@article{10416, abstract = {A fundamental algorithmic problem at the heart of static analysis is Dyck reachability. The input is a graph where the edges are labeled with different types of opening and closing parentheses, and the reachability information is computed via paths whose parentheses are properly matched. We present new results for Dyck reachability problems with applications to alias analysis and data-dependence analysis. Our main contributions, that include improved upper bounds as well as lower bounds that establish optimality guarantees, are as follows: First, we consider Dyck reachability on bidirected graphs, which is the standard way of performing field-sensitive points-to analysis. Given a bidirected graph with n nodes and m edges, we present: (i) an algorithm with worst-case running time O(m + n · α(n)), where α(n) is the inverse Ackermann function, improving the previously known O(n2) time bound; (ii) a matching lower bound that shows that our algorithm is optimal wrt to worst-case complexity; and (iii) an optimal average-case upper bound of O(m) time, improving the previously known O(m · logn) bound. Second, we consider the problem of context-sensitive data-dependence analysis, where the task is to obtain analysis summaries of library code in the presence of callbacks. Our algorithm preprocesses libraries in almost linear time, after which the contribution of the library in the complexity of the client analysis is only linear, and only wrt the number of call sites. Third, we prove that combinatorial algorithms for Dyck reachability on general graphs with truly sub-cubic bounds cannot be obtained without obtaining sub-cubic combinatorial algorithms for Boolean Matrix Multiplication, which is a long-standing open problem. Thus we establish that the existing combinatorial algorithms for Dyck reachability are (conditionally) optimal for general graphs. We also show that the same hardness holds for graphs of constant treewidth. Finally, we provide a prototype implementation of our algorithms for both alias analysis and data-dependence analysis. Our experimental evaluation demonstrates that the new algorithms significantly outperform all existing methods on the two problems, over real-world benchmarks.}, author = {Chatterjee, Krishnendu and Choudhary, Bhavya and Pavlogiannis, Andreas}, issn = {2475-1421}, journal = {Proceedings of the ACM on Programming Languages}, location = {Los Angeles, CA, United States}, number = {POPL}, publisher = {Association for Computing Machinery}, title = {{Optimal Dyck reachability for data-dependence and Alias analysis}}, doi = {10.1145/3158118}, volume = {2}, year = {2017}, } @article{10418, abstract = {We present a new proof rule for proving almost-sure termination of probabilistic programs, including those that contain demonic non-determinism. An important question for a probabilistic program is whether the probability mass of all its diverging runs is zero, that is that it terminates "almost surely". Proving that can be hard, and this paper presents a new method for doing so. It applies directly to the program's source code, even if the program contains demonic choice. Like others, we use variant functions (a.k.a. "super-martingales") that are real-valued and decrease randomly on each loop iteration; but our key innovation is that the amount as well as the probability of the decrease are parametric. We prove the soundness of the new rule, indicate where its applicability goes beyond existing rules, and explain its connection to classical results on denumerable (non-demonic) Markov chains.}, author = {Mciver, Annabelle and Morgan, Carroll and Kaminski, Benjamin Lucien and Katoen, Joost P}, issn = {2475-1421}, journal = {Proceedings of the ACM on Programming Languages}, location = {Los Angeles, CA, United States}, number = {POPL}, publisher = {Association for Computing Machinery}, title = {{A new proof rule for almost-sure termination}}, doi = {10.1145/3158121}, volume = {2}, year = {2017}, } @article{1063, abstract = {Severe environmental change can drive a population extinct unless the population adapts in time to the new conditions (“evolutionary rescue”). How does biparental sexual reproduction influence the chances of population persistence compared to clonal reproduction or selfing? In this article, we set up a one‐locus two‐allele model for adaptation in diploid species, where rescue is contingent on the establishment of the mutant homozygote. Reproduction can occur by random mating, selfing, or clonally. Random mating generates and destroys the rescue mutant; selfing is efficient at generating it but at the same time depletes the heterozygote, which can lead to a low mutant frequency in the standing genetic variation. Due to these (and other) antagonistic effects, we find a nontrivial dependence of population survival on the rate of sex/selfing, which is strongly influenced by the dominance coefficient of the mutation before and after the environmental change. Importantly, since mating with the wild‐type breaks the mutant homozygote up, a slow decay of the wild‐type population size can impede rescue in randomly mating populations.