TY - GEN
AB - This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the actual initiatives, projects and standards related to the project. It supports the preparation of standards and specifications for the project, which should be considered and followed to ensure interoperability and visibility of the uploaded data.
AU - Porsche, Jana
ID - 5401
TI - Initiatives and projects related to RD
ER -
TY - GEN
AB - Linearizability requires that the outcome of calls by competing threads to a concurrent data structure is the same as some sequential execution where each thread has exclusive access to the data structure. In an ordered data structure, such as a queue or a stack, linearizability is ensured by requiring threads commit in the order dictated by the sequential semantics of the data structure; e.g., in a concurrent queue implementation a dequeue can only remove the oldest element.
In this paper, we investigate the impact of this strict ordering, by comparing what linearizability allows to what existing implementations do. We first give an operational definition for linearizability which allows us to build the most general linearizable implementation as a transition system for any given sequential specification. We then use this operational definition to categorize linearizable implementations based on whether they are bound or free. In a bound implementation, whenever all threads observe the same logical state, the updates to the logical state and the temporal order of commits coincide. All existing queue implementations we know of are bound. We then proceed to present, to the best of our knowledge, the first ever free queue implementation. Our experiments show that free implementations have the potential for better performance by suffering less from contention.
AU - Henzinger, Thomas A
AU - Sezgin, Ali
ID - 5402
SN - 2664-1690
TI - How free is your linearizable concurrent data structure?
ER -
TY - GEN
AB - We consider concurrent games played by two-players on a finite state graph, where in every round the players simultaneously choose a move, and the current state along with the joint moves determine the successor state. We study the most fundamental objective for concurrent games, namely, mean-payoff or limit-average objective, where a reward is associated to every transition, and the goal of player 1 is to maximize the long-run average of the rewards, and the objective of player 2 is strictly the opposite (i.e., the games are zero-sum). The path constraint for player 1 could be qualitative, i.e., the mean-payoff is the maximal reward, or arbitrarily close to it; or quantitative, i.e., a given threshold between the minimal and maximal reward. We consider the computation of the almost-sure (resp. positive) winning sets, where player 1 can ensure that the path constraint is satisfied with probability 1 (resp. positive probability). Almost-sure winning with qualitative constraint exactly corresponds to the question whether there exists a strategy to ensure that the payoff is the maximal reward of the game. Our main results for qualitative path constraints are as follows: (1) we establish qualitative determinacy results that show for every state either player 1 has a strategy to ensure almost-sure (resp. positive) winning against all player-2 strategies or player 2 has a spoiling strategy to falsify almost-sure (resp. positive) winning against all player-1 strategies; (2) we present optimal strategy complexity results that precisely characterize the classes of strategies required for almost-sure and positive winning for both players; and (3) we present quadratic time algorithms to compute the almost-sure and the positive winning sets, matching the best known bound of the algorithms for much simpler problems (such as reachability objectives). For quantitative constraints we show that a polynomial time solution for the almost-sure or the positive winning set would imply a solution to a long-standing open problem (of solving the value problem of mean-payoff games) that is not known to be in polynomial time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 5403
SN - 2664-1690
TI - Qualitative analysis of concurrent mean-payoff games
ER -
TY - GEN
AB - We study finite-state two-player (zero-sum) concurrent mean-payoff games played on a graph. We focus on the important sub-class of ergodic games where all states are visited infinitely often with probability 1. The algorithmic study of ergodic games was initiated in a seminal work of Hoffman and Karp in 1966, but all basic complexity questions have remained unresolved. Our main results for ergodic games are as follows: We establish (1) an optimal exponential bound on the patience of stationary strategies (where patience of a distribution is the inverse of the smallest positive probability and represents a complexity measure of a stationary strategy); (2) the approximation problem lie in FNP; (3) the approximation problem is at least as hard as the decision problem for simple stochastic games (for which NP and coNP is the long-standing best known bound). We show that the exact value can be expressed in the existential theory of the reals, and also establish square-root sum hardness for a related class of games.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 5404
SN - 2664-1690
TI - The complexity of ergodic games
ER -
TY - GEN
AB - The theory of graph games is the foundation for modeling and synthesizing reactive processes. In the synthesis of stochastic processes, we use 2-1/2-player games where some transitions of the game graph are controlled by two adversarial players, the System and the Environment, and the other transitions are determined probabilistically. We consider 2-1/2-player games where the objective of the System is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a mean-payoff condition). We establish that the problem of deciding whether the System can ensure that the probability to satisfy the mean-payoff parity objective is at least a given threshold is in NP ∩ coNP, matching the best known bound in the special case of 2-player games (where all transitions are deterministic) with only parity objectives, or with only mean-payoff objectives. We present an algorithm running
in time O(d · n^{2d}·MeanGame) to compute the set of almost-sure winning states from which the objective
can be ensured with probability 1, where n is the number of states of the game, d the number of priorities
of the parity objective, and MeanGame is the complexity to compute the set of almost-sure winning states
in 2-1/2-player mean-payoff games. Our results are useful in the synthesis of stochastic reactive systems
with both functional requirement (given as a qualitative objective) and performance requirement (given
as a quantitative objective).
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Gimbert, Hugo
AU - Oualhadj, Youssouf
ID - 5405
SN - 2664-1690
TI - Perfect-information stochastic mean-payoff parity games
ER -
TY - GEN
AB - We consider the distributed synthesis problem fortemporal logic specifications. Traditionally, the problem has been studied for LTL, and the previous results show that the problem is decidable iff there is no information fork in the architecture. We consider the problem for fragments of LTLand our main results are as follows: (1) We show that the problem is undecidable for architectures with information forks even for the fragment of LTL with temporal operators restricted to next and eventually. (2) For specifications restricted to globally along with non-nested next operators, we establish decidability (in EXPSPACE) for star architectures where the processes receive disjoint inputs, whereas we establish undecidability for architectures containing an information fork-meet structure. (3)Finally, we consider LTL without the next operator, and establish decidability (NEXPTIME-complete) for all architectures for a fragment that consists of a set of safety assumptions, and a set of guarantees where each guarantee is a safety, reachability, or liveness condition.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Pavlogiannis, Andreas
ID - 5406
SN - 2664-1690
TI - Distributed synthesis for LTL Fragments
ER -
TY - GEN
AB - This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the mandatory features, which need to be fulfilled to provide an institutional repository as a platform and also a service to the scientists at the institute. It also includes optional features, which would be of strong benefit for the scientists and would increase the usage of the repository, and hence the visibility of research at IST Austria.
AU - Porsche, Jana
ID - 5407
TI - Technical requirements and features
ER -
TY - GEN
AB - We consider two-player partial-observation stochastic games where player 1 has partial observation and player 2 has perfect observation. The winning condition we study are omega-regular conditions specified as parity objectives. The qualitative analysis problem given a partial-observation stochastic game and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, they were shown to be decidable in 2EXPTIME under finite-memory strategies. We improve the complexity and show that the qualitative analysis problems for partial-observation stochastic parity games under finite-memory strategies are
EXPTIME-complete; and also establish optimal (exponential) memory bounds for finite-memory strategies required for qualitative analysis.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Nain, Sumit
AU - Vardi, Moshe
ID - 5408
SN - 2664-1690
TI - The complexity of partial-observation stochastic parity games with finite-memory strategies
ER -
TY - GEN
AB - The edit distance between two (untimed) traces is the minimum cost of a sequence of edit operations (insertion, deletion, or substitution) needed to transform one trace to the other. Edit distances have been extensively studied in the untimed setting, and form the basis for approximate matching of sequences in different domains such as coding theory, parsing, and speech recognition.
