TY - JOUR
AB - For programs whose data variables range over Boolean or finite domains, program verification is decidable, and this forms the basis of recent tools for software model checking. In this article, we consider algorithmic verification of programs that use Boolean variables, and in addition, access a single read-only array whose length is potentially unbounded, and whose elements range over an unbounded data domain. We show that the reachability problem, while undecidable in general, is (1) PSPACE-complete for programs in which the array-accessing for-loops are not nested, (2) decidable for a restricted class of programs with doubly nested loops. The second result establishes connections to automata and logics defining languages over data words.
AU - Alur, Rajeev
AU - Cerny, Pavol
AU - Weinstein, Scott
ID - 2967
IS - 3
JF - ACM Transactions on Computational Logic (TOCL)
TI - Algorithmic analysis of array-accessing programs
VL - 13
ER -
TY - JOUR
AB - Little is known about the stability of trophic relationships in complex natural communities over evolutionary timescales. Here, we use sequence data from 18 nuclear loci to reconstruct and compare the intraspecific histories of major Pleistocene refugial populations in the Middle East, the Balkans and Iberia in a guild of four Chalcid parasitoids (Cecidostiba fungosa, Cecidostiba semifascia, Hobbya stenonota and Mesopolobus amaenus) all attacking Cynipid oak galls. We develop a likelihood method to numerically estimate models of divergence between three populations from multilocus data. We investigate the power of this framework on simulated data, and-using triplet alignments of intronic loci-quantify the support for all possible divergence relationships between refugial populations in the four parasitoids. Although an East to West order of population divergence has highest support in all but one species, we cannot rule out alternative population tree topologies. Comparing the estimated times of population splits between species, we find that one species, M. amaenus, has a significantly older history than the rest of the guild and must have arrived in central Europe at least one glacial cycle prior to other guild members. This suggests that although all four species may share a common origin in the East, they expanded westwards into Europe at different times. © 2012 Blackwell Publishing Ltd.
AU - Lohse, Konrad
AU - Barton, Nicholas H
AU - Melika, George
AU - Stone, Graham
ID - 2968
IS - 18
JF - Molecular Ecology
TI - A likelihood based comparison of population histories in a parasitoid guild
VL - 21
ER -
TY - JOUR
AB - The coupling between presynaptic Ca^(2+) channels and Ca^(2+) sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca^(2+) channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic
opening of presynaptic Ca^(2+) channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal
granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca^(2+) concentration and the unselective Ca^(2+) channel blocker Cd^(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ~50%, suggesting that the opening of presynaptic Ca^(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca^(2+) channel blocker
ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced
mIPSC frequency. Furthermore, both the fast Ca^(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency,
suggesting that Ca^(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB_(1) receptor
agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca^(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca^(2+) channels may be important for hippocampal information processing.
AU - Goswami, Sarit
AU - Bucurenciu, Iancu
AU - Jonas, Peter M
ID - 2969
IS - 41
JF - Journal of Neuroscience
TI - Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca^(2+) channels via microdomain coupling
VL - 32
ER -
TY - JOUR
AB - Morphogen gradients regulate the patterning and growth of many tissues, hence a key question is how they are established and maintained during development. Theoretical descriptions have helped to explain how gradient shape is controlled by the rates of morphogen production, spreading and degradation. These effective rates have been measured using fluorescence recovery after photobleaching (FRAP) and photoactivation. To unravel which molecular events determine the effective rates, such tissue-level assays have been combined with genetic analysis, high-resolution assays, and models that take into account interactions with receptors, extracellular components and trafficking. Nevertheless, because of the natural and experimental data variability, and the underlying assumptions of transport models, it remains challenging to conclusively distinguish between cellular mechanisms.
AU - Kicheva, Anna
AU - Bollenbach, Mark Tobias
AU - Wartlick, Ortrud
AU - Julicher, Frank
AU - Gonzalez Gaitan, Marcos
ID - 2970
IS - 6
JF - Current Opinion in Genetics & Development
TI - Investigating the principles of morphogen gradient formation: from tissues to cells
VL - 22
ER -
TY - CONF
AB - We study the task of interactive semantic labeling of a segmentation hierarchy. To this end we propose a framework interleaving two components: an automatic labeling step, based on a Conditional Random Field whose dependencies are defined by the inclusion tree of the segmentation hierarchy, and an interaction step that integrates incremental input from a human user. Evaluated on two distinct datasets, the proposed interactive approach efficiently integrates human interventions and illustrates the advantages of structured prediction in an interactive framework.
AU - Zankl, Georg
AU - Haxhimusa, Yll
AU - Ion, Adrian
ID - 2971
TI - Interactive labeling of image segmentation hierarchies
VL - 7476
ER -
TY - JOUR
AB - Energy parity games are infinite two-player turn-based games played on weighted graphs. The objective of the game combines a (qualitative) parity condition with the (quantitative) requirement that the sum of the weights (i.e., the level of energy in the game) must remain positive. Beside their own interest in the design and synthesis of resource-constrained omega-regular specifications, energy parity games provide one of the simplest model of games with combined qualitative and quantitative objectives. Our main results are as follows: (a) exponential memory is sufficient and may be necessary for winning strategies in energy parity games; (b) the problem of deciding the winner in energy parity games can be solved in NP ∩ coNP; and (c) we give an algorithm to solve energy parity by reduction to energy games. We also show that the problem of deciding the winner in energy parity games is logspace-equivalent to the problem of deciding the winner in mean-payoff parity games, which can thus be solved in NP ∩ coNP. As a consequence we also obtain a conceptually simple algorithm to solve mean-payoff parity games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 2972
JF - Theoretical Computer Science
TI - Energy parity games
VL - 458
ER -
TY - CONF
AB - We construct a perfectly binding string commitment scheme whose security is based on the learning parity with noise (LPN) assumption, or equivalently, the hardness of decoding random linear codes. Our scheme not only allows for a simple and efficient zero-knowledge proof of knowledge for committed values (essentially a Σ-protocol), but also for such proofs showing any kind of relation amongst committed values, i.e. proving that messages m_0,...,m_u, are such that m_0=C(m_1,...,m_u) for any circuit C.
To get soundness which is exponentially small in a security parameter t, and when the zero-knowledge property relies on the LPN problem with secrets of length l, our 3 round protocol has communication complexity O(t|C|l log(l)) and computational complexity of O(t|C|l) bit operations. The hidden constants are small, and the computation consists mostly of computing inner products of bit-vectors.
AU - Jain, Abhishek
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Tentes, Aris
ED - Wang, Xiaoyun
ED - Sako, Kazue
ID - 2974
TI - Commitments and efficient zero knowledge proofs from learning parity with noise
VL - 7658
ER -
TY - JOUR
AB - We consider the offset-deconstruction problem: Given a polygonal shape Q with n vertices, can it be expressed, up to a tolerance ε in Hausdorff distance, as the Minkowski sum of another polygonal shape P with a disk of fixed radius? If it does, we also seek a preferably simple-looking solution P; then, P's offset constitutes an accurate, vertex-reduced, and smoothened approximation of Q. We give an O(nlogn)-time exact decision algorithm that handles any polygonal shape, assuming the real-RAM model of computation. A variant of the algorithm, which we have implemented using the cgal library, is based on rational arithmetic and answers the same deconstruction problem up to an uncertainty parameter δ its running time additionally depends on δ. If the input shape is found to be approximable, this algorithm also computes an approximate solution for the problem. It also allows us to solve parameter-optimization problems induced by the offset-deconstruction problem. For convex shapes, the complexity of the exact decision algorithm drops to O(n), which is also the time required to compute a solution P with at most one more vertex than a vertex-minimal one.