}, author = {Uecker, Hildegard}, issn = {0014-3820}, journal = {Evolution}, number = {4}, pages = {845 -- 858}, publisher = {Wiley}, title = {{Evolutionary rescue in randomly mating, selfing, and clonal populations}}, doi = {10.1111/evo.13191}, volume = {71}, year = {2017}, } @article{1065, abstract = {We consider the problem of reachability in pushdown graphs. We study the problem for pushdown graphs with constant treewidth. Even for pushdown graphs with treewidth 1, for the reachability problem we establish the following: (i) the problem is PTIME-complete, and (ii) any subcubic algorithm for the problem would contradict the k-clique conjecture and imply faster combinatorial algorithms for cliques in graphs.}, author = {Chatterjee, Krishnendu and Osang, Georg F}, issn = {0020-0190}, journal = {Information Processing Letters}, pages = {25 -- 29}, publisher = {Elsevier}, title = {{Pushdown reachability with constant treewidth}}, doi = {10.1016/j.ipl.2017.02.003}, volume = {122}, year = {2017}, } @article{1066, abstract = {Simulation is an attractive alternative to language inclusion for automata as it is an under-approximation of language inclusion, but usually has much lower complexity. Simulation has also been extended in two orthogonal directions, namely, (1) fair simulation, for simulation over specified set of infinite runs; and (2) quantitative simulation, for simulation between weighted automata. While fair trace inclusion is PSPACE-complete, fair simulation can be computed in polynomial time. For weighted automata, the (quantitative) language inclusion problem is undecidable in general, whereas the (quantitative) simulation reduces to quantitative games, which admit pseudo-polynomial time algorithms. In this work, we study (quantitative) simulation for weighted automata with Büchi acceptance conditions, i.e., we generalize fair simulation from non-weighted automata to weighted automata. We show that imposing Büchi acceptance conditions on weighted automata changes many fundamental properties of the simulation games, yet they still admit pseudo-polynomial time algorithms.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan and Velner, Yaron}, journal = {Information and Computation}, number = {2}, pages = {143 -- 166}, publisher = {Elsevier}, title = {{Quantitative fair simulation games}}, doi = {10.1016/j.ic.2016.10.006}, volume = {254}, year = {2017}, } @article{1067, abstract = {Embryo morphogenesis relies on highly coordinated movements of different tissues. However, remarkably little is known about how tissues coordinate their movements to shape the embryo. In zebrafish embryogenesis, coordinated tissue movements first become apparent during “doming,” when the blastoderm begins to spread over the yolk sac, a process involving coordinated epithelial surface cell layer expansion and mesenchymal deep cell intercalations. Here, we find that active surface cell expansion represents the key process coordinating tissue movements during doming. By using a combination of theory and experiments, we show that epithelial surface cells not only trigger blastoderm expansion by reducing tissue surface tension, but also drive blastoderm thinning by inducing tissue contraction through radial deep cell intercalations. Thus, coordinated tissue expansion and thinning during doming relies on surface cells simultaneously controlling tissue surface tension and radial tissue contraction.}, author = {Morita, Hitoshi and Grigolon, Silvia and Bock, Martin and Krens, Gabriel and Salbreux, Guillaume and Heisenberg, Carl-Philipp J}, issn = {1534-5807}, journal = {Developmental Cell}, number = {4}, pages = {354 -- 366}, publisher = {Cell Press}, title = {{The physical basis of coordinated tissue spreading in zebrafish gastrulation}}, doi = {10.1016/j.devcel.2017.01.010}, volume = {40}, year = {2017}, } @article{1072, abstract = {Given a finite set of points in Rn and a radius parameter, we study the Čech, Delaunay–Čech, Delaunay (or alpha), and Wrap complexes in the light of generalized discrete Morse theory. Establishing the Čech and Delaunay complexes as sublevel sets of generalized discrete Morse functions, we prove that the four complexes are simple-homotopy equivalent by a sequence of simplicial collapses, which are explicitly described by a single discrete gradient field.