TY - CONF
AB - Quantitative automata are nondeterministic finite automata with edge weights. They value a
run by some function from the sequence of visited weights to the reals, and value a word by its
minimal/maximal run. They generalize boolean automata, and have gained much attention in
recent years. Unfortunately, important automaton classes, such as sum, discounted-sum, and
limit-average automata, cannot be determinized. Yet, the quantitative setting provides the potential
of approximate determinization. We define approximate determinization with respect to
a distance function, and investigate this potential.
We show that sum automata cannot be determinized approximately with respect to any
distance function. However, restricting to nonnegative weights allows for approximate determinization
with respect to some distance functions.
Discounted-sum automata allow for approximate determinization, as the influence of a word’s
suffix is decaying. However, the naive approach, of unfolding the automaton computations up
to a sufficient level, is shown to be doubly exponential in the discount factor. We provide an
alternative construction that is singly exponential in the discount factor, in the precision, and
in the number of states. We prove matching lower bounds, showing exponential dependency on
each of these three parameters.
Average and limit-average automata are shown to prohibit approximate determinization with
respect to any distance function, and this is the case even for two weights, 0 and 1.
AU - Boker, Udi
AU - Henzinger, Thomas A
ID - 2891
T2 - Leibniz International Proceedings in Informatics
TI - Approximate determinization of quantitative automata
VL - 18
ER -
TY - CONF
AB - In order to enjoy a digital version of the Jordan Curve Theorem, it is common to use the closed topology for the foreground and the open topology for the background of a 2-dimensional binary image. In this paper, we introduce a single topology that enjoys this theorem for all thresholds decomposing a real-valued image into foreground and background. This topology is easy to construct and it generalizes to n-dimensional images.
AU - Edelsbrunner, Herbert
AU - Symonova, Olga
ID - 2903
TI - The adaptive topology of a digital image
ER -
TY - JOUR
AB - Generalized van der Corput sequences are onedimensional, infinite sequences in the unit interval. They are generated from permutations in integer base b and are the building blocks of the multi-dimensional Halton sequences. Motivated by recent progress of Atanassov on the uniform distribution behavior of Halton sequences, we study, among others, permutations of the form P(i) = ai (mod b) for coprime integers a and b. We show that multipliers a that either divide b - 1 or b + 1 generate van der Corput sequences with weak distribution properties. We give explicit lower bounds for the asymptotic distribution behavior of these sequences and relate them to sequences generated from the identity permutation in smaller bases, which are, due to Faure, the weakest distributed generalized van der Corput sequences.
AU - Pausinger, Florian
ID - 2904
IS - 3
JF - Journal de Theorie des Nombres des Bordeaux
SN - 2118-8572
TI - Weak multipliers for generalized van der Corput sequences
VL - 24
ER -
TY - CONF
AB - The classical (boolean) notion of refinement for behavioral interfaces of system components is the alternating refinement preorder. In this paper, we define a quantitative measure for interfaces, called interface simulation distance. It makes the alternating refinement preorder quantitative by, intu- itively, tolerating errors (while counting them) in the alternating simulation game. We show that the interface simulation distance satisfies the triangle inequality, that the distance between two interfaces does not increase under parallel composition with a third interface, and that the distance between two interfaces can be bounded from above and below by distances between abstractions of the two interfaces. We illustrate the framework, and the properties of the distances under composition of interfaces, with two case studies.
AU - Cerny, Pavol
AU - Chmelik, Martin
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 2916
T2 - Electronic Proceedings in Theoretical Computer Science
TI - Interface Simulation Distances
VL - 96
ER -
TY - GEN
AB - This paper addresses the problem of approximate MAP-MRF inference in general graphical models. Following [36], we consider a family of linear programming relaxations of the problem where each relaxation is specified by a set of nested pairs of factors for which the marginalization constraint needs to be enforced. We develop a generalization of the TRW-S algorithm [9] for this problem, where we use a decomposition into junction chains, monotonic w.r.t. some ordering on the nodes. This generalizes the monotonic chains in [9] in a natural way. We also show how to deal with nested factors in an efficient way. Experiments show an improvement over min-sum diffusion, MPLP and subgradient ascent algorithms on a number of computer vision and natural language processing problems.
AU - Kolmogorov, Vladimir
AU - Schoenemann, Thomas
ID - 2928
T2 - arXiv
TI - Generalized sequential tree-reweighted message passing
ER -
TY - CONF
AB - In this paper we investigate k-submodular functions. This natural family of discrete functions includes submodular and bisubmodular functions as the special cases k = 1 and k = 2 respectively.
In particular we generalize the known Min-Max-Theorem for submodular and bisubmodular functions. This theorem asserts that the minimum of the (bi)submodular function can be found by solving a maximization problem over a (bi)submodular polyhedron. We define a k-submodular polyhedron, prove a Min-Max-Theorem for k-submodular functions, and give a greedy algorithm to construct the vertices of the polyhedron.