In this paper, we lift the study of edit distances from untimed languages to the timed setting. We define an edit distance between timed words which incorporates both the edit distance between the untimed words and the absolute difference in timestamps. Our edit distance between two timed words is computable in polynomial time. Further, we show that the edit distance between a timed word and a timed language generated by a timed automaton, defined as the edit distance between the word and the closest word in the language, is PSPACE-complete. While computing the edit distance between two timed automata is undecidable, we show that the approximate version, where we decide if the edit distance between two timed automata is either less than a given parameter or more than delta away from the parameter, for delta>0, can be solved in exponential space and is EXPSPACE-hard. Our definitions and techniques can be generalized to the setting of hybrid systems, and we show analogous decidability results for rectangular automata.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Majumdar, Rupak
ID - 5409
SN - 2664-1690
TI - Edit distance for timed automata
ER -
TY - GEN
AB - Board games, like Tic-Tac-Toe and CONNECT-4, play an important role not only in development of mathematical and logical skills, but also in emotional and social development. In this paper, we address the problem of generating targeted starting positions for such games. This can facilitate new approaches for bringing novice players to mastery, and also leads to discovery of interesting game variants.
Our approach generates starting states of varying hardness levels for player 1 in a two-player board game, given rules of the board game, the desired number of steps required for player 1 to win, and the expertise levels of the two players. Our approach leverages symbolic methods and iterative simulation to efficiently search the extremely large state space. We present experimental results that include discovery of states of varying hardness levels for several simple grid-based board games. Also, the presence of such states for standard game variants like Tic-Tac-Toe on board size 4x4 opens up new games to be played that have not been played for ages since the default start state is heavily biased.
AU - Ahmed, Umair
AU - Chatterjee, Krishnendu
AU - Gulwani, Sumit
ID - 5410
SN - 2664-1690
TI - Automatic generation of alternative starting positions for traditional board games
ER -
TY - CHAP
AU - Dragoi, Cezara
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
ID - 5747
SN - 0302-9743
T2 - Computer Aided Verification
TI - Automatic Linearizability Proofs of Concurrent Objects with Cooperating Updates
VL - 8044
ER -
TY - JOUR
AB - We consider non-interacting particles subject to a fixed external potential V and a self-generated magnetic field B. The total energy includes the field energy β∫B2 and we minimize over all particle states and magnetic fields. In the case of spin-1/2 particles this minimization leads to the coupled Maxwell-Pauli system. The parameter β tunes the coupling strength between the field and the particles and it effectively determines the strength of the field. We investigate the stability and the semiclassical asymptotics, h→0, of the total ground state energy E(β,h,V). The relevant parameter measuring the field strength in the semiclassical limit is κ=βh. We are not able to give the exact leading order semiclassical asymptotics uniformly in κ or even for fixed κ. We do however give upper and lower bounds on E with almost matching dependence on κ. In the simultaneous limit h→0 and κ→∞ we show that the standard non-magnetic Weyl asymptotics holds. The same result also holds for the spinless case, i.e. where the Pauli operator is replaced by the Schrödinger operator.
AU - Erdös, László
AU - Fournais, Søren
AU - Solovej, Jan
ID - 2698
IS - 6
JF - Journal of the European Mathematical Society
TI - Stability and semiclassics in self-generated fields
VL - 15
ER -
TY - CONF
AB - Even though both population and quantitative genetics, and evolutionary computation, deal with the same questions, they have developed largely independently of each other. I review key results from each field, emphasising those that apply independently of the (usually unknown) relation between genotype and phenotype. The infinitesimal model provides a simple framework for predicting the response of complex traits to selection, which in biology has proved remarkably successful. This allows one to choose the schedule of population sizes and selection intensities that will maximise the response to selection, given that the total number of individuals realised, C = ∑t Nt, is constrained. This argument shows that for an additive trait (i.e., determined by the sum of effects of the genes), the optimum population size and the maximum possible response (i.e., the total change in trait mean) are both proportional to √C.
AU - Barton, Nicholas H
AU - Paixao, Tiago
ID - 2718
T2 - Proceedings of the 15th annual conference on Genetic and evolutionary computation
TI - Can quantitative and population genetics help us understand evolutionary computation?
ER -
TY - JOUR
AB - Knowledge of the rate and fitness effects of mutations is essential for understanding the process of evolution. Mutations are inherently difficult to study because they are rare and are frequently eliminated by natural selection. In the ciliate Tetrahymena thermophila, mutations can accumulate in the germline genome without being exposed to selection. We have conducted a mutation accumulation (MA) experiment in this species. Assuming that all mutations are deleterious and have the same effect, we estimate that the deleterious mutation rate per haploid germline genome per generation is U = 0.0047 (95% credible interval: 0.0015, 0.0125), and that germline mutations decrease fitness by s = 11% when expressed in a homozygous state (95% CI: 4.4%, 27%). We also estimate that deleterious mutations are partially recessive on average (h = 0.26; 95% CI: –0.022, 0.62) and that the rate of lethal mutations is <10% of the deleterious mutation rate. Comparisons between the observed evolutionary responses in the germline and somatic genomes and the results from individual-based simulations of MA suggest that the two genomes have similar mutational parameters. These are the first estimates of the deleterious mutation rate and fitness effects from the eukaryotic supergroup Chromalveolata and are within the range of those of other eukaryotes.
AU - Long, Hongan
AU - Paixao, Tiago
AU - Azevedo, Ricardo
AU - Zufall, Rebecca
ID - 2720
IS - 2
JF - Genetics
TI - Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila
VL - 195
ER -
TY - JOUR
AB - We consider random n×n matrices of the form (XX*+YY*)^{-1/2}YY*(XX*+YY*)^{-1/2}, where X and Y have independent entries with zero mean and variance one. These matrices are the natural generalization of the Gaussian case, which are known as MANOVA matrices and which have joint eigenvalue density given by the third classical ensemble, the Jacobi ensemble. We show that, away from the spectral edge, the eigenvalue density converges to the limiting density of the Jacobi ensemble even on the shortest possible scales of order 1/n (up to log n factors). This result is the analogue of the local Wigner semicircle law and the local Marchenko-Pastur law for general MANOVA matrices.