AU - Berberich, Eric
AU - Halperin, Dan
AU - Kerber, Michael
AU - Pogalnikova, Roza
ID - 3115
IS - 4
JF - Discrete & Computational Geometry
TI - Deconstructing approximate offsets
VL - 48
ER -
TY - JOUR
AB - We consider the problem of minimizing a function represented as a sum of submodular terms. We assume each term allows an efficient computation of exchange capacities. This holds, for example, for terms depending on a small number of variables, or for certain cardinality-dependent terms. A naive application of submodular minimization algorithms would not exploit the existence of specialized exchange capacity subroutines for individual terms. To overcome this, we cast the problem as a submodular flow (SF) problem in an auxiliary graph in such a way that applying most existing SF algorithms would rely only on these subroutines. We then explore in more detail Iwata's capacity scaling approach for submodular flows (Iwata 1997 [19]). In particular, we show how to improve its complexity in the case when the function contains cardinality-dependent terms.
AU - Kolmogorov, Vladimir
ID - 3117
IS - 15
JF - Discrete Applied Mathematics
TI - Minimizing a sum of submodular functions
VL - 160
ER -
TY - CONF
AB - We present an approach for artist-directed animation of liquids using multiple levels of control over the simulation, ranging from the overall tracking of desired shapes to highly detailed secondary effects such as dripping streams, separating sheets of fluid, surface waves and ripples. The first portion of our technique is a volume preserving morph that allows the animator to produce a plausible fluid-like motion from a sparse set of control meshes. By rasterizing the resulting control meshes onto the simulation grid, the mesh velocities act as boundary conditions during the projection step of the fluid simulation. We can then blend this motion together with uncontrolled fluid velocities to achieve a more relaxed control over the fluid that captures natural inertial effects. Our method can produce highly detailed liquid surfaces with control over sub-grid details by using a mesh-based surface tracker on top of a coarse grid-based fluid simulation. We can create ripples and waves on the fluid surface attracting the surface mesh to the control mesh with spring-like forces and also by running a wave simulation over the surface mesh. Our video results demonstrate how our control scheme can be used to create animated characters and shapes that are made of water.
AU - Raveendran, Karthik
AU - Thuerey, Nils
AU - Wojtan, Christopher J
AU - Turk, Greg
ID - 3119
T2 - Proceedings of the ACM SIGGRAPH/Eurographics Symposium on Computer Animation
TI - Controlling liquids using meshes
ER -
TY - JOUR
AB - We introduce a strategy based on Kustin-Miller unprojection that allows us to construct many hundreds of Gorenstein codimension 4 ideals with 9 × 16 resolutions (that is, nine equations and sixteen first syzygies). Our two basic games are called Tom and Jerry; the main application is the biregular construction of most of the anticanonically polarised Mori Fano 3-folds of Altinok's thesis. There are 115 cases whose numerical data (in effect, the Hilbert series) allow a Type I projection. In every case, at least one Tom and one Jerry construction works, providing at least two deformation families of quasismooth Fano 3-folds having the same numerics but different topology. © 2012 Copyright Foundation Compositio Mathematica.
AU - Brown, Gavin
AU - Kerber, Michael
AU - Reid, Miles
ID - 3120
IS - 4
JF - Compositio Mathematica
TI - Fano 3 folds in codimension 4 Tom and Jerry Part I
VL - 148
ER -
TY - JOUR
AB - Voltage-activated Ca(2+) channels (VACCs) mediate Ca(2+) influx to trigger action potential-evoked neurotransmitter release, but the mechanism by which Ca(2+) regulates spontaneous transmission is unclear. We found that VACCs are the major physiological triggers for spontaneous release at mouse neocortical inhibitory synapses. Moreover, despite the absence of a synchronizing action potential, we found that spontaneous fusion of a GABA-containing vesicle required the activation of multiple tightly coupled VACCs of variable type.
AU - Williams, Courtney
AU - Chen, Wenyan
AU - Lee, Chia
AU - Yaeger, Daniel
AU - Vyleta, Nicholas
AU - Smith, Stephen
ID - 3121
IS - 9
JF - Nature Neuroscience
TI - Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA
VL - 15
ER -
TY - JOUR
AB - Since Darwin's pioneering research on plant reproductive biology (e.g. Darwin 1877), understanding the mechanisms maintaining the diverse sexual strategies of plants has remained an important challenge for evolutionary biologists. In some species, populations are sexually polymorphic and contain two or more mating morphs (sex phenotypes). Differences in morphology or phenology among the morphs influence patterns of non-random mating. In these populations, negative frequency-dependent selection arising from disassortative (intermorph) mating is usually required for the evolutionary maintenance of sexual polymorphism, but few studies have demonstrated the required patterns of non-random mating. In the current issue of Molecular Ecology, Shang (2012) make an important contribution to our understanding of how disassortative mating influences sex phenotype ratios in Acer pictum subsp. mono (painted maple), a heterodichogamous, deciduous tree of eastern China. They monitored sex expression in 97 adults and used paternity analysis of open-pollinated seed to examine disassortative mating among three sex phenotypes. Using a deterministic 'pollen transfer' model, Shang et al. present convincing evidence that differences in the degree of disassortative mating in progeny arrays of the sex phenotypes can explain their uneven frequencies in the adult population. This study provides a useful example of how the deployment of genetic markers, demographic monitoring and modelling can be integrated to investigate the maintenance of sexual diversity in plants.
AU - Field, David
AU - Barrett, Spencer
ID - 3122
IS - 15
JF - Molecular Ecology
TI - Disassortative mating and the maintenance of sexual polymorphism in painted maple
VL - 21
ER -
TY - CONF
AB - We introduce the idea of using an explicit triangle mesh to track the air/fluid interface in a smoothed particle hydrodynamics (SPH) simulator. Once an initial surface mesh is created, this mesh is carried forward in time using nearby particle velocities to advect the mesh vertices. The mesh connectivity remains mostly unchanged across time-steps; it is only modified locally for topology change events or for the improvement of triangle quality. In order to ensure that the surface mesh does not diverge from the underlying particle simulation, we periodically project the mesh surface onto an implicit surface defined by the physics simulation. The mesh surface gives us several advantages over previous SPH surface tracking techniques. We demonstrate a new method for surface tension calculations that clearly outperforms the state of the art in SPH surface tension for computer graphics. We also demonstrate a method for tracking detailed surface information (like colors) that is less susceptible to numerical diffusion than competing techniques. Finally, our temporally-coherent surface mesh allows us to simulate high-resolution surface wave dynamics without being limited by the particle resolution of the SPH simulation.
AU - Yu, Jihun
AU - Wojtan, Christopher J
AU - Turk, Greg
AU - Yap, Chee
ID - 3123
IS - 2
T2 - Computer Graphics Forum
TI - Explicit mesh surfaces for particle based fluids
VL - 31
ER -
TY - CONF
AB - We consider the problem of inference in a graphical model with binary variables. While in theory it is arguably preferable to compute marginal probabilities, in practice researchers often use MAP inference due to the availability of efficient discrete optimization algorithms. We bridge the gap between the two approaches by introducing the Discrete Marginals technique in which approximate marginals are obtained by minimizing an objective function with unary and pairwise terms over a discretized domain. This allows the use of techniques originally developed for MAP-MRF inference and learning. We explore two ways to set up the objective function - by discretizing the Bethe free energy and by learning it from training data. Experimental results show that for certain types of graphs a learned function can outperform the Bethe approximation. We also establish a link between the Bethe free energy and submodular functions.
AU - Korc, Filip
AU - Kolmogorov, Vladimir
AU - Lampert, Christoph
ID - 3124
TI - Approximating marginals using discrete energy minimization
ER -
TY - CONF
AB - We propose a new learning method to infer a mid-level feature representation that combines the advantage of semantic attribute representations with the higher expressive power of non-semantic features. The idea lies in augmenting an existing attribute-based representation with additional dimensions for which an autoencoder model is coupled with a large-margin principle. This construction allows a smooth transition between the zero-shot regime with no training example, the unsupervised regime with training examples but without class labels, and the supervised regime with training examples and with class labels. The resulting optimization problem can be solved efficiently, because several of the necessity steps have closed-form solutions. Through extensive experiments we show that the augmented representation achieves better results in terms of object categorization accuracy than the semantic representation alone.
