication protocols. Being provably secure means that the scheme comes with a proof showing that the existence of an efficient adversary against the scheme implies that the underlying hardness assumption is wrong. LPN based schemes are appealing for theoretical and practical reasons. On the theoretical side, LPN based schemes offer a very strong security guarantee. The LPN problem is equivalent to the problem of decoding random linear codes, a problem that has been extensively studied in the last half century. The fastest known algorithms run in exponential time and unlike most number-theoretic problems used in cryptography, the LPN problem does not succumb to known quantum algorithms. On the practical side, LPN based schemes are often extremely simple and efficient in terms of code-size as well as time and space requirements. This makes them prime candidates for light-weight devices like RFID tags, which are too weak to implement standard cryptographic primitives like the AES block-cipher. This talk will be a gentle introduction to provable security using simple LPN based schemes as examples. Starting from pseudorandom generators and symmetric key encryption, over secret-key authentication protocols, and, if time admits, touching on recent constructions of public-key identification, commitments and zero-knowledge proofs.
AU - Pietrzak, Krzysztof Z
ID - 3250
TI - Cryptography from learning parity with noise
VL - 7147
ER -
TY - CONF
AB - We study the automatic synthesis of fair non-repudiation protocols, a class of fair exchange protocols, used for digital contract signing. First, we show how to specify the objectives of the participating agents, the trusted third party (TTP) and the protocols as path formulas in Linear Temporal Logic (LTL) and prove that the satisfaction of the objectives of the agents and the TTP imply satisfaction of the protocol objectives. We then show that weak (co-operative) co-synthesis and classical (strictly competitive) co-synthesis fail in synthesizing these protocols, whereas assume-guarantee synthesis (AGS) succeeds. We demonstrate the success of assume-guarantee synthesis as follows: (a) any solution of assume-guarantee synthesis is attack-free; no subset of participants can violate the objectives of the other participants without violating their own objectives; (b) the Asokan-Shoup-Waidner (ASW) certified mail protocol that has known vulnerabilities is not a solution of AGS; and (c) the Kremer-Markowitch (KM) non-repudiation protocol is a solution of AGS. To our knowledge this is the first application of synthesis to fair non-repudiation protocols, and our results show how synthesis can generate correct protocols and automatically discover vulnerabilities. The solution to assume-guarantee synthesis can be computed efficiently as the secure equilibrium solution of three-player graph games. © 2012 Springer-Verlag.
AU - Chatterjee, Krishnendu
AU - Raman, Vishwanath
ID - 3252
TI - Synthesizing protocols for digital contract signing
VL - 7148
ER -
TY - CONF
AB - We describe a framework for reasoning about programs with lists carrying integer numerical data. We use abstract domains to describe and manipulate complex constraints on configurations of these programs mixing constraints on the shape of the heap, sizes of the lists, on the multisets of data stored in these lists, and on the data at their different positions. Moreover, we provide powerful techniques for automatic validation of Hoare-triples and invariant checking, as well as for automatic synthesis of invariants and procedure summaries using modular inter-procedural analysis. The approach has been implemented in a tool called Celia and experimented successfully on a large benchmark of programs.
AU - Bouajjani, Ahmed
AU - Dragoi, Cezara
AU - Enea, Constantin
AU - Sighireanu, Mihaela
ID - 3253
TI - Abstract domains for automated reasoning about list manipulating programs with infinite data
VL - 7148
ER -
TY - JOUR
AB - The theory of graph games with ω-regular winning conditions is the foundation for modeling and synthesizing reactive processes. In the case of stochastic reactive processes, the corresponding stochastic graph games have three players, two of them (System and Environment) behaving adversarially, and the third (Uncertainty) behaving probabilistically. We consider two problems for stochastic graph games: the qualitative problem asks for the set of states from which a player can win with probability 1 (almost-sure winning); and the quantitative problem asks for the maximal probability of winning (optimal winning) from each state. We consider ω-regular winning conditions formalized as Müller winning conditions. We present optimal memory bounds for pure (deterministic) almost-sure winning and optimal winning strategies in stochastic graph games with Müller winning conditions. We also study the complexity of stochastic Müller games and show that both the qualitative and quantitative analysis problems are PSPACE-complete. Our results are relevant in synthesis of stochastic reactive processes.
AU - Chatterjee, Krishnendu
ID - 3254
JF - Information and Computation
TI - The complexity of stochastic Müller games
VL - 211
ER -
TY - CONF
AB - In this paper we survey results of two-player games on graphs and Markov decision processes with parity, mean-payoff and energy objectives, and the combination of mean-payoff and energy objectives with parity objectives. These problems have applications in verification and synthesis of reactive systems in resource-constrained environments.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 3255
TI - Games and Markov decision processes with mean payoff parity and energy parity objectives
VL - 7119
ER -
TY - JOUR
AB - We use a distortion to define the dual complex of a cubical subdivision of ℝ n as an n-dimensional subcomplex of the nerve of the set of n-cubes. Motivated by the topological analysis of high-dimensional digital image data, we consider such subdivisions defined by generalizations of quad- and oct-trees to n dimensions. Assuming the subdivision is balanced, we show that mapping each vertex to the center of the corresponding n-cube gives a geometric realization of the dual complex in ℝ n.
AU - Edelsbrunner, Herbert
AU - Kerber, Michael
ID - 3256
IS - 2
JF - Discrete & Computational Geometry
TI - Dual complexes of cubical subdivisions of ℝn
VL - 47
ER -
TY - JOUR
AB - Consider a convex relaxation f̂ of a pseudo-Boolean function f. We say that the relaxation is totally half-integral if f̂(x) is a polyhedral function with half-integral extreme points x, and this property is preserved after adding an arbitrary combination of constraints of the form x i=x j, x i=1-x j, and x i=γ where γ∈{0,1,1/2} is a constant. A well-known example is the roof duality relaxation for quadratic pseudo-Boolean functions f. We argue that total half-integrality is a natural requirement for generalizations of roof duality to arbitrary pseudo-Boolean functions. Our contributions are as follows. First, we provide a complete characterization of totally half-integral relaxations f̂ by establishing a one-to-one correspondence with bisubmodular functions. Second, we give a new characterization of bisubmodular functions. Finally, we show some relationships between general totally half-integral relaxations and relaxations based on the roof duality. On the conceptual level, our results show that bisubmodular functions provide a natural generalization of the roof duality approach to higher-order terms. This can be viewed as a non-submodular analogue of the fact that submodular functions generalize the s-t minimum cut problem with non-negative weights to higher-order terms.
AU - Kolmogorov, Vladimir
ID - 3257
IS - 4-5
JF - Discrete Applied Mathematics
TI - Generalized roof duality and bisubmodular functions
VL - 160
ER -
TY - JOUR
AB - CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network.