AU - Erdös, László
AU - Farrell, Brendan
ID - 2782
IS - 6
JF - Journal of Statistical Physics
TI - Local eigenvalue density for general MANOVA matrices
VL - 152
ER -
TY - CONF
AB - We consider several basic problems of algebraic topology, with connections to combinatorial and geometric questions, from the point of view of computational complexity. The extension problem asks, given topological spaces X; Y , a subspace A ⊆ X, and a (continuous) map f : A → Y , whether f can be extended to a map X → Y . For computational purposes, we assume that X and Y are represented as finite simplicial complexes, A is a subcomplex of X, and f is given as a simplicial map. In this generality the problem is undecidable, as follows from Novikov's result from the 1950s on uncomputability of the fundamental group π1(Y ). We thus study the problem under the assumption that, for some k ≥ 2, Y is (k - 1)-connected; informally, this means that Y has \no holes up to dimension k-1" (a basic example of such a Y is the sphere Sk). We prove that, on the one hand, this problem is still undecidable for dimX = 2k. On the other hand, for every fixed k ≥ 2, we obtain an algorithm that solves the extension problem in polynomial time assuming Y (k - 1)-connected and dimX ≤ 2k - 1. For dimX ≤ 2k - 2, the algorithm also provides a classification of all extensions up to homotopy (continuous deformation). This relies on results of our SODA 2012 paper, and the main new ingredient is a machinery of objects with polynomial-time homology, which is a polynomial-time analog of objects with effective homology developed earlier by Sergeraert et al. We also consider the computation of the higher homotopy groups πk(Y ), k ≥ 2, for a 1-connected Y . Their computability was established by Brown in 1957; we show that πk(Y ) can be computed in polynomial time for every fixed k ≥ 2. On the other hand, Anick proved in 1989 that computing πk(Y ) is #P-hard if k is a part of input, where Y is a cell complex with certain rather compact encoding. We strengthen his result to #P-hardness for Y given as a simplicial complex.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Matoušek, Jiří
AU - Vokřínek, Lukáš
AU - Wagner, Uli
ID - 2807
T2 - 45th Annual ACM Symposium on theory of computing
TI - Extending continuous maps: Polynomiality and undecidability
ER -
TY - JOUR
AB - In order to establish a reference for analysis of the function of auxin and the auxin biosynthesis regulators SHORT INTERNODE/ STYLISH (SHI/STY) during Physcomitrella patens reproductive development, we have described male (antheridial) and female (archegonial) development in detail, including temporal and positional information of organ initiation. This has allowed us to define discrete stages of organ morphogenesis and to show that reproductive organ development in P. patens is highly organized and that organ phyllotaxis differs between vegetative and reproductive development. Using the PpSHI1 and PpSHI2 reporter and knockout lines, the auxin reporters GmGH3pro:GUS and PpPINApro:GFP-GUS, and the auxin-conjugating transgene PpSHI2pro:IAAL, we could show that the PpSHI genes, and by inference also auxin, play important roles for reproductive organ development in moss. The PpSHI genes are required for the apical opening of the reproductive organs, the final differentiation of the egg cell, and the progression of canal cells into a cell death program. The apical cells of the archegonium, the canal cells, and the egg cell are also sites of auxin responsiveness and are affected by reduced levels of active auxin, suggesting that auxin mediates PpSHI function in the reproductive organs.
AU - Landberg, Katarina
AU - Pederson, Eric
AU - Viaene, Tom
AU - Bozorg, Behruz
AU - Friml, Jirí
AU - Jönsson, Henrik
AU - Thelander, Mattias
AU - Sundberg, Eva
ID - 2808
IS - 3
JF - Plant Physiology
TI - The moss physcomitrella patens reproductive organ development is highly organized, affected by the two SHI/STY genes and by the level of active auxin in the SHI/STY expression domain
VL - 162
ER -
TY - JOUR
AB - The epistatic interactions that underlie evolutionary constraint have mainly been studied for constant external conditions. However, environmental changes may modulate epistasis and hence affect genetic constraints. Here we investigate genetic constraints in the adaptive evolution of a novel regulatory function in variable environments, using the lac repressor, LacI, as a model system. We have systematically reconstructed mutational trajectories from wild type LacI to three different variants that each exhibit an inverse response to the inducing ligand IPTG, and analyzed the higher-order interactions between genetic and environmental changes. We find epistasis to depend strongly on the environment. As a result, mutational steps essential to inversion but inaccessible by positive selection in one environment, become accessible in another. We present a graphical method to analyze the observed complex higher-order interactions between multiple mutations and environmental change, and show how the interactions can be explained by a combination of mutational effects on allostery and thermodynamic stability. This dependency of genetic constraint on the environment should fundamentally affect evolutionary dynamics and affects the interpretation of phylogenetic data.
AU - De Vos, Marjon
AU - Poelwijk, Frank
AU - Battich, Nico
AU - Ndika, Joseph
AU - Tans, Sander
ID - 2810
IS - 6
JF - PLoS Genetics
TI - Environmental dependence of genetic constraint
VL - 9
ER -
TY - JOUR
AB - In pipe, channel, and boundary layer flows turbulence first occurs intermittently in space and time: at moderate Reynolds numbers domains of disordered turbulent motion are separated by quiescent laminar regions. Based on direct numerical simulations of pipe flow we argue here that the spatial intermittency has its origin in a nearest neighbor interaction between turbulent regions. We further show that in this regime turbulent flows are intrinsically intermittent with a well-defined equilibrium turbulent fraction but without ever assuming a steady pattern. This transition scenario is analogous to that found in simple models such as coupled map lattices. The scaling observed implies that laminar intermissions of the turbulent flow will persist to arbitrarily large Reynolds numbers.
AU - Avila, Marc
AU - Hof, Björn
ID - 2811
IS - 6
JF - Physical Review E
TI - Nature of laminar-turbulence intermittency in shear flows
VL - 87
ER -
TY - CONF
AB - We consider the problem of deciding whether the persistent homology group of a simplicial pair (K, L) can be realized as the homology H* (X) of some complex X with L ⊂ X ⊂ K. We show that this problem is NP-complete even if K is embedded in ℝ3. As a consequence, we show that it is NP-hard to simplify level and sublevel sets of scalar functions on S3 within a given tolerance constraint. This problem has relevance to the visualization of medical images by isosurfaces. We also show an implication to the theory of well groups of scalar functions: not every well group can be realized by some level set, and deciding whether a well group can be realized is NP-hard.
AU - Attali, Dominique
AU - Bauer, Ulrich
AU - Devillers, Olivier
AU - Glisse, Marc
AU - Lieutier, André
ID - 2812
T2 - Proceedings of the 29th annual symposium on Computational Geometry
TI - Homological reconstruction and simplification in R3
ER -
TY - JOUR
AB - Turbulence is ubiquitous in nature, yet even for the case of ordinary Newtonian fluids like water, our understanding of this phenomenon is limited. Many liquids of practical importance are more complicated (e.g., blood, polymer melts, paints), however; they exhibit elastic as well as viscous characteristics, and the relation between stress and strain is nonlinear. We demonstrate here for a model system of such complex fluids that at high shear rates, turbulence is not simply modified as previously believed but is suppressed and replaced by a different type of disordered motion, elasto-inertial turbulence. Elasto-inertial turbulence is found to occur at much lower Reynolds numbers than Newtonian turbulence, and the dynamical properties differ significantly. The friction scaling observed coincides with the so-called "maximum drag reduction" asymptote, which is exhibited by a wide range of viscoelastic fluids.