AU - Huber, Anna
AU - Kolmogorov, Vladimir
ID - 2930
TI - Towards minimizing k-submodular functions
VL - 7422
ER -
TY - CONF
AB - The notion of delays arises naturally in many computational models, such as, in the design of circuits, control systems, and dataflow languages. In this work, we introduce automata with delay blocks (ADBs), extending finite state automata with variable time delay blocks, for deferring individual transition output symbols, in a discrete-time setting. We show that the ADB languages strictly subsume the regular languages, and are incomparable in expressive power to the context-free languages. We show that ADBs are closed under union, concatenation and Kleene star, and under intersection with regular languages, but not closed under complementation and intersection with other ADB languages. We show that the emptiness and the membership problems are decidable in polynomial time for ADBs, whereas the universality problem is undecidable. Finally we consider the linear-time model checking problem, i.e., whether the language of an ADB is contained in a regular language, and show that the model checking problem is PSPACE-complete. Copyright 2012 ACM.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Prabhu, Vinayak
ID - 2936
T2 - roceedings of the tenth ACM international conference on Embedded software
TI - Finite automata with time delay blocks
ER -
TY - CONF
AB - Developers building cryptography into security-sensitive applications face a daunting task. Not only must they understand the security guarantees delivered by the constructions they choose, they must also implement and combine them correctly and efficiently. Cryptographic compilers free developers from this task by turning high-level specifications of security goals into efficient implementations. Yet, trusting such tools is hard as they rely on complex mathematical machinery and claim security properties that are subtle and difficult to verify. In this paper we present ZKCrypt, an optimizing cryptographic compiler achieving an unprecedented level of assurance without sacrificing practicality for a comprehensive class of cryptographic protocols, known as Zero-Knowledge Proofs of Knowledge. The pipeline of ZKCrypt integrates purpose-built verified compilers and verifying compilers producing formal proofs in the CertiCrypt framework. By combining the guarantees delivered by each stage, ZKCrypt provides assurance that the output implementation securely realizes the abstract proof goal given as input. We report on the main characteristics of ZKCrypt, highlight new definitions and concepts at its foundations, and illustrate its applicability through a representative example of an anonymous credential system.
AU - Almeida, José
AU - Barbosa, Manuel
AU - Bangerter, Endre
AU - Barthe, Gilles
AU - Krenn, Stephan
AU - Béguelin, Santiago
ID - 2937
T2 - Proceedings of the 2012 ACM conference on Computer and communications security
TI - Full proof cryptography: Verifiable compilation of efficient zero-knowledge protocols
ER -
TY - JOUR
AU - Dolbilin, Nikolai
AU - Edelsbrunner, Herbert
AU - Musin, Oleg
ID - 2941
IS - 4
JF - Russian Mathematical Surveys
TI - On the optimality of functionals over triangulations of Delaunay sets
VL - 67
ER -
TY - JOUR
AB - We examine whether the Escherichia coli chromosome is folded into a self-adherent nucleoprotein complex, or alternately is a confined but otherwise unconstrained self-avoiding polymer. We address this through in vivo visualization, using an inducible GFP fusion to the nucleoid-associated protein Fis to non-specifically decorate the entire chromosome. For a range of different growth conditions, the chromosome is a compact structure that does not fill the volume of the cell, and which moves from the new pole to the cell centre. During rapid growth, chromosome segregation occurs well before cell division, with daughter chromosomes coupled by a thin inter-daughter filament before complete segregation, whereas during slow growth chromosomes stay adjacent until cell division occurs. Image correlation analysis indicates that sub-nucleoid structure is stable on a 1min timescale, comparable to the timescale for redistribution time measured for GFP-Fis after photobleaching. Optical deconvolution and writhe calculation analysis indicate that the nucleoid has a large-scale coiled organization rather than being an amorphous mass. Our observations are consistent with the chromosome having a self-adherent filament organization.
AU - Hadizadeh Yazdi, Nastaran
AU - Guet, Calin C
AU - Johnson, Reid
AU - Marko, John
ID - 2943
IS - 6
JF - Molecular Microbiology
TI - Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions
VL - 86
ER -
TY - JOUR
AB - MicroRNAs (miRNAs) are small noncoding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3′-untranslated region (3′-UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected.
