TY - CONF
AB - We present a method and a tool for generating succinct representations of sets of concurrent traces. We focus on trace sets that contain all correct or all incorrect permutations of events from a given trace. We represent trace sets as HB-Formulas that are Boolean combinations of happens-before constraints between events. To generate a representation of incorrect interleavings, our method iteratively explores interleavings that violate the specification and gathers generalizations of the discovered interleavings into an HB-Formula; its complement yields a representation of correct interleavings.
We claim that our trace set representations can drive diverse verification, fault localization, repair, and synthesis techniques for concurrent programs. We demonstrate this by using our tool in three case studies involving synchronization synthesis, bug summarization, and abstraction refinement based verification. In each case study, our initial experimental results have been promising.
In the first case study, we present an algorithm for inferring missing synchronization from an HB-Formula representing correct interleavings of a given trace. The algorithm applies rules to rewrite specific patterns in the HB-Formula into locks, barriers, and wait-notify constructs. In the second case study, we use an HB-Formula representing incorrect interleavings for bug summarization. While the HB-Formula itself is a concise counterexample summary, we present additional inference rules to help identify specific concurrency bugs such as data races, define-use order violations, and two-stage access bugs. In the final case study, we present a novel predicate learning procedure that uses HB-Formulas representing abstract counterexamples to accelerate counterexample-guided abstraction refinement (CEGAR). In each iteration of the CEGAR loop, the procedure refines the abstraction to eliminate multiple spurious abstract counterexamples drawn from the HB-Formula.
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Samanta, Roopsha
AU - Tarrach, Thorsten
ID - 1992
SN - 978-1-4503-3300-9
TI - Succinct representation of concurrent trace sets
ER -
TY - JOUR
AB - The fitness effects of symbionts on their hosts can be context-dependent, with usually benign symbionts causing detrimental effects when their hosts are stressed, or typically parasitic symbionts providing protection towards their hosts (e.g. against pathogen infection). Here, we studied the novel association between the invasive garden ant Lasius neglectus and its fungal ectosymbiont Laboulbenia formicarum for potential costs and benefits. We tested ants with different Laboulbenia levels for their survival and immunity under resource limitation and exposure to the obligate killing entomopathogen Metarhizium brunneum. While survival of L. neglectus workers under starvation was significantly decreased with increasing Laboulbenia levels, host survival under Metarhizium exposure increased with higher levels of the ectosymbiont, suggesting a symbiont-mediated anti-pathogen protection, which seems to be driven mechanistically by both improved sanitary behaviours and an upregulated immune system. Ants with high Laboulbenia levels showed significantly longer self-grooming and elevated expression of immune genes relevant for wound repair and antifungal responses (β-1,3-glucan binding protein, Prophenoloxidase), compared with ants carrying low Laboulbenia levels. This suggests that the ectosymbiont Laboulbenia formicarum weakens its ant host by either direct resource exploitation or the costs of an upregulated behavioural and immunological response, which, however, provides a prophylactic protection upon later exposure to pathogens.
AU - Konrad, Matthias
AU - Grasse, Anna V
AU - Tragust, Simon
AU - Cremer, Sylvia
ID - 1993
IS - 1799
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Anti-pathogen protection versus survival costs mediated by an ectosymbiont in an ant host
VL - 282
ER -
TY - JOUR
AB - We prove that the three-state toric homogeneous Markov chain model has Markov degree two. In algebraic terminology this means, that a certain class of toric ideals is generated by quadratic binomials. This was conjectured by Haws, Martin del Campo, Takemura and Yoshida, who proved that they are generated by degree six binomials.
AU - Noren, Patrik
ID - 1997
IS - May-June
JF - Journal of Symbolic Computation
TI - The three-state toric homogeneous Markov chain model has Markov degree two
VL - 68/Part 2
ER -
TY - JOUR
AB - The monotone secant conjecture posits a rich class of polynomial systems, all of whose solutions are real. These systems come from the Schubert calculus on flag manifolds, and the monotone secant conjecture is a compelling generalization of the Shapiro conjecture for Grassmannians (Theorem of Mukhin, Tarasov, and Varchenko). We present some theoretical evidence for this conjecture, as well as computational evidence obtained by 1.9 teraHertz-years of computing, and we discuss some of the phenomena we observed in our data.
AU - Hein, Nicolas
AU - Hillar, Christopher
AU - Martin Del Campo Sanchez, Abraham
AU - Sottile, Frank
AU - Teitler, Zach
ID - 2006
IS - 3
JF - Experimental Mathematics
TI - The monotone secant conjecture in the real Schubert calculus
VL - 24
ER -
TY - JOUR
AB - The paper describes a generalized iterative proportional fitting procedure that can be used for maximum likelihood estimation in a special class of the general log-linear model. The models in this class, called relational, apply to multivariate discrete sample spaces that do not necessarily have a Cartesian product structure and may not contain an overall effect. When applied to the cell probabilities, the models without the overall effect are curved exponential families and the values of the sufficient statistics are reproduced by the MLE only up to a constant of proportionality. The paper shows that Iterative Proportional Fitting, Generalized Iterative Scaling, and Improved Iterative Scaling fail to work for such models. The algorithm proposed here is based on iterated Bregman projections. As a by-product, estimates of the multiplicative parameters are also obtained. An implementation of the algorithm is available as an R-package.
AU - Klimova, Anna
AU - Rudas, Tamás
ID - 2008
IS - 3
JF - Scandinavian Journal of Statistics
TI - Iterative scaling in curved exponential families
VL - 42
ER -
TY - JOUR
AB - The concepts of faithfulness and strong-faithfulness are important for statistical learning of graphical models. Graphs are not sufficient for describing the association structure of a discrete distribution. Hypergraphs representing hierarchical log-linear models are considered instead, and the concept of parametric (strong-) faithfulness with respect to a hypergraph is introduced. Strong-faithfulness ensures the existence of uniformly consistent parameter estimators and enables building uniformly consistent procedures for a hypergraph search. The strength of association in a discrete distribution can be quantified with various measures, leading to different concepts of strong-faithfulness. Lower and upper bounds for the proportions of distributions that do not satisfy strong-faithfulness are computed for different parameterizations and measures of association.
AU - Klimova, Anna
AU - Uhler, Caroline
AU - Rudas, Tamás
ID - 2014
IS - 7
JF - Computational Statistics & Data Analysis
TI - Faithfulness and learning hypergraphs from discrete distributions
VL - 87
ER -
TY - JOUR
AB - Small GTP-binding proteins of the Ras superfamily play diverse roles in intracellular trafficking. Among them, the Rab, Arf, and Rho families function in successive steps of vesicle transport, in forming vesicles from donor membranes, directing vesicle trafficking toward target membranes and docking vesicles onto target membranes. These proteins act as molecular switches that are controlled by a cycle of GTP binding and hydrolysis regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In this study we explored the role of GAPs in the regulation of the endocytic pathway using fluorescently labeled yeast mating pheromone α-factor. Among 25 non-essential GAP mutants, we found that deletion of the GLO3 gene, encoding Arf-GAP protein, caused defective internalization of fluorescently labeled α-factor. Quantitative analysis revealed that glo3Δ cells show defective α-factor binding to the cell surface. Interestingly, Ste2p, the α-factor receptor, was mis-localized from the plasma membrane to the vacuole in glo3Δ cells. Domain deletion mutants of Glo3p revealed that a GAP-independent function, as well as the GAP activity, of Glo3p is important for both α-factor binding and Ste2p localization at the cell surface. Additionally, we found that deletion of the GLO3 gene affects the size and number of Arf1p-residing Golgi compartments and causes a defect in transport from the TGN to the plasma membrane. Furthermore, we demonstrated that glo3Δ cells were defective in the late endosome-to-TGN transport pathway, but not in the early endosome-to-TGN transport pathway. These findings suggest novel roles for Arf-GAP Glo3p in endocytic recycling of cell surface proteins.
AU - Kawada, Daiki
AU - Kobayashi, Hiromu
AU - Tomita, Tsuyoshi
AU - Nakata, Eisuke
AU - Nagano, Makoto
AU - Siekhaus, Daria E
AU - Toshima, Junko
AU - Toshimaa, Jiro
ID - 2025
IS - 1
JF - Biochimica et Biophysica Acta - Molecular Cell Research
TI - The yeast Arf-GAP Glo3p is required for the endocytic recycling of cell surface proteins
VL - 1853
ER -
TY - JOUR
AB - A hybrid-parallel direct-numerical-simulation method with application to turbulent Taylor-Couette flow is presented. The Navier-Stokes equations are discretized in cylindrical coordinates with the spectral Fourier-Galerkin method in the axial and azimuthal directions, and high-order finite differences in the radial direction. Time is advanced by a second-order, semi-implicit projection scheme, which requires the solution of five Helmholtz/Poisson equations, avoids staggered grids and renders very small slip velocities. Nonlinear terms are evaluated with the pseudospectral method. The code is parallelized using a hybrid MPI-OpenMP strategy, which, compared with a flat MPI parallelization, is simpler to implement, allows to reduce inter-node communications and MPI overhead that become relevant at high processor-core counts, and helps to contain the memory footprint. A strong scaling study shows that the hybrid code maintains scalability up to more than 20,000 processor cores and thus allows to perform simulations at higher resolutions than previously feasible. In particular, it opens up the possibility to simulate turbulent Taylor-Couette flows at Reynolds numbers up to O(105). This enables to probe hydrodynamic turbulence in Keplerian flows in experimentally relevant regimes.
AU - Shi, Liang
AU - Rampp, Markus
AU - Hof, Björn
AU - Avila, Marc
ID - 2030
IS - 1
JF - Computers and Fluids
TI - A hybrid MPI-OpenMP parallel implementation for pseudospectral simulations with application to Taylor-Couette flow
VL - 106
ER -
TY - JOUR
AB - Opacity is a generic security property, that has been defined on (non-probabilistic) transition systems and later on Markov chains with labels. For a secret predicate, given as a subset of runs, and a function describing the view of an external observer, the value of interest for opacity is a measure of the set of runs disclosing the secret. We extend this definition to the richer framework of Markov decision processes, where non-deterministicchoice is combined with probabilistic transitions, and we study related decidability problems with partial or complete observation hypotheses for the schedulers. We prove that all questions are decidable with complete observation and ω-regular secrets. With partial observation, we prove that all quantitative questions are undecidable but the question whether a system is almost surely non-opaquebecomes decidable for a restricted class of ω-regular secrets, as well as for all ω-regular secrets under finite-memory schedulers.
AU - Bérard, Béatrice
AU - Chatterjee, Krishnendu
AU - Sznajder, Nathalie
ID - 2034
IS - 1
JF - Information Processing Letters
TI - Probabilistic opacity for Markov decision processes
VL - 115
ER -
TY - JOUR
AB - Considering a continuous self-map and the induced endomorphism on homology, we study the eigenvalues and eigenspaces of the latter. Taking a filtration of representations, we define the persistence of the eigenspaces, effectively introducing a hierarchical organization of the map. The algorithm that computes this information for a finite sample is proved to be stable, and to give the correct answer for a sufficiently dense sample. Results computed with an implementation of the algorithm provide evidence of its practical utility.
AU - Edelsbrunner, Herbert
AU - Jablonski, Grzegorz
AU - Mrozek, Marian
ID - 2035
IS - 5
JF - Foundations of Computational Mathematics
TI - The persistent homology of a self-map
VL - 15
ER -
TY - JOUR
AB - We study the spectrum of a large system of N identical bosons interacting via a two-body potential with strength 1/N. In this mean-field regime, Bogoliubov's theory predicts that the spectrum of the N-particle Hamiltonian can be approximated by that of an effective quadratic Hamiltonian acting on Fock space, which describes the fluctuations around a condensed state. Recently, Bogoliubov's theory has been justified rigorously in the case that the low-energy eigenvectors of the N-particle Hamiltonian display complete condensation in the unique minimizer of the corresponding Hartree functional. In this paper, we shall justify Bogoliubov's theory for the high-energy part of the spectrum of the N-particle Hamiltonian corresponding to (non-linear) excited states of the Hartree functional. Moreover, we shall extend the existing results on the excitation spectrum to the case of non-uniqueness and/or degeneracy of the Hartree minimizer. In particular, the latter covers the case of rotating Bose gases, when the rotation speed is large enough to break the symmetry and to produce multiple quantized vortices in the Hartree minimizer.
AU - Nam, Phan
AU - Seiringer, Robert
ID - 2085
IS - 2
JF - Archive for Rational Mechanics and Analysis
TI - Collective excitations of Bose gases in the mean-field regime
VL - 215
ER -
TY - JOUR
AB - We consider the spectral statistics of large random band matrices on mesoscopic energy scales. We show that the correlation function of the local eigenvalue density exhibits a universal power law behaviour that differs from the Wigner-Dyson- Mehta statistics. This law had been predicted in the physics literature by Altshuler and Shklovskii in (Zh Eksp Teor Fiz (Sov Phys JETP) 91(64):220(127), 1986); it describes the correlations of the eigenvalue density in general metallic sampleswith weak disorder. Our result rigorously establishes the Altshuler-Shklovskii formulas for band matrices. In two dimensions, where the leading term vanishes owing to an algebraic cancellation, we identify the first non-vanishing term and show that it differs substantially from the prediction of Kravtsov and Lerner in (Phys Rev Lett 74:2563-2566, 1995). The proof is given in the current paper and its companion (Ann. H. Poincaré. arXiv:1309.5107, 2014).