AU - Samanta, Devranjan
AU - Dubief, Yves
AU - Holzner, Markus
AU - Schäfer, Christof
AU - Morozov, Alexander
AU - Wagner, Christian
AU - Hof, Björn
ID - 2813
IS - 26
JF - PNAS
TI - Elasto-inertial turbulence
VL - 110
ER -
TY - JOUR
AB - We study the problem of generating a test sequence that achieves maximal coverage for a reactive system under test. We formulate the problem as a repeated game between the tester and the system, where the system state space is partitioned according to some coverage criterion and the objective of the tester is to maximize the set of partitions (or coverage goals) visited during the game. We show the complexity of the maximal coverage problem for non-deterministic systems is PSPACE-complete, but is NP-complete for deterministic systems. For the special case of non-deterministic systems with a re-initializing "reset" action, which represent running a new test input on a re-initialized system, we show that the complexity is coNP-complete. Our proof technique for reset games uses randomized testing strategies that circumvent the exponentially large memory requirement of deterministic testing strategies. We also discuss the memory requirement for deterministic strategies and extensions of our results to other models, such as pushdown systems and timed systems.
AU - Chatterjee, Krishnendu
AU - Alfaro, Luca
AU - Majumdar, Ritankar
ID - 2814
IS - 2
JF - International Journal of Foundations of Computer Science
TI - The complexity of coverage
VL - 24
ER -
TY - JOUR
AB - In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed. We also find that simultaneous therapy with two drugs is much more effective than sequential therapy. Our results provide realistic expectations for the efficacy of new drug combinations and inform the design of trials for new cancer therapeutics.
AU - Božić, Ivana
AU - Reiter, Johannes
AU - Allen, Benjamin
AU - Antal, Tibor
AU - Chatterjee, Krishnendu
AU - Shah, Preya
AU - Moon, Yo
AU - Yaqubie, Amin
AU - Kelly, Nicole
AU - Le, Dung
AU - Lipson, Evan
AU - Chapman, Paul
AU - Diaz, Luis
AU - Vogelstein, Bert
AU - Nowak, Martin
ID - 2816
JF - eLife
TI - Evolutionary dynamics of cancer in response to targeted combination therapy
VL - 2
ER -
TY - JOUR
AB - The basic idea of evolutionary game theory is that payoff determines reproductive rate. Successful individuals have a higher payoff and produce more offspring. But in evolutionary and ecological situations there is not only reproductive rate but also carrying capacity. Individuals may differ in their exposure to density limiting effects. Here we explore an alternative approach to evolutionary game theory by assuming that the payoff from the game determines the carrying capacity of individual phenotypes. Successful strategies are less affected by density limitation (crowding) and reach higher equilibrium abundance. We demonstrate similarities and differences between our framework and the standard replicator equation. Our equation is defined on the positive orthant, instead of the simplex, but has the same equilibrium points as the replicator equation. Linear stability analysis produces the classical conditions for asymptotic stability of pure strategies, but the stability properties of internal equilibria can differ in the two frameworks. For example, in a two-strategy game with an internal equilibrium that is always stable under the replicator equation, the corresponding equilibrium can be unstable in the new framework resulting in a limit cycle.
AU - Novak, Sebastian
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 2817
JF - Journal of Theoretical Biology
TI - Density games
VL - 334
ER -
TY - JOUR
AB - Models of neural responses to stimuli with complex spatiotemporal correlation structure often assume that neurons are selective for only a small number of linear projections of a potentially high-dimensional input. In this review, we explore recent modeling approaches where the neural response depends on the quadratic form of the input rather than on its linear projection, that is, the neuron is sensitive to the local covariance structure of the signal preceding the spike. To infer this quadratic dependence in the presence of arbitrary (e.g., naturalistic) stimulus distribution, we review several inference methods, focusing in particular on two information theory–based approaches (maximization of stimulus energy and of noise entropy) and two likelihood-based approaches (Bayesian spike-triggered covariance and extensions of generalized linear models). We analyze the formal relationship between the likelihood-based and information-based approaches to demonstrate how they lead to consistent inference. We demonstrate the practical feasibility of these procedures by using model neurons responding to a flickering variance stimulus.
AU - Rajan, Kanaka
AU - Marre, Olivier
AU - Tkacik, Gasper
ID - 2818
IS - 7
JF - Neural Computation
TI - Learning quadratic receptive fields from neural responses to natural stimuli
VL - 25
ER -
TY - CONF
AB - We introduce quantatitive timed refinement metrics and quantitative timed simulation functions, incorporating zenoness checks, for timed systems. These functions assign positive real numbers between zero and infinity which quantify the timing mismatches between two timed systems, amongst non-zeno runs. We quantify timing mismatches in three ways: (1) the maximum timing mismatch that can arise, (2) the "steady-state" maximum timing mismatches, where initial transient timing mismatches are ignored; and (3) the (long-run) average timing mismatches amongst two systems. These three kinds of mismatches constitute three important types of timing differences. Our event times are the global times, measured from the start of the system execution, not just the time durations of individual steps. We present algorithms over timed automata for computing the three quantitative simulation functions to within any desired degree of accuracy. In order to compute the values of the quantitative simulation functions, we use a game theoretic formulation. We introduce two new kinds of objectives for two player games on finite state game graphs: (1) eventual debit-sum level objectives, and (2) average debit-sum level objectives. We present algorithms for computing the optimal values for these objectives for player 1, and then use these algorithms to compute the values of the quantitative timed simulation functions.
AU - Chatterjee, Krishnendu
AU - Prabhu, Vinayak
ID - 2819
T2 - Proceedings of the 16th International Conference on Hybrid Systems: Computation and Control
TI - Quantitative timed simulation functions and refinement metrics for real-time systems
VL - 1
ER -
TY - JOUR
AB - Many key aspects of plant development are regulated by the polarized transport of the phytohormone auxin. Cellular auxin efflux, the rate-limiting step in this process, has been shown to rely on the coordinated action of PIN-formed (PIN) and B-type ATP binding cassette (ABCB) carriers. Here, we report that polar auxin transport in the Arabidopsis thaliana root also requires the action of a Major Facilitator Superfamily (MFS) transporter, Zinc-Induced Facilitator-Like 1 (ZIFL1). Sequencing, promoter-reporter, and fluorescent protein fusion experiments indicate that the full-length ZIFL1.1 protein and a truncated splice isoform, ZIFL1.3, localize to the tonoplast of root cells and the plasma membrane of leaf stomatal guard cells, respectively. Using reverse genetics, we show that the ZIFL1.1 transporter regulates various root auxin-related processes, while the ZIFL1.3 isoform mediates drought tolerance by regulating stomatal closure. Auxin transport and immunolocalization assays demonstrate that ZIFL1.1 indirectly modulates cellular auxin efflux during shootward auxin transport at the root tip, likely by regulating plasma membrane PIN2 abundance. Finally, heterologous expression in yeast revealed that ZIFL1.1 and ZIFL1.3 share H+-coupled K+ transport activity. Thus, by determining the subcellular and tissue distribution of two isoforms, alternative splicing dictates a dual function for the ZIFL1 transporter. We propose that this MFS carrier regulates stomatal movements and polar auxin transport by modulating potassium and proton fluxes in Arabidopsis cells.