AU - Sharmanska, Viktoriia
AU - Quadrianto, Novi
AU - Lampert, Christoph
ID - 3125
IS - PART 5
TI - Augmented attribute representations
VL - 7576
ER -
TY - CONF
AB - In this work we propose a new information-theoretic clustering algorithm that infers cluster memberships by direct optimization of a non-parametric mutual information estimate between data distribution and cluster assignment. Although the optimization objective has a solid theoretical foundation it is hard to optimize. We propose an approximate optimization formulation that leads to an efficient algorithm with low runtime complexity. The algorithm has a single free parameter, the number of clusters to find. We demonstrate superior performance on several synthetic and real datasets.
AU - Müller, Andreas
AU - Nowozin, Sebastian
AU - Lampert, Christoph
ID - 3126
TI - Information theoretic clustering using minimal spanning trees
VL - 7476
ER -
TY - CONF
AB - When searching for characteristic subpatterns in potentially noisy graph data, it appears self-evident that having multiple observations would be better than having just one. However, it turns out that the inconsistencies introduced when different graph instances have different edge sets pose a serious challenge. In this work we address this challenge for the problem of finding maximum weighted cliques.
We introduce the concept of most persistent soft-clique. This is subset of vertices, that 1) is almost fully or at least densely connected, 2) occurs in all or almost all graph instances, and 3) has the maximum weight. We present a measure of clique-ness, that essentially counts the number of edge missing to make a subset of vertices into a clique. With this measure, we show that the problem of finding the most persistent soft-clique problem can be cast either as: a) a max-min two person game optimization problem, or b) a min-min soft margin optimization problem. Both formulations lead to the same solution when using a partial Lagrangian method to solve the optimization problems. By experiments on synthetic data and on real social network data, we show that the proposed method is able to reliably find soft cliques in graph data, even if that is distorted by random noise or unreliable observations.
AU - Quadrianto, Novi
AU - Lampert, Christoph
AU - Chen, Chao
ID - 3127
T2 - Proceedings of the 29th International Conference on Machine Learning
TI - The most persistent soft-clique in a set of sampled graphs
ER -
TY - JOUR
AB - We consider two-player zero-sum stochastic games on graphs with ω-regular winning conditions specified as parity objectives. These games have applications in the design and control of reactive systems. We survey the complexity results for the problem of deciding the winner in such games, and in classes of interest obtained as special cases, based on the information and the power of randomization available to the players, on the class of objectives and on the winning mode. On the basis of information, these games can be classified as follows: (a) partial-observation (both players have partial view of the game); (b) one-sided partial-observation (one player has partial-observation and the other player has complete-observation); and (c) complete-observation (both players have complete view of the game). The one-sided partial-observation games have two important subclasses: the one-player games, known as partial-observation Markov decision processes (POMDPs), and the blind one-player games, known as probabilistic automata. 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. Finally, various classes of games are obtained by restricting the parity objective to a reachability, safety, Büchi, or coBüchi condition. We also consider several winning modes, such as sure-winning (i.e., all outcomes of a strategy have to satisfy the winning condition), almost-sure winning (i.e., winning with probability 1), limit-sure winning (i.e., winning with probability arbitrarily close to 1), and value-threshold winning (i.e., winning with probability at least ν, where ν is a given rational).
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ID - 3128
IS - 2
JF - Formal Methods in System Design
TI - A survey of partial-observation stochastic parity games
VL - 43
ER -
TY - CONF
AB - Let K be a simplicial complex and g the rank of its p-th homology group Hp(K) defined with ℤ2 coefficients. We show that we can compute a basis H of Hp(K) and annotate each p-simplex of K with a binary vector of length g with the following property: the annotations, summed over all p-simplices in any p-cycle z, provide the coordinate vector of the homology class [z] in the basis H. The basis and the annotations for all simplices can be computed in O(n ω ) time, where n is the size of K and ω < 2.376 is a quantity so that two n×n matrices can be multiplied in O(n ω ) time. The precomputed annotations permit answering queries about the independence or the triviality of p-cycles efficiently.
Using annotations of edges in 2-complexes, we derive better algorithms for computing optimal basis and optimal homologous cycles in 1 - dimensional homology. Specifically, for computing an optimal basis of H1(K) , we improve the previously known time complexity from O(n 4) to O(n ω + n 2 g ω − 1). Here n denotes the size of the 2-skeleton of K and g the rank of H1(K) . Computing an optimal cycle homologous to a given 1-cycle is NP-hard even for surfaces and an algorithm taking 2 O(g) nlogn time is known for surfaces. We extend this algorithm to work with arbitrary 2-complexes in O(n ω ) + 2 O(g) n 2logn time using annotations.
AU - Busaryev, Oleksiy
AU - Cabello, Sergio
AU - Chen, Chao
AU - Dey, Tamal
AU - Wang, Yusu
ID - 3129
TI - Annotating simplices with a homology basis and its applications
VL - 7357
ER -
TY - JOUR
AB - Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes.
AU - Bergmiller, Tobias
AU - Ackermann, Martin
AU - Silander, Olin
ID - 3130
IS - 6
JF - PLoS Genetics
TI - Patterns of evolutionary conservation of essential genes correlate with their compensability
VL - 8
ER -
TY - JOUR
AB - In large populations, many beneficial mutations may be simultaneously available and may compete with one another, slowing adaptation. By finding the probability of fixation of a favorable allele in a simple model of a haploid sexual population, we find limits to the rate of adaptive substitution, Λ, that depend on simple parameter combinations. When variance in fitness is low and linkage is loose, the baseline rate of substitution is Λ 0=2NU〈s〉 is the population size, U is the rate of beneficial mutations per genome, and 〈s〉 is their mean selective advantage. Heritable variance ν in log fitness due to unlinked loci reduces Λ by e -4ν under polygamy and e -8ν under monogamy. With a linear genetic map of length R Morgans, interference is yet stronger. We use a scaling argument to show that the density of adaptive substitutions depends on s, N, U, and R only through the baseline density: Λ/R=F(Λ 0/R). Under the approximation that the interference due to different sweeps adds up, we show that Λ/R~(Λ 0/R)/(1+2Λ 0/R), implying that interference prevents the rate of adaptive substitution from exceeding one per centimorgan per 200 generations. Simulations and numerical calculations confirm the scaling argument and confirm the additive approximation for Λ 0/R 1; for higher Λ 0/R, the rate of adaptation grows above R/2, but only very slowly. We also consider the effect of sweeps on neutral diversity and show that, while even occasional sweeps can greatly reduce neutral diversity, this effect saturates as sweeps become more common-diversity can be maintained even in populations experiencing very strong interference. Our results indicate that for some organisms the rate of adaptive substitution may be primarily recombination-limited, depending only weakly on the mutation supply and the strength of selection.
AU - Weissman, Daniel
AU - Barton, Nicholas H
ID - 3131
IS - 6
JF - PLoS Genetics
TI - Limits to the rate of adaptive substitution in sexual populations
VL - 8
ER -
TY - JOUR
AB - Reproductive division of labour is a characteristic trait of social insects. The dominant reproductive individual, often the queen, uses chemical communication and/or behaviour to maintain her social status. Queens of many social insects communicate their fertility status via cuticle-bound substances. As these substances usually possess a low volatility, their range in queen–worker communication is potentially limited. Here, we investigate the range and impact of behavioural and chemical queen signals on workers of the ant Temnothorax longispinosus. We compared the behaviour and ovary development of workers subjected to three different treatments: workers with direct chemical and physical contact to the queen, those solely under the influence of volatile queen substances and those entirely separated from the queen. In addition to short-ranged queen signals preventing ovary development in workers, we discovered a novel secondary pathway influencing worker behaviour. Workers with no physical contact to the queen, but exposed to volatile substances, started to develop their ovaries, but did not change their behaviour compared to workers in direct contact to the queen. In contrast, workers in queen-separated groups showed both increased ovary development and aggressive dominance interactions. We conclude that T. longispinosus queens influence worker ovary development and behaviour via two independent signals, both ensuring social harmony within the colony.