AU - Kim, Sooyun
AU - Guzmán, José
AU - Hu, Hua
AU - Jonas, Peter M
ID - 3258
IS - 4
JF - Nature Neuroscience
TI - Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons
VL - 15
ER -
TY - JOUR
AB - Many scenarios in the living world, where individual organisms compete for winning positions (or resources), have properties of auctions. Here we study the evolution of bids in biological auctions. For each auction, n individuals are drawn at random from a population of size N. Each individual makes a bid which entails a cost. The winner obtains a benefit of a certain value. Costs and benefits are translated into reproductive success (fitness). Therefore, successful bidding strategies spread in the population. We compare two types of auctions. In “biological all-pay auctions”, the costs are the bid for every participating individual. In “biological second price all-pay auctions”, the cost for everyone other than the winner is the bid, but the cost for the winner is the second highest bid. Second price all-pay auctions are generalizations of the “war of attrition” introduced by Maynard Smith. We study evolutionary dynamics in both types of auctions. We calculate pairwise invasion plots and evolutionarily stable distributions over the continuous strategy space. We find that the average bid in second price all-pay auctions is higher than in all-pay auctions, but the average cost for the winner is similar in both auctions. In both cases, the average bid is a declining function of the number of participants, n. The more individuals participate in an auction the smaller is the chance of winning, and thus expensive bids must be avoided.
AU - Chatterjee, Krishnendu
AU - Reiter, Johannes
AU - Nowak, Martin
ID - 3260
IS - 1
JF - Theoretical Population Biology
TI - Evolutionary dynamics of biological auctions
VL - 81
ER -
TY - JOUR
AB - Living cells must control the reading out or "expression" of information encoded in their genomes, and this regulation often is mediated by transcription factors--proteins that bind to DNA and either enhance or repress the expression of nearby genes. But the expression of transcription factor proteins is itself regulated, and many transcription factors regulate their own expression in addition to responding to other input signals. Here we analyze the simplest of such self-regulatory circuits, asking how parameters can be chosen to optimize information transmission from inputs to outputs in the steady state. Some nonzero level of self-regulation is almost always optimal, with self-activation dominant when transcription factor concentrations are low and self-repression dominant when concentrations are high. In steady state the optimal self-activation is never strong enough to induce bistability, although there is a limit in which the optimal parameters are very close to the critical point.
AU - Tkacik, Gasper
AU - Walczak, Aleksandra
AU - Bialek, William
ID - 3262
IS - 4
JF - Physical Review E statistical nonlinear and soft matter physics
TI - Optimizing information flow in small genetic networks. III. A self-interacting gene
VL - 85
ER -
TY - CONF
AB - We propose a mid-level statistical model for image segmentation that composes multiple figure-ground hypotheses (FG) obtained by applying constraints at different locations and scales, into larger interpretations (tilings) of the entire image. Inference is cast as optimization over sets of maximal cliques sampled from a graph connecting all non-overlapping figure-ground segment hypotheses. Potential functions over cliques combine unary, Gestalt-based figure qualities, and pairwise compatibilities among spatially neighboring segments, constrained by T-junctions and the boundary interface statistics of real scenes. Learning the model parameters is based on maximum likelihood, alternating between sampling image tilings and optimizing their potential function parameters. State of the art results are reported on the Berkeley and Stanford segmentation datasets, as well as VOC2009, where a 28% improvement was achieved.
AU - Ion, Adrian
AU - Carreira, Joao
AU - Sminchisescu, Cristian
ID - 3265
TI - Image segmentation by figure-ground composition into maximal cliques
ER -
TY - JOUR
AB - A boundary element model of a tunnel running through horizontally layered soil with anisotropic material properties is presented. Since there is no analytical fundamental solution for wave propagation inside a layered orthotropic medium in 3D, the fundamental displacements and stresses have to be calculated numerically. In our model this is done in the Fourier domain with respect to space and time. The assumption of a straight tunnel with infinite extension in the x direction makes it possible to decouple the system for every wave number kx, leading to a 2.5D-problem, which is suited for parallel computation. The special form of the fundamental solution, resulting from our Fourier ansatz, and the fact, that the calculation of the boundary integral equation is performed in the Fourier domain, enhances the stability and efficiency of the numerical calculations.
AU - Rieckh, Georg
AU - Kreuzer, Wolfgang
AU - Waubke, Holger
AU - Balazs, Peter
ID - 3274
IS - 6
JF - Engineering Analysis with Boundary Elements
TI - A 2.5D-Fourier-BEM model for vibrations in a tunnel running through layered anisotropic soil
VL - 36
ER -
TY - CHAP
AB - The problem of the origin of metazoa is becoming more urgent in the context of astrobiology. By now it is clear that clues to the understanding of this crucial transition in the evolution of life can arise in a fourth pathway besides the three possibilities in the quest for simplicity outlined by Bonner in his classical book. In other words, solar system exploration seems to be one way in the long-term to elucidate the simplicity of evolutionary development. We place these ideas in the context of different inheritance systems, namely the genotypic and phenotypic replicators with limited or unlimited heredity, and ask which of these can support multicellular development, and to which degree of complexity. However, the quest for evidence on the evolution of biotas from planets around other stars does not seem to be feasible with present technology with direct visualization of living organisms on exoplanets. But this may be attempted on the Galilean moons of Jupiter where there is a possibility of detecting reliable biomarkers in the next decade with the Europa Jupiter System Mission, in view of recent progress by landing micropenetrators on planetary, or satellite surfaces. Mars is a second possibility in the inner Solar System, in spite of the multiple difficulties faced by the fleet of past, present and future missions. We discuss a series of preliminary ideas for elucidating the origin of metazoan analogues with available instrumentation in potential payloads of feasible space missions to the Galilean moons.
AU - de Vladar, Harold
AU - Chela Flores, Julian
ID - 3277
T2 - Life on Earth and other planetary bodies
TI - Can the evolution of multicellularity be anticipated in the exploration of the solar system?
VL - 24
ER -
TY - CONF
AB - We show a hardness-preserving construction of a PRF from any length doubling PRG which improves upon known constructions whenever we can put a non-trivial upper bound q on the number of queries to the PRF. Our construction requires only O(logq) invocations to the underlying PRG with each query. In comparison, the number of invocations by the best previous hardness-preserving construction (GGM using Levin's trick) is logarithmic in the hardness of the PRG. For example, starting from an exponentially secure PRG {0,1} n → {0,1} 2n, we get a PRF which is exponentially secure if queried at most q = exp(√n)times and where each invocation of the PRF requires Θ(√n) queries to the underlying PRG. This is much less than the Θ(n) required by known constructions.