AU - Remy, Estelle
AU - Cabrito, Tânia
AU - Baster, Pawel
AU - Batista, Rita
AU - Teixeira, Miguel
AU - Friml, Jirí
AU - Sá Correia, Isabel
AU - Duque, Paula
ID - 2821
IS - 3
JF - Plant Cell
TI - A major facilitator superfamily transporter plays a dual role in polar auxin transport and drought stress tolerance in Arabidopsis
VL - 25
ER -
TY - JOUR
AB - Identification of genes that control root system architecture in crop plants requires innovations that enable high-throughput and accurate measurements of root system architecture through time. We demonstrate the ability of a semiautomated 3D in vivo imaging and digital phenotyping pipeline to interrogate the quantitative genetic basis of root system growth in a rice biparental mapping population, Bala x Azucena. We phenotyped >1,400 3D root models and >57,000 2D images for a suite of 25 traits that quantified the distribution, shape, extent of exploration, and the intrinsic size of root networks at days 12, 14, and 16 of growth in a gellan gum medium. From these data we identified 89 quantitative trait loci, some of which correspond to those found previously in soil-grown plants, and provide evidence for genetic tradeoffs in root growth allocations, such as between the extent and thoroughness of exploration. We also developed a multivariate method for generating and mapping central root architecture phenotypes and used it to identify five major quantitative trait loci (r2 = 24-37%), two of which were not identified by our univariate analysis. Our imaging and analytical platform provides a means to identify genes with high potential for improving root traits and agronomic qualities of crops.
AU - Topp, Christopher
AU - Iyer Pascuzzi, Anjali
AU - Anderson, Jill
AU - Lee, Cheng
AU - Zurek, Paul
AU - Symonova, Olga
AU - Zheng, Ying
AU - Bucksch, Alexander
AU - Mileyko, Yuriy
AU - Galkovskyi, Taras
AU - Moore, Brad
AU - Harer, John
AU - Edelsbrunner, Herbert
AU - Mitchell Olds, Thomas
AU - Weitz, Joshua
AU - Benfey, Philip
ID - 2822
IS - 18
JF - PNAS
TI - 3D phenotyping and quantitative trait locus mapping identify core regions of the rice genome controlling root architecture
VL - 110
ER -
TY - JOUR
AB - Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than -6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is highly heritable, and to date multiple gene loci have been reported. We performed exome sequencing in 4 individuals from an 11-member family of European descent from the United States. Affected individuals had a mean dioptric spherical equivalent of -22.00 sphere. A premature stop codon mutation c.157C>T (p.Gln53*) cosegregating with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent analyses identified three additional mutations in three highly myopic unrelated individuals (c.341G>A, c.418G>A, and c.776C>T). To determine differential gene expression in a developmental mouse model, we induced myopia by applying a -15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Copper deficiencies have been linked with photoreceptor loss and myopia with increased scleral wall elasticity. Retinal thinning has been reported with an SC02 variant. Human mutation identification with support from an induced myopic animal provides biological insights of myopic development.
AU - Tran Viet, Khanh
AU - Powell, Caldwell
AU - Barathi, Veluchamy
AU - Klemm, Thomas
AU - Maurer Stroh, Sebastian
AU - Limviphuvadh, Vachiranee
AU - Soler, Vincent
AU - Ho, Candice
AU - Yanovitch, Tammy
AU - Schneider, Georg
AU - Li, Yi
AU - Nading, Erica
AU - Metlapally, Ravikanth
AU - Saw, Seang
AU - Goh, Liang
AU - Rozen, Steve
AU - Young, Terri
ID - 2826
IS - 5
JF - American Journal of Human Genetics
TI - Mutations in SCO2 are associated with autosomal-dominant high-grade myopia
VL - 92
ER -
TY - JOUR
AB - Removal of cargos from the cell surface via endocytosis is an efficient mechanism to regulate activities of plasma membrane (PM)-resident proteins, such as receptors or transporters. Salicylic acid (SA) is an important plant hormone that is traditionally associated with pathogen defense. Here, we describe an unanticipated effect of SA on subcellular endocytic cycling of proteins. Both exogenous treatments and endogenously enhanced SA levels repressed endocytosis of different PM proteins. The SA effect on endocytosis did not involve transcription or known components of the SA signaling pathway for transcriptional regulation. SA likely targets an endocytic mechanism that involves the coat protein clathrin, because SA interfered with the clathrin incidence at the PM and clathrin-deficient mutants were less sensitive to the impact of SA on the auxin distribution and root bending during the gravitropic response. By contrast, SA did not affect the ligand-induced endocytosis of the FLAGELLIN SENSING2 (FLS2) receptor during pathogen responses. Our data suggest that the established SA impact on transcription in plant immunity and the nontranscriptional effect of SA on clathrin-mediated endocytosis are independent mechanisms by which SA regulates distinct aspects of plant physiology.
AU - Du, Yunlong
AU - Tejos, Ricardo
AU - Beck, Martina
AU - Himschoot, Ellie
AU - Li, Hongjiang
AU - Robatzek, Silke
AU - Vanneste, Steffen
AU - Friml, Jirí
ID - 2827
IS - 19
JF - PNAS
TI - Salicylic acid interferes with clathrin-mediated endocytic protein trafficking
VL - 110
ER -
TY - JOUR
AB - We study the complexity of valued constraint satisfaction problems (VCSPs) parametrized by a constraint language, a fixed set of cost functions over a finite domain. An instance of the problem is specified by a sum of cost functions from the language and the goal is to minimize the sum. Under the unique games conjecture, the approximability of finite-valued VCSPs is well understood, see Raghavendra [2008]. However, there is no characterization of finite-valued VCSPs, let alone general-valued VCSPs, that can be solved exactly in polynomial time, thus giving insights from a combinatorial optimization perspective. We consider the case of languages containing all possible unary cost functions. In the case of languages consisting of only {0, ∞}-valued cost functions (i.e., relations), such languages have been called conservative and studied by Bulatov [2003, 2011] and recently by Barto [2011]. Since we study valued languages, we call a language conservative if it contains all finite-valued unary cost functions. The computational complexity of conservative valued languages has been studied by Cohen et al. [2006] for languages over Boolean domains, by Deineko et al. [2008] for {0, 1}-valued languages (a.k.a Max-CSP), and by Takhanov [2010a] for {0, ∞}-valued languages containing all finite-valued unary cost functions (a.k.a. Min-Cost-Hom). We prove a Schaefer-like dichotomy theorem for conservative valued languages: if all cost functions in the language satisfy a certain condition (specified by a complementary combination of STP and MJN multimor-phisms), then any instance can be solved in polynomial time (via a new algorithm developed in this article), otherwise the language is NP-hard. This is the first complete complexity classification of general-valued constraint languages over non-Boolean domains. It is a common phenomenon that complexity classifications of problems over non-Boolean domains are significantly harder than the Boolean cases. The polynomial-time algorithm we present for the tractable cases is a generalization of the submodular minimization problem and a result of Cohen et al. [2008]. Our results generalize previous results by Takhanov [2010a] and (a subset of results) by Cohen et al. [2006] and Deineko et al. [2008]. Moreover, our results do not rely on any computer-assisted search as in Deineko et al. [2008], and provide a powerful tool for proving hardness of finite-valued and general-valued languages.