AU - Dueck, Anne
AU - Ziegler, Christian
AU - Eichner, Alexander
AU - Berezikov, Eugène
AU - Meister, Gunter
ID - 2946
IS - 19
JF - Nucleic Acids Research
TI - MicroRNAs associated with the different human Argonaute proteins
VL - 40
ER -
TY - CONF
AB - We introduce games with probabilistic uncertainty, a model for controller synthesis in which the controller observes the state through imprecise sensors that provide correct information about the current state with a fixed probability. That is, in each step, the sensors return an observed state, and given the observed state, there is a probability distribution (due to the estimation error) over the actual current state. The controller must base its decision on the observed state (rather than the actual current state, which it does not know). On the other hand, we assume that the environment can perfectly observe the current state. We show that controller synthesis for qualitative ω-regular objectives in our model can be reduced in polynomial time to standard partial-observation stochastic games, and vice-versa. As a consequence we establish the precise decidability frontier for the new class of games, and establish optimal complexity results for all the decidable problems.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Majumdar, Ritankar
ID - 2947
TI - Equivalence of games with probabilistic uncertainty and partial observation games
VL - 7561
ER -
TY - JOUR
AB - Spontaneous postsynaptic currents (PSCs) provide key information about the mechanisms of synaptic transmission and the activity modes of neuronal networks. However, detecting spontaneous PSCs in vitro and in vivo has been challenging, because of the small amplitude, the variable kinetics, and the undefined time of generation of these events. Here, we describe a, to our knowledge, new method for detecting spontaneous synaptic events by deconvolution, using a template that approximates the average time course of spontaneous PSCs. A recorded PSC trace is deconvolved from the template, resulting in a series of delta-like functions. The maxima of these delta-like events are reliably detected, revealing the precise onset times of the spontaneous PSCs. Among all detection methods, the deconvolution-based method has a unique temporal resolution, allowing the detection of individual events in high-frequency bursts. Furthermore, the deconvolution-based method has a high amplitude resolution, because deconvolution can substantially increase the signal/noise ratio. When tested against previously published methods using experimental data, the deconvolution-based method was superior for spontaneous PSCs recorded in vivo. Using the high-resolution deconvolution-based detection algorithm, we show that the frequency of spontaneous excitatory postsynaptic currents in dentate gyrus granule cells is 4.5 times higher in vivo than in vitro.
AU - Pernia-Andrade, Alejandro
AU - Goswami, Sarit
AU - Stickler, Yvonne
AU - Fröbe, Ulrich
AU - Schlögl, Alois
AU - Jonas, Peter M
ID - 2954
IS - 7
JF - Biophysical Journal
TI - A deconvolution based method with high sensitivity and temporal resolution for detection of spontaneous synaptic currents in vitro and in vivo
VL - 103
ER -
TY - CONF
AB - We consider two-player stochastic games played on finite graphs with reachability objectives where the first player tries to ensure a target state to be visited almost-surely (i.e., with probability 1), or positively (i.e., with positive probability), no matter the strategy of the second player. We classify such games according to the information and the power of randomization available to the players. On the basis of information, the game can be one-sided with either (a) player 1, or (b) player 2 having partial observation (and the other player has perfect observation), or two-sided with (c) both players having partial observation. On the basis of randomization, the players (a) may not be allowed to use randomization (pure strategies), or (b) may choose a probability distribution over actions but the actual random choice is external and not visible to the player (actions invisible), or (c) may use full randomization. Our main results for pure strategies are as follows. (1) For one-sided games with player 1 having partial observation we show that (in contrast to full randomized strategies) belief-based (subset-construction based) strategies are not sufficient, and we present an exponential upper bound on memory both for almostsure and positive winning strategies; we show that the problem of deciding the existence of almost-sure and positive winning strategies for player 1 is EXPTIME-complete. (2) For one-sided games with player 2 having partial observation we show that non-elementary memory is both necessary and sufficient for both almost-sure and positive winning strategies. (3) We show that for the general (two-sided) case finite-memory strategies are sufficient for both positive and almost-sure winning, and at least non-elementary memory is required. We establish the equivalence of the almost-sure winning problems for pure strategies and for randomized strategies with actions invisible. Our equivalence result exhibits serious flaws in previous results of the literature: we show a non-elementary memory lower bound for almost-sure winning whereas an exponential upper bound was previously claimed.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 2955
T2 - Proceedings of the 2012 27th Annual ACM/IEEE Symposium on Logic in Computer Science
TI - Partial-observation stochastic games: How to win when belief fails
ER -
TY - CONF
AB - We consider probabilistic automata on infinite words with acceptance defined by parity conditions. We consider three qualitative decision problems: (i) the positive decision problem asks whether there is a word that is accepted with positive probability; (ii) the almost decision problem asks whether there is a word that is accepted with probability 1; and (iii) the limit decision problem asks whether words are accepted with probability arbitrarily close to 1. We unify and generalize several decidability results for probabilistic automata over infinite words, and identify a robust (closed under union and intersection) subclass of probabilistic automata for which all the qualitative decision problems are decidable for parity conditions. We also show that if the input words are restricted to lasso shape (regular) words, then the positive and almost problems are decidable for all probabilistic automata with parity conditions. For most decidable problems we show an optimal PSPACE-complete complexity bound.