AU - Erdös, László
AU - Knowles, Antti
ID - 2166
IS - 3
JF - Communications in Mathematical Physics
TI - The Altshuler-Shklovskii formulas for random band matrices I: the unimodular case
VL - 333
ER -
TY - JOUR
AB - A class of valued constraint satisfaction problems (VCSPs) is characterised by a valued constraint language, a fixed set of cost functions on a finite domain. Finite-valued constraint languages contain functions that take on rational costs and general-valued constraint languages contain functions that take on rational or infinite costs. An instance of the problem is specified by a sum of functions from the language with the goal to minimise the sum. This framework includes and generalises well-studied constraint satisfaction problems (CSPs) and maximum constraint satisfaction problems (Max-CSPs).
Our main result is a precise algebraic characterisation of valued constraint languages whose instances can be solved exactly by the basic linear programming relaxation (BLP). For a general-valued constraint language Γ, BLP is a decision procedure for Γ if and only if Γ admits a symmetric fractional polymorphism of every arity. For a finite-valued constraint language Γ, BLP is a decision procedure if and only if Γ admits a symmetric fractional polymorphism of some arity, or equivalently, if Γ admits a symmetric fractional polymorphism of arity 2.
Using these results, we obtain tractability of several novel and previously widely-open classes of VCSPs, including problems over valued constraint languages that are: (1) submodular on arbitrary lattices; (2) bisubmodular (also known as k-submodular) on arbitrary finite domains; (3) weakly (and hence strongly) tree-submodular on arbitrary trees.
AU - Kolmogorov, Vladimir
AU - Thapper, Johan
AU - Živný, Stanislav
ID - 2271
IS - 1
JF - SIAM Journal on Computing
TI - The power of linear programming for general-valued CSPs
VL - 44
ER -
TY - JOUR
AB - We show that a non-singular integral form of degree d is soluble over the integers if and only if it is soluble over ℝ and over ℚp for all primes p, provided that the form has at least (d - 1/2 √d)2d variables. This improves on a longstanding result of Birch.
AU - Timothy Browning
AU - Prendiville, Sean M
ID - 256
IS - 731
JF - Journal fur die Reine und Angewandte Mathematik
TI - Improvements in Birch's theorem on forms in many variables
VL - 2017
ER -
TY - JOUR
AB - For suitable pairs of diagonal quadratic forms in eight variables we use the circle method to investigate the density of simultaneous integer solutions and relate this to the problem of estimating linear correlations among sums of two squares.
AU - Timothy Browning
AU - Munshi, Ritabrata
ID - 257
IS - 4
JF - Forum Mathematicum
TI - Pairs of diagonal quadratic forms and linear correlations among sums of two squares
VL - 27
ER -
TY - CHAP
AB - Given a number field k and a projective algebraic variety X defined over k, the question of whether X contains a k-rational point is both very natural and very difficult. In the event that the set X(k) of k-rational points is not empty, one can also ask how the points of X(k) are distributed. Are they dense in X under the Zariski topology? Are they dense in the set.
AU - Browning, Timothy D
ID - 258
T2 - Arithmetic and Geometry
TI - A survey of applications of the circle method to rational points
ER -
TY - JOUR
AB - The Hasse principle and weak approximation is established for non-singular cubic hypersurfaces X over the function field
AU - Timothy Browning
AU - Vishe, Pankaj
ID - 259
IS - 3
JF - Geometric and Functional Analysis
TI - Rational points on cubic hypersurfaces over F_q(t)
VL - 25
ER -
TY - JOUR
AU - Timothy Browning
AU - Dietmann, Rainer
AU - Heath-Brown, Roger
ID - 260
IS - 4
JF - Journal of the Institute of Mathematics of Jussieu
TI - Erratum Rational points on intersections of cubic and quadric hypersurfaces
VL - 14
ER -
TY - JOUR
AB - The rational design of monodisperse ferroelectric nanocrystals with controlled size and shape and their organization into hierarchical structures has been a critical step for understanding the polar ordering in nanoscale ferroelectrics, as well as the design of nanocrystal-based functional materials which harness the properties of individual nanoparticles and the collective interactions between them. We report here on the synthesis and self-assembly of aggregate-free, single-crystalline titanium-based perovskite nanoparticles with controlled morphology and surface composition by using a simple, easily scalable and highly versatile colloidal route. Single-crystalline, non-aggregated BaTiO3 colloidal nanocrystals, used as a model system, have been prepared under solvothermal conditions at temperatures as low as 180 °C. The shape of the nanocrystals was tuned from spheroidal to cubic upon changing the polarity of the solvent, whereas their size was varied from 16 to 30 nm for spheres and 5 to 78 nm for cubes by changing the concentration of the precursors and the reaction time, respectively. The hydrophobic, oleic acid-passivated nanoparticles exhibit very good solubility in non-polar solvents and can be rendered dispersible in polar solvents by a simple process involving the oxidative cleavage of the double bond upon treating the nanopowders with the Lemieux–von Rudloff reagent. Lattice dynamic analysis indicated that regardless of their size, BaTiO3 nanocrystals present local disorder within the perovskite unit cell, associated with the existence of polar ordering. We also demonstrate for the first time that, in addition to being used for fabricating large area, crack-free, highly uniform films, BaTiO3 nanocubes can serve as building blocks for the design of 2D and 3D mesoscale structures, such as superlattices and superparticles. Interestingly, the type of superlattice structure (simple cubic or face centered cubic) appears to be determined by the type of solvent in which the nanocrystals were dispersed. This approach provides an excellent platform for the synthesis of other titanium-based perovskite colloidal nanocrystals with controlled chemical composition, surface structure and morphology and for their assembly into complex architectures, therefore opening the door for the design of novel mesoscale functional materials/nanocomposites with potential applications in energy conversion, data storage and the biomedical field.
AU - Caruntu, Daniela
AU - Rostamzadeh, Taha
AU - Costanzo, Tommaso
AU - Salemizadeh Parizi, Saman
AU - Caruntu, Gabriel
ID - 7456
IS - 30
JF - Nanoscale
SN - 2040-3364
TI - Solvothermal synthesis and controlled self-assembly of monodisperse titanium-based perovskite colloidal nanocrystals
VL - 7
ER -
TY - JOUR
AB - A new organic–inorganic ferroelectric hybrid capacitor designed by uniformly incorporating surface modified monodisperse 15 nm ferroelectric BaTiO3 nanocubes into non-polar polymer blends of poly(methyl methacrylate) (PMMA) polymer and acrylonitrile-butadiene-styrene (ABS) terpolymer is described. The investigation of spatial distribution of nanofillers via a non-distractive thermal pulse method illustrates that the surface functionalization of nanocubes plays a key role in the uniform distribution of charge polarization within the polymer matrix. The discharged energy density of the nanocomposite with 30 vol% BaTiO3 nanocubes is ∼44 × 10−3 J cm−3, which is almost six times higher than that of the neat polymer. The facile processing, along with the superior mechanical and electrical properties of the BaTiO3/PMMA–ABS nanocomposites make them suitable for implementation into capacitive electrical energy storage devices.
AU - Parizi, Saman Salemizadeh
AU - Conley, Gavin
AU - Costanzo, Tommaso
AU - Howell, Bob
AU - Mellinger, Axel
AU - Caruntu, Gabriel
ID - 7457
IS - 93
JF - RSC Advances
SN - 2046-2069
TI - Fabrication of barium titanate/acrylonitrile-butadiene styrene/poly(methyl methacrylate) nanocomposite films for hybrid ferroelectric capacitors
VL - 5
ER -
TY - JOUR
AB - Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic variation in different populations? Great tits (Parus major) have been studied extensively in long‐term studies across Europe and consequently are considered an ecological ‘model organism’. Recently, genomic resources have been developed for the great tit, including a custom SNP chip and genetic linkage map. In this study, we used a suite of approaches to investigate the genetic architecture of eight quantitative traits in two long‐term study populations of great tits—one in the Netherlands and the other in the United Kingdom. Overall, we found little evidence for the presence of genes of large effects in either population. Instead, traits appeared to be influenced by many genes of small effect, with conservative estimates of the number of contributing loci ranging from 31 to 310. Despite concordance between population‐specific heritabilities, we found no evidence for the presence of loci having similar effects in both populations. While population‐specific genetic architectures are possible, an undetected shared architecture cannot be rejected because of limited power to map loci of small and moderate effects. This study is one of few examples of genetic architecture analysis in replicated wild populations and highlights some of the challenges and limitations researchers will face when attempting similar molecular quantitative genetic studies in free‐living populations.
AU - Santure, Anna W.
AU - Poissant, Jocelyn
AU - De Cauwer, Isabelle
AU - van Oers, Kees
AU - Robinson, Matthew Richard
AU - Quinn, John L.
AU - Groenen, Martien A. M.
AU - Visser, Marcel E.
AU - Sheldon, Ben C.
AU - Slate, Jon
ID - 7739
JF - Molecular Ecology
SN - 0962-1083
TI - Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations
VL - 24
ER -
TY - JOUR
AB - Phenotypes expressed in a social context are not only a function of the individual, but can also be shaped by the phenotypes of social partners. These social effects may play a major role in the evolution of cooperative breeding if social partners differ in the quality of care they provide and if individual carers adjust their effort in relation to that of other carers. When applying social effects models to wild study systems, it is also important to explore sources of individual plasticity that could masquerade as social effects. We studied offspring provisioning rates of parents and helpers in a wild population of long-tailed tits Aegithalos caudatus using a quantitative genetic framework to identify these social effects and partition them into genetic, permanent environment and current environment components. Controlling for other effects, individuals were consistent in their provisioning effort at a given nest, but adjusted their effort based on who was in their social group, indicating the presence of social effects. However, these social effects differed between years and social contexts, indicating a current environment effect, rather than indicating a genetic or permanent environment effect. While this study reveals the importance of examining environmental and genetic sources of social effects, the framework we present is entirely general, enabling a greater understanding of potentially important social effects within any ecological population.
AU - Adams, Mark James
AU - Robinson, Matthew Richard
AU - Mannarelli, Maria-Elena
AU - Hatchwell, Ben J.
ID - 7741
IS - 1810
JF - Proceedings of the Royal Society B: Biological Sciences
SN - 0962-8452
TI - Social genetic and social environment effects on parental and helper care in a cooperatively breeding bird
VL - 282
ER -
TY - JOUR
AB - Across-nation differences in the mean values for complex traits are common1,2,3,4,5,6,7,8, but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 × 10−8; BMI, P < 5.95 × 10−4), and we find an among-population genetic correlation for tall and slender individuals (r = −0.80, 95% CI = −0.95, −0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).
AU - Robinson, Matthew Richard
AU - Hemani, Gibran
AU - Medina-Gomez, Carolina
AU - Mezzavilla, Massimo
AU - Esko, Tonu
AU - Shakhbazov, Konstantin
AU - Powell, Joseph E
AU - Vinkhuyzen, Anna
AU - Berndt, Sonja I
AU - Gustafsson, Stefan
AU - Justice, Anne E
AU - Kahali, Bratati
AU - Locke, Adam E
AU - Pers, Tune H
AU - Vedantam, Sailaja
AU - Wood, Andrew R
AU - van Rheenen, Wouter
AU - Andreassen, Ole A
AU - Gasparini, Paolo
AU - Metspalu, Andres
AU - Berg, Leonard H van den
AU - Veldink, Jan H
AU - Rivadeneira, Fernando
AU - Werge, Thomas M
AU - Abecasis, Goncalo R
AU - Boomsma, Dorret I
AU - Chasman, Daniel I
AU - de Geus, Eco J C
AU - Frayling, Timothy M
AU - Hirschhorn, Joel N
AU - Hottenga, Jouke Jan
AU - Ingelsson, Erik
AU - Loos, Ruth J F
AU - Magnusson, Patrik K E
AU - Martin, Nicholas G
AU - Montgomery, Grant W
AU - North, Kari E
AU - Pedersen, Nancy L
AU - Spector, Timothy D
AU - Speliotes, Elizabeth K
AU - Goddard, Michael E
AU - Yang, Jian
AU - Visscher, Peter M
ID - 7742
IS - 11
JF - Nature Genetics
SN - 1061-4036
TI - Population genetic differentiation of height and body mass index across Europe
VL - 47
ER -
TY - CONF
AB - High-performance concurrent priority queues are essential for applications such as task scheduling and discrete event simulation. Unfortunately, even the best performing implementations do not scale past a number of threads in the single digits. This is because of the sequential bottleneck in accessing the elements at the head of the queue in order to perform a DeleteMin operation. In this paper, we present the SprayList, a scalable priority queue with relaxed ordering semantics. Starting from a non-blocking SkipList, the main innovation behind our design is that the DeleteMin operations avoid a sequential bottleneck by "spraying" themselves onto the head of the SkipList list in a coordinated fashion. The spraying is implemented using a carefully designed random walk, so that DeleteMin returns an element among the first O(plog3p) in the list, with high probability, where p is the number of threads. We prove that the running time of a DeleteMin operation is O(log3p), with high probability, independent of the size of the list. Our experiments show that the relaxed semantics allow the data structure to scale for high thread counts, comparable to a classic unordered SkipList. Furthermore, we observe that, for reasonably parallel workloads, the scalability benefits of relaxation considerably outweigh the additional work due to out-of-order execution.
AU - Alistarh, Dan
AU - Kopinsky, Justin
AU - Li, Jerry
AU - Shavit, Nir N
ID - 776
TI - The SprayList: A scalable relaxed priority queue
VL - 2015-January
ER -
TY - JOUR
AB - We introduce a principle unique to disordered solids wherein the contribution of any bond to one global perturbation is uncorrelated with its contribution to another. Coupled with sufficient variability in the contributions of different bonds, this “independent bond-level response” paves the way for the design of real materials with unusual and exquisitely tuned properties. To illustrate this, we choose two global perturbations: compression and shear. By applying a bond removal procedure that is both simple and experimentally relevant to remove a very small fraction of bonds, we can drive disordered spring networks to both the incompressible and completely auxetic limits of mechanical behavior.