AU - Kolmogorov, Vladimir
AU - Živný, Stanislav
ID - 2828
IS - 2
JF - Journal of the ACM
TI - The complexity of conservative valued CSPs
VL - 60
ER -
TY - JOUR
AB - Laminar-turbulent intermittency is intrinsic to the transitional regime of a wide range of fluid flows including pipe, channel, boundary layer, and Couette flow. In the latter turbulent spots can grow and form continuous stripes, yet in the stripe-normal direction they remain interspersed by laminar fluid. We carry out direct numerical simulations in a long narrow domain and observe that individual turbulent stripes are transient. In agreement with recent observations in pipe flow, we find that turbulence becomes sustained at a distinct critical point once the spatial proliferation outweighs the inherent decaying process. By resolving the asymptotic size distributions close to criticality we can for the first time demonstrate scale invariance at the onset of turbulence.
AU - Shi, Liang
AU - Avila, Marc
AU - Hof, Björn
ID - 2829
IS - 20
JF - Physical Review Letters
TI - Scale invariance at the onset of turbulence in couette flow
VL - 110
ER -
TY - JOUR
AB - We consider Markov decision processes (MDPs) with Büchi (liveness) objectives. We consider the problem of computing the set of almost-sure winning states from where the objective can be ensured with probability 1. Our contributions are as follows: First, we present the first subquadratic symbolic algorithm to compute the almost-sure winning set for MDPs with Büchi objectives; our algorithm takes O(n · √ m) symbolic steps as compared to the previous known algorithm that takes O(n 2) symbolic steps, where n is the number of states and m is the number of edges of the MDP. In practice MDPs have constant out-degree, and then our symbolic algorithm takes O(n · √ n) symbolic steps, as compared to the previous known O(n 2) symbolic steps algorithm. Second, we present a new algorithm, namely win-lose algorithm, with the following two properties: (a) the algorithm iteratively computes subsets of the almost-sure winning set and its complement, as compared to all previous algorithms that discover the almost-sure winning set upon termination; and (b) requires O(n · √ K) symbolic steps, where K is the maximal number of edges of strongly connected components (scc's) of the MDP. The win-lose algorithm requires symbolic computation of scc's. Third, we improve the algorithm for symbolic scc computation; the previous known algorithm takes linear symbolic steps, and our new algorithm improves the constants associated with the linear number of steps. In the worst case the previous known algorithm takes 5×n symbolic steps, whereas our new algorithm takes 4×n symbolic steps.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
AU - Joglekar, Manas
AU - Shah, Nisarg
ID - 2831
IS - 3
JF - Formal Methods in System Design
TI - Symbolic algorithms for qualitative analysis of Markov decision processes with Büchi objectives
VL - 42
ER -
TY - JOUR
AB - PIN-FORMED (PIN) proteins localize asymmetrically at the plasma membrane and mediate intercellular polar transport of the plant hormone auxin that is crucial for a multitude of developmental processes in plants. PIN localization is under extensive control by environmental or developmental cues, but mechanisms regulating PIN localization are not fully understood. Here we show that early endosomal components ARF GEF BEN1 and newly identified Sec1/Munc18 family protein BEN2 are involved in distinct steps of early endosomal trafficking. BEN1 and BEN2 are collectively required for polar PIN localization, for their dynamic repolarization, and consequently for auxin activity gradient formation and auxin-related developmental processes including embryonic patterning, organogenesis, and vasculature venation patterning. These results show that early endosomal trafficking is crucial for cell polarity and auxin-dependent regulation of plant architecture.
AU - Tanaka, Hirokazu
AU - Kitakura, Saeko
AU - Rakusová, Hana
AU - Uemura, Tomohiro
AU - Feraru, Mugurel
AU - De Rycke, Riet
AU - Robert, Stéphanie
AU - Kakimoto, Tatsuo
AU - Friml, Jirí
ID - 2832
IS - 5
JF - PLoS Genetics
TI - Cell polarity and patterning by PIN trafficking through early endosomal compartments in arabidopsis thaliana
VL - 9
ER -
TY - JOUR
AB - Although the equations governing fluid flow are well known, there are no analytical expressions that describe the complexity of turbulent motion. A recent proposition is that in analogy to low dimensional chaotic systems, turbulence is organized around unstable solutions of the governing equations which provide the building blocks of the disordered dynamics. We report the discovery of periodic solutions which just like intermittent turbulence are spatially localized and show that turbulent transients arise from one such solution branch.
AU - Avila, Marc
AU - Mellibovsky, Fernando
AU - Roland, Nicolas
AU - Hof, Björn
ID - 2834
IS - 22
JF - Physical Review Letters
TI - Streamwise-localized solutions at the onset of turbulence in pipe flow
VL - 110
ER -
TY - JOUR
AB - The phytohormone auxin regulates virtually every aspect of plant development. To identify new genes involved in auxin activity, a genetic screen was performed for Arabidopsis (Arabidopsis thaliana) mutants with altered expression of the auxin-responsive reporter DR5rev:GFP. One of the mutants recovered in the screen, designated as weak auxin response3 (wxr3), exhibits much lower DR5rev:GFP expression when treated with the synthetic auxin 2,4-dichlorophenoxyacetic acid and displays severe defects in root development. The wxr3 mutant decreases polar auxin transport and results in a disruption of the asymmetric auxin distribution. The levels of the auxin transporters AUXIN1 and PIN-FORMED are dramatically reduced in the wxr3 root tip. Molecular analyses demonstrate that WXR3 is ROOT ULTRAVIOLET B-SENSITIVE1 (RUS1), a member of the conserved Domain of Unknown Function647 protein family found in diverse eukaryotic organisms. Our data suggest that RUS1/WXR3 plays an essential role in the regulation of polar auxin transport by maintaining the proper level of auxin transporters on the plasma membrane.
AU - Yu, Hong
AU - Karampelias, Michael
AU - Robert, Stéphanie
AU - Peer, Wendy
AU - Swarup, Ranjan
AU - Ye, Songqing
AU - Ge, Lei
AU - Cohen, Jerry
AU - Murphy, Angus
AU - Friml, Jirí
AU - Estelle, Mark
ID - 2835
IS - 2
JF - Plant Physiology
TI - Root ultraviolet b-sensitive1/weak auxin response3 is essential for polar auxin transport in arabidopsis
VL - 162
ER -
TY - JOUR
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 and the trusted third party as path formulas in linear temporal logic and prove that the satisfaction of these objectives imply fairness; a property required of fair exchange protocols. We then show that weak (co-operative) co-synthesis and classical (strictly competitive) co-synthesis fail, whereas assume-guarantee synthesis (AGS) succeeds. We demonstrate the success of AGS as follows: (a) any solution of AGS is attack-free; no subset of participants can violate the objectives of the other participants; (b) the Asokan-Shoup-Waidner certified mail protocol that has known vulnerabilities is not a solution of AGS; (c) the Kremer-Markowitch non-repudiation protocol is a solution of AGS; and (d) AGS presents a new and symmetric fair non-repudiation protocol that is attack-free. To our knowledge this is the first application of synthesis to fair non-repudiation protocols, and our results show how synthesis can both automatically discover vulnerabilities in protocols and generate correct protocols. The solution to AGS can be computed efficiently as the secure equilibrium solution of three-player graph games.