AU - Jain, Abhishek
AU - Pietrzak, Krzysztof Z
AU - Tentes, Aris
ID - 3279
TI - Hardness preserving constructions of pseudorandom functions
VL - 7194
ER -
TY - CONF
AB - The (decisional) learning with errors problem (LWE) asks to distinguish "noisy" inner products of a secret vector with random vectors from uniform. The learning parities with noise problem (LPN) is the special case where the elements of the vectors are bits. In recent years, the LWE and LPN problems have found many applications in cryptography. In this paper we introduce a (seemingly) much stronger adaptive assumption, called "subspace LWE" (SLWE), where the adversary can learn the inner product of the secret and random vectors after they were projected into an adaptively and adversarially chosen subspace. We prove that, surprisingly, the SLWE problem mapping into subspaces of dimension d is almost as hard as LWE using secrets of length d (the other direction is trivial.) This result immediately implies that several existing cryptosystems whose security is based on the hardness of the LWE/LPN problems are provably secure in a much stronger sense than anticipated. As an illustrative example we show that the standard way of using LPN for symmetric CPA secure encryption is even secure against a very powerful class of related key attacks.
AU - Pietrzak, Krzysztof Z
ID - 3280
TI - Subspace LWE
VL - 7194
ER -
TY - CONF
AB - We consider the problem of amplifying the "lossiness" of functions. We say that an oracle circuit C*: {0,1} m → {0,1}* amplifies relative lossiness from ℓ/n to L/m if for every function f:{0,1} n → {0,1} n it holds that 1 If f is injective then so is C f. 2 If f has image size of at most 2 n-ℓ, then C f has image size at most 2 m-L. The question is whether such C* exists for L/m ≫ ℓ/n. This problem arises naturally in the context of cryptographic "lossy functions," where the relative lossiness is the key parameter. We show that for every circuit C* that makes at most t queries to f, the relative lossiness of C f is at most L/m ≤ ℓ/n + O(log t)/n. In particular, no black-box method making a polynomial t = poly(n) number of queries can amplify relative lossiness by more than an O(logn)/n additive term. We show that this is tight by giving a simple construction (cascading with some randomization) that achieves such amplification.
AU - Pietrzak, Krzysztof Z
AU - Rosen, Alon
AU - Segev, Gil
ID - 3281
TI - Lossy functions do not amplify well
VL - 7194
ER -
TY - CONF
AB - Traditionally, symmetric-key message authentication codes (MACs) are easily built from pseudorandom functions (PRFs). In this work we propose a wide variety of other approaches to building efficient MACs, without going through a PRF first. In particular, unlike deterministic PRF-based MACs, where each message has a unique valid tag, we give a number of probabilistic MAC constructions from various other primitives/assumptions. Our main results are summarized as follows: We show several new probabilistic MAC constructions from a variety of general assumptions, including CCA-secure encryption, Hash Proof Systems and key-homomorphic weak PRFs. By instantiating these frameworks under concrete number theoretic assumptions, we get several schemes which are more efficient than just using a state-of-the-art PRF instantiation under the corresponding assumption. For probabilistic MACs, unlike deterministic ones, unforgeability against a chosen message attack (uf-cma ) alone does not imply security if the adversary can additionally make verification queries (uf-cmva ). We give an efficient generic transformation from any uf-cma secure MAC which is "message-hiding" into a uf-cmva secure MAC. This resolves the main open problem of Kiltz et al. from Eurocrypt'11; By using our transformation on their constructions, we get the first efficient MACs from the LPN assumption. While all our new MAC constructions immediately give efficient actively secure, two-round symmetric-key identification schemes, we also show a very simple, three-round actively secure identification protocol from any weak PRF. In particular, the resulting protocol is much more efficient than the trivial approach of building a regular PRF from a weak PRF. © 2012 International Association for Cryptologic Research.
AU - Dodis, Yevgeniy
AU - Pietrzak, Krzysztof Z
AU - Kiltz, Eike
AU - Wichs, Daniel
ID - 3282
TI - Message authentication, revisited
VL - 7237
ER -
TY - JOUR
AB - Viral manipulation of transduction pathways associated with key cellular functions such as survival, response to microbial infection, and cytoskeleton reorganization can provide the supportive milieu for a productive infection. Here, we demonstrate that vaccinia virus (VACV) infection leads to activation of the stress-activated protein kinase (SAPK)/extracellular signal-regulated kinase (ERK) 4/7 (MKK4/7)-c-Jun N-terminal protein kinase 1/2 (JNK1/2) pathway; further, the stimulation of this pathway requires postpenetration, prereplicative events in the viral replication cycle. Although the formation of intracellular mature virus (IMV) was not affected in MKK4/7- or JNK1/2-knockout (KO) cells, we did note an accentuated deregulation of microtubule and actin network organization in infected JNK1/2-KO cells. This was followed by deregulated viral trafficking to the periphery and enhanced enveloped particle release. Furthermore, VACV infection induced alterations in the cell contractility and morphology, and cell migration was reduced in the JNK-KO cells. In addition, phosphorylation of proteins implicated with early cell contractility and cell migration, such as microtubule-associated protein 1B and paxillin, respectively, was not detected in the VACV-infected KO cells. In sum, our findings uncover a regulatory role played by the MKK4/7-JNK1/2 pathway in cytoskeleton reorganization during VACV infection.
AU - Pereira, Anna
AU - Leite, Flávia
AU - Brasil, Bruno
AU - Soares Martins, Jamaria
AU - Torres, Alice
AU - Pimenta, Paulo
AU - Souto Padrón, Thais
AU - Tranktman, Paula
AU - Ferreira, Paulo
AU - Kroon, Erna
AU - Bonjardim, Cláudio
ID - 3289
IS - 1
JF - Journal of Virology
TI - A vaccinia virus-driven interplay between the MKK4/7-JNK1/2 pathway and cytoskeleton reorganization
VL - 86
ER -
TY - JOUR
AB - The theory of persistent homology opens up the possibility to reason about topological features of a space or a function quantitatively and in combinatorial terms. We refer to this new angle at a classical subject within algebraic topology as a point calculus, which we present for the family of interlevel sets of a real-valued function. Our account of the subject is expository, devoid of proofs, and written for non-experts in algebraic topology.