}, author = {Bauer, Ulrich and Edelsbrunner, Herbert}, journal = {Transactions of the American Mathematical Society}, number = {5}, pages = {3741 -- 3762}, publisher = {American Mathematical Society}, title = {{The Morse theory of Čech and delaunay complexes}}, doi = {10.1090/tran/6991}, volume = {369}, year = {2017}, } @article{1073, abstract = {Let X and Y be finite simplicial sets (e.g. finite simplicial complexes), both equipped with a free simplicial action of a finite group G. Assuming that Y is d-connected and dimX≤2d, for some d≥1, we provide an algorithm that computes the set of all equivariant homotopy classes of equivariant continuous maps |X|→|Y|; the existence of such a map can be decided even for dimX≤2d+1. This yields the first algorithm for deciding topological embeddability of a k-dimensional finite simplicial complex into Rn under the condition k≤23n−1. More generally, we present an algorithm that, given a lifting-extension problem satisfying an appropriate stability assumption, computes the set of all homotopy classes of solutions. This result is new even in the non-equivariant situation.}, author = {Čadek, Martin and Krcál, Marek and Vokřínek, Lukáš}, issn = {01795376}, journal = {Discrete & Computational Geometry}, number = {4}, pages = {915 -- 965}, publisher = {Springer}, title = {{Algorithmic solvability of the lifting extension problem}}, doi = {10.1007/s00454-016-9855-6}, volume = {54}, year = {2017}, } @article{1074, abstract = {Recently it has become feasible to detect long blocks of nearly identical sequence shared between pairs of genomes. These IBD blocks are direct traces of recent coalescence events and, as such, contain ample signal to infer recent demography. Here, we examine sharing of such blocks in two-dimensional populations with local migration. Using a diffusion approximation to trace genetic ancestry, we derive analytical formulae for patterns of isolation by distance of IBD blocks, which can also incorporate recent population density changes. We introduce an inference scheme that uses a composite likelihood approach to fit these formulae. We then extensively evaluate our theory and inference method on a range of scenarios using simulated data. We first validate the diffusion approximation by showing that the theoretical results closely match the simulated block sharing patterns. We then demonstrate that our inference scheme can accurately and robustly infer dispersal rate and effective density, as well as bounds on recent dynamics of population density. To demonstrate an application, we use our estimation scheme to explore the fit of a diffusion model to Eastern European samples in the POPRES data set. We show that ancestry diffusing with a rate of σ ≈ 50–100 km/√gen during the last centuries, combined with accelerating population growth, can explain the observed exponential decay of block sharing with increasing pairwise sample distance.}, author = {Ringbauer, Harald and Coop, Graham and Barton, Nicholas H}, issn = {0016-6731}, journal = {Genetics}, number = {3}, pages = {1335 -- 1351}, publisher = {Genetics Society of America}, title = {{Inferring recent demography from isolation by distance of long shared sequence blocks}}, doi = {10.1534/genetics.116.196220}, volume = {205}, year = {2017}, } @article{1079, abstract = {We study the ionization problem in the Thomas-Fermi-Dirac-von Weizsäcker theory for atoms and molecules. We prove the nonexistence of minimizers for the energy functional when the number of electrons is large and the total nuclear charge is small. This nonexistence result also applies to external potentials decaying faster than the Coulomb potential. In the case of arbitrary nuclear charges, we obtain the nonexistence of stable minimizers and radial minimizers.