AU - Chatterjee, Krishnendu
AU - Tracol, Mathieu
ID - 2957
T2 - Proceedings of the 2012 27th Annual ACM/IEEE Symposium on Logic in Computer Science
TI - Decidable problems for probabilistic automata on infinite words
ER -
TY - JOUR
AB - The activity of hippocampal pyramidal cells reflects both the current position of the animal and information related to its current behavior. Here we investigated whether single hippocampal neurons can encode several independent features defining trials during a memory task. We also tested whether task-related information is represented by partial remapping of the place cell population or, instead, via firing rate modulation of spatially stable place cells. To address these two questions, the activity of hippocampal neurons was recorded in rats performing a conditional discrimination task on a modified T-maze in which the identity of a food reward guided behavior. When the rat was on the central arm of the maze, the firing rate of pyramidal cells changed depending on two independent factors: (1) the identity of the food reward given to the animal and (2) the previous location of the animal on the maze. Importantly, some pyramidal cells encoded information relative to both factors. This trial-type specific and retrospective coding did not interfere with the spatial representation of the maze: hippocampal cells had stable place fields and their theta-phase precession profiles were unaltered during the task, indicating that trial-related information was encoded via rate remapping. During error trials, encoding of both trial-related information and spatial location was impaired. Finally, we found that pyramidal cells also encode trial-related information via rate remapping during the continuous version of the rewarded alternation task without delays. These results suggest that hippocampal neurons can encode several task-related cognitive aspects via rate remapping.
AU - Allen, Kevin
AU - Rawlins, J Nick
AU - Bannerman, David
AU - Csicsvari, Jozsef L
ID - 2958
IS - 42
JF - Journal of Neuroscience
TI - Hippocampal place cells can encode multiple trial-dependent features through rate remapping
VL - 32
ER -
TY - JOUR
AB - We study maximum likelihood estimation in Gaussian graphical models from a geometric point of view. An algebraic elimination criterion allows us to find exact lower bounds on the number of observations needed to ensure that the maximum likelihood estimator (MLE) exists with probability one. This is applied to bipartite graphs, grids and colored graphs. We also study the ML degree, and we present the first instance of a graph for which the MLE exists with probability one, even when the number of observations equals the treewidth.
AU - Uhler, Caroline
ID - 2959
IS - 1
JF - Annals of Statistics
TI - Geometry of maximum likelihood estimation in Gaussian graphical models
VL - 40
ER -
TY - JOUR
AB - The choice of summary statistics is a crucial step in approximate Bayesian computation (ABC). Since statistics are often not sufficient, this choice involves a trade-off between loss of information and reduction of dimensionality. The latter may increase the efficiency of ABC. Here, we propose an approach for choosing summary statistics based on boosting, a technique from the machine learning literature. We consider different types of boosting and compare them to partial least squares regression as an alternative. To mitigate the lack of sufficiency, we also propose an approach for choosing summary statistics locally, in the putative neighborhood of the true parameter value. We study a demographic model motivated by the re-introduction of Alpine ibex (Capra ibex) into the Swiss Alps. The parameters of interest are the mean and standard deviation across microsatellites of the scaled ancestral mutation rate (θanc = 4 Ne u), and the proportion of males obtaining access to matings per breeding season (ω). By simulation, we assess the properties of the posterior distribution obtained with the various methods. According to our criteria, ABC with summary statistics chosen locally via boosting with the L2-loss performs best. Applying that method to the ibex data, we estimate θanc ≈ 1.288, and find that most of the variation across loci of the ancestral mutation rate u is between 7.7×10−4 and 3.5×10−3 per locus per generation. The proportion of males with access to matings is estimated to ω ≈ 0.21, which is in good agreement with recent independent estimates.
AU - Aeschbacher, Simon
AU - Beaumont, Mark
AU - Futschik, Andreas
ID - 2962
IS - 3
JF - Genetics
TI - A novel approach for choosing summary statistics in approximate Bayesian computation
VL - 192
ER -
TY - JOUR
AB - Dieser Artikel soll die sechs verschiedenen Creative Commons Lizenzen erläutern und ihre Bedeutung im Rahmen des wissenschaftlichen Publizierens und des Open Access erklären (CC-BY, CC-BY-SA, CC-BY-NC, CC-BY-ND, CC-BYNC-SA, CC-BY-NC-ND).