AU - Konrad, Matthias
AU - Pamminger, Tobias
AU - Foitzik, Susanne
ID - 3132
IS - 8
JF - Naturwissenschaften
TI - Two pathways ensuring social harmony
VL - 99
ER -
TY - CONF
AB - This note contributes to the point calculus of persistent homology by extending Alexander duality from spaces to real-valued functions. Given a perfect Morse function f: S n+1 →[0, 1 and a decomposition S n+1 = U ∪ V into two (n + 1)-manifolds with common boundary M, we prove elementary relationships between the persistence diagrams of f restricted to U, to V, and to M.
AU - Edelsbrunner, Herbert
AU - Kerber, Michael
ID - 3133
T2 - Proceedings of the twenty-eighth annual symposium on Computational geometry
TI - Alexander duality for functions: The persistent behavior of land and water and shore
ER -
TY - CONF
AB - We introduce consumption games, a model for discrete interactive system with multiple resources that are consumed or reloaded independently. More precisely, a consumption game is a finite-state graph where each transition is labeled by a vector of resource updates, where every update is a non-positive number or ω. The ω updates model the reloading of a given resource. Each vertex belongs either to player □ or player ◇, where the aim of player □ is to play so that the resources are never exhausted. We consider several natural algorithmic problems about consumption games, and show that although these problems are computationally hard in general, they are solvable in polynomial time for every fixed number of resource types (i.e., the dimension of the update vectors) and bounded resource updates.
AU - Brázdil, Brázdil
AU - Chatterjee, Krishnendu
AU - Kučera, Antonín
AU - Novotny, Petr
ID - 3135
TI - Efficient controller synthesis for consumption games with multiple resource types
VL - 7358
ER -
TY - CONF
AB - Continuous-time Markov chains (CTMC) with their rich theory and efficient simulation algorithms have been successfully used in modeling stochastic processes in diverse areas such as computer science, physics, and biology. However, systems that comprise non-instantaneous events cannot be accurately and efficiently modeled with CTMCs. In this paper we define delayed CTMCs, an extension of CTMCs that allows for the specification of a lower bound on the time interval between an event's initiation and its completion, and we propose an algorithm for the computation of their behavior. Our algorithm effectively decomposes the computation into two stages: a pure CTMC governs event initiations while a deterministic process guarantees lower bounds on event completion times. Furthermore, from the nature of delayed CTMCs, we obtain a parallelized version of our algorithm. We use our formalism to model genetic regulatory circuits (biological systems where delayed events are common) and report on the results of our numerical algorithm as run on a cluster. We compare performance and accuracy of our results with results obtained by using pure CTMCs. © 2012 Springer-Verlag.
AU - Guet, Calin C
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
AU - Mateescu, Maria
AU - Sezgin, Ali
ID - 3136
TI - Delayed continuous time Markov chains for genetic regulatory circuits
VL - 7358
ER -
TY - CONF
AB - We propose synchronous interfaces, a new interface theory for discrete-time systems. We use an application to time-triggered scheduling to drive the design choices for our formalism; in particular, additionally to deriving useful mathematical properties, we focus on providing a syntax which is adapted to natural high-level system modeling. As a result, we develop an interface model that relies on a guarded-command based language and is equipped with shared variables and explicit discrete-time clocks. We define all standard interface operations: compatibility checking, composition, refinement, and shared refinement. Apart from the synchronous interface model, the contribution of this paper is the establishment of a formal relation between interface theories and real-time scheduling, where we demonstrate a fully automatic framework for the incremental computation of time-triggered schedules.
AU - Delahaye, Benoît
AU - Fahrenberg, Uli
AU - Henzinger, Thomas A
AU - Legay, Axel
AU - Nickovic, Dejan
ID - 3155
TI - Synchronous interface theories and time triggered scheduling
VL - 7273
ER -
TY - JOUR
AB - Dispersal is crucial for gene flow and often determines the long-term stability of meta-populations, particularly in rare species with specialized life cycles. Such species are often foci of conservation efforts because they suffer disproportionally from degradation and fragmentation of their habitat. However, detailed knowledge of effective gene flow through dispersal is often missing, so that conservation strategies have to be based on mark-recapture observations that are suspected to be poor predictors of long-distance dispersal. These constraints have been especially severe in the study of butterfly populations, where microsatellite markers have been difficult to develop. We used eight microsatellite markers to analyse genetic population structure of the Large Blue butterfly Maculinea arion in Sweden. During recent decades, this species has become an icon of insect conservation after massive decline throughout Europe and extinction in Britain followed by reintroduction of a seed population from the Swedish island of Öland. We find that populations are highly structured genetically, but that gene flow occurs over distances 15 times longer than the maximum distance recorded from mark-recapture studies, which can only be explained by maximum dispersal distances at least twice as large as previously accepted. However, we also find evidence that gaps between sites with suitable habitat exceeding ∼ 20 km induce genetic erosion that can be detected from bottleneck analyses. Although further work is needed, our results suggest that M. arion can maintain fully functional metapopulations when they consist of optimal habitat patches that are no further apart than ∼10 km.
AU - Ugelvig, Line V
AU - Andersen, Anne
AU - Boomsma, Jacobus
AU - Nash, David
ID - 3156
IS - 13
JF - Molecular Ecology
TI - Dispersal and gene flow in the rare parasitic Large Blue butterfly Maculinea arion
VL - 21
ER -
TY - JOUR
AB - Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.
AU - Diaz Jr, Luis
AU - Williams, Richard
AU - Wu, Jian
AU - Kinde, Isaac
AU - Hecht, Joel
AU - Berlin, Jordan
AU - Allen, Benjamin
AU - Božić, Ivana
AU - Reiter, Johannes
AU - Nowak, Martin
AU - Kinzler, Kenneth
AU - Oliner, Kelly
AU - Vogelstein, Bert
ID - 3157
IS - 7404
JF - Nature
TI - The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers
VL - 486
ER -
TY - JOUR
AB - We describe here the development and characterization of a conditionally inducible mouse model expressing Lifeact-GFP, a peptide that reports the dynamics of filamentous actin. We have used this model to study platelets, megakaryocytes and melanoblasts and we provide evidence that Lifeact-GFP is a useful reporter in these cell types ex vivo. In the case of platelets and megakaryocytes, these cells are not transfectable by traditional methods, so conditional activation of Lifeact allows the study of actin dynamics in these cells live. We studied melanoblasts in native skin explants from embryos, allowing the visualization of live actin dynamics during cytokinesis and migration. Our study revealed that melanoblasts lacking the small GTPase Rac1 show a delay in the formation of new pseudopodia following cytokinesis that accounts for the previously reported cytokinesis delay in these cells. Thus, through use of this mouse model, we were able to gain insights into the actin dynamics of cells that could only previously be studied using fixed specimens or following isolation from their native tissue environment.
AU - Schachtner, Hannah
AU - Li, Ang
AU - Stevenson, David
AU - Calaminus, Simon
AU - Thomas, Steven
AU - Watson, Steve
AU - Sixt, Michael K
AU - Wedlich Söldner, Roland
AU - Strathdee, Douglas
AU - Machesky, Laura
ID - 3158
IS - 11-12
JF - European Journal of Cell Biology
TI - Tissue inducible Lifeact expression allows visualization of actin dynamics in vivo and ex vivo
VL - 91
ER -
TY - JOUR
AB - The structure of hierarchical networks in biological and physical systems has long been characterized using the Horton-Strahler ordering scheme. The scheme assigns an integer order to each edge in the network based on the topology of branching such that the order increases from distal parts of the network (e.g., mountain streams or capillaries) to the "root" of the network (e.g., the river outlet or the aorta). However, Horton-Strahler ordering cannot be applied to networks with loops because they they create a contradiction in the edge ordering in terms of which edge precedes another in the hierarchy. Here, we present a generalization of the Horton-Strahler order to weighted planar reticular networks, where weights are assumed to correlate with the importance of network edges, e.g., weights estimated from edge widths may correlate to flow capacity. Our method assigns hierarchical levels not only to edges of the network, but also to its loops, and classifies the edges into reticular edges, which are responsible for loop formation, and tree edges. In addition, we perform a detailed and rigorous theoretical analysis of the sensitivity of the hierarchical levels to weight perturbations. In doing so, we show that the ordering of the reticular edges is more robust to noise in weight estimation than is the ordering of the tree edges. We discuss applications of this generalized Horton-Strahler ordering to the study of leaf venation and other biological networks.