}, author = {Nam, Phan and Van Den Bosch, Hanne}, issn = {1385-0172}, journal = {Mathematical Physics, Analysis and Geometry}, number = {2}, publisher = {Springer}, title = {{Nonexistence in Thomas Fermi-Dirac-von Weizsäcker theory with small nuclear charges}}, doi = {10.1007/s11040-017-9238-0}, volume = {20}, year = {2017}, } @article{1080, abstract = {Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications. Genome-wide sequencing data has enabled modern phylogenomic methods to accurately dissect subclones and their phylogenies from noisy and impure bulk tumour samples at unprecedented depth. However, existing methods are not designed to infer metastatic seeding patterns. Here we develop a tool, called Treeomics, to reconstruct the phylogeny of metastases and map subclones to their anatomic locations. Treeomics infers comprehensive seeding patterns for pancreatic, ovarian, and prostate cancers. Moreover, Treeomics correctly disambiguates true seeding patterns from sequencing artifacts; 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumour heterogeneity among distinct samples. In silico benchmarking on simulated tumour phylogenies across a wide range of sample purities (15–95%) and sequencing depths (25-800 × ) demonstrates the accuracy of Treeomics compared with existing methods.}, author = {Reiter, Johannes and Makohon Moore, Alvin and Gerold, Jeffrey and Božić, Ivana and Chatterjee, Krishnendu and Iacobuzio Donahue, Christine and Vogelstein, Bert and Nowak, Martin}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Reconstructing metastatic seeding patterns of human cancers}}, doi = {10.1038/ncomms14114}, volume = {8}, year = {2017}, } @inproceedings{791, abstract = {Consider the following random process: we are given n queues, into which elements of increasing labels are inserted uniformly at random. To remove an element, we pick two queues at random, and remove the element of lower label (higher priority) among the two. The cost of a removal is the rank of the label removed, among labels still present in any of the queues, that is, the distance from the optimal choice at each step. Variants of this strategy are prevalent in state-of-the-art concurrent priority queue implementations. Nonetheless, it is not known whether such implementations provide any rank guarantees, even in a sequential model. We answer this question, showing that this strategy provides surprisingly strong guarantees: Although the single-choice process, where we always insert and remove from a single randomly chosen queue, has degrading cost, going to infinity as we increase the number of steps, in the two choice process, the expected rank of a removed element is O(n) while the expected worst-case cost is O(n log n). These bounds are tight, and hold irrespective of the number of steps for which we run the process. The argument is based on a new technical connection between "heavily loaded" balls-into-bins processes and priority scheduling. Our analytic results inspire a new concurrent priority queue implementation, which improves upon the state of the art in terms of practical performance.}, author = {Alistarh, Dan-Adrian and Kopinsky, Justin and Li, Jerry and Nadiradze, Giorgi}, booktitle = {Proceedings of the ACM Symposium on Principles of Distributed Computing}, isbn = {978-145034992-5}, location = {Washington, WA, USA}, pages = {283 -- 292}, publisher = {ACM}, title = {{The power of choice in priority scheduling}}, doi = {10.1145/3087801.3087810}, volume = {Part F129314}, year = {2017}, } @article{792, abstract = {The chaotic dynamics of low-dimensional systems, such as Lorenz or Rössler flows, is guided by the infinity of periodic orbits embedded in their strange attractors. Whether this is also the case for the infinite-dimensional dynamics of Navier–Stokes equations has long been speculated, and is a topic of ongoing study. Periodic and relative periodic solutions have been shown to be involved in transitions to turbulence. Their relevance to turbulent dynamics – specifically, whether periodic orbits play the same role in high-dimensional nonlinear systems like the Navier–Stokes equations as they do in lower-dimensional systems – is the focus of the present investigation. We perform here a detailed study of pipe flow relative periodic orbits with energies and mean dissipations close to turbulent values. We outline several approaches to reduction of the translational symmetry of the system. We study pipe flow in a minimal computational cell at Re=2500, and report a library of invariant solutions found with the aid of the method of slices. Detailed study of the unstable manifolds of a sample of these solutions is consistent with the picture that relative periodic orbits are embedded in the chaotic saddle and that they guide the turbulent dynamics.