AU - Chatterjee, Krishnendu
AU - Raman, Vishwanath
ID - 2836
IS - 4
JF - Formal Aspects of Computing
TI - Assume-guarantee synthesis for digital contract signing
VL - 26
ER -
TY - JOUR
AB - We consider a general class of N × N random matrices whose entries hij are independent up to a symmetry constraint, but not necessarily identically distributed. Our main result is a local semicircle law which improves previous results [17] both in the bulk and at the edge. The error bounds are given in terms of the basic small parameter of the model, maxi,j E|hij|2. As a consequence, we prove the universality of the local n-point correlation functions in the bulk spectrum for a class of matrices whose entries do not have comparable variances, including random band matrices with band width W ≫N1-εn with some εn > 0 and with a negligible mean-field component. In addition, we provide a coherent and pedagogical proof of the local semicircle law, streamlining and strengthening previous arguments from [17, 19, 6].
AU - Erdös, László
AU - Knowles, Antti
AU - Yau, Horng
AU - Yin, Jun
ID - 2837
IS - 59
JF - Electronic Journal of Probability
TI - The local semicircle law for a general class of random matrices
VL - 18
ER -
TY - JOUR
AB - Individuals with Down syndrome (DS) present important motor deficits that derive from altered motor development of infants and young children. DYRK1A, a candidate gene for DS abnormalities has been implicated in motor function due to its expression in motor nuclei in the adult brain, and its overexpression in DS mouse models leads to hyperactivity and altered motor learning. However, its precise role in the adult motor system, or its possible involvement in postnatal locomotor development has not yet been clarified. During the postnatal period we observed time-specific expression of Dyrk1A in discrete subsets of brainstem nuclei and spinal cord motor neurons. Interestingly, we describe for the first time the presence of Dyrk1A in the presynaptic terminal of the neuromuscular junctions and its axonal transport from the facial nucleus, suggesting a function for Dyrk1A in these structures. Relevant to DS, Dyrk1A overexpression in transgenic mice (TgDyrk1A) produces motor developmental alterations possibly contributing to DS motor phenotypes and modifies the numbers of motor cholinergic neurons, suggesting that the kinase may have a role in the development of the brainstem and spinal cord motor system.
AU - Arquè Fuste, Gloria
AU - Casanovas, Anna
AU - Dierssen, Mara
ID - 2838
IS - 1
JF - PLoS One
TI - Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: Possible role in Down syndrome
VL - 8
ER -
TY - JOUR
AB - Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues.
AU - Weber, Michele
AU - Hauschild, Robert
AU - Schwarz, Jan
AU - Moussion, Christine
AU - De Vries, Ingrid
AU - Legler, Daniel
AU - Luther, Sanjiv
AU - Bollenbach, Mark Tobias
AU - Sixt, Michael K
ID - 2839
IS - 6117
JF - Science
TI - Interstitial dendritic cell guidance by haptotactic chemokine gradients
VL - 339
ER -
TY - JOUR
AB - We outline two approaches to inference of neighbourhood size, N, and dispersal rate, σ2, based on either allele frequencies or on the lengths of sequence blocks that are shared between genomes. Over intermediate timescales (10-100 generations, say), populations that live in two dimensions approach a quasi-equilibrium that is independent of both their local structure and their deeper history. Over such scales, the standardised covariance of allele frequencies (i.e. pairwise FS T) falls with the logarithm of distance, and depends only on neighbourhood size, N, and a 'local scale', κ; the rate of gene flow, σ2, cannot be inferred. We show how spatial correlations can be accounted for, assuming a Gaussian distribution of allele frequencies, giving maximum likelihood estimates of N and κ. Alternatively, inferences can be based on the distribution of the lengths of sequence that are identical between blocks of genomes: long blocks (>0.1 cM, say) tell us about intermediate timescales, over which we assume a quasi-equilibrium. For large neighbourhood size, the distribution of long blocks is given directly by the classical Wright-Malécot formula; this relationship can be used to infer both N and σ2. With small neighbourhood size, there is an appreciable chance that recombinant lineages will coalesce back before escaping into the distant past. For this case, we show that if genomes are sampled from some distance apart, then the distribution of lengths of blocks that are identical in state is geometric, with a mean that depends on N and σ2.
AU - Barton, Nicholas H
AU - Etheridge, Alison
AU - Kelleher, Jerome
AU - Véber, Amandine
ID - 2842
IS - 1
JF - Theoretical Population Biology
TI - Inference in two dimensions: Allele frequencies versus lengths of shared sequence blocks
VL - 87
ER -
TY - JOUR
AB - The Red Queen hypothesis proposes that coevolving parasites select for outcrossing in the host. Outcrossing relies on males, which often show lower immune investment due to, for example, sexual selection. Here, we demonstrate that such sex differences in immunity interfere with parasite-mediated selection for outcrossing. Two independent coevolution experiments with Caenorhabditis elegans and its microparasite Bacillus thuringiensis produced decreased yet stable frequencies of outcrossing male hosts. A subsequent systematic analysis verified that male C. elegans suffered from a direct selective disadvantage under parasite pressure (i.e. lower resistance, decreased sexual activity, increased escape behaviour), which can reduce outcrossing and thus male frequencies. At the same time, males offered an indirect selective benefit, because male-mediated outcrossing increased offspring resistance, thus favouring male persistence in the evolving populations. As sex differences in immunity are widespread, such interference of opposing selective constraints is likely of central importance during host adaptation to a coevolving parasite.
AU - El Masri, Leila
AU - Schulte, Rebecca
AU - Timmermeyer, Nadine
AU - Thanisch, Stefanie
AU - Crummenerl, Lena
AU - Jansen, Gunther
AU - Michiels, Nico
AU - Schulenburg, Hinrich
ID - 2846
IS - 4
JF - Ecology Letters
TI - Sex differences in host defence interfere with parasite-mediated selection for outcrossing during host-parasite coevolution
VL - 16
ER -
TY - CONF
AB - Depth-Bounded Systems form an expressive class of well-structured transition systems. They can model a wide range of concurrent infinite-state systems including those with dynamic thread creation, dynamically changing communication topology, and complex shared heap structures. We present the first method to automatically prove fair termination of depth-bounded systems. Our method uses a numerical abstraction of the system, which we obtain by systematically augmenting an over-approximation of the system’s reachable states with a finite set of counters. This numerical abstraction can be analyzed with existing termination provers. What makes our approach unique is the way in which it exploits the well-structuredness of the analyzed system. We have implemented our work in a prototype tool and used it to automatically prove liveness properties of complex concurrent systems, including nonblocking algorithms such as Treiber’s stack and several distributed processes. Many of these examples are beyond the scope of termination analyses that are based on traditional counter abstractions.