AU - Mileyko, Yuriy
AU - Edelsbrunner, Herbert
AU - Price, Charles
AU - Weitz, Joshua
ID - 3159
IS - 6
JF - PLoS One
TI - Hierarchical ordering of reticular networks
VL - 7
ER -
TY - JOUR
AB - There is a long-running controversy about how early cell fate decisions are made in the developing mammalian embryo. 1,2 In particular, it is controversial when the first events that can predict the establishment of the pluripotent and extra-embryonic lineages in the blastocyst of the pre-implantation embryo occur. It has long been proposed that the position and polarity of cells at the 16- to 32-cell stage embryo influence their decision to either give rise to the pluripotent cell lineage that eventually contributes to the inner cell mass (ICM), comprising the primitive endoderm (PE) and the epiblast (EPI), or the extra-embryonic trophectoderm (TE) surrounding the blastocoel. The positioning of cells in the embryo at this developmental stage could largely be the result of random events, making this a stochastic model of cell lineage allocation. Contrary to such a stochastic model, some studies have detected putative differences in the lineage potential of individual blastomeres before compaction, indicating that the first cell fate decisions may occur as early as at the 4-cell stage. Using a non-invasive, quantitative in vivo imaging assay to study the kinetic behavior of Oct4 (also known as POU5F1), a key transcription factor (TF) controlling pre-implantation development in the mouse embryo, 3-5 a recent study identifies Oct4 kinetics as a predictive measure of cell lineage patterning in the early mouse embryo. 6 Here, we discuss the implications of such molecular heterogeneities in early development and offer potential avenues toward a mechanistic understanding of these observations, contributing to the resolution of the controversy of developmental cell lineage allocation.
AU - Pantazis, Periklis
AU - Bollenbach, Tobias
ID - 3160
IS - 11
JF - Cell Cycle
TI - Transcription factor kinetics and the emerging asymmetry in the early mammalian embryo
VL - 11
ER -
TY - JOUR
AB - Some inflammatory stimuli trigger activation of the NLRP3 inflammasome by inducing efflux of cellular potassium. Loss of cellular potassium is known to potently suppress protein synthesis, leading us to test whether the inhibition of protein synthesis itself serves as an activating signal for the NLRP3 inflammasome. Murine bone marrow-derived macrophages, either primed by LPS or unprimed, were exposed to a panel of inhibitors of ribosomal function: ricin, cycloheximide, puromycin, pactamycin, and anisomycin. Macrophages were also exposed to nigericin, ATP, monosodium urate (MSU), and poly I:C. Synthesis of pro-IL-ß and release of IL-1ß from cells in response to these agents was detected by immunoblotting and ELISA. Release of intracellular potassium was measured by mass spectrometry. Inhibition of translation by each of the tested translation inhibitors led to processing of IL-1ß, which was released from cells. Processing and release of IL-1ß was reduced or absent from cells deficient in NLRP3, ASC, or caspase-1, demonstrating the role of the NLRP3 inflammasome. Despite the inability of these inhibitors to trigger efflux of intracellular potassium, the addition of high extracellular potassium suppressed activation of the NLRP3 inflammasome. MSU and double-stranded RNA, which are known to activate the NLRP3 inflammasome, also substantially inhibited protein translation, supporting a close association between inhibition of translation and inflammasome activation. These data demonstrate that translational inhibition itself constitutes a heretofore-unrecognized mechanism underlying IL-1ß dependent inflammatory signaling and that other physical, chemical, or pathogen-associated agents that impair translation may lead to IL-1ß-dependent inflammation through activation of the NLRP3 inflammasome. For agents that inhibit translation through decreased cellular potassium, the application of high extracellular potassium restores protein translation and suppresses activation of the NLRP inflammasome. For agents that inhibit translation through mechanisms that do not involve loss of potassium, high extracellular potassium suppresses IL-1ß processing through a mechanism that remains undefined.
AU - Vyleta, Meghan
AU - Wong, John
AU - Magun, Bruce
ID - 3161
IS - 5
JF - PLoS One
TI - Suppression of ribosomal function triggers innate immune signaling through activation of the NLRP3 inflammasome
VL - 7
ER -
TY - CONF
AB - Given a dense-time real-valued signal and a parameterized temporal logic formula with both magnitude and timing parameters, we compute the subset of the parameter space that renders the formula satisfied by the trace. We provide two preliminary implementations, one which follows the exact semantics and attempts to compute the validity domain by quantifier elimination in linear arithmetics and one which conducts adaptive search in the parameter space.
AU - Asarin, Eugene
AU - Donzé, Alexandre
AU - Maler, Oded
AU - Nickovic, Dejan
ID - 3162
TI - Parametric identification of temporal properties
VL - 7186
ER -
TY - JOUR
AB - Overview of the Special Issue on structured prediction and inference.
AU - Blaschko, Matthew
AU - Lampert, Christoph
ID - 3164
IS - 3
JF - International Journal of Computer Vision
TI - Guest editorial: Special issue on structured prediction and inference
VL - 99
ER -
TY - CONF
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 Õ(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 Õ(n·m) boundary by presenting a new technique that reduces the running time to O(n 2). This bound also leads to O(n 2) 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 Õ(n·m)), (2) in concurrent graph games with constant actions (improving an earlier bound of O(n 3)), and (3) in Markov decision processes (improving for m > n 4/3 an earlier bound of O(min(m 1.5, m·n 2/3)). We also show that the same technique can be used to compute the maximal end-component decomposition of a graph in time O(n 2), which is an improvement over earlier bounds for m > n 4/3. 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 - 3165
T2 - Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms
TI - An O(n2) time algorithm for alternating Büchi games
ER -
TY - JOUR
AB - There is evidence that the genetic code was established prior to the existence of proteins, when metabolism was powered by ribozymes. Also, early proto-organisms had to rely on simple anaerobic bioenergetic processes. In this work I propose that amino acid fermentation powered metabolism in the RNA world, and that this was facilitated by proto-adapters, the precursors of the tRNAs. Amino acids were used as carbon sources rather than as catalytic or structural elements. In modern bacteria, amino acid fermentation is known as the Stickland reaction. This pathway involves two amino acids: the first undergoes oxidative deamination, and the second acts as an electron acceptor through reductive deamination. This redox reaction results in two keto acids that are employed to synthesise ATP via substrate-level phosphorylation. The Stickland reaction is the basic bioenergetic pathway of some bacteria of the genus Clostridium. Two other facts support Stickland fermentation in the RNA world. First, several Stickland amino acid pairs are synthesised in abiotic amino acid synthesis. This suggests that amino acids that could be used as an energy substrate were freely available. Second, anticodons that have complementary sequences often correspond to amino acids that form Stickland pairs. The main hypothesis of this paper is that pairs of complementary proto-adapters were assigned to Stickland amino acids pairs. There are signatures of this hypothesis in the genetic code. Furthermore, it is argued that the proto-adapters formed double strands that brought amino acid pairs into proximity to facilitate their mutual redox reaction, structurally constraining the anticodon pairs that are assigned to these amino acid pairs. Significance tests which randomise the code are performed to study the extent of the variability of the energetic (ATP) yield. Random assignments can lead to a substantial yield of ATP and maintain enough variability, thus selection can act and refine the assignments into a proto-code that optimises the energetic yield. Monte Carlo simulations are performed to evaluate the establishment of these simple proto-codes, based on amino acid substitutions and codon swapping. In all cases, donor amino acids are assigned to anticodons composed of U+G, and have low redundancy (1-2 codons), whereas acceptor amino acids are assigned to the the remaining codons. These bioenergetic and structural constraints allow for a metabolic role for amino acids before their co-option as catalyst cofactors. Reviewers: this article was reviewed by Prof. William Martin, Prof. Eors Szathmary (nominated by Dr. Gaspar Jekely) and Dr. Adam Kun (nominated by Dr. Sandor Pongor)
AU - Vladar, Harold
ID - 3166
JF - Biology Direct
TI - Amino acid fermentation at the origin of the genetic code
VL - 7
ER -
TY - JOUR
AU - Weber, Michele
ID - 3167
IS - 6077
JF - Science
TI - NextGen speaks 13
VL - 336
ER -
TY - JOUR
AB - The induction of a signaling pathway is characterized by transient complex formation and mutual posttranslational modification of proteins. To faithfully capture this combinatorial process in a mathematical model is an important challenge in systems biology. Exploiting the limited context on which most binding and modification events are conditioned, attempts have been made to reduce the combinatorial complexity by quotienting the reachable set of molecular species into species aggregates while preserving the deterministic semantics of the thermodynamic limit. Recently, we proposed a quotienting that also preserves the stochastic semantics and that is complete in the sense that the semantics of individual species can be recovered from the aggregate semantics. In this paper, we prove that this quotienting yields a sufficient condition for weak lumpability (that is to say that the quotient system is still Markovian for a given set of initial distributions) and that it gives rise to a backward Markov bisimulation between the original and aggregated transition system (which means that the conditional probability of being in a given state in the original system knowing that we are in its equivalence class is an invariant of the system). We illustrate the framework on a case study of the epidermal growth factor (EGF)/insulin receptor crosstalk.