AU - Bendich, Paul
AU - Cabello, Sergio
AU - Edelsbrunner, Herbert
ID - 3310
IS - 11
JF - Pattern Recognition Letters
TI - A point calculus for interlevel set homology
VL - 33
ER -
TY - JOUR
AB - We introduce two-level discounted and mean-payoff games played by two players on a perfect-information stochastic game graph. The upper level game is a discounted or mean-payoff game and the lower level game is a (undiscounted) reachability game. Two-level games model hierarchical and sequential decision making under uncertainty across different time scales. For both discounted and mean-payoff two-level games, we show the existence of pure memoryless optimal strategies for both players and an ordered field property. 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 or mean-payoff games can be decided in NP ∩ coNP. We also give an alternate strategy improvement algorithm to compute the value. © 2012 World Scientific Publishing Company.
AU - Chatterjee, Krishnendu
AU - Majumdar, Ritankar
ID - 3314
IS - 3
JF - International Journal of Foundations of Computer Science
TI - Discounting and averaging in games across time scales
VL - 23
ER -
TY - JOUR
AB - The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors that trigger exocytosis of neurotransmitter-containing vesicles is a key determinant of the signalling properties of synapses in the nervous system. Recent functional analysis indicates that in some fast central synapses, transmitter release is triggered by a small number of Ca2+ channels that are coupled to Ca2+ sensors at the nanometre scale. Molecular analysis suggests that this tight coupling is generated by protein–protein interactions involving Ca2+ channels, Ca2+ sensors and various other synaptic proteins. Nanodomain coupling has several functional advantages, as it increases the efficacy, speed and energy efficiency of synaptic transmission.
AU - Eggermann, Emmanuel
AU - Bucurenciu, Iancu
AU - Goswami, Sarit
AU - Jonas, Peter M
ID - 3317
IS - 1
JF - Nature Reviews Neuroscience
TI - Nanodomain coupling between Ca(2+) channels and sensors of exocytosis at fast mammalian synapses
VL - 13
ER -
TY - JOUR
AB - Computing the topology of an algebraic plane curve C means computing a combinatorial graph that is isotopic to C and thus represents its topology in R2. We prove that, for a polynomial of degree n with integer coefficients bounded by 2ρ, the topology of the induced curve can be computed with bit operations ( indicates that we omit logarithmic factors). Our analysis improves the previous best known complexity bounds by a factor of n2. The improvement is based on new techniques to compute and refine isolating intervals for the real roots of polynomials, and on the consequent amortized analysis of the critical fibers of the algebraic curve.
AU - Kerber, Michael
AU - Sagraloff, Michael
ID - 3331
IS - 3
JF - Journal of Symbolic Computation
TI - A worst case bound for topology computation of algebraic curves
VL - 47
ER -
TY - CONF
AB - We consider two-player stochastic games played on a finite state space for an infinite number of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine a probability distribution over the successor states. We also consider the important special case of turn-based stochastic games where players make moves in turns, rather than concurrently. We study concurrent games with \omega-regular winning conditions specified as parity objectives. The value for player 1 for a parity objective is the maximal probability with which the player can guarantee the satisfaction of the objective against all strategies of the opponent. We study the problem of continuity and robustness of the value function in concurrent and turn-based stochastic parity gameswith respect to imprecision in the transition probabilities. We present quantitative bounds on the difference of the value function (in terms of the imprecision of the transition probabilities) and show the value continuity for structurally equivalent concurrent games (two games are structurally equivalent if the support of the transition function is same and the probabilities differ). We also show robustness of optimal strategies for structurally equivalent turn-based stochastic parity games. Finally we show that the value continuity property breaks without the structurally equivalent assumption (even for Markov chains) and show that our quantitative bound is asymptotically optimal. Hence our results are tight (the assumption is both necessary and sufficient) and optimal (our quantitative bound is asymptotically optimal).
AU - Chatterjee, Krishnendu
ID - 3341
TI - Robustness of structurally equivalent concurrent parity games
VL - 7213
ER -
TY - CONF
AB - Many infinite state systems can be seen as well-structured transition systems (WSTS), i.e., systems equipped with a well-quasi-ordering on states that is also a simulation relation. WSTS are an attractive target for formal analysis because there exist generic algorithms that decide interesting verification problems for this class. Among the most popular algorithms are acceleration-based forward analyses for computing the covering set. Termination of these algorithms can only be guaranteed for flattable WSTS. Yet, many WSTS of practical interest are not flattable and the question whether any given WSTS is flattable is itself undecidable. We therefore propose an analysis that computes the covering set and captures the essence of acceleration-based algorithms, but sacrifices precision for guaranteed termination. Our analysis is an abstract interpretation whose abstract domain builds on the ideal completion of the well-quasi-ordered state space, and a widening operator that mimics acceleration and controls the loss of precision of the analysis. We present instances of our framework for various classes of WSTS. Our experience with a prototype implementation indicates that, despite the inherent precision loss, our analysis often computes the precise covering set of the analyzed system.
AU - Zufferey, Damien
AU - Wies, Thomas
AU - Henzinger, Thomas A
ID - 3251
TI - Ideal abstractions for well structured transition systems
VL - 7148
ER -
TY - JOUR
AB - Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors among group members—that is, active versus passive immunisation. We found no evidence for involvement of passive immunisation via transfer of antimicrobials among colony members. Instead, intensive allogrooming behaviour between naive and pathogen-exposed ants before fungal conidia firmly attached to their cuticle suggested passage of the pathogen from the exposed individuals to their nestmates. By tracing fluorescence-labelled conidia we indeed detected frequent pathogen transfer to the nestmates, where they caused low-level infections as revealed by growth of small numbers of fungal colony forming units from their dissected body content. These infections rarely led to death, but instead promoted an enhanced ability to inhibit fungal growth and an active upregulation of immune genes involved in antifungal defences (defensin and prophenoloxidase, PPO). Contrarily, there was no upregulation of the gene cathepsin L, which is associated with antibacterial and antiviral defences, and we found no increased antibacterial activity of nestmates of fungus-exposed ants. This indicates that social immunisation after fungal exposure is specific, similar to recent findings for individual-level immune priming in invertebrates. Epidemiological modeling further suggests that active social immunisation is adaptive, as it leads to faster elimination of the disease and lower death rates than passive immunisation. Interestingly, humans have also utilised the protective effect of low-level infections to fight smallpox by intentional transfer of low pathogen doses (“variolation” or “inoculation”).