AU - Bansal, Kshitij
AU - Koskinen, Eric
AU - Wies, Thomas
AU - Zufferey, Damien
ED - Piterman, Nir
ED - Smolka, Scott
ID - 2847
TI - Structural Counter Abstraction
VL - 7795
ER -
TY - JOUR
AB - Recent work emphasizes that the maximum entropy principle provides a bridge between statistical mechanics models for collective behavior in neural networks and experiments on networks of real neurons. Most of this work has focused on capturing the measured correlations among pairs of neurons. Here we suggest an alternative, constructing models that are consistent with the distribution of global network activity, i.e. the probability that K out of N cells in the network generate action potentials in the same small time bin. The inverse problem that we need to solve in constructing the model is analytically tractable, and provides a natural 'thermodynamics' for the network in the limit of large N. We analyze the responses of neurons in a small patch of the retina to naturalistic stimuli, and find that the implied thermodynamics is very close to an unusual critical point, in which the entropy (in proper units) is exactly equal to the energy. © 2013 IOP Publishing Ltd and SISSA Medialab srl.
AU - Tkacik, Gasper
AU - Marre, Olivier
AU - Mora, Thierry
AU - Amodei, Dario
AU - Berry, Michael
AU - Bialek, William
ID - 2850
IS - 3
JF - Journal of Statistical Mechanics Theory and Experiment
TI - The simplest maximum entropy model for collective behavior in a neural network
VL - 2013
ER -
TY - JOUR
AB - High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared with its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low, because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation.
AU - Refardt, Dominik
AU - Bergmiller, Tobias
AU - Kümmerli, Rolf
ID - 2853
IS - 1759
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection
VL - 280
ER -
TY - JOUR
AB - We consider concurrent games played on graphs. At every round of a game, each player simultaneously and independently selects a move; the moves jointly determine the transition to a successor state. Two basic objectives are the safety objective to stay forever in a given set of states, and its dual, the reachability objective to reach a given set of states. First, we present a simple proof of the fact that in concurrent reachability games, for all ε>0, memoryless ε-optimal strategies exist. A memoryless strategy is independent of the history of plays, and an ε-optimal strategy achieves the objective with probability within ε of the value of the game. In contrast to previous proofs of this fact, our proof is more elementary and more combinatorial. Second, we present a strategy-improvement (a.k.a. policy-iteration) algorithm for concurrent games with reachability objectives. Finally, we present a strategy-improvement algorithm for turn-based stochastic games (where each player selects moves in turns) with safety objectives. Our algorithms yield sequences of player-1 strategies which ensure probabilities of winning that converge monotonically (from below) to the value of the game. © 2012 Elsevier Inc.
AU - Chatterjee, Krishnendu
AU - De Alfaro, Luca
AU - Henzinger, Thomas A
ID - 2854
IS - 5
JF - Journal of Computer and System Sciences
TI - Strategy improvement for concurrent reachability and turn based stochastic safety games
VL - 79
ER -
TY - JOUR
AB - Genomic imprinting leads to preferred expression of either the maternal or paternal alleles of a subset of genes. Imprinting is essential for mammalian development, and its deregulation causes many diseases. However, the functional relevance of imprinting at the cellular level is poorly understood for most imprinted genes. We used mosaic analysis with double markers (MADM) in mice to create uniparental disomies (UPDs) and to visualize imprinting effects with single-cell resolution. Although chromosome 12 UPD did not produce detectable phenotypes, chromosome 7 UPD caused highly significant paternal growth dominance in the liver and lung, but not in the brain or heart. A single gene on chromosome 7, encoding the secreted insulin-like growth factor 2 (IGF2), accounts for most of the paternal dominance effect. Mosaic analyses implied additional imprinted loci on chromosome 7 acting cell autonomously to transmit the IGF2 signal. Our study reveals chromosome- and cell-type specificity of genomic imprinting effects.
AU - Hippenmeyer, Simon
AU - Johnson, Randy
AU - Luo, Liqun
ID - 2855
IS - 3
JF - Cell Reports
TI - Mosaic analysis with double markers reveals cell type specific paternal growth dominance
VL - 3
ER -
TY - JOUR
AB - G protein–coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering of native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized mGluRs (LimGluRs). The light-agonized LimGluR2, on which we focused, was fast, bistable and supported multiple rounds of on/off switching. Light gated two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. We found that the light-antagonized tool LimGluR2-block was able to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalized the optical control to two additional family members: mGluR3 and mGluR6. This system worked in rodent brain slices and in zebrafish in vivo, where we found that mGluR2 modulated the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease.
AU - Levitz, Joshua
AU - Pantoja, Carlos
AU - Gaub, Benjamin
AU - Janovjak, Harald L
AU - Reiner, Andreas
AU - Hoagland, Adam
AU - Schoppik, David
AU - Kane, Brian
AU - Stawski, Philipp
AU - Schier, Alexander
AU - Trauner, Dirk
AU - Isacoff, Ehud
ID - 2856
JF - Nature Neuroscience
TI - Optical control of metabotropic glutamate receptors
VL - 16
ER -
TY - JOUR
AB - In the vibrant field of optogenetics, optics and genetic targeting are combined to commandeer cellular functions, such as the neuronal action potential, by optically stimulating light-sensitive ion channels expressed in the cell membrane. One broadly applicable manifestation of this approach are covalently attached photochromic tethered ligands (PTLs) that allow activating ligand-gated ion channels with outstanding spatial and temporal resolution. Here, we describe all steps towards the successful development and application of PTL-gated ion channels in cell lines and primary cells. The basis for these experiments forms a combination of molecular modeling, genetic engineering, cell culture, and electrophysiology. The light-gated glutamate receptor (LiGluR), which consists of the PTL-functionalized GluK2 receptor, serves as a model.
AU - Szobota, Stephanie
AU - Mckenzie, Catherine
AU - Janovjak, Harald L
ID - 2857
JF - Methods in Molecular Biology
TI - Optical control of ligand-gated ion channels
VL - 998
ER -
TY - JOUR
AB - Tumor growth is caused by the acquisition of driver mutations, which enhance the net reproductive rate of cells. Driver mutations may increase cell division, reduce cell death, or allow cells to overcome density-limiting effects. We study the dynamics of tumor growth as one additional driver mutation is acquired. Our models are based on two-type branching processes that terminate in either tumor disappearance or tumor detection. In our first model, both cell types grow exponentially, with a faster rate for cells carrying the additional driver. We find that the additional driver mutation does not affect the survival probability of the lesion, but can substantially reduce the time to reach the detectable size if the lesion is slow growing. In our second model, cells lacking the additional driver cannot exceed a fixed carrying capacity, due to density limitations. In this case, the time to detection depends strongly on this carrying capacity. Our model provides a quantitative framework for studying tumor dynamics during different stages of progression. We observe that early, small lesions need additional drivers, while late stage metastases are only marginally affected by them. These results help to explain why additional driver mutations are typically not detected in fast-growing metastases.
AU - Reiter, Johannes
AU - Božić, Ivana
AU - Allen, Benjamin
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 2858
IS - 1
JF - Evolutionary Applications
TI - The effect of one additional driver mutation on tumor progression
VL - 6
ER -