AU - Feret, Jérôme
AU - Henzinger, Thomas A
AU - Koeppl, Heinz
AU - Petrov, Tatjana
ID - 3168
JF - Theoretical Computer Science
TI - Lumpability abstractions of rule based systems
VL - 431
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 - JOUR
AU - Danowski, Patrick
ID - 3243
JF - Büchereiperspektiven
TI - Zwischen Technologie und Information
VL - 1/2012
ER -
TY - JOUR
AU - Danowski, Patrick
ID - 3244
IS - 4
JF - BuB – Forum Bibliothek und Information
TI - Die Zeit des Abwartens ist vorbei!
VL - 64
ER -
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 - 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 - 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 - 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 - JOUR
AB - The BCI competition IV stands in the tradition of prior BCI competitions that aim to provide high quality neuroscientific data for open access to the scientific community. As experienced already in prior competitions not only scientists from the narrow field of BCI compete, but scholars with a broad variety of backgrounds and nationalities. They include high specialists as well as students.The goals of all BCI competitions have always been to challenge with respect to novel paradigms and complex data. We report on the following challenges: (1) asynchronous data, (2) synthetic, (3) multi-class continuous data, (4) sessionto-session transfer, (5) directionally modulated MEG, (6) finger movements recorded by ECoG. As after past competitions, our hope is that winning entries may enhance the analysis methods of future BCIs.
AU - Tangermann, Michael
AU - Müller, Klaus
AU - Aertsen, Ad
AU - Birbaumer, Niels
AU - Braun, Christoph
AU - Brunner, Clemens
AU - Leeb, Robert
AU - Mehring, Carsten
AU - Miller, Kai
AU - Müller Putz, Gernot
AU - Nolte, Guido
AU - Pfurtscheller, Gert
AU - Preissl, Hubert
AU - Schalk, Gerwin
AU - Schlögl, Alois
AU - Vidaurre, Carmen
AU - Waldert, Stephan
AU - Blankertz, Benjamin
ID - 493
JF - Frontiers in Neuroscience
TI - Review of the BCI competition IV
VL - 6
ER -
TY - JOUR
AB - We solve the longstanding open problems of the blow-up involved in the translations, when possible, of a nondeterministic Büchi word automaton (NBW) to a nondeterministic co-Büchi word automaton (NCW) and to a deterministic co-Büchi word automaton (DCW). For the NBW to NCW translation, the currently known upper bound is 2o(nlog n) and the lower bound is 1.5n. We improve the upper bound to n2n and describe a matching lower bound of 2ω(n). For the NBW to DCW translation, the currently known upper bound is 2o(nlog n). We improve it to 2 o(n), which is asymptotically tight. Both of our upper-bound constructions are based on a simple subset construction, do not involve intermediate automata with richer acceptance conditions, and can be implemented symbolically. We continue and solve the open problems of translating nondeterministic Streett, Rabin, Muller, and parity word automata to NCW and to DCW. Going via an intermediate NBW is not optimal and we describe direct, simple, and asymptotically tight constructions, involving a 2o(n) blow-up. The constructions are variants of the subset construction, providing a unified approach for translating all common classes of automata to NCW and DCW. Beyond the theoretical importance of the results, we point to numerous applications of the new constructions. In particular, they imply a simple subset-construction based translation, when possible, of LTL to deterministic Büchi word automata.
AU - Boker, Udi
AU - Kupferman, Orna
ID - 494
IS - 4
JF - ACM Transactions on Computational Logic (TOCL)
TI - Translating to Co-Büchi made tight, unified, and useful
VL - 13
ER -
TY - CONF
AB - An automaton with advice is a finite state automaton which has access to an additional fixed infinite string called an advice tape. We refine the Myhill-Nerode theorem to characterize the languages of finite strings that are accepted by automata with advice. We do the same for tree automata with advice.
AU - Kruckman, Alex
AU - Rubin, Sasha
AU - Sheridan, John
AU - Zax, Ben
ID - 495
T2 - Proceedings GandALF 2012
TI - A Myhill Nerode theorem for automata with advice
VL - 96
ER -
TY - CONF
AB - We study the expressive power of logical interpretations on the class of scattered trees, namely those with countably many infinite branches. Scattered trees can be thought of as the tree analogue of scattered linear orders. Every scattered tree has an ordinal rank that reflects the structure of its infinite branches. We prove, roughly, that trees and orders of large rank cannot be interpreted in scattered trees of small rank. We consider a quite general notion of interpretation: each element of the interpreted structure is represented by a set of tuples of subsets of the interpreting tree. Our trees are countable, not necessarily finitely branching, and may have finitely many unary predicates as labellings. We also show how to replace injective set-interpretations in (not necessarily scattered) trees by 'finitary' set-interpretations.
AU - Rabinovich, Alexander
AU - Rubin, Sasha
ID - 496
TI - Interpretations in trees with countably many branches
ER -
TY - CONF
AB - One central issue in the formal design and analysis of reactive systems is the notion of refinement that asks whether all behaviors of the implementation is allowed by the specification. The local interpretation of behavior leads to the notion of simulation. Alternating transition systems (ATSs) provide a general model for composite reactive systems, and the simulation relation for ATSs is known as alternating simulation. The simulation relation for fair transition systems is called fair simulation. In this work our main contributions are as follows: (1) We present an improved algorithm for fair simulation with Büchi fairness constraints; our algorithm requires O(n 3·m) time as compared to the previous known O(n 6)-time algorithm, where n is the number of states and m is the number of transitions. (2) We present a game based algorithm for alternating simulation that requires O(m2)-time as compared to the previous known O((n·m)2)-time algorithm, where n is the number of states and m is the size of transition relation. (3) We present an iterative algorithm for alternating simulation that matches the time complexity of the game based algorithm, but is more space efficient than the game based algorithm. © Krishnendu Chatterjee, Siddhesh Chaubal, and Pritish Kamath.