AU - Konrad, Matthias
AU - Vyleta, Meghan
AU - Theis, Fabian
AU - Stock, Miriam
AU - Tragust, Simon
AU - Klatt, Martina
AU - Drescher, Verena
AU - Marr, Carsten
AU - Ugelvig, Line V
AU - Cremer, Sylvia
ID - 3242
IS - 4
JF - PLoS Biology
TI - Social transfer of pathogenic fungus promotes active immunisation in ant colonies
VL - 10
ER -
TY - GEN
AB - Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors among group members—that is, active versus passive immunisation. We found no evidence for involvement of passive immunisation via transfer of antimicrobials among colony members. Instead, intensive allogrooming behaviour between naive and pathogen-exposed ants before fungal conidia firmly attached to their cuticle suggested passage of the pathogen from the exposed individuals to their nestmates. By tracing fluorescence-labelled conidia we indeed detected frequent pathogen transfer to the nestmates, where they caused low-level infections as revealed by growth of small numbers of fungal colony forming units from their dissected body content. These infections rarely led to death, but instead promoted an enhanced ability to inhibit fungal growth and an active upregulation of immune genes involved in antifungal defences (defensin and prophenoloxidase, PPO). Contrarily, there was no upregulation of the gene cathepsin L, which is associated with antibacterial and antiviral defences, and we found no increased antibacterial activity of nestmates of fungus-exposed ants. This indicates that social immunisation after fungal exposure is specific, similar to recent findings for individual-level immune priming in invertebrates. Epidemiological modeling further suggests that active social immunisation is adaptive, as it leads to faster elimination of the disease and lower death rates than passive immunisation. Interestingly, humans have also utilised the protective effect of low-level infections to fight smallpox by intentional transfer of low pathogen doses (“variolation” or “inoculation”).
AU - Konrad, Matthias
AU - Vyleta, Meghan
AU - Theis, Fabian
AU - Stock, Miriam
AU - Klatt, Martina
AU - Drescher, Verena
AU - Marr, Carsten
AU - Ugelvig, Line V
AU - Cremer, Sylvia
ID - 9755
TI - Data from: Social transfer of pathogenic fungus promotes active immunisation in ant colonies
ER -
TY - GEN
AB - To fight infectious diseases, host immune defences are employed at multiple levels. Sanitary behaviour, such as pathogen avoidance and removal, acts as a first line of defence to prevent infection [1] before activation of the physiological immune system. Insect societies have evolved a wide range of collective hygiene measures and intensive health care towards pathogen-exposed group members [2]. One of the most common behaviours is allogrooming, in which nestmates remove infectious particles from the body surfaces of exposed individuals [3]. Here we show that, in invasive garden ants, grooming of fungus-exposed brood is effective beyond the sheer mechanical removal of fungal conidiospores as it also includes chemical disinfection through the application of poison produced by the ants themselves. Formic acid is the main active component of the poison. It inhibits fungal growth of conidiospores remaining on the brood surface after grooming and also those collected in the mouth of the grooming ant. This dual function is achieved by uptake of the poison droplet into the mouth through acidopore self-grooming and subsequent application onto the infectious brood via brood grooming. This extraordinary behaviour extends current understanding of grooming and the establishment of social immunity in insect societies.
AU - Tragust, Simon
AU - Mitteregger, Barbara
AU - Barone, Vanessa
AU - Konrad, Matthias
AU - Ugelvig, Line V
AU - Cremer, Sylvia
ID - 9757
TI - Data from: Ants disinfect fungus-exposed brood by oral uptake and spread of their poison
ER -
TY - GEN
AB - We propose a two-step procedure for estimating multiple migration rates in an approximate Bayesian computation (ABC) framework, accounting for global nuisance parameters. The approach is not limited to migration, but generally of interest for inference problems with multiple parameters and a modular structure (e.g. independent sets of demes or loci). We condition on a known, but complex demographic model of a spatially subdivided population, motivated by the reintroduction of Alpine ibex (Capra ibex) into Switzerland. In the first step, the global parameters ancestral mutation rate and male mating skew have been estimated for the whole population in Aeschbacher et al. (Genetics 2012; 192: 1027). In the second step, we estimate in this study the migration rates independently for clusters of demes putatively connected by migration. For large clusters (many migration rates), ABC faces the problem of too many summary statistics. We therefore assess by simulation if estimation per pair of demes is a valid alternative. We find that the trade-off between reduced dimensionality for the pairwise estimation on the one hand and lower accuracy due to the assumption of pairwise independence on the other depends on the number of migration rates to be inferred: the accuracy of the pairwise approach increases with the number of parameters, relative to the joint estimation approach. To distinguish between low and zero migration, we perform ABC-type model comparison between a model with migration and one without. Applying the approach to microsatellite data from Alpine ibex, we find no evidence for substantial gene flow via migration, except for one pair of demes in one direction.
AU - Aeschbacher, Simon
AU - Futschik, Andreas
AU - Beaumont, Mark
ID - 9758
TI - Data from: Approximate Bayesian computation for modular inference problems with many parameters: the example of migration rates
ER -
TY - JOUR
AB - The Arabidopsis thaliana central cell, the companion cell of the egg, undergoes DNA demethylation before fertilization, but the targeting preferences, mechanism, and biological significance of this process remain unclear. Here, we show that active DNA demethylation mediated by the DEMETER DNA glycosylase accounts for all of the demethylation in the central cell and preferentially targets small, AT-rich, and nucleosome-depleted euchromatic transposable elements. The vegetative cell, the companion cell of sperm, also undergoes DEMETER-dependent demethylation of similar sequences, and lack of DEMETER in vegetative cells causes reduced small RNA–directed DNA methylation of transposons in sperm. Our results demonstrate that demethylation in companion cells reinforces transposon methylation in plant gametes and likely contributes to stable silencing of transposable elements across generations.
AU - Ibarra, Christian A.
AU - Feng, Xiaoqi
AU - Schoft, Vera K.
AU - Hsieh, Tzung-Fu
AU - Uzawa, Rie
AU - Rodrigues, Jessica A.
AU - Zemach, Assaf
AU - Chumak, Nina
AU - Machlicova, Adriana
AU - Nishimura, Toshiro
AU - Rojas, Denisse
AU - Fischer, Robert L.
AU - Tamaru, Hisashi
AU - ZILBERMAN, Daniel
ID - 9451
IS - 6100
JF - Science
SN - 0036-8075
TI - Active DNA demethylation in plant companion cells reinforces transposon methylation in gametes
VL - 337
ER -
TY - JOUR
AB - The regulation of eukaryotic chromatin relies on interactions between many epigenetic factors, including histone modifications, DNA methylation, and the incorporation of histone variants. H2A.Z, one of the most conserved but enigmatic histone variants that is enriched at the transcriptional start sites of genes, has been implicated in a variety of chromosomal processes. Recently, we reported a genome-wide anticorrelation between H2A.Z and DNA methylation, an epigenetic hallmark of heterochromatin that has also been found in the bodies of active genes in plants and animals. Here, we investigate the basis of this anticorrelation using a novel h2a.z loss-of-function line in Arabidopsis thaliana. Through genome-wide bisulfite sequencing, we demonstrate that loss of H2A.Z in Arabidopsis has only a minor effect on the level or profile of DNA methylation in genes, and we propose that the global anticorrelation between DNA methylation and H2A.Z is primarily caused by the exclusion of H2A.Z from methylated DNA. RNA sequencing and genomic mapping of H2A.Z show that H2A.Z enrichment across gene bodies, rather than at the TSS, is correlated with lower transcription levels and higher measures of gene responsiveness. Loss of H2A.Z causes misregulation of many genes that are disproportionately associated with response to environmental and developmental stimuli. We propose that H2A.Z deposition in gene bodies promotes variability in levels and patterns of gene expression, and that a major function of genic DNA methylation is to exclude H2A.Z from constitutively expressed genes.