AU - Goodrich, Carl Peter
AU - Liu, Andrea J.
AU - Nagel, Sidney R.
ID - 7765
IS - 22
JF - Physical Review Letters
SN - 0031-9007
TI - The principle of independent bond-level response: Tuning by pruning to exploit disorder for global behavior
VL - 114
ER -
TY - JOUR
AB - We study the vibrational properties near a free surface of disordered spring networks derived from jammed sphere packings. In bulk systems, without surfaces, it is well understood that such systems have a plateau in the density of vibrational modes extending down to a frequency scale ω*. This frequency is controlled by ΔZ = 〈Z〉 − 2d, the difference between the average coordination of the spheres and twice the spatial dimension, d, of the system, which vanishes at the jamming transition. In the presence of a free surface we find that there is a density of disordered vibrational modes associated with the surface that extends far below ω*. The total number of these low-frequency surface modes is controlled by ΔZ, and the profile of their decay into the bulk has two characteristic length scales, which diverge as ΔZ−1/2 and ΔZ−1 as the jamming transition is approached.
AU - Sussman, Daniel M.
AU - Goodrich, Carl Peter
AU - Liu, Andrea J.
AU - Nagel, Sidney R.
ID - 7766
IS - 14
JF - Soft Matter
SN - 1744-683X
TI - Disordered surface vibrations in jammed sphere packings
VL - 11
ER -
TY - JOUR
AB - We present a model of soft active particles that leads to a rich array of collective behavior found also in dense biological swarms of bacteria and other unicellular organisms. Our model uses only local interactions, such as Vicsek-type nearest-neighbor alignment, short-range repulsion, and a local boundary term. Changing the relative strength of these interactions leads to migrating swarms, rotating swarms, and jammed swarms, as well as swarms that exhibit run-and-tumble motion, alternating between migration and either rotating or jammed states. Interestingly, although a migrating swarm moves slower than an individual particle, the diffusion constant can be up to three orders of magnitude larger, suggesting that collective motion can be highly advantageous, for example, when searching for food.
AU - van Drongelen, Ruben
AU - Pal, Anshuman
AU - Goodrich, Carl Peter
AU - Idema, Timon
ID - 7767
IS - 3
JF - Physical Review E
SN - 1539-3755
TI - Collective dynamics of soft active particles
VL - 91
ER -
TY - CONF
AB - In many applications, the data is of rich structure that can be represented by a hypergraph, where the data items are represented by vertices and the associations among items are represented by hyperedges. Equivalently, we are given an input bipartite graph with two types of vertices: items, and associations (which we refer to as topics). We consider the problem of partitioning the set of items into a given number of components such that the maximum number of topics covered by a component is minimized. This is a clustering problem with various applications, e.g. partitioning of a set of information objects such as documents, images, and videos, and load balancing in the context of modern computation platforms.Inthis paper, we focus on the streaming computation model for this problem, in which items arrive online one at a time and each item must be assigned irrevocably to a component at its arrival time. Motivated by scalability requirements, we focus on the class of streaming computation algorithms with memory limited to be at most linear in the number of components. We show that a greedy assignment strategy is able to recover a hidden co-clustering of items under a natural set of recovery conditions. We also report results of an extensive empirical evaluation, which demonstrate that this greedy strategy yields superior performance when compared with alternative approaches.
AU - Alistarh, Dan
AU - Iglesias, Jennifer
AU - Vojnović, Milan
ID - 777
TI - Streaming min-max hypergraph partitioning
VL - 2015-January
ER -
TY - GEN
AB - The fact that a disordered material is not constrained in its properties in
the same way as a crystal presents significant and yet largely untapped
potential for novel material design. However, unlike their crystalline
counterparts, disordered solids are not well understood. One of the primary
obstacles is the lack of a theoretical framework for thinking about disorder
and its relation to mechanical properties. To this end, we study an idealized
system of frictionless athermal soft spheres that, when compressed, undergoes a
jamming phase transition with diverging length scales and clean power-law
signatures. This critical point is the cornerstone of a much larger "jamming
scenario" that has the potential to provide the essential theoretical
foundation necessary for a unified understanding of the mechanics of disordered
solids. We begin by showing that jammed sphere packings have a valid linear
regime despite the presence of "contact nonlinearities." We then investigate
the critical nature of the transition, focusing on diverging length scales and
finite-size effects. Next, we argue that jamming plays the same role for
disordered solids as the perfect crystal plays for crystalline solids. Not only
can it be considered an idealized starting point for understanding disordered
materials, but it can even influence systems that have a relatively high amount
of crystalline order. The behavior of solids can thus be thought of as existing
on a spectrum, with the perfect crystal and the jamming transition at opposing
ends. Finally, we introduce a new principle wherein the contribution of an
individual bond to one global property is independent of its contribution to
another. This principle allows the different global responses of a disordered
system to be manipulated independently and provides a great deal of flexibility
in designing materials with unique, textured and tunable properties.
AU - Goodrich, Carl Peter
ID - 7779
T2 - arXiv:1510.08820
TI - Unearthing the anticrystal: Criticality in the linear response of disordered solids
ER -
TY - CONF
AB - Several Hybrid Transactional Memory (HyTM) schemes have recently been proposed to complement the fast, but best-effort nature of Hardware Transactional Memory (HTM) with a slow, reliable software backup. However, the costs of providing concurrency between hardware and software transactions in HyTM are still not well understood. In this paper, we propose a general model for HyTM implementations, which captures the ability of hardware transactions to buffer memory accesses. The model allows us to formally quantify and analyze the amount of overhead (instrumentation) caused by the potential presence of software transactions.We prove that (1) it is impossible to build a strictly serializable HyTM implementation that has both uninstrumented reads and writes, even for very weak progress guarantees, and (2) the instrumentation cost incurred by a hardware transaction in any progressive opaque HyTM is linear in the size of the transaction’s data set.We further describe two implementations which exhibit optimal instrumentation costs for two different progress conditions. In sum, this paper proposes the first formal HyTM model and captures for the first time the trade-off between the degree of hardware-software TM concurrency and the amount of instrumentation overhead.
AU - Alistarh, Dan-Adrian
AU - Kopinsky, Justin
AU - Kuznetsov, Petr
AU - Ravi, Srivatsan
AU - Shavit, Nir
ID - 778
TI - Inherent limitations of hybrid transactional memory
VL - 9363
ER -
TY - CONF
AB - The concurrent memory reclamation problem is that of devising a way for a deallocating thread to verify that no other concurrent threads hold references to a memory block being deallocated. To date, in the absence of automatic garbage collection, there is no satisfactory solution to this problem; existing tracking methods like hazard pointers, reference counters, or epoch-based techniques like RCU, are either prohibitively expensive or require significant programming expertise, to the extent that implementing them efficiently can be worthy of a publication. None of the existing techniques are automatic or even semi-automated. In this paper, we take a new approach to concurrent memory reclamation: instead of manually tracking access to memory locations as done in techniques like hazard pointers, or restricting shared accesses to specific epoch boundaries as in RCU, our algorithm, called ThreadScan, leverages operating system signaling to automatically detect which memory locations are being accessed by concurrent threads. Initial empirical evidence shows that ThreadScan scales surprisingly well and requires negligible programming effort beyond the standard use of Malloc and Free.
AU - Alistarh, Dan
AU - Matveev, Alexander
AU - Leiserson, William M
AU - Shavit, Nir N
ID - 779
TI - ThreadScan: Automatic and scalable memory reclamation
VL - 2015-June
ER -
TY - CONF
AB - Population protocols are networks of finite-state agents, interacting randomly, and updating their states using simple rules. Despite their extreme simplicity, these systems have been shown to cooperatively perform complex computational tasks, such as simulating register machines to compute standard arithmetic functions. The election of a unique leader agent is a key requirement in such computational constructions. Yet, the fastest currently known population protocol for electing a leader only has linear convergence time, and it has recently been shown that no population protocol using a constant number of states per node may overcome this linear bound. In this paper, we give the first population protocol for leader election with polylogarithmic convergence time, using polylogarithmic memory states per node. The protocol structure is quite simple: each node has an associated value, and is either a leader (still in contention) or a minion (following some leader). A leader keeps incrementing its value and “defeats” other leaders in one-to-one interactions, and will drop from contention and become a minion if it meets a leader with higher value. Importantly, a leader also drops out if it meets a minion with higher absolute value. While these rules are quite simple, the proof that this algorithm achieves polylogarithmic convergence time is non-trivial. In particular, the argument combines careful use of concentration inequalities with anti-concentration bounds, showing that the leaders’ values become spread apart as the execution progresses, which in turn implies that straggling leaders get quickly eliminated. We complement our analysis with empirical results, showing that our protocol converges extremely fast, even for large network sizes.
AU - Alistarh, Dan-Adrian
AU - Gelashvili, Rati
ID - 780
TI - Polylogarithmic-time leader election in population protocols
VL - 9135
ER -
TY - CONF
AB - Population protocols, roughly defined as systems consisting of large numbers of simple identical agents, interacting at random and updating their state following simple rules, are an important research topic at the intersection of distributed computing and biology. One of the fundamental tasks that a population protocol may solve is majority: each node starts in one of two states; the goal is for all nodes to reach a correct consensus on which of the two states was initially the majority. Despite considerable research effort, known protocols for this problem are either exact but slow (taking linear parallel time to converge), or fast but approximate (with non-zero probability of error). In this paper, we show that this trade-off between preciasion and speed is not inherent. We present a new protocol called Average and Conquer (AVC) that solves majority ex-actly in expected parallel convergence time O(log n/(sε) + log n log s), where n is the number of nodes, εn is the initial node advantage of the majority state, and s = Ω(log n log log n) is the number of states the protocol employs. This shows that the majority problem can be solved exactly in time poly-logarithmic in n, provided that the memory per node is s = Ω(1/ε + lognlog1/ε). On the negative side, we establish a lower bound of Ω(1/ε) on the expected paraallel convergence time for the case of four memory states per node, and a lower bound of Ω(logn) parallel time for protocols using any number of memory states per node.per node, and a lower bound of (log n) parallel time for protocols using any number of memory states per node.
AU - Alistarh, Dan
AU - Gelashvili, Rati
AU - Vojnović, Milan
ID - 781
TI - Fast and exact majority in population protocols
VL - 2015-July
ER -
TY - CONF
AB - In this work, we consider the following random process, mo- Tivated by the analysis of lock-free concurrent algorithms under high memory contention. In each round, a new scheduling step is allocated to one of n threads, according to a distribution p = (p1; p2; : : : ; pn), where thread i is scheduled with probability pi. When some thread first reaches a set threshold of executed steps, it registers a win, completing its current operation, and resets its step count to 1. At the same time, threads whose step count was close to the threshold also get reset because of the win, but to 0 steps, being penalized for almost winning. We are interested in two questions: how often does some thread complete an operation (system latency), and how often does a specific thread complete an operation (individual latency)? We provide asymptotically tight bounds for the system and individual latency of this general concurrency pattern, for arbitrary scheduling distributions p. Surprisingly, a sim- ple characterization exists: in expectation, the system will complete a new operation every Θ(1/p 2) steps, while thread i will complete a new operation every Θ(1/2=p i ) steps. The proof is interesting in its own right, as it requires a careful analysis of how the higher norms of the vector p inuence the thread step counts and latencies in this random process. Our result offers a simple connection between the scheduling distribution and the average performance of concurrent algorithms, which has several applications.
AU - Alistarh, Dan
AU - Sauerwald, Thomas
AU - Vojnović, Milan
ID - 782
TI - Lock-Free algorithms under stochastic schedulers
VL - 2015-July
ER -
TY - CONF
AB - The problem of electing a leader from among n contenders is one of the fundamental questions in distributed computing. In its simplest formulation, the task is as follows: given n processors, all participants must eventually return a win or lose indication, such that a single contender may win. Despite a considerable amount of work on leader election, the following question is still open: can we elect a leader in an asynchronous fault-prone system faster than just running a Θ(log n)-time tournament, against a strong adaptive adversary? In this paper, we answer this question in the affirmative, improving on a decades-old upper bound. We introduce two new algorithmic ideas to reduce the time complexity of electing a leader to O(log∗ n), using O(n2) point-to-point messages. A non-trivial application of our algorithm is a new upper bound for the tight renaming problem, assigning n items to the n participants in expected O(log2 n) time and O(n2) messages. We complement our results with lower bound of Ω(n2) messages for solving these two problems, closing the question of their message complexity.
AU - Alistarh, Dan
AU - Gelashvili, Rati
AU - Vladu, Adrian V
ID - 783
TI - How to elect a leader faster than a tournament
VL - 2015-July
ER -
TY - CONF
AB - We demonstrate an optical switch design that can scale up to a thousand ports with high per-port bandwidth (25 Gbps+) and low switching latency (40 ns). Our design uses a broadcast and select architecture, based on a passive star coupler and fast tunable transceivers. In addition we employ time division multiplexing to achieve very low switching latency. Our demo shows the feasibility of the switch data plane using a small testbed, comprising two transmitters and a receiver, connected through a star coupler.