AU - Chatterjee, Krishnendu
AU - Chaubal, Siddhesh
AU - Kamath, Pritish
ID - 497
TI - Faster algorithms for alternating refinement relations
VL - 16
ER -
TY - JOUR
AB - Understanding patterns and correlates of local adaptation in heterogeneous landscapes can provide important information in the selection of appropriate seed sources for restoration. We assessed the extent of local adaptation of fitness components in 12 population pairs of the perennial herb Rutidosis leptorrhynchoides (Asteraceae) and examined whether spatial scale (0.7-600 km), environmental distance, quantitative (QST) and neutral (FST) genetic differentiation, and size of the local and foreign populations could predict patterns of adaptive differentiation. Local adaptation varied among populations and fitness components. Including all population pairs, local adaptation was observed for seedling survival, but not for biomass, while foreign genotype advantage was observed for reproduction (number of inflorescences). Among population pairs, local adaptation increased with QST and local population size for biomass. QST was associated with environmental distance, suggesting ecological selection for phenotypic divergence. However, low FST and variation in population structure in small populations demonstrates the interaction of gene flow and drift in constraining local adaptation in R. leptorrhynchoides. Our study indicates that for species in heterogeneous landscapes, collecting seed from large populations from similar environments to candidate sites is likely to provide the most appropriate seed sources for restoration.
AU - Pickup, Melinda
AU - Field, David
AU - Rowell, David
AU - Young, Andrew
ID - 498
IS - 8
JF - Evolutionary Applications
TI - Predicting local adaptation in fragmented plant populations: Implications for restoration genetics
VL - 5
ER -
TY - JOUR
AU - Sixt, Michael K
ID - 506
IS - 3
JF - Journal of Cell Biology
TI - Cell migration: Fibroblasts find a new way to get ahead
VL - 197
ER -
TY - GEN
AB - Two-player games on graphs are central in many problems in formal verification and program analysis such as synthesis and verification of open systems. In this work we consider solving recursive game graphs (or pushdown game graphs) that can model the control flow of sequential programs with recursion. While pushdown games have been studied before with qualitative objectives, such as reachability and ω-regular objectives, in this work we study for the first time such games with the most well-studied quantitative objective, namely, mean-payoff objectives. In pushdown games two types of strategies are relevant: (1) global strategies, that depend on the entire global history; and (2) modular strategies, that have only local memory and thus do not depend on the context of invocation, but only on the history of the current invocation of the module. Our main results are as follows: (1) One-player pushdown games with mean-payoff objectives under global strategies are decidable in polynomial time. (2) Two- player pushdown games with mean-payoff objectives under global strategies are undecidable. (3) One-player pushdown games with mean-payoff objectives under modular strategies are NP- hard. (4) Two-player pushdown games with mean-payoff objectives under modular strategies can be solved in NP (i.e., both one-player and two-player pushdown games with mean-payoff objectives under modular strategies are NP-complete). We also establish the optimal strategy complexity showing that global strategies for mean-payoff objectives require infinite memory even in one-player pushdown games; and memoryless modular strategies are sufficient in two- player pushdown games. Finally we also show that all the problems have the same complexity if the stack boundedness condition is added, where along with the mean-payoff objective the player must also ensure that the stack height is bounded.
AU - Chatterjee, Krishnendu
AU - Velner, Yaron
ID - 5377
SN - 2664-1690
TI - Mean-payoff pushdown games
ER -
TY - GEN
AB - One central issue in the formal design and analysis of reactive systems is the notion of refinement that asks whether all behaviors of the implementation is allowed by the specification. The local interpretation of behavior leads to the notion of simulation. Alternating transition systems (ATSs) provide a general model for composite reactive systems, and the simulation relation for ATSs is known as alternating simulation. The simulation relation for fair transition systems is called fair simulation. In this work our main contributions are as follows: (1) We present an improved algorithm for fair simulation with Büchi fairness constraints; our algorithm requires O(n3 · m) time as compared to the previous known O(n6)-time algorithm, where n is the number of states and m is the number of transitions. (2) We present a game based algorithm for alternating simulation that requires O(m2)-time as compared to the previous known O((n · m)2)-time algorithm, where n is the number of states and m is the size of transition relation. (3) We present an iterative algorithm for alternating simulation that matches the time complexity of the game based algorithm, but is more space efficient than the game based algorithm.
AU - Chatterjee, Krishnendu
AU - Chaubal, Siddhesh
AU - Kamath, Pritish
ID - 5378
SN - 2664-1690
TI - Faster algorithms for alternating refinement relations
ER -
TY - GEN
AB - We consider the problem of inference in agraphical model with binary variables. While in theory it is arguably preferable to compute marginal probabilities, in practice researchers often use MAP inference due to the availability of efficient discrete optimization algorithms. We bridge the gap between the two approaches by introducing the Discrete Marginals technique in which approximate marginals are obtained by minimizing an objective function with unary and pair-wise terms over a discretized domain. This allows the use of techniques originally devel-oped for MAP-MRF inference and learning. We explore two ways to set up the objective function - by discretizing the Bethe free energy and by learning it from training data. Experimental results show that for certain types of graphs a learned function can out-perform the Bethe approximation. We also establish a link between the Bethe free energy and submodular functions.
AU - Korc, Filip
AU - Kolmogorov, Vladimir
AU - Lampert, Christoph
ID - 5396
SN - 2664-1690
TI - Approximating marginals using discrete energy minimization
ER -
TY - GEN
AB - This document is created as a part of the project “Repository for Research Data on IST Austria”. It summarises the actual state of research data at IST Austria, based on survey results. It supports the choice of appropriate software, which would best fit the requirements of their users, the researchers.
AU - Porsche, Jana
ID - 5398
TI - Actual state of research data @ ISTAustria
ER -
TY - CHAP
AU - Gupta, Ashutosh
ID - 5745
SN - 0302-9743
T2 - Automated Technology for Verification and Analysis
TI - Improved Single Pass Algorithms for Resolution Proof Reduction
VL - 7561
ER -
TY - JOUR
AB - First we note that the best polynomial approximation to vertical bar x vertical bar on the set, which consists of an interval on the positive half-axis and a point on the negative half-axis, can be given by means of the classical Chebyshev polynomials. Then we explore the cases when a solution of the related problem on two intervals can be given in elementary functions.
AU - Pausinger, Florian
ID - 6588
IS - 1
JF - Journal of Mathematical Physics, Analysis, Geometry
SN - 1812-9471
TI - Elementary solutions of the Bernstein problem on two intervals
VL - 8
ER -
TY - CONF
AB - Software model checking, as an undecidable problem, has three possible outcomes: (1) the program satisfies the specification, (2) the program does not satisfy the specification, and (3) the model checker fails. The third outcome usually manifests itself in a space-out, time-out, or one component of the verification tool giving up; in all of these failing cases, significant computation is performed by the verification tool before the failure, but no result is reported. We propose to reformulate the model-checking problem as follows, in order to have the verification tool report a summary of the performed work even in case of failure: given a program and a specification, the model checker returns a condition Ψ - usually a state predicate - such that the program satisfies the specification under the condition Ψ - that is, as long as the program does not leave the states in which Ψ is satisfied. In our experiments, we investigated as one major application of conditional model checking the sequential combination of model checkers with information passing. We give the condition that one model checker produces, as input to a second conditional model checker, such that the verification problem for the second is restricted to the part of the state space that is not covered by the condition, i.e., the second model checker works on the problems that the first model checker could not solve. Our experiments demonstrate that repeated application of conditional model checkers, passing information from one model checker to the next, can significantly improve the verification results and performance, i.e., we can now verify programs that we could not verify before.