AU - Danowski, Patrick
ID - 2965
IS - 2
JF - Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen & Bibliothekare
TI - Kontext Open Access: Creative Commons
VL - 65
ER -
TY - JOUR
AB - Background: The outcome of male-male competition can be predicted from the relative fighting qualities of the opponents, which often depend on their age. In insects, freshly emerged and still sexually inactive males are morphologically indistinct from older, sexually active males. These young inactive males may thus be easy targets for older males if they cannot conceal themselves from their attacks. The ant Cardiocondyla obscurior is characterised by lethal fighting between wingless (" ergatoid" ) males. Here, we analyse for how long young males are defenceless after eclosion, and how early adult males can detect the presence of rival males.Results: We found that old ergatoid males consistently won fights against ergatoid males younger than two days. Old males did not differentiate between different types of unpigmented pupae several days before emergence, but had more frequent contact to ready-to-eclose pupae of female sexuals and winged males than of workers and ergatoid males. In rare cases, old ergatoid males displayed alleviated biting of pigmented ergatoid male pupae shortly before adult eclosion, as well as copulation attempts to dark pupae of female sexuals and winged males. Ergatoid male behaviour may be promoted by a closer similarity of the chemical profile of ready-to-eclose pupae to the profile of adults than that of young pupae several days prior to emergence.Conclusion: Young ergatoid males of C. obscurior would benefit greatly by hiding their identity from older, resident males, as they are highly vulnerable during the first two days of their adult lives. In contrast to the winged males of the same species, which are able to prevent ergatoid male attacks by chemical female mimicry, young ergatoids do not seem to be able to produce a protective chemical profile. Conflicts in male-male competition between ergatoid males of different age thus seem to be resolved in favour of the older males. This might represent selection at the colony level rather than the individual level. © 2012 Cremer et al.; licensee BioMed Central Ltd.
AU - Cremer, Sylvia
AU - Suefuji, Masaki
AU - Schrempf, Alexandra
AU - Heinze, Jürgen
ID - 2966
JF - BMC Ecology
TI - The dynamics of male-male competition in Cardiocondyla obscurior ants
VL - 12
ER -
TY - JOUR
AB - Little is known about the stability of trophic relationships in complex natural communities over evolutionary timescales. Here, we use sequence data from 18 nuclear loci to reconstruct and compare the intraspecific histories of major Pleistocene refugial populations in the Middle East, the Balkans and Iberia in a guild of four Chalcid parasitoids (Cecidostiba fungosa, Cecidostiba semifascia, Hobbya stenonota and Mesopolobus amaenus) all attacking Cynipid oak galls. We develop a likelihood method to numerically estimate models of divergence between three populations from multilocus data. We investigate the power of this framework on simulated data, and-using triplet alignments of intronic loci-quantify the support for all possible divergence relationships between refugial populations in the four parasitoids. Although an East to West order of population divergence has highest support in all but one species, we cannot rule out alternative population tree topologies. Comparing the estimated times of population splits between species, we find that one species, M. amaenus, has a significantly older history than the rest of the guild and must have arrived in central Europe at least one glacial cycle prior to other guild members. This suggests that although all four species may share a common origin in the East, they expanded westwards into Europe at different times. © 2012 Blackwell Publishing Ltd.
AU - Lohse, Konrad
AU - Barton, Nicholas H
AU - Melika, George
AU - Stone, Graham
ID - 2968
IS - 18
JF - Molecular Ecology
TI - A likelihood based comparison of population histories in a parasitoid guild
VL - 21
ER -
TY - JOUR
AB - The coupling between presynaptic Ca^(2+) channels and Ca^(2+) sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca^(2+) channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic
opening of presynaptic Ca^(2+) channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal
granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca^(2+) concentration and the unselective Ca^(2+) channel blocker Cd^(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ~50%, suggesting that the opening of presynaptic Ca^(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca^(2+) channel blocker
ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced
mIPSC frequency. Furthermore, both the fast Ca^(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency,
suggesting that Ca^(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB_(1) receptor
agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca^(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca^(2+) channels may be important for hippocampal information processing.
AU - Goswami, Sarit
AU - Bucurenciu, Iancu
AU - Jonas, Peter M
ID - 2969
IS - 41
JF - Journal of Neuroscience
TI - Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca^(2+) channels via microdomain coupling
VL - 32
ER -
TY - JOUR
AB - Energy parity games are infinite two-player turn-based games played on weighted graphs. The objective of the game combines a (qualitative) parity condition with the (quantitative) requirement that the sum of the weights (i.e., the level of energy in the game) must remain positive. Beside their own interest in the design and synthesis of resource-constrained omega-regular specifications, energy parity games provide one of the simplest model of games with combined qualitative and quantitative objectives. Our main results are as follows: (a) exponential memory is sufficient and may be necessary for winning strategies in energy parity games; (b) the problem of deciding the winner in energy parity games can be solved in NP ∩ coNP; and (c) we give an algorithm to solve energy parity by reduction to energy games. We also show that the problem of deciding the winner in energy parity games is logspace-equivalent to the problem of deciding the winner in mean-payoff parity games, which can thus be solved in NP ∩ coNP. As a consequence we also obtain a conceptually simple algorithm to solve mean-payoff parity games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 2972
JF - Theoretical Computer Science
TI - Energy parity games
VL - 458
ER -
TY - CONF
AB - We construct a perfectly binding string commitment scheme whose security is based on the learning parity with noise (LPN) assumption, or equivalently, the hardness of decoding random linear codes. Our scheme not only allows for a simple and efficient zero-knowledge proof of knowledge for committed values (essentially a Σ-protocol), but also for such proofs showing any kind of relation amongst committed values, i.e. proving that messages m_0,...,m_u, are such that m_0=C(m_1,...,m_u) for any circuit C.