AU - Alistarh, Dan-Adrian
AU - Ballani, Hitesh
AU - Costa, Paolo
AU - Funnell, Adam
AU - Benjamin, Joshua
AU - Watts, Philip
AU - Thomsen, Benn
ID - 784
SN - 978-1-4503-3542-3
TI - A high-radix, low-latency optical switch for data centers
ER -
TY - JOUR
AB - We prove that nonlinear Gibbs measures can be obtained from the corresponding many-body, grand-canonical, quantum Gibbs states, in a mean-field limit where the temperature T diverges and the interaction strength behaves as 1/T. We proceed by characterizing the interacting Gibbs state as minimizing a functional counting the free-energy relatively to the non-interacting case. We then perform an infinite-dimensional analogue of phase-space semiclassical analysis, using fine properties of the quantum relative entropy, the link between quantum de Finetti measures and upper/lower symbols in a coherent state basis, as well as Berezin-Lieb type inequalities. Our results cover the measure built on the defocusing nonlinear Schrödinger functional on a finite interval, as well as smoother interactions in dimensions d 2.
AU - Lewin, Mathieu
AU - Phan Thanh, Nam
AU - Rougerie, Nicolas
ID - 473
JF - Journal de l'Ecole Polytechnique - Mathematiques
TI - Derivation of nonlinear gibbs measures from many-body quantum mechanics
VL - 2
ER -
TY - JOUR
AB - Dendritic cells are potent antigen-presenting cells endowed with the unique ability to initiate adaptive immune responses upon inflammation. Inflammatory processes are often associated with an increased production of serotonin, which operates by activating specific receptors. However, the functional role of serotonin receptors in regulation of dendritic cell functions is poorly understood. Here, we demonstrate that expression of serotonin receptor 5-HT7 (5-HT7TR) as well as its downstream effector Cdc42 is upregulated in dendritic cells upon maturation. Although dendritic cell maturation was independent of 5-HT7TR, receptor stimulation affected dendritic cell morphology through Cdc42-mediated signaling. In addition, basal activity of 5-HT7TR was required for the proper expression of the chemokine receptor CCR7, which is a key factor that controls dendritic cell migration. Consistent with this, we observed that 5-HT7TR enhances chemotactic motility of dendritic cells in vitro by modulating their directionality and migration velocity. Accordingly, migration of dendritic cells in murine colon explants was abolished after pharmacological receptor inhibition. Our results indicate that there is a crucial role for 5-HT7TR-Cdc42-mediated signaling in the regulation of dendritic cell morphology and motility, suggesting that 5-HT7TR could be a new target for treatment of a variety of inflammatory and immune disorders.
AU - Holst, Katrin
AU - Guseva, Daria
AU - Schindler, Susann
AU - Sixt, Michael K
AU - Braun, Armin
AU - Chopra, Himpriya
AU - Pabst, Oliver
AU - Ponimaskin, Evgeni
ID - 477
IS - 15
JF - Journal of Cell Science
TI - The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells
VL - 128
ER -
TY - JOUR
AB - We consider two-player games played on weighted directed graphs with mean-payoff and total-payoff objectives, two classical quantitative objectives. While for single-dimensional games the complexity and memory bounds for both objectives coincide, we show that in contrast to multi-dimensional mean-payoff games that are known to be coNP-complete, multi-dimensional total-payoff games are undecidable. We introduce conservative approximations of these objectives, where the payoff is considered over a local finite window sliding along a play, instead of the whole play. For single dimension, we show that (i) if the window size is polynomial, deciding the winner takes polynomial time, and (ii) the existence of a bounded window can be decided in NP ∩ coNP, and is at least as hard as solving mean-payoff games. For multiple dimensions, we show that (i) the problem with fixed window size is EXPTIME-complete, and (ii) there is no primitive-recursive algorithm to decide the existence of a bounded window.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Randour, Mickael
AU - Raskin, Jean
ID - 523
IS - 6
JF - Information and Computation
TI - Looking at mean-payoff and total-payoff through windows
VL - 242
ER -
TY - JOUR
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 each 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 of 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 that 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 turn-based deterministic mean-payoff games) that is not known to be solvable in polynomial time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 524
IS - 6
JF - Information and Computation
TI - Qualitative analysis of concurrent mean payoff games
VL - 242
ER -
TY - JOUR
AB - Ethylene is a gaseous phytohormone that plays vital roles in plant growth and development. Previous studies uncovered EIN2 as an essential signal transducer linking ethylene perception on ER to transcriptional regulation in the nucleus through a “cleave and shuttle” model. In this study, we report another mechanism of EIN2-mediated ethylene signaling, whereby EIN2 imposes the translational repression of EBF1 and EBF2 mRNA. We find that the EBF1/2 3′ UTRs mediate EIN2-directed translational repression and identify multiple poly-uridylates (PolyU) motifs as functional cis elements of 3′ UTRs. Furthermore, we demonstrate that ethylene induces EIN2 to associate with 3′ UTRs and target EBF1/2 mRNA to cytoplasmic processing-body (P-body) through interacting with multiple P-body factors, including EIN5 and PABs. Our study illustrates translational regulation as a key step in ethylene signaling and presents mRNA 3′ UTR functioning as a “signal transducer” to sense and relay cellular signaling in plants.
AU - Li, Wenyang
AU - Ma, Mengdi
AU - Feng, Ying
AU - Li, Hongjiang
AU - Wang, Yichuan
AU - Ma, Yutong
AU - Li, Mingzhe
AU - An, Fengying
AU - Guo, Hongwei
ID - 532
IS - 3
JF - Cell
TI - EIN2-directed translational regulation of ethylene signaling in arabidopsis
VL - 163
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives.
There have been two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector.
We consider the problem where the goal is to optimize the expectation under the constraint that the satisfaction semantics is ensured, and thus consider a generalization that unifies the existing semantics.
Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensures certain probabilistic guarantee).
Our main results are algorithms for the decision problem which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions.
Finally, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Komarkova, Zuzana
AU - Kretinsky, Jan
ID - 5429
SN - 2664-1690
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
ER -
TY - GEN
AB - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean- payoff property, the ratio property, and the minimum initial credit for energy property. The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let n denote the number of nodes of a graph, m the number of edges (for constant treewidth graphs m = O ( n ) ) and W the largest absolute value of the weights. Our main theoretical results are as follows. First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a mul- tiplicative factor of ∊ in time O ( n · log( n/∊ )) and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time O ( n · log( | a · b · n | )) = O ( n · log( n · W )) , when the output is a b , as compared to the previously best known algorithm with running time O ( n 2 · log( n · W )) . Third, for the minimum initial credit problem we show that (i) for general graphs the problem can be solved in O ( n 2 · m ) time and the associated decision problem can be solved in O ( n · m ) time, improving the previous known O ( n 3 · m · log( n · W )) and O ( n 2 · m ) bounds, respectively; and (ii) for constant treewidth graphs we present an algorithm that requires O ( n · log n ) time, improving the previous known O ( n 4 · log( n · W )) bound. We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5430
SN - 2664-1690
TI - Faster algorithms for quantitative verification in constant treewidth graphs
ER -
TY - GEN
AB - We consider finite-state concurrent stochastic games, played by k>=2 players for an infinite number of rounds, where in every round, each player simultaneously and independently of the other players chooses an action, whereafter the successor state is determined by a probability distribution given by the current state and the chosen actions. We consider reachability objectives that given a target set of states require that some state in the target set is visited, and the dual safety objectives that given a target set require that only states in the target set are visited. We are interested in the complexity of stationary strategies measured by their patience, which is defined as the inverse of the smallest non-zero probability employed.
Our main results are as follows: We show that in two-player zero-sum concurrent stochastic games (with reachability objective for one player and the complementary safety objective for the other player): (i) the optimal bound on the patience of optimal and epsilon-optimal strategies, for both players is doubly exponential; and (ii) even in games with a single non-absorbing state exponential (in the number of actions) patience is necessary. In general we study the class of non-zero-sum games admitting epsilon-Nash equilibria. We show that if there is at least one player with reachability objective, then doubly-exponential patience is needed in general for epsilon-Nash equilibrium strategies, whereas in contrast if all players have safety objectives, then the optimal bound on patience for epsilon-Nash equilibrium strategies is only exponential.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Hansen, Kristoffer
ID - 5431
SN - 2664-1690
TI - The patience of concurrent stochastic games with safety and reachability objectives
ER -
TY - GEN
AB - Evolution occurs in populations of reproducing individuals. The structure of the population affects the outcome of the evolutionary process. Evolutionary graph theory is a powerful approach to study this phenomenon. There are two graphs. The interaction graph specifies who interacts with whom in the context of evolution.The replacement graph specifies who competes with whom for reproduction.
The vertices of the two graphs are the same, and each vertex corresponds to an individual of the population. A key quantity is the fixation probability of a new mutant. It is defined as the probability that a newly introduced mutant (on a single vertex) generates a lineage of offspring which eventually takes over the entire population of resident individuals. The basic computational questions are as follows: (i) the qualitative question asks whether the fixation probability is positive; and (ii) the quantitative approximation question asks for an approximation of the fixation probability.
Our main results are:
(1) We show that the qualitative question is NP-complete and the quantitative approximation question is #P-hard in the special case when the interaction and the replacement graphs coincide and even with the restriction that the resident individuals do not reproduce (which corresponds to an invading population taking over an empty structure).
(2) We show that in general the qualitative question is PSPACE-complete and the quantitative approximation question is PSPACE-hard and can be solved in exponential time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Nowak, Martin
ID - 5432
SN - 2664-1690
TI - The complexity of evolutionary games on graphs
ER -
TY - GEN
AB - DEC-POMDPs extend POMDPs to a multi-agent setting, where several agents operate in an uncertain environment independently to achieve a joint objective. DEC-POMDPs have been studied with finite-horizon and infinite-horizon discounted-sum objectives, and there exist solvers both for exact and approximate solutions. In this work we consider Goal-DEC-POMDPs, where given a set of target states, the objective is to ensure that the target set is reached with minimal cost. We consider the indefinite-horizon (infinite-horizon with either discounted-sum, or undiscounted-sum, where absorbing goal states have zero-cost) problem. We present a new method to solve the problem that extends methods for finite-horizon DEC- POMDPs and the RTDP-Bel approach for POMDPs. We present experimental results on several examples, and show our approach presents promising results.
AU - Anonymous, 1
AU - Anonymous, 2
ID - 5434
SN - 2664-1690
TI - Optimal cost indefinite-horizon reachability in goal DEC-POMDPs
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives.
There have been two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector.
We consider the problem where the goal is to optimize the expectation under the constraint that the satisfaction semantics is ensured, and thus consider a generalization that unifies the existing semantics. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensures certain probabilistic guarantee).
Our main results are algorithms for the decision problem which are always polynomial in the size of the MDP.
We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Finally, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Komarkova, Zuzana
AU - Kretinsky, Jan
ID - 5435
SN - 2664-1690
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
ER -
TY - GEN
AB - Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata, nor in any other know decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata which makes it possible to express important quantitative properties such as average response time.
In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in run-time verification. We establish an almost complete decidability picture for the basic decision problems about nested weighted automata, and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5436
SN - 2664-1690
TI - Nested weighted automata
ER -
TY - GEN
AB - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean-payoff property, the ratio property, and the minimum initial credit for energy property.
The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let $n$ denote the number of nodes of a graph, $m$ the number of edges (for constant treewidth graphs $m=O(n)$) and $W$ the largest absolute value of the weights.
Our main theoretical results are as follows.
First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a multiplicative factor of $\epsilon$ in time $O(n \cdot \log (n/\epsilon))$ and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time $O(n \cdot \log (|a\cdot b|))=O(n\cdot\log (n\cdot W))$, when the output is $\frac{a}{b}$, as compared to the previously best known algorithm with running time $O(n^2 \cdot \log (n\cdot W))$. Third, for the minimum initial credit problem we show that (i)~for general graphs the problem can be solved in $O(n^2\cdot m)$ time and the associated decision problem can be solved in $O(n\cdot m)$ time, improving the previous known $O(n^3\cdot m\cdot \log (n\cdot W))$ and $O(n^2 \cdot m)$ bounds, respectively; and (ii)~for constant treewidth graphs we present an algorithm that requires $O(n\cdot \log n)$ time, improving the previous known $O(n^4 \cdot \log (n \cdot W))$ bound.
We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5437
SN - 2664-1690
TI - Faster algorithms for quantitative verification in constant treewidth graphs
ER -
TY - GEN
AB - The edit distance between two words w1, w2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w1 to w2. The edit distance generalizes to languages L1, L2, where the edit distance is the minimal number k such that for every word from L1 there exists a word in L2 with edit distance at most k. We study the edit distance computation problem between pushdown automata and their subclasses.
The problem of computing edit distance to a pushdown automaton is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for deciding whether, for a given threshold k, the edit distance from a pushdown automaton to a finite automaton is at most k.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Ibsen-Jensen, Rasmus
AU - Otop, Jan
ID - 5438
SN - 2664-1690
TI - Edit distance for pushdown automata
ER -
TY - GEN
AB - The target discounted-sum problem is the following: Given a rational discount factor 0 < λ < 1 and three rational values a, b, and t, does there exist a finite or an infinite sequence w ε(a, b)∗ or w ε(a, b)w, such that Σ|w| i=0 w(i)λi equals t? The problem turns out to relate to many fields of mathematics and computer science, and its decidability question is surprisingly hard to solve. We solve the finite version of the problem, and show the hardness of the infinite version, linking it to various areas and open problems in mathematics and computer science: β-expansions, discounted-sum automata, piecewise affine maps, and generalizations of the Cantor set. We provide some partial results to the infinite version, among which are solutions to its restriction to eventually-periodic sequences and to the cases that λ λ 1/2 or λ = 1/n, for every n ε N. We use our results for solving some open problems on discounted-sum automata, among which are the exact-value problem for nondeterministic automata over finite words and the universality and inclusion problems for functional automata.