AU - Beyer, Dirk
AU - Henzinger, Thomas A
AU - Keremoglu, Mehmet
AU - Wendler, Philipp
ID - 1384
T2 - Proceedings of the ACM SIGSOFT 20th International Symposium on the Foundations of Software Engineering
TI - Conditional model checking: A technique to pass information between verifiers
ER -
TY - CONF
AB - Leakage resilient cryptography attempts to incorporate side-channel leakage into the black-box security model and designs cryptographic schemes that are provably secure within it. Informally, a scheme is leakage-resilient if it remains secure even if an adversary learns a bounded amount of arbitrary information about the schemes internal state. Unfortunately, most leakage resilient schemes are unnecessarily complicated in order to achieve strong provable security guarantees. As advocated by Yu et al. [CCS’10], this mostly is an artefact of the security proof and in practice much simpler construction may already suffice to protect against realistic side-channel attacks. In this paper, we show that indeed for simpler constructions leakage-resilience can be obtained when we aim for relaxed security notions where the leakage-functions and/or the inputs to the primitive are chosen non-adaptively. For example, we show that a three round Feistel network instantiated with a leakage resilient PRF yields a leakage resilient PRP if the inputs are chosen non-adaptively (This complements the result of Dodis and Pietrzak [CRYPTO’10] who show that if a adaptive queries are allowed, a superlogarithmic number of rounds is necessary.) We also show that a minor variation of the classical GGM construction gives a leakage resilient PRF if both, the leakage-function and the inputs, are chosen non-adaptively.
AU - Faust, Sebastian
AU - Pietrzak, Krzysztof Z
AU - Schipper, Joachim
ID - 2048
T2 - Conference proceedings CHES 2012
TI - Practical leakage-resilient symmetric cryptography
VL - 7428
ER -
TY - CONF
AB - We propose a new authentication protocol that is provably secure based on a ring variant of the learning parity with noise (LPN) problem. The protocol follows the design principle of the LPN-based protocol from Eurocrypt’11 (Kiltz et al.), and like it, is a two round protocol secure against active attacks. Moreover, our protocol has small communication complexity and a very small footprint which makes it applicable in scenarios that involve low-cost, resource-constrained devices.
Performance-wise, our protocol is more efficient than previous LPN-based schemes, such as the many variants of the Hopper-Blum (HB) protocol and the aforementioned protocol from Eurocrypt’11. Our implementation results show that it is even comparable to the standard challenge-and-response protocols based on the AES block-cipher. Our basic protocol is roughly 20 times slower than AES, but with the advantage of having 10 times smaller code size. Furthermore, if a few hundred bytes of non-volatile memory are available to allow the storage of some off-line pre-computations, then the online phase of our protocols is only twice as slow as AES.
AU - Heyse, Stefan
AU - Kiltz, Eike
AU - Lyubashevsky, Vadim
AU - Paar, Christof
AU - Pietrzak, Krzysztof Z
ID - 2049
T2 - Conference proceedings FSE 2012
TI - Lapin: An efficient authentication protocol based on ring-LPN
VL - 7549
ER -
TY - JOUR
AB - Nestin-cre transgenic mice have been widely used to direct recombination to neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs). Here we report that a readily utilized, and the only commercially available, Nestin-cre line is insufficient for directing recombination in early embryonic NSCs and NPCs. Analysis of recombination efficiency in multiple cre-dependent reporters and a genetic mosaic line revealed consistent temporal and spatial patterns of recombination in NSCs and NPCs. For comparison we utilized a knock-in Emx1cre line and found robust recombination in NSCs and NPCs in ventricular and subventricular zones of the cerebral cortices as early as embryonic day 12.5. In addition we found that the rate of Nestin-cre driven recombination only reaches sufficiently high levels in NSCs and NPCs during late embryonic and early postnatal periods. These findings are important when commercially available cre lines are considered for directing recombination to embryonic NSCs and NPCs.
AU - Liang, Huixuan
AU - Hippenmeyer, Simon
AU - Ghashghaei, H.
ID - 2263
IS - 12
JF - Biology open
TI - A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors
VL - 1
ER -
TY - JOUR
AB - We introduce propagation models (PMs), a formalism able to express several kinds of equations that describe the behavior of biochemical reaction networks. Furthermore, we introduce the propagation abstract data type (PADT), which separates concerns regarding different numerical algorithms for the transient analysis of biochemical reaction networks from concerns regarding their implementation, thus allowing for portable and efficient solutions. The state of a propagation abstract data type is given by a vector that assigns mass values to a set of nodes, and its (next) operator propagates mass values through this set of nodes. We propose an approximate implementation of the (next) operator, based on threshold abstraction, which propagates only "significant" mass values and thus achieves a compromise between efficiency and accuracy. Finally, we give three use cases for propagation models: the chemical master equation (CME), the reaction rate equation (RRE), and a hybrid method that combines these two equations. These three applications use propagation models in order to propagate probabilities and/or expected values and variances of the model's variables.
AU - Henzinger, Thomas A
AU - Mateescu, Maria
ID - 2302
IS - 2
JF - IEEE ACM Transactions on Computational Biology and Bioinformatics
TI - The propagation approach for computing biochemical reaction networks
VL - 10
ER -
TY - JOUR
AB - We show that bosons interacting via pair potentials with negative scattering length form bound states for a suitable number of particles. In other words, the absence of many-particle bound states of any kind implies the non-negativity of the scattering length of the interaction potential.
AU - Seiringer, Robert
ID - 2318
IS - 3
JF - Journal of Spectral Theory
TI - Absence of bound states implies non-negativity of the scattering length
VL - 2
ER -
TY - JOUR
AB - The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data-a common practice in phylogenomic analyses-introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses.
AU - Ebersberger, Ingo
AU - De Matos Simoes, Ricardo
AU - Kupczok, Anne
AU - Gube, Matthias
AU - Kothe, Erika
AU - Voigt, Kerstin
AU - Von Haeseler, Arndt
ID - 2411
IS - 5
JF - Molecular Biology and Evolution
TI - A consistent phylogenetic backbone for the fungi
VL - 29
ER -
TY - CONF
AB - We consider Markov decision processes (MDPs) with specifications given as Büchi (liveness) objectives. We consider the problem of computing the set of almost-sure winning vertices from where the objective can be ensured with probability 1. We study for the first time the average case complexity of the classical algorithm for computing the set of almost-sure winning vertices for MDPs with Büchi objectives. Our contributions are as follows: First, we show that for MDPs with constant out-degree the expected number of iterations is at most logarithmic and the average case running time is linear (as compared to the worst case linear number of iterations and quadratic time complexity). Second, for the average case analysis over all MDPs we show that the expected number of iterations is constant and the average case running time is linear (again as compared to the worst case linear number of iterations and quadratic time complexity). Finally we also show that given that all MDPs are equally likely, the probability that the classical algorithm requires more than constant number of iterations is exponentially small.
AU - Chatterjee, Krishnendu
AU - Joglekar, Manas
AU - Shah, Nisarg
ID - 2715
TI - Average case analysis of the classical algorithm for Markov decision processes with Büchi objectives
VL - 18
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 - 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 - 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 - 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 - Hierarchical Timing Language (HTL) is a coordination language for distributed, hard real-time applications. HTL is a hierarchical extension of Giotto and, like its predecessor, based on the logical execution time (LET) paradigm of real-time programming. Giotto is compiled into code for a virtual machine, called the EmbeddedMachine (or E machine). If HTL is targeted to the E machine, then the hierarchicalprogram structure needs to be flattened; the flattening makes separatecompilation difficult, and may result in E machinecode of exponential size. In this paper, we propose a generalization of the E machine, which supports a hierarchicalprogram structure at runtime through real-time trigger mechanisms that are arranged in a tree. We present the generalized E machine, and a modular compiler for HTL that generates code of linear size. The compiler may generate code for any part of a given HTL program separately in any order.
AU - Ghosal, Arkadeb
AU - Iercan, Daniel
AU - Kirsch, Christoph
AU - Henzinger, Thomas A
AU - Sangiovanni Vincentelli, Alberto
ID - 3836
IS - 2
JF - Science of Computer Programming
TI - Separate compilation of hierarchical real-time programs into linear-bounded embedded machine code
VL - 77
ER -