}, author = {Budanur, Nazmi B and Short, Kimberly and Farazmand, Mohammad and Willis, Ashley and Cvitanović, Predrag}, issn = {0022-1120}, journal = {Journal of Fluid Mechanics}, pages = {274 -- 301}, publisher = {Cambridge University Press}, title = {{Relative periodic orbits form the backbone of turbulent pipe flow}}, doi = {10.1017/jfm.2017.699}, volume = {833}, year = {2017}, } @article{793, abstract = {Let P be a finite point set in the plane. A cordinary triangle in P is a subset of P consisting of three non-collinear points such that each of the three lines determined by the three points contains at most c points of P . Motivated by a question of Erdös, and answering a question of de Zeeuw, we prove that there exists a constant c > 0such that P contains a c-ordinary triangle, provided that P is not contained in the union of two lines. Furthermore, the number of c-ordinary triangles in P is Ω(| P |). }, author = {Fulek, Radoslav and Mojarrad, Hossein and Naszódi, Márton and Solymosi, József and Stich, Sebastian and Szedlák, May}, issn = {0925-7721}, journal = {Computational Geometry: Theory and Applications}, pages = {28 -- 31}, publisher = {Elsevier}, title = {{On the existence of ordinary triangles}}, doi = {10.1016/j.comgeo.2017.07.002}, volume = {66}, year = {2017}, } @article{794, abstract = {We show that c-planarity is solvable in quadratic time for flat clustered graphs with three clusters if the combinatorial embedding of the underlying graph is fixed. In simpler graph-theoretical terms our result can be viewed as follows. Given a graph G with the vertex set partitioned into three parts embedded on a 2-sphere, our algorithm decides if we can augment G by adding edges without creating an edge-crossing so that in the resulting spherical graph the vertices of each part induce a connected sub-graph. We proceed by a reduction to the problem of testing the existence of a perfect matching in planar bipartite graphs. We formulate our result in a slightly more general setting of cyclic clustered graphs, i.e., the simple graph obtained by contracting each cluster, where we disregard loops and multi-edges, is a cycle.}, author = {Fulek, Radoslav}, journal = {Computational Geometry: Theory and Applications}, pages = {1 -- 13}, publisher = {Elsevier}, title = {{C-planarity of embedded cyclic c-graphs}}, doi = {10.1016/j.comgeo.2017.06.016}, volume = {66}, year = {2017}, } @article{796, abstract = {We present the fabrication and characterization of an aluminum transmon qubit on a silicon-on-insulator substrate. Key to the qubit fabrication is the use of an anhydrous hydrofluoric vapor process which selectively removes the lossy silicon oxide buried underneath the silicon device layer. For a 5.6 GHz qubit measured dispersively by a 7.1 GHz resonator, we find T1 = 3.5 μs and T∗2 = 2.2 μs. This process in principle permits the co-fabrication of silicon photonic and mechanical elements, providing a route towards chip-scale integration of electro-opto-mechanical transducers for quantum networking of superconducting microwave quantum circuits. The additional processing steps are compatible with established fabrication techniques for aluminum transmon qubits on silicon.}, author = {Keller, Andrew J and Dieterle, Paul and Fang, Michael and Berger, Brett and Fink, Johannes M and Painter, Oskar}, issn = {0003-6951}, journal = {Applied Physics Letters}, number = {4}, publisher = {American Institute of Physics}, title = {{Al transmon qubits on silicon on insulator for quantum device integration}}, doi = {10.1063/1.4994661}, volume = {111}, year = {2017}, } @article{797, abstract = {Phasenübergänge helfen beim Verständnis von Vielteilchensystemen in der Festkörperphysik und Fluiddynamik bis hin zur Teilchenphysik. Unserer internationalen Kollaboration ist es gelungen, einen neuartigen Phasenübergang in einem Quantensystem zu beobachten [1]. In einem Mikrowellenresonator konnte erstmals die spontane Zustandsänderung von undurchsichtig zu transparent nachgewiesen werden.