AU - Coleman-Derr, Devin
AU - ZILBERMAN, Daniel
ID - 9497
IS - 10
JF - PLoS Genetics
SN - 1553-7390
TI - Deposition of histone variant H2A.Z within gene bodies regulates responsive genes
VL - 8
ER -
TY - JOUR
AB - EMBRYONIC FLOWER1 (EMF1) is a plant-specific gene crucial to Arabidopsis vegetative development. Loss of function mutants in the EMF1 gene mimic the phenotype caused by mutations in Polycomb Group protein (PcG) genes, which encode epigenetic repressors that regulate many aspects of eukaryotic development. In Arabidopsis, Polycomb Repressor Complex 2 (PRC2), made of PcG proteins, catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3) and PRC1-like proteins catalyze H2AK119 ubiquitination. Despite functional similarity to PcG proteins, EMF1 lacks sequence homology with known PcG proteins; thus, its role in the PcG mechanism is unclear. To study the EMF1 functions and its mechanism of action, we performed genome-wide mapping of EMF1 binding and H3K27me3 modification sites in Arabidopsis seedlings. The EMF1 binding pattern is similar to that of H3K27me3 modification on the chromosomal and genic level. ChIPOTLe peak finding and clustering analyses both show that the highly trimethylated genes also have high enrichment levels of EMF1 binding, termed EMF1_K27 genes. EMF1 interacts with regulatory genes, which are silenced to allow vegetative growth, and with genes specifying cell fates during growth and differentiation. H3K27me3 marks not only these genes but also some genes that are involved in endosperm development and maternal effects. Transcriptome analysis, coupled with the H3K27me3 pattern, of EMF1_K27 genes in emf1 and PRC2 mutants showed that EMF1 represses gene activities via diverse mechanisms and plays a novel role in the PcG mechanism.
AU - Kim, Sang Yeol
AU - Lee, Jungeun
AU - Eshed-Williams, Leor
AU - ZILBERMAN, Daniel
AU - Sung, Z. Renee
ID - 9499
IS - 3
JF - PLoS Genetics
SN - 1553-7390
TI - EMF1 and PRC2 cooperate to repress key regulators of Arabidopsis development
VL - 8
ER -
TY - JOUR
AB - The most well-studied function of DNA methylation in eukaryotic cells is the transcriptional silencing of genes and transposons. More recent results showed that many eukaryotes methylate the bodies of genes as well and that this methylation correlates with transcriptional activity rather than repression. The purpose of gene body methylation remains mysterious, but is potentially related to the histone variant H2A.Z. Studies in plants and animals have shown that the genome-wide distributions of H2A.Z and DNA methylation are strikingly anticorrelated. Furthermore, we and other investigators have shown that this relationship is likely to be the result of an ancient but unknown mechanism by which DNA methylation prevents the incorporation of H2A.Z. Recently, we discovered strong correlations between the presence of H2A.Z within gene bodies, the degree to which a gene's expression varies across tissue types or environmental conditions, and transcriptional misregulation in an h2a.z mutant. We propose that one basal function of gene body methylation is the establishment of constitutive expression patterns within housekeeping genes by excluding H2A.Z from their bodies.
AU - Coleman-Derr, D.
AU - ZILBERMAN, Daniel
ID - 9535
JF - Cold Spring Harbor Symposia on Quantitative Biology
SN - 0091-7451
TI - DNA methylation, H2A.Z, and the regulation of constitutive expression
VL - 77
ER -
TY - JOUR
AB - Accumulating evidence points toward diverse functions for plant chromatin. Remarkable progress has been made over the last few years in elucidating the mechanisms for a number of these functions. Activity of the histone demethylase IBM1 accurately targets DNA methylation to silent repeats and transposable elements, not to genes. A genetic screen uncovered the surprising role of H2A.Z-containing nucleosomes in sensing precise differences in ambient temperature and consequent gene regulation. Precise maintenance of chromosome number is assured by a histone modification that suppresses inappropriate DNA replication and by centromeric histone H3 regulation of chromosome segregation. Histones and noncoding RNAs regulate FLOWERING LOCUS C, the expression of which quantitatively measures the duration of cold exposure, functioning as memory of winter. These findings are a testament to the power of using plants to research chromatin organization, and demonstrate examples of how chromatin functions to achieve biological accuracy, precision, and memory.
AU - Huff, Jason T.
AU - ZILBERMAN, Daniel
ID - 9528
IS - 2
JF - Current Opinion in Genetics and Development
SN - 0959-437X
TI - Regulation of biological accuracy, precision, and memory by plant chromatin organization
VL - 22
ER -
TY - JOUR
AB - Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release.
AU - Vyleta, Nicholas
AU - Smith, Stephen
ID - 469
IS - 12
JF - European Journal of Neuroscience
TI - Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor
VL - 31
ER -
TY - JOUR
AB - BioSig is an open source software library for biomedical signal processing. The aim of the BioSig project is to foster research in biomedical signal processing by providing free and open source software tools for many different application areas. Some of the areas where BioSig can be employed are neuroinformatics, brain-computer interfaces, neurophysiology, psychology, cardiovascular systems, and sleep research. Moreover, the analysis of biosignals such as the electroencephalogram (EEG), electrocorticogram (ECoG), electrocardiogram (ECG), electrooculogram (EOG), electromyogram (EMG), or respiration signals is a very relevant element of the BioSig project. Specifically, BioSig provides solutions for data acquisition, artifact processing, quality control, feature extraction, classification, modeling, and data visualization, to name a few. In this paper, we highlight several methods to help students and researchers to work more efficiently with biomedical signals.