To get soundness which is exponentially small in a security parameter t, and when the zero-knowledge property relies on the LPN problem with secrets of length l, our 3 round protocol has communication complexity O(t|C|l log(l)) and computational complexity of O(t|C|l) bit operations. The hidden constants are small, and the computation consists mostly of computing inner products of bit-vectors.
AU - Jain, Abhishek
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Tentes, Aris
ED - Wang, Xiaoyun
ED - Sako, Kazue
ID - 2974
TI - Commitments and efficient zero knowledge proofs from learning parity with noise
VL - 7658
ER -
TY - JOUR
AB - We consider the offset-deconstruction problem: Given a polygonal shape Q with n vertices, can it be expressed, up to a tolerance ε in Hausdorff distance, as the Minkowski sum of another polygonal shape P with a disk of fixed radius? If it does, we also seek a preferably simple-looking solution P; then, P's offset constitutes an accurate, vertex-reduced, and smoothened approximation of Q. We give an O(nlogn)-time exact decision algorithm that handles any polygonal shape, assuming the real-RAM model of computation. A variant of the algorithm, which we have implemented using the cgal library, is based on rational arithmetic and answers the same deconstruction problem up to an uncertainty parameter δ its running time additionally depends on δ. If the input shape is found to be approximable, this algorithm also computes an approximate solution for the problem. It also allows us to solve parameter-optimization problems induced by the offset-deconstruction problem. For convex shapes, the complexity of the exact decision algorithm drops to O(n), which is also the time required to compute a solution P with at most one more vertex than a vertex-minimal one.
AU - Berberich, Eric
AU - Halperin, Dan
AU - Kerber, Michael
AU - Pogalnikova, Roza
ID - 3115
IS - 4
JF - Discrete & Computational Geometry
TI - Deconstructing approximate offsets
VL - 48
ER -
TY - JOUR
AB - We consider the problem of minimizing a function represented as a sum of submodular terms. We assume each term allows an efficient computation of exchange capacities. This holds, for example, for terms depending on a small number of variables, or for certain cardinality-dependent terms. A naive application of submodular minimization algorithms would not exploit the existence of specialized exchange capacity subroutines for individual terms. To overcome this, we cast the problem as a submodular flow (SF) problem in an auxiliary graph in such a way that applying most existing SF algorithms would rely only on these subroutines. We then explore in more detail Iwata's capacity scaling approach for submodular flows (Iwata 1997 [19]). In particular, we show how to improve its complexity in the case when the function contains cardinality-dependent terms.
AU - Kolmogorov, Vladimir
ID - 3117
IS - 15
JF - Discrete Applied Mathematics
TI - Minimizing a sum of submodular functions
VL - 160
ER -
TY - JOUR
AB - We present a method for recovering a temporally coherent, deforming triangle mesh with arbitrarily changing topology from an incoherent sequence of static closed surfaces. We solve this problem using the surface geometry alone, without any prior information like surface templates or velocity fields. Our system combines a proven strategy for triangle mesh improvement, a robust multi-resolution non-rigid registration routine, and a reliable technique for changing surface mesh topology. We also introduce a novel topological constraint enforcement algorithm to ensure that the output and input always have similar topology. We apply our technique to a series of diverse input data from video reconstructions, physics simulations, and artistic morphs. The structured output of our algorithm allows us to efficiently track information like colors and displacement maps, recover velocity information, and solve PDEs on the mesh as a post process.
AU - Bojsen-Hansen, Morten
AU - Li, Hao
AU - Wojtan, Christopher J
ID - 3118
IS - 4
JF - ACM Transactions on Graphics
TI - Tracking surfaces with evolving topology
VL - 31
ER -
TY - CONF
AB - We present an approach for artist-directed animation of liquids using multiple levels of control over the simulation, ranging from the overall tracking of desired shapes to highly detailed secondary effects such as dripping streams, separating sheets of fluid, surface waves and ripples. The first portion of our technique is a volume preserving morph that allows the animator to produce a plausible fluid-like motion from a sparse set of control meshes. By rasterizing the resulting control meshes onto the simulation grid, the mesh velocities act as boundary conditions during the projection step of the fluid simulation. We can then blend this motion together with uncontrolled fluid velocities to achieve a more relaxed control over the fluid that captures natural inertial effects. Our method can produce highly detailed liquid surfaces with control over sub-grid details by using a mesh-based surface tracker on top of a coarse grid-based fluid simulation. We can create ripples and waves on the fluid surface attracting the surface mesh to the control mesh with spring-like forces and also by running a wave simulation over the surface mesh. Our video results demonstrate how our control scheme can be used to create animated characters and shapes that are made of water.