AU - Boker, Udi
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5439
SN - 2664-1690
TI - The target discounted-sum problem
ER -
TY - GEN
AB - Evolution occurs in populations of reproducing individuals. The structure of the population affects the outcome of the evolutionary process. Evolutionary graph theory is a powerful approach to study this phenomenon. There are two graphs. The interaction graph specifies who interacts with whom for payoff in the context of evolution. The replacement graph specifies who competes with whom for reproduction. The vertices of the two graphs are the same, and each vertex corresponds to an individual of the population. The fitness (or the reproductive rate) is a non-negative number, and depends on the payoff. A key quantity is the fixation probability of a new mutant. It is defined as the probability that a newly introduced mutant (on a single vertex) generates a lineage of offspring which eventually takes over the entire population of resident individuals. The basic computational questions are as follows: (i) the qualitative question asks whether the fixation probability is positive; and (ii) the quantitative approximation question asks for an approximation of the fixation probability. Our main results are as follows: First, we consider a special case of the general problem, where the residents do not reproduce. We show that the qualitative question is NP-complete, and the quantitative approximation question is #P-complete, and the hardness results hold even in the special case where the interaction and the replacement graphs coincide. Second, we show that in general both the qualitative and the quantitative approximation questions are PSPACE-complete. The PSPACE-hardness result for quantitative approximation holds even when the fitness is always positive.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Nowak, Martin
ID - 5440
SN - 2664-1690
TI - The complexity of evolutionary games on graphs
ER -
TY - GEN
AB - We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time. Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Goharshady, Amir
AU - Pavlogiannis, Andreas
ID - 5441
SN - 2664-1690
TI - Algorithms for algebraic path properties in concurrent systems of constant treewidth components
ER -
TY - GEN
AB - We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural properties that arise in program analysis.
We consider that each component of the concurrent system is a graph with constant treewidth, and it is known that the controlflow graphs of most programs have constant treewidth. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis problems (e.g., alias analysis). The study of multiple queries allows us to consider the tradeoff between the resource usage of the \emph{one-time} preprocessing and for \emph{each individual} query. The traditional approaches construct the product graph of all components and apply the best-known graph algorithm on the product. In the traditional approach, even the answer to a single query requires the transitive closure computation (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time.
Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time,
each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results that show that the worst-case running times of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (such as improving
the worst-case bounds for the shortest path problem in general graphs whose current best-known bound has not been improved in five decades). Finally, we provide a prototype implementation of our algorithms which significantly outperforms the existing algorithmic methods on several benchmarks.
AU - Anonymous, 1
AU - Anonymous, 2
AU - Anonymous, 3
AU - Anonymous, 4
ID - 5442
SN - 2664-1690
TI - Algorithms for algebraic path properties in concurrent systems of constant treewidth components
ER -
TY - GEN
AB - POMDPs are standard models for probabilistic planning problems, where an agent interacts with an uncertain environment. We study the problem of almost-sure reachability, where given a set of target states, the question is to decide whether there is a policy to ensure that the target set is reached with probability 1 (almost-surely). While in general the problem is EXPTIME-complete, in many practical cases policies with a small amount of memory suffice. Moreover, the existing solution to the problem is explicit, which first requires to construct explicitly an exponential reduction to a belief-support MDP. In this work, we first study the existence of observation-stationary strategies, which is NP-complete, and then small-memory strategies. We present a symbolic algorithm by an efficient encoding to SAT and using a SAT solver for the problem. We report experimental results demonstrating the scalability of our symbolic (SAT-based) approach.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Davies, Jessica
ID - 5443
SN - 2664-1690
TI - A symbolic SAT-based algorithm for almost-sure reachability with small strategies in POMDPs
ER -
TY - GEN
AB - A comprehensive understanding of the clonal evolution of cancer is critical for understanding neoplasia. Genome-wide sequencing data enables evolutionary studies at unprecedented depth. However, classical phylogenetic methods often struggle with noisy sequencing data of impure DNA samples and fail to detect subclones that have different evolutionary trajectories. We have developed a tool, called Treeomics, that allows us to reconstruct the phylogeny of a cancer with commonly available sequencing technologies. Using Bayesian inference and Integer Linear Programming, robust phylogenies consistent with the biological processes underlying cancer evolution were obtained for pancreatic, ovarian, and prostate cancers. Furthermore, Treeomics correctly identified sequencing artifacts such as those resulting from low statistical power; nearly 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumor heterogeneity among distinct samples. Importantly, we show that the evolutionary trees generated with Treeomics are mathematically optimal.
AU - Reiter, Johannes
AU - Makohon-Moore, Alvin
AU - Gerold, Jeffrey
AU - Bozic, Ivana
AU - Chatterjee, Krishnendu
AU - Iacobuzio-Donahue, Christine
AU - Vogelstein, Bert
AU - Nowak, Martin
ID - 5444
SN - 2664-1690
TI - Reconstructing robust phylogenies of metastatic cancers
ER -
TY - DATA
AB - This repository contains the experimental part of the CAV 2015 publication Counterexample Explanation by Learning Small Strategies in Markov Decision Processes.
We extended the probabilistic model checker PRISM to represent strategies of Markov Decision Processes as Decision Trees.
The archive contains a java executable version of the extended tool (prism_dectree.jar) together with a few examples of the PRISM benchmark library.
To execute the program, please have a look at the README.txt, which provides instructions and further information on the archive.
The archive contains scripts that (if run often enough) reproduces the data presented in the publication.
AU - Fellner, Andreas
ID - 5549
KW - Markov Decision Process
KW - Decision Tree
KW - Probabilistic Verification
KW - Counterexample Explanation
TI - Experimental part of CAV 2015 publication: Counterexample Explanation by Learning Small Strategies in Markov Decision Processes
ER -
TY - JOUR
AB - Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.
AU - Wielgoss, Sébastien
AU - Bergmiller, Tobias
AU - Bischofberger, Anna M.
AU - Hall, Alex R.
ID - 5749
IS - 3
JF - Molecular Biology and Evolution
SN - 0737-4038
TI - Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria
VL - 33
ER -
TY - JOUR
AB - We present here the first integer-based algorithm for constructing a well-defined lattice sphere specified by integer radius and integer center. The algorithm evolves from a unique correspondence between the lattice points comprising the sphere and the distribution of sum of three square numbers in integer intervals. We characterize these intervals to derive a useful set of recurrences, which, in turn, aids in efficient computation. Each point of the lattice sphere is determined by resorting to only a few primitive operations in the integer domain. The symmetry of its quadraginta octants provides an added advantage by confining the computation to its prima quadraginta octant. Detailed theoretical analysis and experimental results have been furnished to demonstrate its simplicity and elegance.
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5804
IS - 4
JF - Theoretical Computer Science
SN - 0304-3975
TI - From prima quadraginta octant to lattice sphere through primitive integer operations
VL - 624
ER -
TY - JOUR
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5807
IS - 11
JF - Theoretical Computer Science
SN - 0304-3975
TI - On different topological classes of spherical geodesic paths and circles inZ3
VL - 605
ER -
TY - JOUR
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5808
IS - 6-8
JF - The Visual Computer
SN - 0178-2789
TI - Layer the sphere
VL - 31
ER -
TY - JOUR
AB - Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, which consists of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA. After two decades of research, the structural basis of transcription initiation is emerging. Crystal structures of many components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has recently been obtained. Although mechanistic details await elucidation, available data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA, and how Pol II directs RNA synthesis and escapes from the promoter.
AU - Sainsbury, Sarah
AU - Bernecky, Carrie A
AU - Cramer, Patrick
ID - 594
IS - 3
JF - Nature Reviews Molecular Cell Biology
TI - Structural basis of transcription initiation by RNA polymerase II
VL - 16
ER -
TY - JOUR
AB - Carbon dioxide (CO2) gradients are ubiquitous and provide animals with information about their environment, such as the potential presence of prey or predators. The nematode Caenorhabditis elegans avoids elevated CO2, and previous work identified three neuron pairs called “BAG,” “AFD,” and “ASE” that respond to CO2 stimuli. Using in vivo Ca2+ imaging and behavioral analysis, we show that C. elegans can detect CO2 independently of these sensory pathways. Many of the C. elegans sensory neurons we examined, including the AWC olfactory neurons, the ASJ and ASK gustatory neurons, and the ASH and ADL nociceptors, respond to a rise in CO2 with a rise in Ca2+. In contrast, glial sheath cells harboring the sensory endings of C. elegans’ major chemosensory neurons exhibit strong and sustained decreases in Ca2+ in response to high CO2. Some of these CO2 responses appear to be cell intrinsic. Worms therefore may couple detection of CO2 to that of other cues at the earliest stages of sensory processing. We show that C. elegans persistently suppresses oviposition at high CO2. Hermaphrodite-specific neurons (HSNs), the executive neurons driving egg-laying, are tonically inhibited when CO2 is elevated. CO2 modulates the egg-laying system partly through the AWC olfactory neurons: High CO2 tonically activates AWC by a cGMP-dependent mechanism, and AWC output inhibits the HSNs. Our work shows that CO2 is a more complex sensory cue for C. elegans than previously thought, both in terms of behavior and neural circuitry.
AU - Fenk, Lorenz A.
AU - de Bono, Mario
ID - 6118
IS - 27
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - Environmental CO2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity
VL - 112
ER -
TY - JOUR
AB - Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed.
AU - Laurent, Patrick
AU - Soltesz, Zoltan
AU - Nelson, Geoffrey M
AU - Chen, Changchun
AU - Arellano-Carbajal, Fausto
AU - Levy, Emmanuel
AU - de Bono, Mario
ID - 6120
JF - eLife
SN - 2050-084X
TI - Decoding a neural circuit controlling global animal state in C. elegans
VL - 4
ER -
TY - JOUR
AB - The osteoclast-associated receptor (OSCAR) is a collagen-binding immune receptor with important roles in dendritic cell maturation and activation of inflammatory monocytes as well as in osteoclastogenesis. The crystal structure of the OSCAR ectodomain is presented, both free and in complex with a consensus triple-helical peptide (THP). The structures revealed a collagen-binding site in each immunoglobulin-like domain (D1 and D2). The THP binds near a predicted collagen-binding groove in D1, but a more extensive interaction with D2 is facilitated by the unusually wide D1-D2 interdomain angle in OSCAR. Direct binding assays, combined with site-directed mutagenesis, confirm that the primary collagen-binding site in OSCAR resides in D2, in marked contrast to the related collagen receptors, glycoprotein VI (GPVI) and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). Monomeric OSCAR D1D2 binds to the consensus THP with a KD of 28 µM measured in solution, but shows a higher affinity (KD 1.5 μM) when binding to a solid-phase THP, most likely due to an avidity effect. These data suggest a 2-stage model for the interaction of OSCAR with a collagen fibril, with transient, low-affinity interactions initiated by the membrane-distal D1, followed by firm adhesion to the primary binding site in D2.
AU - Zhou, Long
AU - Hinerman, J. M.
AU - Blaszczyk, M.
AU - Miller, J. L. C.
AU - Conrady, D. G.
AU - Barrow, A. D.
AU - Chirgadze, D. Y.
AU - Bihan, D.
AU - Farndale, R. W.
AU - Herr, A. B.
ID - 6507
IS - 5
JF - Blood
SN - 0006-4971
TI - Structural basis for collagen recognition by the immune receptor OSCAR
VL - 127
ER -
TY - JOUR
AB - Motivated by the significant performance gains which polar codes experience under successive cancellation list decoding, their scaling exponent is studied as a function of the list size. In particular, the error probability is fixed, and the tradeoff between the block length and back-off from capacity is analyzed. A lower bound is provided on the error probability under MAP decoding with list size L for any binary-input memoryless output-symmetric channel and for any class of linear codes such that their minimum distance is unbounded as the block length grows large. Then, it is shown that under MAP decoding, although the introduction of a list can significantly improve the involved constants, the scaling exponent itself, i.e., the speed at which capacity is approached, stays unaffected for any finite list size. In particular, this result applies to polar codes, since their minimum distance tends to infinity as the block length increases. A similar result is proved for genie-aided successive cancellation decoding when transmission takes place over the binary erasure channel, namely, the scaling exponent remains constant for any fixed number of helps from the genie. Note that since genie-aided successive cancellation decoding might be strictly worse than successive cancellation list decoding, the problem of establishing the scaling exponent of the latter remains open.
AU - Mondelli, Marco
AU - Hassani, Hamed
AU - Urbanke, Rudiger
ID - 6736
IS - 9
JF - IEEE Transactions on Information Theory
TI - Scaling exponent of list decoders with applications to polar codes
VL - 61
ER -
TY - JOUR
AB - This paper presents polar coding schemes for the two-user discrete memoryless broadcast channel (DM-BC) which achieve Marton's region with both common and private messages. This is the best achievable rate region known to date, and it is tight for all classes of two-user DM-BCs whose capacity regions are known. To accomplish this task, we first construct polar codes for both the superposition as well as binning strategy. By combining these two schemes, we obtain Marton's region with private messages only. Finally, we show how to handle the case of common information. The proposed coding schemes possess the usual advantages of polar codes, i.e., they have low encoding and decoding complexity and a superpolynomial decay rate of the error probability. We follow the lead of Goela, Abbe, and Gastpar, who recently introduced polar codes emulating the superposition and binning schemes. To align the polar indices, for both schemes, their solution involves some degradedness constraints that are assumed to hold between the auxiliary random variables and channel outputs. To remove these constraints, we consider the transmission of k blocks and employ a chaining construction that guarantees the proper alignment of the polarized indices. The techniques described in this paper are quite general, and they can be adopted to many other multiterminal scenarios whenever there polar indices need to be aligned.