}, author = {Fink, Johannes M}, journal = {Physik in unserer Zeit}, number = {3}, pages = {111 -- 113}, publisher = {Wiley}, title = {{Photonenblockade aufgelöst}}, doi = {10.1002/piuz.201770305}, volume = {48}, year = {2017}, } @article{798, abstract = {Nonreciprocal circuit elements form an integral part of modern measurement and communication systems. Mathematically they require breaking of time-reversal symmetry, typically achieved using magnetic materials and more recently using the quantum Hall effect, parametric permittivity modulation or Josephson nonlinearities. Here we demonstrate an on-chip magnetic-free circulator based on reservoir-engineered electromechanic interactions. Directional circulation is achieved with controlled phase-sensitive interference of six distinct electro-mechanical signal conversion paths. The presented circulator is compact, its silicon-on-insulator platform is compatible with both superconducting qubits and silicon photonics, and its noise performance is close to the quantum limit. With a high dynamic range, a tunable bandwidth of up to 30 MHz and an in situ reconfigurability as beam splitter or wavelength converter, it could pave the way for superconducting qubit processors with multiplexed on-chip signal processing and readout.}, author = {Barzanjeh, Shabir and Wulf, Matthias and Peruzzo, Matilda and Kalaee, Mahmoud and Dieterle, Paul and Painter, Oskar and Fink, Johannes M}, issn = {2041-1723}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Mechanical on chip microwave circulator}}, doi = {10.1038/s41467-017-01304-x}, volume = {8}, year = {2017}, } @article{799, abstract = {Membrane traffic at the trans-Golgi network (TGN) is crucial for correctly distributing various membrane proteins to their destination. Polarly localized auxin efflux proteins, including PIN-FORMED1 (PIN1), are dynamically transported between the endosomes and the plasma membrane (PM) in the plant cells. The intracellular trafficking of PIN1 protein is sensitive to a fungal toxin brefeldin A (BFA), which is known to inhibit guanine-nucleotide exchange factors for ADP ribosylation factors (ARF GEFs) such as GNOM. However, the molecular details of the BFA-sensitive trafficking pathway have not been revealed fully. In a previous study, we have identified an Arabidopsis mutant BFA-visualized endocytic trafficking defective 3 (ben3) which exhibited reduced sensitivity to BFA in terms of BFA-induced intracellular PIN1 agglomeration. Here, we show that BEN3 encodes a member of BIG family ARF GEFs, BIG2. Fluorescent proteins tagged BEN3/BIG2 co-localized with markers for TGN / early endosome (EE). Inspection of conditionally induced de novo synthesized PIN1 confirmed that its secretion to the PM is BFA-sensitive and established BEN3/BIG2 as a crucial component of this BFA action at the level of TGN/EE. Furthermore, ben3 mutation alleviated BFA-induced agglomeration of another TGN-localized ARF GEF BEN1/MIN7. Taken together our results suggest that BEN3/BIG2 is an ARF GEF component, which confers BFA sensitivity to the TGN/EE in Arabidopsis.}, author = {Kitakura, Saeko and Adamowski, Maciek and Matsuura, Yuki and Santuari, Luca and Kouno, Hirotaka and Arima, Kohei and Hardtke, Christian and Friml, Jirí and Kakimoto, Tatsuo and Tanaka, Hirokazu}, issn = {0032-0781}, journal = {Plant and Cell Physiology}, number = {10}, publisher = {Oxford University Press}, title = {{BEN3/BIG2 ARF GEF is involved in brefeldin a-sensitive trafficking at the trans-Golgi network/early endosome in Arabidopsis thaliana}}, doi = {10.1093/pcp/pcx118}, volume = {58}, year = {2017}, } @article{800, abstract = {Gamma oscillations (30–150 Hz) in neuronal networks are associated with the processing and recall of information. We measured local field potentials in the dentate gyrus of freely moving mice and found that gamma activity occurs in bursts, which are highly heterogeneous in their spatial extensions, ranging from focal to global coherent events. Synaptic communication among perisomatic-inhibitory interneurons (PIIs) is thought to play an important role in the generation of hippocampal gamma patterns. However, how neuronal circuits can generate synchronous oscillations at different spatial scales is unknown. We analyzed paired recordings in dentate gyrus slices and show that synaptic signaling at interneuron-interneuron synapses is distance dependent. Synaptic strength declines whereas the duration of inhibitory signals increases with axonal distance among interconnected PIIs. Using neuronal network modeling, we show that distance-dependent inhibition generates multiple highly synchronous focal gamma bursts allowing the network to process complex inputs in parallel in flexibly organized neuronal centers.}, author = {Strüber, Michael and Sauer, Jonas and Jonas, Peter M and Bartos, Marlene}, issn = {2041-1723}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Distance-dependent inhibition facilitates focality of gamma oscillations in the dentate gyrus}}, doi = {10.1038/s41467-017-00936-3}, volume = {8}, year = {2017}, }