AU - Raveendran, Karthik
AU - Thuerey, Nils
AU - Wojtan, Christopher J
AU - Turk, Greg
ID - 3119
T2 - Proceedings of the ACM SIGGRAPH/Eurographics Symposium on Computer Animation
TI - Controlling liquids using meshes
ER -
TY - JOUR
AB - We introduce a strategy based on Kustin-Miller unprojection that allows us to construct many hundreds of Gorenstein codimension 4 ideals with 9 × 16 resolutions (that is, nine equations and sixteen first syzygies). Our two basic games are called Tom and Jerry; the main application is the biregular construction of most of the anticanonically polarised Mori Fano 3-folds of Altinok's thesis. There are 115 cases whose numerical data (in effect, the Hilbert series) allow a Type I projection. In every case, at least one Tom and one Jerry construction works, providing at least two deformation families of quasismooth Fano 3-folds having the same numerics but different topology. © 2012 Copyright Foundation Compositio Mathematica.
AU - Brown, Gavin
AU - Kerber, Michael
AU - Reid, Miles
ID - 3120
IS - 4
JF - Compositio Mathematica
TI - Fano 3 folds in codimension 4 Tom and Jerry Part I
VL - 148
ER -
TY - JOUR
AB - Voltage-activated Ca(2+) channels (VACCs) mediate Ca(2+) influx to trigger action potential-evoked neurotransmitter release, but the mechanism by which Ca(2+) regulates spontaneous transmission is unclear. We found that VACCs are the major physiological triggers for spontaneous release at mouse neocortical inhibitory synapses. Moreover, despite the absence of a synchronizing action potential, we found that spontaneous fusion of a GABA-containing vesicle required the activation of multiple tightly coupled VACCs of variable type.
AU - Williams, Courtney
AU - Chen, Wenyan
AU - Lee, Chia
AU - Yaeger, Daniel
AU - Vyleta, Nicholas
AU - Smith, Stephen
ID - 3121
IS - 9
JF - Nature Neuroscience
TI - Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA
VL - 15
ER -
TY - CONF
AB - We introduce the idea of using an explicit triangle mesh to track the air/fluid interface in a smoothed particle hydrodynamics (SPH) simulator. Once an initial surface mesh is created, this mesh is carried forward in time using nearby particle velocities to advect the mesh vertices. The mesh connectivity remains mostly unchanged across time-steps; it is only modified locally for topology change events or for the improvement of triangle quality. In order to ensure that the surface mesh does not diverge from the underlying particle simulation, we periodically project the mesh surface onto an implicit surface defined by the physics simulation. The mesh surface gives us several advantages over previous SPH surface tracking techniques. We demonstrate a new method for surface tension calculations that clearly outperforms the state of the art in SPH surface tension for computer graphics. We also demonstrate a method for tracking detailed surface information (like colors) that is less susceptible to numerical diffusion than competing techniques. Finally, our temporally-coherent surface mesh allows us to simulate high-resolution surface wave dynamics without being limited by the particle resolution of the SPH simulation.
AU - Yu, Jihun
AU - Wojtan, Christopher J
AU - Turk, Greg
AU - Yap, Chee
ID - 3123
IS - 2
T2 - Computer Graphics Forum
TI - Explicit mesh surfaces for particle based fluids
VL - 31
ER -
TY - CONF
AB - We consider the problem of inference in a graphical model with binary variables. While in theory it is arguably preferable to compute marginal probabilities, in practice researchers often use MAP inference due to the availability of efficient discrete optimization algorithms. We bridge the gap between the two approaches by introducing the Discrete Marginals technique in which approximate marginals are obtained by minimizing an objective function with unary and pairwise terms over a discretized domain. This allows the use of techniques originally developed for MAP-MRF inference and learning. We explore two ways to set up the objective function - by discretizing the Bethe free energy and by learning it from training data. Experimental results show that for certain types of graphs a learned function can outperform the Bethe approximation. We also establish a link between the Bethe free energy and submodular functions.
AU - Korc, Filip
AU - Kolmogorov, Vladimir
AU - Lampert, Christoph
ID - 3124
TI - Approximating marginals using discrete energy minimization
ER -
TY - CONF
AB - We propose a new learning method to infer a mid-level feature representation that combines the advantage of semantic attribute representations with the higher expressive power of non-semantic features. The idea lies in augmenting an existing attribute-based representation with additional dimensions for which an autoencoder model is coupled with a large-margin principle. This construction allows a smooth transition between the zero-shot regime with no training example, the unsupervised regime with training examples but without class labels, and the supervised regime with training examples and with class labels. The resulting optimization problem can be solved efficiently, because several of the necessity steps have closed-form solutions. Through extensive experiments we show that the augmented representation achieves better results in terms of object categorization accuracy than the semantic representation alone.