AU - Mondelli, Marco
AU - Hassani, Hamed
AU - Sason, Igal
AU - Urbanke, Rudiger
ID - 6737
IS - 2
JF - IEEE Transactions on Information Theory
TI - Achieving Marton’s region for broadcast channels using polar codes
VL - 61
ER -
TY - JOUR
AB - Torque magnetization measurements on YBa2Cu3Oy (YBCO) at doping y=6.67 (p=0.12), in dc fields (B) up to 33 T and temperatures down to 4.5 K, show that weak diamagnetism persists above the extrapolated irreversibility field Hirr(T=0)≈24 T. The differential susceptibility dM/dB, however, is more rapidly suppressed for B≳16 T than expected from the properties of the low field superconducting state, and saturates at a low value for fields B≳24 T. In addition, torque measurements on a p=0.11 YBCO crystal in pulsed field up to 65 T and temperatures down to 8 K show similar behavior, with no additional features at higher fields. We offer two candidate scenarios to explain these observations: (a) superconductivity survives but is heavily suppressed at high field by competition with charge-density-wave (CDW) order; (b) static superconductivity disappears near 24 T and is followed by a region of fluctuating superconductivity, which causes dM/dB to saturate at high field. The diamagnetic signal observed above 50 T for the p=0.11 crystal at 40 K and below may be caused by changes in the normal state susceptibility rather than bulk or fluctuating superconductivity. There will be orbital (Landau) diamagnetism from electron pockets and possibly a reduction in spin susceptibility caused by the stronger three-dimensional ordered CDW.
AU - Yu, Jing Fei
AU - Ramshaw, B. J.
AU - Kokanović, I.
AU - Modic, Kimberly A
AU - Harrison, N.
AU - Day, James
AU - Liang, Ruixing
AU - Hardy, W. N.
AU - Bonn, D. A.
AU - McCollam, A.
AU - Julian, S. R.
AU - Cooper, J. R.
ID - 7070
IS - 18
JF - Physical Review B
SN - 1098-0121
TI - Magnetization of underdoped YBa2Cu3Oy above the irreversibility field
VL - 92
ER -
TY - JOUR
AB - Plant sexual reproduction involves highly structured and specialized organs: stamens (male) and gynoecia (female, containing ovules). These organs synchronously develop within protective flower buds, until anthesis, via tightly coordinated mechanisms that are essential for effective fertilization and production of viable seeds. The phytohormone auxin is one of the key endogenous signalling molecules controlling initiation and development of these, and other, plant organs. In particular, its uneven distribution, resulting from tightly controlled production, metabolism and directional transport, is an important morphogenic factor. In this review we discuss how developmentally controlled and localized auxin biosynthesis and transport contribute to the coordinated development of plants' reproductive organs, and their fertilized derivatives (embryos) via the regulation of auxin levels and distribution within and around them. Current understanding of the links between de novo local auxin biosynthesis, auxin transport and/or signalling is presented to highlight the importance of the non-cell autonomous action of auxin production on development and morphogenesis of reproductive organs and embryos. An overview of transcription factor families, which spatiotemporally define local auxin production by controlling key auxin biosynthetic enzymes, is also presented.
AU - Robert, Hélène
AU - Crhák Khaitová, Lucie
AU - Mroue, Souad
AU - Benková, Eva
ID - 1540
IS - 16
JF - Journal of Experimental Botany
TI - The importance of localized auxin production for morphogenesis of reproductive organs and embryos in Arabidopsis
VL - 66
ER -
TY - CONF
AB - We present XSpeed a parallel state-space exploration algorithm for continuous systems with linear dynamics and nondeterministic inputs. The motivation of having parallel algorithms is to exploit the computational power of multi-core processors to speed-up performance. The parallelization is achieved on two fronts. First, we propose a parallel implementation of the support function algorithm by sampling functions in parallel. Second, we propose a parallel state-space exploration by slicing the time horizon and computing the reachable states in the time slices in parallel. The second method can be however applied only to a class of linear systems with invertible dynamics and fixed input. A GP-GPU implementation is also presented following a lazy evaluation strategy on support functions. The parallel algorithms are implemented in the tool XSpeed. We evaluated the performance on two benchmarks including an 28 dimension Helicopter model. Comparison with the sequential counterpart shows a maximum speed-up of almost 7× on a 6 core, 12 thread Intel Xeon CPU E5-2420 processor. Our GP-GPU implementation shows a maximum speed-up of 12× over the sequential implementation and 53× over SpaceEx (LGG scenario), the state of the art tool for reachability analysis of linear hybrid systems. Experiments illustrate that our parallel algorithm with time slicing not only speeds-up performance but also improves precision.
AU - Ray, Rajarshi
AU - Gurung, Amit
AU - Das, Binayak
AU - Bartocci, Ezio
AU - Bogomolov, Sergiy
AU - Grosu, Radu
ID - 1541
TI - XSpeed: Accelerating reachability analysis on multi-core processors
VL - 9434
ER -
TY - JOUR
AB - The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields.
AU - Paixao, Tiago
AU - Badkobeh, Golnaz
AU - Barton, Nicholas H
AU - Çörüş, Doğan
AU - Dang, Duccuong
AU - Friedrich, Tobias
AU - Lehre, Per
AU - Sudholt, Dirk
AU - Sutton, Andrew
AU - Trubenova, Barbora
ID - 1542
JF - Journal of Theoretical Biology
TI - Toward a unifying framework for evolutionary processes
VL - 383
ER -
TY - JOUR
AB - A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta.
AU - Olvera Carrillo, Yadira
AU - Van Bel, Michiel
AU - Van Hautegem, Tom
AU - Fendrych, Matyas
AU - Huysmans, Marlies
AU - Šimášková, Mária
AU - Van Durme, Matthias
AU - Buscaill, Pierre
AU - Rivas, Susana
AU - Coll, Núria
AU - Coppens, Frederik
AU - Maere, Steven
AU - Nowack, Moritz
ID - 1543
IS - 4
JF - Plant Physiology
TI - A conserved core of programmed cell death indicator genes discriminates developmentally and environmentally induced programmed cell death in plants
VL - 169
ER -
TY - CHAP
AB - Cell division in prokaryotes and eukaryotes is commonly initiated by the well-controlled binding of proteins to the cytoplasmic side of the cell membrane. However, a precise characterization of the spatiotemporal dynamics of membrane-bound proteins is often difficult to achieve in vivo. Here, we present protocols for the use of supported lipid bilayers to rebuild the cytokinetic machineries of cells with greatly different dimensions: the bacterium Escherichia coli and eggs of the vertebrate Xenopus laevis. Combined with total internal reflection fluorescence microscopy, these experimental setups allow for precise quantitative analyses of membrane-bound proteins. The protocols described to obtain glass-supported membranes from bacterial and vertebrate lipids can be used as starting points for other reconstitution experiments. We believe that similar biochemical assays will be instrumental to study the biochemistry and biophysics underlying a variety of complex cellular tasks, such as signaling, vesicle trafficking, and cell motility.
AU - Nguyen, Phuong
AU - Field, Christine
AU - Groen, Aaron
AU - Mitchison, Timothy
AU - Loose, Martin
ID - 1544
T2 - Building a Cell from its Components Parts
TI - Using supported bilayers to study the spatiotemporal organization of membrane-bound proteins
VL - 128
ER -
TY - JOUR
AB - Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.
AU - Nakamura, Yukihiro
AU - Harada, Harumi
AU - Kamasawa, Naomi
AU - Matsui, Ko
AU - Rothman, Jason
AU - Shigemoto, Ryuichi
AU - Silver, R Angus
AU - Digregorio, David
AU - Takahashi, Tomoyuki
ID - 1546
IS - 1
JF - Neuron
TI - Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development
VL - 85
ER -
TY - JOUR
AB - Let G be a graph on the vertex set V(G) = {x1,…,xn} with the edge set E(G), and let R = K[x1,…, xn] be the polynomial ring over a field K. Two monomial ideals are associated to G, the edge ideal I(G) generated by all monomials xixj with {xi,xj} ∈ E(G), and the vertex cover ideal IG generated by monomials ∏xi∈Cxi for all minimal vertex covers C of G. A minimal vertex cover of G is a subset C ⊂ V(G) such that each edge has at least one vertex in C and no proper subset of C has the same property. Indeed, the vertex cover ideal of G is the Alexander dual of the edge ideal of G. In this paper, for an unmixed bipartite graph G we consider the lattice of vertex covers LG and we explicitly describe the minimal free resolution of the ideal associated to LG which is exactly the vertex cover ideal of G. Then we compute depth, projective dimension, regularity and extremal Betti numbers of R/I(G) in terms of the associated lattice.
AU - Mohammadi, Fatemeh
AU - Moradi, Somayeh
ID - 1547
IS - 3
JF - Bulletin of the Korean Mathematical Society
TI - Resolution of unmixed bipartite graphs
VL - 52
ER -
TY - JOUR
AB - Reproduction within a host and transmission to the next host are crucial for the virulence and fitness of pathogens. Nevertheless, basic knowledge about such parameters is often missing from the literature, even for well-studied bacteria, such as Bacillus thuringiensis, an endospore-forming insect pathogen, which infects its hosts via the oral route. To characterize bacterial replication success, we made use of an experimental oral infection system for the red flour beetle Tribolium castaneum and developed a flow cytometric assay for the quantification of both spore ingestion by the individual beetle larvae and the resulting spore load after bacterial replication and resporulation within cadavers. On average, spore numbers increased 460-fold, showing that Bacillus thuringiensis grows and replicates successfully in insect cadavers. By inoculating cadaver-derived spores and spores from bacterial stock cultures into nutrient medium, we next investigated outgrowth characteristics of vegetative cells and found that cadaver- derived bacteria showed reduced growth compared to bacteria from the stock cultures. Interestingly, this reduced growth was a consequence of inhibited spore germination, probably originating from the host and resulting in reduced host mortality in subsequent infections by cadaver-derived spores. Nevertheless, we further showed that Bacillus thuringiensis transmission was possible via larval cannibalism when no other food was offered. These results contribute to our understanding of the ecology of Bacillus thuringiensis as an insect pathogen.
AU - Milutinovic, Barbara
AU - Höfling, Christina
AU - Futo, Momir
AU - Scharsack, Jörn
AU - Kurtz, Joachim
ID - 1548
IS - 23
JF - Applied and Environmental Microbiology
TI - Infection of Tribolium castaneum with Bacillus thuringiensis: Quantification of bacterial replication within cadavers, transmission via cannibalism, and inhibition of spore germination
VL - 81
ER -
TY - CHAP
AB - Nature has incorporated small photochromic molecules, colloquially termed 'photoswitches', in photoreceptor proteins to sense optical cues in photo-taxis and vision. While Nature's ability to employ light-responsive functionalities has long been recognized, it was not until recently that scientists designed, synthesized and applied synthetic photochromes to manipulate many of which open rapidly and locally in their native cell types, biological processes with the temporal and spatial resolution of light. Ion channels in particular have come to the forefront of proteins that can be put under the designer control of synthetic photochromes. Photochromic ion channel controllers are comprised of three classes, photochromic soluble ligands (PCLs), photochromic tethered ligands (PTLs) and photochromic crosslinkers (PXs), and in each class ion channel functionality is controlled through reversible changes in photochrome structure. By acting as light-dependent ion channel agonists, antagonist or modulators, photochromic controllers effectively converted a wide range of ion channels, including voltage-gated ion channels, 'leak channels', tri-, tetra- and pentameric ligand-gated ion channels, and temperaturesensitive ion channels, into man-made photoreceptors. Control by photochromes can be reversible, unlike in the case of 'caged' compounds, and non-invasive with high spatial precision, unlike pharmacology and electrical manipulation. Here, we introduce design principles of emerging photochromic molecules that act on ion channels and discuss the impact that these molecules are beginning to have on ion channel biophysics and neuronal physiology.
AU - Mckenzie, Catherine
AU - Sanchez Romero, Inmaculada
AU - Janovjak, Harald L
ID - 1549
SN - 978-1-4939-2844-6
T2 - Novel chemical tools to study ion channel biology
TI - Flipping the photoswitch: Ion channels under light control
VL - 869
ER -
TY - JOUR
AB - The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute.
AU - Mayer, Christian
AU - Jaglin, Xavier
AU - Cobbs, Lucy
AU - Bandler, Rachel
AU - Streicher, Carmen
AU - Cepko, Constance
AU - Hippenmeyer, Simon
AU - Fishell, Gord
ID - 1550
IS - 5
JF - Neuron
TI - Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries
VL - 87
ER -
TY - JOUR
AB - Reciprocal coevolution between host and pathogen is widely seen as a major driver of evolution and biological innovation. Yet, to date, the underlying genetic mechanisms and associated trait functions that are unique to rapid coevolutionary change are generally unknown. We here combined experimental evolution of the bacterial biocontrol agent Bacillus thuringiensis and its nematode host Caenorhabditis elegans with large-scale phenotyping, whole genome analysis, and functional genetics to demonstrate the selective benefit of pathogen virulence and the underlying toxin genes during the adaptation process. We show that: (i) high virulence was specifically favoured during pathogen–host coevolution rather than pathogen one-sided adaptation to a nonchanging host or to an environment without host; (ii) the pathogen genotype BT-679 with known nematocidal toxin genes and high virulence specifically swept to fixation in all of the independent replicate populations under coevolution but only some under one-sided adaptation; (iii) high virulence in the BT-679-dominated populations correlated with elevated copy numbers of the plasmid containing the nematocidal toxin genes; (iv) loss of virulence in a toxin-plasmid lacking BT-679 isolate was reconstituted by genetic reintroduction or external addition of the toxins.We conclude that sustained coevolution is distinct from unidirectional selection in shaping the pathogen's genome and life history characteristics. To our knowledge, this study is the first to characterize the pathogen genes involved in coevolutionary adaptation in an animal host–pathogen interaction system.
