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
AU - Bernecky, Carrie A
AU - Cramer, Patrick
ID - 595
IS - 6
JF - EMBO Journal
TI - Struggling to let go: A non-coding RNA directs its own extension and destruction
VL - 32
ER -
TY - JOUR
AB - Different interoceptive systems must be integrated to ensure that multiple homeostatic insults evoke appropriate behavioral and physiological responses. Little is known about how this is achieved. Using C. elegans, we dissect cross-modulation between systems that monitor temperature, O2 and CO2. CO2 is less aversive to animals acclimated to 15°C than those grown at 22°C. This difference requires the AFD neurons, which respond to both temperature and CO2 changes. CO2 evokes distinct AFD Ca2+ responses in animals acclimated at 15°C or 22°C. Mutants defective in synaptic transmission can reprogram AFD CO2 responses according to temperature experience, suggesting reprogramming occurs cell autonomously. AFD is exquisitely sensitive to CO2. Surprisingly, gradients of 0.01% CO2/second evoke very different Ca2+ responses from gradients of 0.04% CO2/second. Ambient O2 provides further contextual modulation of CO2 avoidance. At 21% O2 tonic signalling from the O2-sensing neuron URX inhibits CO2 avoidance. This inhibition can be graded according to O2 levels. In a natural wild isolate, a switch from 21% to 19% O2 is sufficient to convert CO2 from a neutral to an aversive cue. This sharp tuning is conferred partly by the neuroglobin GLB-5. The modulatory effects of O2 on CO2 avoidance involve the RIA interneurons, which are post-synaptic to URX and exhibit CO2-evoked Ca2+ responses. Ambient O2 and acclimation temperature act combinatorially to modulate CO2 responsiveness. Our work highlights the integrated architecture of homeostatic responses in C. elegans.
AU - Kodama-Namba, Eiji
AU - Fenk, Lorenz A.
AU - Bretscher, Andrew J.
AU - Gross, Einav
AU - Busch, K. Emanuel
AU - de Bono, Mario
ID - 6128
IS - 12
JF - PLoS Genetics
SN - 1553-7404
TI - Cross-modulation of homeostatic responses to temperature, oxygen and carbon dioxide in C. elegans
VL - 9
ER -
TY - JOUR
AB - Cas9 is an RNA-guided double-stranded DNA nuclease that participates in clustered regularly interspaced short palindromic repeats (CRISPR)-mediated adaptive immunity in prokaryotes. CRISPR–Cas9 has recently been used to generate insertion and deletion mutations in Caenorhabditis elegans, but not to create tailored changes (knock-ins). We show that the CRISPR–CRISPR-associated (Cas) system can be adapted for efficient and precise editing of the C. elegans genome. The targeted double-strand breaks generated by CRISPR are substrates for transgene-instructed gene conversion. This allows customized changes in the C. elegans genome by homologous recombination: sequences contained in the repair template (the transgene) are copied by gene conversion into the genome. The possibility to edit the C. elegans genome at selected locations will facilitate the systematic study of gene function in this widely used model organism.
AU - Chen, Changchun
AU - Fenk, Lorenz A.
AU - de Bono, Mario
ID - 6130
IS - 20
JF - Nucleic Acids Research
SN - 1362-4962
TI - Efficient genome editing in Caenorhabditis elegans by CRISPR-targeted homologous recombination
VL - 41
ER -
TY - JOUR
AB - cGMP signaling is widespread in the nervous system. However, it has proved difficult to visualize and genetically probe endogenously evoked cGMP dynamics in neurons in vivo. Here, we combine cGMP and Ca2+ biosensors to image and dissect a cGMP signaling network in a Caenorhabditis elegans oxygen-sensing neuron. We show that a rise in O2 can evoke a tonic increase in cGMP that requires an atypical O2-binding soluble guanylate cyclase and that is sustained until oxygen levels fall. Increased cGMP leads to a sustained Ca2+ response in the neuron that depends on cGMP-gated ion channels. Elevated levels of cGMP and Ca2+ stimulate competing negative feedback loops that shape cGMP dynamics. Ca2+-dependent negative feedback loops, including activation of phosphodiesterase-1 (PDE-1), dampen the rise of cGMP. A different negative feedback loop, mediated by phosphodiesterase-2 (PDE-2) and stimulated by cGMP-dependent kinase (PKG), unexpectedly promotes cGMP accumulation following a rise in O2, apparently by keeping in check gating of cGMP channels and limiting activation of Ca2+-dependent negative feedback loops. Simultaneous imaging of Ca2+ and cGMP suggests that cGMP levels can rise close to cGMP channels while falling elsewhere. O2-evoked cGMP and Ca2+ responses are highly reproducible when the same neuron in an individual animal is stimulated repeatedly, suggesting that cGMP transduction has high intrinsic reliability. However, responses vary substantially across individuals, despite animals being genetically identical and similarly reared. This variability may reflect stochastic differences in expression of cGMP signaling components. Our work provides in vivo insights into the architecture of neuronal cGMP signaling.