AU - Schlögl, Alois
AU - Vidaurre, Carmen
AU - Sander, Tilmann
ID - 490
JF - Computational Intelligence and Neuroscience
TI - BioSig: The free and open source software library for biomedical signal processing
VL - 2011
ER -
TY - JOUR
AB - In their search for antigens, lymphocytes continuously shuttle among blood vessels, lymph vessels, and lymphatic tissues. Chemokines mediate entry of lymphocytes into lymphatic tissues, and sphingosine 1-phosphate (S1P) promotes localization of lymphocytes to the vasculature. Both signals are sensed through G protein-coupled receptors (GPCRs). Most GPCRs undergo ligand-dependent homologous receptor desensitization, a process that decreases their signaling output after previous exposure to high ligand concentration. Such desensitization can explain why lymphocytes do not take an intermediate position between two signals but rather oscillate between them. The desensitization of S1P receptor 1 (S1PR1) is mediated by GPCR kinase 2 (GRK2). Deletion of GRK2 in lymphocytes compromises desensitization by high vascular S1P concentrations, thereby reducing responsiveness to the chemokine signal and trapping the cells in the vascular compartment. The desensitization kinetics of S1PR1 allows lymphocytes to dynamically shuttle between vasculature and lymphatic tissue, although the positional information in both compartments is static.
AU - Eichner, Alexander
AU - Sixt, Michael K
ID - 491
IS - 198
JF - Science Signaling
TI - Setting the clock for recirculating lymphocytes
VL - 4
ER -
TY - JOUR
AB - Cancer stem cells or cancer initiating cells are believed to contribute to cancer recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with fundamental roles in gene regulation. The role of miRNAs in cancer stem cells is only poorly understood. Here, we report miRNA expression profiles of glioblastoma stem cell-containing CD133 + cell populations. We find that miR-9, miR-9 * (referred to as miR-9/9 *), miR-17 and miR-106b are highly abundant in CD133 + cells. Furthermore, inhibition of miR-9/9 * or miR-17 leads to reduced neurosphere formation and stimulates cell differentiation. Calmodulin-binding transcription activator 1 (CAMTA1) is a putative transcription factor, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA). We identify CAMTA1 as an miR-9/9 * and miR-17 target. CAMTA1 expression leads to reduced neurosphere formation and tumour growth in nude mice, suggesting that CAMTA1 can function as tumour suppressor. Consistently, CAMTA1 and NPPA expression correlate with patient survival. Our findings could provide a basis for novel strategies of glioblastoma therapy.
AU - Schraivogel, Daniel
AU - Weinmann, Lasse
AU - Beier, Dagmar
AU - Tabatabai, Ghazaleh
AU - Eichner, Alexander
AU - Zhu, Jia
AU - Anton, Martina
AU - Sixt, Michael K
AU - Weller, Michael
AU - Beier, Christoph
AU - Meister, Gunter
ID - 518
IS - 20
JF - EMBO Journal
TI - CAMTA1 is a novel tumour suppressor regulated by miR-9/9 * in glioblastoma stem cells
VL - 30
ER -
TY - JOUR
AB - Software transactional memories (STM) are described in the literature with assumptions of sequentially consistent program execution and atomicity of high level operations like read, write, and abort. However, in a realistic setting, processors use relaxed memory models to optimize hardware performance. Moreover, the atomicity of operations depends on the underlying hardware. This paper presents the first approach to verify STMs under relaxed memory models with atomicity of 32 bit loads and stores, and read-modify-write operations. We describe RML, a simple language for expressing concurrent programs. We develop a semantics of RML parametrized by a relaxed memory model. We then present our tool, FOIL, which takes as input the RML description of an STM algorithm restricted to two threads and two variables, and the description of a memory model, and automatically determines the locations of fences, which if inserted, ensure the correctness of the restricted STM algorithm under the given memory model. We use FOIL to verify DSTM, TL2, and McRT STM under the memory models of sequential consistency, total store order, partial store order, and relaxed memory order for two threads and two variables. Finally, we extend the verification results for DSTM and TL2 to an arbitrary number of threads and variables by manually proving that the structural properties of STMs are satisfied at the hardware level of atomicity under the considered relaxed memory models.
AU - Guerraoui, Rachid
AU - Henzinger, Thomas A
AU - Singh, Vasu
ID - 531
IS - 3
JF - Formal Methods in System Design
TI - Verification of STM on relaxed memory models
VL - 39
ER -
TY - GEN
AB - Computing the winning set for Büchi objectives in alternating games on graphs is a central problem in computer aided verification with a large number of applications. The long standing best known upper bound for solving the problem is ̃O(n·m), where n is the number of vertices and m is the number of edges in the graph. We are the first to break the ̃O(n·m) boundary by presenting a new technique that reduces the running time to O(n2). This bound also leads to O(n2) time algorithms for computing the set of almost-sure winning vertices for Büchi objectives (1) in alternating games with probabilistic transitions (improving an earlier bound of O(n·m)), (2) in concurrent graph games with constant actions (improving an earlier bound of O(n3)), and (3) in Markov decision processes (improving for m > n4/3 an earlier bound of O(min(m1.5, m·n2/3)). We also show that the same technique can be used to compute the maximal end-component decomposition of a graph in time O(n2), which is an improvement over earlier bounds for m > n4/3. Finally, we show how to maintain the winning set for Büchi objectives in alternating games under a sequence of edge insertions or a sequence of edge deletions in O(n) amortized time per operation. This is the first dynamic algorithm for this problem.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
ID - 5379
SN - 2664-1690
TI - An O(n2) time algorithm for alternating Büchi games
ER -
TY - GEN
AB - We consider 2-player games played on a finite state space for an infinite number of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine the successor state. We study concurrent games with ω-regular winning conditions specified as parity objectives. We consider the qualitative analysis problems: the computation of the almost-sure and limit-sure winning set of states, where player 1 can ensure to win with probability 1 and with probability arbitrarily close to 1, respectively. In general the almost-sure and limit-sure winning strategies require both infinite-memory as well as infinite-precision (to describe probabilities). We study the bounded-rationality problem for qualitative analysis of concurrent parity games, where the strategy set for player 1 is restricted to bounded-resource strategies. In terms of precision, strategies can be deterministic, uniform, finite-precision or infinite-precision; and in terms of memory, strategies can be memoryless, finite-memory or infinite-memory. We present a precise and complete characterization of the qualitative winning sets for all combinations of classes of strategies. In particular, we show that uniform memoryless strategies are as powerful as finite-precision infinite-memory strategies, and infinite-precision memoryless strategies are as powerful as infinite-precision finite-memory strategies. We show that the winning sets can be computed in O(n2d+3) time, where n is the size of the game structure and 2d is the number of priorities (or colors), and our algorithms are symbolic. The membership problem of whether a state belongs to a winning set can be decided in NP ∩ coNP. While this complexity is the same as for the simpler class of turn-based parity games, where in each state only one of the two players has a choice of moves, our algorithms,that are obtained by characterization of the winning sets as μ-calculus formulas, are considerably more involved than those for turn-based games.