AU - El Masri, Leila
AU - Branca, Antoine
AU - Sheppard, Anna
AU - Papkou, Andrei
AU - Laehnemann, David
AU - Guenther, Patrick
AU - Prahl, Swantje
AU - Saebelfeld, Manja
AU - Hollensteiner, Jacqueline
AU - Liesegang, Heiko
AU - Brzuszkiewicz, Elzbieta
AU - Daniel, Rolf
AU - Michiels, Nico
AU - Schulte, Rebecca
AU - Kurtz, Joachim
AU - Rosenstiel, Philip
AU - Telschow, Arndt
AU - Bornberg Bauer, Erich
AU - Schulenburg, Hinrich
ID - 1551
IS - 6
JF - PLoS Biology
TI - Host–pathogen coevolution: The selective advantage of Bacillus thuringiensis virulence and its cry toxin genes
VL - 13
ER -
TY - JOUR
AB - Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, we show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns.
AU - Maiuri, Paolo
AU - Rupprecht, Jean
AU - Wieser, Stefan
AU - Ruprecht, Verena
AU - Bénichou, Olivier
AU - Carpi, Nicolas
AU - Coppey, Mathieu
AU - De Beco, Simon
AU - Gov, Nir
AU - Heisenberg, Carl-Philipp J
AU - Lage Crespo, Carolina
AU - Lautenschlaeger, Franziska
AU - Le Berre, Maël
AU - Lennon Duménil, Ana
AU - Raab, Matthew
AU - Thiam, Hawa
AU - Piel, Matthieu
AU - Sixt, Michael K
AU - Voituriez, Raphaël
ID - 1553
IS - 2
JF - Cell
TI - Actin flows mediate a universal coupling between cell speed and cell persistence
VL - 161
ER -
TY - JOUR
AB - The visualization of hormonal signaling input and output is key to understanding how multicellular development is regulated. The plant signaling molecule auxin triggers many growth and developmental responses, but current tools lack the sensitivity or precision to visualize these. We developed a set of fluorescent reporters that allow sensitive and semiquantitative readout of auxin responses at cellular resolution in Arabidopsis thaliana. These generic tools are suitable for any transformable plant species.
AU - Liao, Cheyang
AU - Smet, Wouter
AU - Brunoud, Géraldine
AU - Yoshida, Saiko
AU - Vernoux, Teva
AU - Weijers, Dolf
ID - 1554
IS - 3
JF - Nature Methods
TI - Reporters for sensitive and quantitative measurement of auxin response
VL - 12
ER -
TY - JOUR
AB - We show that incorporating spatial dispersal of individuals into a simple vaccination epidemic model may give rise to a model that exhibits rich dynamical behavior. Using an SIVS (susceptible-infected-vaccinated-susceptible) model as a basis, we describe the spread of an infectious disease in a population split into two regions. In each subpopulation, both forward and backward bifurcations can occur. This implies that for disconnected regions the two-patch system may admit several steady states. We consider traveling between the regions and investigate the impact of spatial dispersal of individuals on the model dynamics. We establish conditions for the existence of multiple nontrivial steady states in the system, and we study the structure of the equilibria. The mathematical analysis reveals an unusually rich dynamical behavior, not normally found in the simple epidemic models. In addition to the disease-free equilibrium, eight endemic equilibria emerge from backward transcritical and saddle-node bifurcation points, forming an interesting bifurcation diagram. Stability of steady states, their bifurcations, and the global dynamics are investigated with analytical tools, numerical simulations, and rigorous set-oriented numerical computations.
AU - Knipl, Diána
AU - Pilarczyk, Pawel
AU - Röst, Gergely
ID - 1555
IS - 2
JF - SIAM Journal on Applied Dynamical Systems
TI - Rich bifurcation structure in a two patch vaccination model
VL - 14
ER -
TY - JOUR
AB - The elongator complex subunit 2 (ELP2) protein, one subunit of an evolutionarily conserved histone acetyltransferase complex, has been shown to participate in leaf patterning, plant immune and abiotic stress responses in Arabidopsis thaliana. Here, its role in root development was explored. Compared to the wild type, the elp2 mutant exhibited an accelerated differentiation of its root stem cells and cell division was more active in its quiescent centre (QC). The key transcription factors responsible for maintaining root stem cell and QC identity, such as AP2 transcription factors PLT1 (PLETHORA1) and PLT2 (PLETHORA2), GRAS transcription factors such as SCR (SCARECROW) and SHR (SHORT ROOT) and WUSCHEL-RELATED HOMEOBOX5 transcription factor WOX5, were all strongly down-regulated in the mutant. On the other hand, expression of the G2/M transition activator CYCB1 was substantially induced in elp2. The auxin efflux transporters PIN1 and PIN2 showed decreased protein levels and PIN1 also displayed mild polarity alterations in elp2, which resulted in a reduced auxin content in the root tip. Either the acetylation or methylation level of each of these genes differed between the mutant and the wild type, suggesting that the ELP2 regulation of root development involves the epigenetic modification of a range of transcription factors and other developmental regulators.
AU - Jia, Yuebin
AU - Tian, Huiyu
AU - Li, Hongjiang
AU - Yu, Qianqian
AU - Wang, Lei
AU - Friml, Jirí
AU - Ding, Zhaojun
ID - 1556
IS - 15
JF - Journal of Experimental Botany
TI - The Arabidopsis thaliana elongator complex subunit 2 epigenetically affects root development
VL - 66
ER -
TY - JOUR
AB - γ-Aminobutyric acid (GABA)- and glycine-mediated hyperpolarizing inhibition is associated with a chloride influx that depends on the inwardly directed chloride electrochemical gradient. In neurons, the extrusion of chloride from the cytosol primarily depends on the expression of an isoform of potassium-chloride cotransporters (KCC2s). KCC2 is crucial in the regulation of the inhibitory tone of neural circuits, including pain processing neural assemblies. Thus we investigated the cellular distribution of KCC2 in neurons underlying pain processing in the superficial spinal dorsal horn of rats by using high-resolution immunocytochemical methods. We demonstrated that perikarya and dendrites widely expressed KCC2, but axon terminals proved to be negative for KCC2. In single ultrathin sections, silver deposits labeling KCC2 molecules showed different densities on the surface of dendritic profiles, some of which were negative for KCC2. In freeze fracture replicas and tissue sections double stained for the β3-subunit of GABAA receptors and KCC2, GABAA receptors were revealed on dendritic segments with high and also with low KCC2 densities. By measuring the distances between spots immunoreactive for gephyrin (a scaffolding protein of GABAA and glycine receptors) and KCC2 on the surface of neurokinin 1 (NK1) receptor-immunoreactive dendrites, we found that gephyrin-immunoreactive spots were located at various distances from KCC2 cotransporters; 5.7 % of them were recovered in the middle of 4-10-μm-long dendritic segments that were free of KCC2 immunostaining. The variable local densities of KCC2 may result in variable postsynaptic potentials evoked by the activation of GABAA and glycine receptors along the dendrites of spinal neurons.
AU - Javdani, Fariba
AU - Holló, Krisztina
AU - Hegedűs, Krisztina
AU - Kis, Gréta
AU - Hegyi, Zoltán
AU - Dócs, Klaudia
AU - Kasugai, Yu
AU - Fukazawa, Yugo
AU - Shigemoto, Ryuichi
AU - Antal, Miklós
ID - 1557
IS - 13
JF - Journal of Comparative Neurology
TI - Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats
VL - 523
ER -
TY - JOUR
AB - CyclophilinAis a conserved peptidyl-prolyl cis-trans isomerase (PPIase) best known as the cellular receptor of the immunosuppressant cyclosporine A. Despite significant effort, evidence of developmental functions of cyclophilin A in non-plant systems has remained obscure. Mutations in a tomato (Solanum lycopersicum) cyclophilin A ortholog, DIAGEOTROPICA (DGT), have been shown to abolish the organogenesis of lateral roots; however, a mechanistic explanation of the phenotype is lacking. Here, we show that the dgt mutant lacks auxin maxima relevant to priming and specification of lateral root founder cells. DGT is expressed in shoot and root, and localizes to both the nucleus and cytoplasm during lateral root organogenesis. Mutation of ENTIRE/ IAA9, a member of the auxin-responsive Aux/IAA protein family of transcriptional repressors, partially restores the inability of dgt to initiate lateral root primordia but not the primordia outgrowth. By comparison, grafting of a wild-type scion restores the process of lateral root formation, consistent with participation of a mobile signal. Antibodies do not detect movement of the DGT protein into the dgt rootstock; however, experiments with radiolabeled auxin and an auxin-specific microelectrode demonstrate abnormal auxin fluxes. Functional studies of DGT in heterologous yeast and tobacco-leaf auxin-transport systems demonstrate that DGT negatively regulates PIN-FORMED (PIN) auxin efflux transporters by affecting their plasma membrane localization. Studies in tomato support complex effects of the dgt mutation on PIN expression level, expression domain and plasma membrane localization. Our data demonstrate that DGT regulates auxin transport in lateral root formation.
AU - Ivanchenko, Maria
AU - Zhu, Jinsheng
AU - Wang, Bangjun
AU - Medvecka, Eva
AU - Du, Yunlong
AU - Azzarello, Elisa
AU - Mancuso, Stefano
AU - Megraw, Molly
AU - Filichkin, Sergei
AU - Dubrovsky, Joseph
AU - Friml, Jirí
AU - Geisler, Markus
ID - 1558
IS - 4
JF - Development
TI - The cyclophilin a DIAGEOTROPICA gene affects auxin transport in both root and shoot to control lateral root formation
VL - 142
ER -
TY - JOUR
AB - There are deep, yet largely unexplored, connections between computer science and biology. Both disciplines examine how information proliferates in time and space. Central results in computer science describe the complexity of algorithms that solve certain classes of problems. An algorithm is deemed efficient if it can solve a problem in polynomial time, which means the running time of the algorithm is a polynomial function of the length of the input. There are classes of harder problems for which the fastest possible algorithm requires exponential time. Another criterion is the space requirement of the algorithm. There is a crucial distinction between algorithms that can find a solution, verify a solution, or list several distinct solutions in given time and space. The complexity hierarchy that is generated in this way is the foundation of theoretical computer science. Precise complexity results can be notoriously difficult. The famous question whether polynomial time equals nondeterministic polynomial time (i.e., P = NP) is one of the hardest open problems in computer science and all of mathematics. Here, we consider simple processes of ecological and evolutionary spatial dynamics. The basic question is: What is the probability that a new invader (or a new mutant)will take over a resident population?We derive precise complexity results for a variety of scenarios. We therefore show that some fundamental questions in this area cannot be answered by simple equations (assuming that P is not equal to NP).
AU - Ibsen-Jensen, Rasmus
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 1559
IS - 51
JF - PNAS
TI - Computational complexity of ecological and evolutionary spatial dynamics
VL - 112
ER -
TY - JOUR
AB - Stromal cells in the subcapsular sinus of the lymph node 'decide' which cells and molecules are allowed access to the deeper parenchyma. The glycoprotein PLVAP is a crucial component of this selector function.
AU - Hons, Miroslav
AU - Sixt, Michael K
ID - 1560
IS - 4
JF - Nature Immunology
TI - The lymph node filter revealed
VL - 16
ER -
TY - JOUR
AB - Replication-deficient recombinant adenoviruses are potent vectors for the efficient transient expression of exogenous genes in resting immune cells. However, most leukocytes are refractory to efficient adenoviral transduction as they lack expression of the coxsackie/adenovirus receptor (CAR). To circumvent this obstacle, we generated the R26/CAG-CARΔ1StopF (where R26 is ROSA26 and CAG is CMV early enhancer/chicken β actin promoter) knock-in mouse line. This strain allows monitoring of in situ Cre recombinase activity through expression of CARΔ1. Simultaneously, CARΔ1 expression permits selective and highly efficient adenoviral transduction of immune cell populations, such as mast cells or T cells, directly ex vivo in bulk cultures without prior cell purification or activation. Furthermore, we show that CARΔ1 expression dramatically improves adenoviral infection of in vitro differentiated conventional and plasmacytoid dendritic cells (DCs), basophils, mast cells, as well as Hoxb8-immortalized hematopoietic progenitor cells. This novel dual function mouse strain will hence be a valuable tool to rapidly dissect the function of specific genes in leukocyte physiology.