AU - Couto, A.
AU - Oda, S.
AU - Nikolaev, V. O.
AU - Soltesz, Z.
AU - de Bono, Mario
ID - 6133
IS - 35
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - In vivo genetic dissection of O2-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor
VL - 110
ER -
TY - JOUR
AB - We consider Hermitian and symmetric random band matrices H = (h xy ) in d⩾1 d ⩾ 1 dimensions. The matrix entries h xy , indexed by x,y∈(Z/LZ)d x , y ∈ ( Z / L Z ) d , are independent, centred random variables with variances sxy=E|hxy|2 s x y = E | h x y | 2 . We assume that s xy is negligible if |x − y| exceeds the band width W. In one dimension we prove that the eigenvectors of H are delocalized if W≫L4/5 W ≫ L 4 / 5 . We also show that the magnitude of the matrix entries |Gxy|2 | G x y | 2 of the resolvent G=G(z)=(H−z)−1 G = G ( z ) = ( H - z ) - 1 is self-averaging and we compute E|Gxy|2 E | G x y | 2 . We show that, as L→∞ L → ∞ and W≫L4/5 W ≫ L 4 / 5 , the behaviour of E|Gxy|2 E | G x y | 2 is governed by a diffusion operator whose diffusion constant we compute. Similar results are obtained in higher dimensions.
AU - László Erdös
AU - Knowles, Antti
AU - Yau, Horng-Tzer
AU - Yin, Jun
ID - 2697
IS - 1
JF - Communications in Mathematical Physics
TI - Delocalization and diffusion profile for random band matrices
VL - 323
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 a general class of random matrices whose entries are centred random variables, independent up to a symmetry constraint. We establish precise high-probability bounds on the averages of arbitrary monomials in the resolvent matrix entries. Our results generalize the previous results of Erdős et al. (Ann Probab, arXiv:1103.1919, 2013; Commun Math Phys, arXiv:1103.3869, 2013; J Combin 1(2):15-85, 2011) which constituted a key step in the proof of the local semicircle law with optimal error bound in mean-field random matrix models. Our bounds apply to random band matrices and improve previous estimates from order 2 to order 4 in the cases relevant to applications. In particular, they lead to a proof of the diffusion approximation for the magnitude of the resolvent of random band matrices. This, in turn, implies new delocalization bounds on the eigenvectors. The applications are presented in a separate paper (Erdős et al., arXiv:1205.5669, 2013).
AU - László Erdös
AU - Knowles, Antti
AU - Yau, Horng-Tzer
ID - 2780
IS - 8
JF - Annales Henri Poincare
TI - Averaging fluctuations in resolvents of random band matrices
VL - 14
ER -
TY - JOUR
AB - We consider the ensemble of adjacency matrices of Erdős-Rényi random graphs, that is, graphs on N vertices where every edge is chosen independently and with probability p = p(N). We rescale the matrix so that its bulk eigenvalues are of order one. We prove that, as long as pN→∞(with a speed at least logarithmic in N), the density of eigenvalues of the Erdős-Rényi ensemble is given by the Wigner semicircle law for spectral windows of length larger than N-1 (up to logarithmic corrections). As a consequence, all eigenvectors are proved to be completely delocalized in the sense that the ℓ∞-norms of the ℓ2-normalized eigenvectors are at most of order N-1/2 with a very high probability. The estimates in this paper will be used in the companion paper [Spectral statistics of Erdős-Rényi graphs II: Eigenvalue spacing and the extreme eigenvalues (2011) Preprint] to prove the universality of eigenvalue distributions both in the bulk and at the spectral edges under the further restriction that pN »N2/3.
AU - László Erdös
AU - Knowles, Antti
AU - Yau, Horng-Tzer
AU - Yin, Jun
ID - 2781
IS - 3 B
JF - Annals of Probability
TI - Spectral statistics of Erdős-Rényi graphs I: Local semicircle law
VL - 41
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 -