AU - Chatterjee, Krishnendu
ID - 5380
SN - 2664-1690
TI - Bounded rationality in concurrent parity games
ER -
TY - GEN
AB - In two-player finite-state stochastic games of partial obser- vation on graphs, in every state of the graph, the players simultaneously choose an action, and their joint actions determine a probability distri- bution over the successor states. The game is played for infinitely many rounds and thus the players construct an infinite path in the graph. We consider reachability objectives where the first player tries to ensure a target state to be visited almost-surely (i.e., with probability 1) or pos- itively (i.e., with positive probability), no matter the strategy of the second player.
We classify such games according to the information and to the power of randomization available to the players. On the basis of information, the game can be one-sided with either (a) player 1, or (b) player 2 having partial observation (and the other player has perfect observation), or two- sided with (c) both players having partial observation. On the basis of randomization, (a) the players may not be allowed to use randomization (pure strategies), or (b) they may choose a probability distribution over actions but the actual random choice is external and not visible to the player (actions invisible), or (c) they may use full randomization.
Our main results for pure strategies are as follows: (1) For one-sided games with player 2 perfect observation we show that (in contrast to full randomized strategies) belief-based (subset-construction based) strate- gies are not sufficient, and present an exponential upper bound on mem- ory both for almost-sure and positive winning strategies; we show that the problem of deciding the existence of almost-sure and positive winning strategies for player 1 is EXPTIME-complete and present symbolic algo- rithms that avoid the explicit exponential construction. (2) For one-sided games with player 1 perfect observation we show that non-elementary memory is both necessary and sufficient for both almost-sure and posi- tive winning strategies. (3) We show that for the general (two-sided) case finite-memory strategies are sufficient for both positive and almost-sure winning, and at least non-elementary memory is required. We establish the equivalence of the almost-sure winning problems for pure strategies and for randomized strategies with actions invisible. Our equivalence re- sult exhibit serious flaws in previous results in the literature: we show a non-elementary memory lower bound for almost-sure winning whereas an exponential upper bound was previously claimed.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 5381
SN - 2664-1690
TI - Partial-observation stochastic games: How to win when belief fails
ER -
TY - GEN
AB - We consider two-player stochastic games played on a finite state space for an infinite num- ber of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine a probability distribution over the successor states. We also consider the important special case of turn-based stochastic games where players make moves in turns, rather than concurrently. We study concurrent games with ω-regular winning conditions specified as parity objectives. The value for player 1 for a parity objective is the maximal probability with which the player can guarantee the satisfaction of the objective against all strategies of the opponent. We study the problem of continuity and robustness of the value function in concurrent and turn-based stochastic parity games with respect to imprecision in the transition probabilities. We present quantitative bounds on the difference of the value function (in terms of the imprecision of the transition probabilities) and show the value continuity for structurally equivalent concurrent games (two games are structurally equivalent if the support of the transition func- tion is same and the probabilities differ). We also show robustness of optimal strategies for structurally equivalent turn-based stochastic parity games. Finally we show that the value continuity property breaks without the structurally equivalent assumption (even for Markov chains) and show that our quantitative bound is asymptotically optimal. Hence our results are tight (the assumption is both necessary and sufficient) and optimal (our quantitative bound is asymptotically optimal).
AU - Chatterjee, Krishnendu
ID - 5382
SN - 2664-1690
TI - Robustness of structurally equivalent concurrent parity games
ER -
TY - GEN
AB - We present a new decidable logic called TREX for expressing constraints about imperative tree data structures. In particular, TREX supports a transitive closure operator that can express reachability constraints, which often appear in data structure invariants. We show that our logic is closed under weakest precondition computation, which enables its use for automated software verification. We further show that satisfiability of formulas in TREX is decidable in NP. The low complexity makes it an attractive alternative to more expensive logics such as monadic second-order logic (MSOL) over trees, which have been traditionally used for reasoning about tree data structures.
AU - Wies, Thomas
AU - Muñiz, Marco
AU - Kuncak, Viktor
ID - 5383
SN - 2664-1690
TI - On an efficient decision procedure for imperative tree data structures
ER -
TY - GEN
AB - We consider probabilistic automata on infinite words with acceptance defined by parity conditions. We consider three qualitative decision problems: (i) the positive decision problem asks whether there is a word that is accepted with positive probability; (ii) the almost decision problem asks whether there is a word that is accepted with probability 1; and (iii) the limit decision problem asks whether for every ε > 0 there is a word that is accepted with probability at least 1 − ε. We unify and generalize several decidability results for probabilistic automata over infinite words, and identify a robust (closed under union and intersection) subclass of probabilistic automata for which all the qualitative decision problems are decidable for parity conditions. We also show that if the input words are restricted to lasso shape words, then the positive and almost problems are decidable for all probabilistic automata with parity conditions.
AU - Chatterjee, Krishnendu
AU - Tracol, Mathieu
ID - 5384
SN - 2664-1690
TI - Decidable problems for probabilistic automata on infinite words
ER -
TY - GEN
AB - There is recently a significant effort to add quantitative objectives to formal verification and synthesis. We introduce and investigate the extension of temporal logics with quantitative atomic assertions, aiming for a general and flexible framework for quantitative-oriented specifications. In the heart of quantitative objectives lies the accumulation of values along a computation. It is either the accumulated summation, as with the energy objectives, or the accumulated average, as with the mean-payoff objectives. We investigate the extension of temporal logics with the prefix-accumulation assertions Sum(v) ≥ c and Avg(v) ≥ c, where v is a numeric variable of the system, c is a constant rational number, and Sum(v) and Avg(v) denote the accumulated sum and average of the values of v from the beginning of the computation up to the current point of time. We also allow the path-accumulation assertions LimInfAvg(v) ≥ c and LimSupAvg(v) ≥ c, referring to the average value along an entire computation. We study the border of decidability for extensions of various temporal logics. In particular, we show that extending the fragment of CTL that has only the EX, EF, AX, and AG temporal modalities by prefix-accumulation assertions and extending LTL with path-accumulation assertions, result in temporal logics whose model-checking problem is decidable. The extended logics allow to significantly extend the currently known energy and mean-payoff objectives. Moreover, the prefix-accumulation assertions may be refined with “controlled-accumulation”, allowing, for example, to specify constraints on the average waiting time between a request and a grant. On the negative side, we show that the fragment we point to is, in a sense, the maximal logic whose extension with prefix-accumulation assertions permits a decidable model-checking procedure. Extending a temporal logic that has the EG or EU modalities, and in particular CTL and LTL, makes the problem undecidable.
AU - Boker, Udi
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Kupferman, Orna
ID - 5385
SN - 2664-1690
TI - Temporal specifications with accumulative values
ER -