AU - Heger, Klaus
AU - Kober, Maike
AU - Rieß, David
AU - Drees, Christoph
AU - De Vries, Ingrid
AU - Bertossi, Arianna
AU - Roers, Axel
AU - Sixt, Michael K
AU - Schmidt Supprian, Marc
ID - 1561
IS - 6
JF - European Journal of Immunology
TI - A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors
VL - 45
ER -
TY - JOUR
AB - The plant hormone auxin is a key regulator of plant growth and development. Auxin levels are sensed and interpreted by distinct receptor systems that activate a broad range of cellular responses. The Auxin-Binding Protein1 (ABP1) that has been identified based on its ability to bind auxin with high affinity is a prime candidate for the extracellular receptor responsible for mediating a range of auxin effects, in particular, the fast non-transcriptional ones. Contradictory genetic studies suggested prominent or no importance of ABP1 in many developmental processes. However, how crucial the role of auxin binding to ABP1 is for its functions has not been addressed. Here, we show that the auxin-binding pocket of ABP1 is essential for its gain-of-function cellular and developmental roles. In total, 16 different abp1 mutants were prepared that possessed substitutions in the metal core or in the hydrophobic amino acids of the auxin-binding pocket as well as neutral mutations. Their analysis revealed that an intact auxin-binding pocket is a prerequisite for ABP1 to activate downstream components of the ABP1 signalling pathway, such as Rho of Plants (ROPs) and to mediate the clathrin association with membranes for endocytosis regulation. In planta analyses demonstrated the importance of the auxin binding pocket for all known ABP1-mediated postembryonic developmental processes, including morphology of leaf epidermal cells, root growth and root meristem activity, and vascular tissue differentiation. Taken together, these findings suggest that auxin binding to ABP1 is central to its function, supporting the role of ABP1 as auxin receptor.
AU - Grones, Peter
AU - Chen, Xu
AU - Simon, Sibu
AU - Kaufmann, Walter
AU - De Rycke, Riet
AU - Nodzyński, Tomasz
AU - Zažímalová, Eva
AU - Friml, Jirí
ID - 1562
IS - 16
JF - Journal of Experimental Botany
TI - Auxin-binding pocket of ABP1 is crucial for its gain-of-function cellular and developmental roles
VL - 66
ER -
TY - JOUR
AB - For a given self-map $f$ of $M$, a closed smooth connected and simply-connected manifold of dimension $m\geq 4$, we provide an algorithm for estimating the values of the topological invariant $D^m_r[f]$, which equals the minimal number of $r$-periodic points in the smooth homotopy class of $f$. Our results are based on the combinatorial scheme for computing $D^m_r[f]$ introduced by G. Graff and J. Jezierski [J. Fixed Point Theory Appl. 13 (2013), 63-84]. An open-source implementation of the algorithm programmed in C++ is publicly available at {\tt http://www.pawelpilarczyk.com/combtop/}.
AU - Graff, Grzegorz
AU - Pilarczyk, Pawel
ID - 1563
IS - 1
JF - Topological Methods in Nonlinear Analysis
TI - An algorithmic approach to estimating the minimal number of periodic points for smooth self-maps of simply-connected manifolds
VL - 45
ER -
TY - JOUR
AU - Gilson, Matthieu
AU - Savin, Cristina
AU - Zenke, Friedemann
ID - 1564
IS - 11
JF - Frontiers in Computational Neuroscience
TI - Editorial: Emergent neural computation from the interaction of different forms of plasticity
VL - 9
ER -
TY - JOUR
AB - Leptin is an adipokine produced by the adipose tissue regulating body weight through its appetite-suppressing effect. Besides being expressed in the hypothalamus and hippocampus, leptin receptors (ObRs) are also present in chromaffin cells of the adrenal medulla. In the present study, we report the effect of leptin on mouse chromaffin cell (MCC) functionality, focusing on cell excitability and catecholamine secretion. Acute application of leptin (1 nm) on spontaneously firing MCCs caused a slowly developing membrane hyperpolarization followed by complete blockade of action potential (AP) firing. This inhibitory effect at rest was abolished by the BK channel blocker paxilline (1 μm), suggesting the involvement of BK potassium channels. Single-channel recordings in 'perforated microvesicles' confirmed that leptin increased BK channel open probability without altering its unitary conductance. BK channel up-regulation was associated with the phosphoinositide 3-kinase (PI3K) signalling cascade because the PI3K specific inhibitor wortmannin (100 nm) fully prevented BK current increase. We also tested the effect of leptin on evoked AP firing and Ca2+-driven exocytosis. Although leptin preserves well-adapted AP trains of lower frequency, APs are broader and depolarization-evoked exocytosis is increased as a result of the larger size of the ready-releasable pool and higher frequency of vesicle release. The kinetics and quantal size of single secretory events remained unaltered. Leptin had no effect on firing and secretion in db-/db- mice lacking the ObR gene, confirming its specificity. In conclusion, leptin exhibits a dual action on MCC activity. It dampens AP firing at rest but preserves AP firing and increases catecholamine secretion during sustained stimulation, highlighting the importance of the adipo-adrenal axis in the leptin-mediated increase of sympathetic tone and catecholamine release.
AU - Gavello, Daniela
AU - Vandael, David H
AU - Gosso, Sara
AU - Carbone, Emilio
AU - Carabelli, Valentina
ID - 1565
IS - 22
JF - Journal of Physiology
TI - Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells
VL - 593
ER -
TY - JOUR
AB - Deposits of misfolded proteins in the human brain are associated with the development of many neurodegenerative diseases. Recent studies show that these proteins have common traits even at the monomer level. Among them, a polyglutamine region that is present in huntingtin is known to exhibit a correlation between the length of the chain and the severity as well as the earliness of the onset of Huntington disease. Here, we apply bias exchange molecular dynamics to generate structures of polyglutamine expansions of several lengths and characterize the resulting independent conformations. We compare the properties of these conformations to those of the standard proteins, as well as to other homopolymeric tracts. We find that, similar to the previously studied polyvaline chains, the set of possible transient folds is much broader than the set of known-to-date folds, although the conformations have different structures. We show that the mechanical stability is not related to any simple geometrical characteristics of the structures. We demonstrate that long polyglutamine expansions result in higher mechanical stability than the shorter ones. They also have a longer life span and are substantially more prone to form knotted structures. The knotted region has an average length of 35 residues, similar to the typical threshold for most polyglutamine-related diseases. Similarly, changes in shape and mechanical stability appear once the total length of the peptide exceeds this threshold of 35 glutamine residues. We suggest that knotted conformers may also harm the cellular machinery and thus lead to disease.
AU - Gómez Sicilia, Àngel
AU - Sikora, Mateusz K
AU - Cieplak, Marek
AU - Carrión Vázquez, Mariano
ID - 1566
IS - 10
JF - PLoS Computational Biology
TI - An exploration of the universe of polyglutamine structures
VL - 11
ER -
TY - CONF
AB - My personal journey to the fascinating world of geometric forms started more than 30 years ago with the invention of alpha shapes in the plane. It took about 10 years before we generalized the concept to higher dimensions, we produced working software with a graphics interface for the three-dimensional case. At the same time, we added homology to the computations. Needless to say that this foreshadowed the inception of persistent homology, because it suggested the study of filtrations to capture the scale of a shape or data set. Importantly, this method has fast algorithms. The arguably most useful result on persistent homology is the stability of its diagrams under perturbations.
AU - Edelsbrunner, Herbert
ID - 1567
TI - Shape, homology, persistence, and stability
VL - 9411
ER -
TY - CONF
AB - Aiming at the automatic diagnosis of tumors from narrow band imaging (NBI) magnifying endoscopy (ME) images of the stomach, we combine methods from image processing, computational topology, and machine learning to classify patterns into normal, tubular, vessel. Training the algorithm on a small number of images of each type, we achieve a high rate of correct classifications. The analysis of the learning algorithm reveals that a handful of geometric and topological features are responsible for the overwhelming majority of decisions.
AU - Dunaeva, Olga
AU - Edelsbrunner, Herbert
AU - Lukyanov, Anton
AU - Machin, Michael
AU - Malkova, Daria
ID - 1568
T2 - Proceedings - 16th International Symposium on Symbolic and Numeric Algorithms for Scientific Computing
TI - The classification of endoscopy images with persistent homology
ER -
TY - JOUR
AB - Spatial regulation of the plant hormone indole-3-acetic acid (IAA, or auxin) is essential for plant development. Auxin gradient establishment is mediated by polarly localized auxin transporters, including PIN-FORMED (PIN) proteins. Their localization and abundance at the plasma membrane are tightly regulated by endomembrane machinery, especially the endocytic and recycling pathways mediated by the ADP ribosylation factor guanine nucleotide exchange factor (ARF-GEF) GNOM. We assessed the role of the early secretory pathway in establishing PIN1 polarity in Arabidopsis thaliana by pharmacological and genetic approaches. We identified the compound endosidin 8 (ES8), which selectively interferes with PIN1 basal polarity without altering the polarity of apical proteins. ES8 alters the auxin distribution pattern in the root and induces a strong developmental phenotype, including reduced root length. The ARF-GEF- defective mutants gnom-like 1 ( gnl1-1) and gnom ( van7) are significantly resistant to ES8. The compound does not affect recycling or vacuolar trafficking of PIN1 but leads to its intracellular accumulation, resulting in loss of PIN1 basal polarity at the plasma membrane. Our data confirm a role for GNOM in endoplasmic reticulum (ER) - Golgi trafficking and reveal that a GNL1/GNOM-mediated early secretory pathway selectively regulates PIN1 basal polarity establishment in a manner essential for normal plant development.
AU - Doyle, Siamsa
AU - Haegera, Ash
AU - Vain, Thomas
AU - Rigala, Adeline
AU - Viotti, Corrado
AU - Łangowskaa, Małgorzata
AU - Maa, Qian
AU - Friml, Jirí
AU - Raikhel, Natasha
AU - Hickse, Glenn
AU - Robert, Stéphanie
ID - 1569
IS - 7
JF - PNAS
TI - An early secretory pathway mediated by gnom-like 1 and gnom is essential for basal polarity establishment in Arabidopsis thaliana
VL - 112
ER -
TY - JOUR
AB - Grounding autonomous behavior in the nervous system is a fundamental challenge for neuroscience. In particular, self-organized behavioral development provides more questions than answers. Are there special functional units for curiosity, motivation, and creativity? This paper argues that these features can be grounded in synaptic plasticity itself, without requiring any higher-level constructs. We propose differential extrinsic plasticity (DEP) as a new synaptic rule for self-learning systems and apply it to a number of complex robotic systems as a test case. Without specifying any purpose or goal, seemingly purposeful and adaptive rhythmic behavior is developed, displaying a certain level of sensorimotor intelligence. These surprising results require no systemspecific modifications of the DEP rule. They rather arise from the underlying mechanism of spontaneous symmetry breaking,which is due to the tight brain body environment coupling. The new synaptic rule is biologically plausible and would be an interesting target for neurobiological investigation. We also argue that this neuronal mechanism may have been a catalyst in natural evolution.
AU - Der, Ralf
AU - Martius, Georg S
ID - 1570
IS - 45
JF - PNAS
TI - Novel plasticity rule can explain the development of sensorimotor intelligence
VL - 112
ER -
TY - JOUR
AB - Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may fail to evolve when essential mutations are only accessible through positive selection if they are fixed simultaneously. How environmental variability affects such constraints is poorly understood. Here, we studied genetic constraints in fixed and fluctuating environments using the Escherichia coli lac operon as a model system for genotype-environment interactions. We found that, in different fixed environments, all trajectories that were reconstructed by applying point mutations within the transcription factor-operator interface became trapped at suboptima, where no additional improvements were possible. Paradoxically, repeated switching between these same environments allows unconstrained adaptation by continuous improvements. This evolutionary mode is explained by pervasive cross-environmental tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach, we developed a mathematical framework to quantify the landscape-crossing rates and show that this ratchet-like adaptive mechanism is robust in a wide spectrum of fluctuating environments. Overall, this study shows that genetic constraints can be overcome by environmental change and that crossenvironmental tradeoffs do not necessarily impede but also, can facilitate adaptive evolution. Because tradeoffs and environmental variability are ubiquitous in nature, we speculate this evolutionary mode to be of general relevance.
AU - De Vos, Marjon
AU - Dawid, Alexandre
AU - Šunderlíková, Vanda
AU - Tans, Sander
ID - 1571
IS - 48
JF - PNAS
TI - Breaking evolutionary constraint with a tradeoff ratchet
VL - 112
ER -
TY - JOUR
AB - We consider the quantum ferromagnetic Heisenberg model in three dimensions, for all spins S ≥ 1/2. We rigorously prove the validity of the spin-wave approximation for the excitation spectrum, at the level of the first non-trivial contribution to the free energy at low temperatures. Our proof comes with explicit, constructive upper and lower bounds on the error term. It uses in an essential way the bosonic formulation of the model in terms of the Holstein-Primakoff representation. In this language, the model describes interacting bosons with a hard-core on-site repulsion and a nearest-neighbor attraction. This attractive interaction makes the lower bound on the free energy particularly tricky: the key idea there is to prove a differential inequality for the two-particle density, which is thereby shown to be smaller than the probability density of a suitably weighted two-particle random process on the lattice.
AU - Correggi, Michele
AU - Giuliani, Alessandro
AU - Seiringer, Robert
ID - 1572
IS - 1
JF - Communications in Mathematical Physics
TI - Validity of the spin-wave approximation for the free energy of the Heisenberg ferromagnet
VL - 339
ER -
TY - JOUR
AB - We present a new, simpler proof of the unconditional uniqueness of solutions to the cubic Gross-Pitaevskii hierarchy in ℝ3. One of the main tools in our analysis is the quantum de Finetti theorem. Our uniqueness result is equivalent to the one established in the celebrated works of Erdos, Schlein, and Yau.
AU - Chen, Thomas
AU - Hainzl, Christian
AU - Pavlović, Nataša
AU - Seiringer, Robert
ID - 1573
IS - 10
JF - Communications on Pure and Applied Mathematics
TI - Unconditional uniqueness for the cubic gross pitaevskii hierarchy via quantum de finetti
VL - 68
ER -