AU - Sharmanska, Viktoriia
AU - Quadrianto, Novi
AU - Lampert, Christoph
ID - 3125
IS - PART 5
TI - Augmented attribute representations
VL - 7576
ER -
TY - CONF
AB - When searching for characteristic subpatterns in potentially noisy graph data, it appears self-evident that having multiple observations would be better than having just one. However, it turns out that the inconsistencies introduced when different graph instances have different edge sets pose a serious challenge. In this work we address this challenge for the problem of finding maximum weighted cliques.
We introduce the concept of most persistent soft-clique. This is subset of vertices, that 1) is almost fully or at least densely connected, 2) occurs in all or almost all graph instances, and 3) has the maximum weight. We present a measure of clique-ness, that essentially counts the number of edge missing to make a subset of vertices into a clique. With this measure, we show that the problem of finding the most persistent soft-clique problem can be cast either as: a) a max-min two person game optimization problem, or b) a min-min soft margin optimization problem. Both formulations lead to the same solution when using a partial Lagrangian method to solve the optimization problems. By experiments on synthetic data and on real social network data, we show that the proposed method is able to reliably find soft cliques in graph data, even if that is distorted by random noise or unreliable observations.
AU - Quadrianto, Novi
AU - Lampert, Christoph
AU - Chen, Chao
ID - 3127
T2 - Proceedings of the 29th International Conference on Machine Learning
TI - The most persistent soft-clique in a set of sampled graphs
ER -
TY - JOUR
AB - We consider two-player zero-sum stochastic games on graphs with ω-regular winning conditions specified as parity objectives. These games have applications in the design and control of reactive systems. We survey the complexity results for the problem of deciding the winner in such games, and in classes of interest obtained as special cases, based on the information and the power of randomization available to the players, on the class of objectives and on the winning mode. On the basis of information, these games can be classified as follows: (a) partial-observation (both players have partial view of the game); (b) one-sided partial-observation (one player has partial-observation and the other player has complete-observation); and (c) complete-observation (both players have complete view of the game). The one-sided partial-observation games have two important subclasses: the one-player games, known as partial-observation Markov decision processes (POMDPs), and the blind one-player games, known as probabilistic automata. On the basis of randomization, (a) the players may not be allowed to use randomization (pure strategies), or (b) they may choose a probability distribution over actions but the actual random choice is external and not visible to the player (actions invisible), or (c) they may use full randomization. Finally, various classes of games are obtained by restricting the parity objective to a reachability, safety, Büchi, or coBüchi condition. We also consider several winning modes, such as sure-winning (i.e., all outcomes of a strategy have to satisfy the winning condition), almost-sure winning (i.e., winning with probability 1), limit-sure winning (i.e., winning with probability arbitrarily close to 1), and value-threshold winning (i.e., winning with probability at least ν, where ν is a given rational).
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ID - 3128
IS - 2
JF - Formal Methods in System Design
TI - A survey of partial-observation stochastic parity games
VL - 43
ER -
TY - CONF
AB - Let K be a simplicial complex and g the rank of its p-th homology group Hp(K) defined with ℤ2 coefficients. We show that we can compute a basis H of Hp(K) and annotate each p-simplex of K with a binary vector of length g with the following property: the annotations, summed over all p-simplices in any p-cycle z, provide the coordinate vector of the homology class [z] in the basis H. The basis and the annotations for all simplices can be computed in O(n ω ) time, where n is the size of K and ω < 2.376 is a quantity so that two n×n matrices can be multiplied in O(n ω ) time. The precomputed annotations permit answering queries about the independence or the triviality of p-cycles efficiently.
Using annotations of edges in 2-complexes, we derive better algorithms for computing optimal basis and optimal homologous cycles in 1 - dimensional homology. Specifically, for computing an optimal basis of H1(K) , we improve the previously known time complexity from O(n 4) to O(n ω + n 2 g ω − 1). Here n denotes the size of the 2-skeleton of K and g the rank of H1(K) . Computing an optimal cycle homologous to a given 1-cycle is NP-hard even for surfaces and an algorithm taking 2 O(g) nlogn time is known for surfaces. We extend this algorithm to work with arbitrary 2-complexes in O(n ω ) + 2 O(g) n 2logn time using annotations.
AU - Busaryev, Oleksiy
AU - Cabello, Sergio
AU - Chen, Chao
AU - Dey, Tamal
AU - Wang, Yusu
ID - 3129
TI - Annotating simplices with a homology basis and its applications
VL - 7357
ER -
TY - JOUR
AB - Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes.
AU - Bergmiller, Tobias
AU - Ackermann, Martin
AU - Silander, Olin
ID - 3130
IS - 6
JF - PLoS Genetics
TI - Patterns of evolutionary conservation of essential genes correlate with their compensability
VL - 8
ER -
TY - JOUR
AB - In large populations, many beneficial mutations may be simultaneously available and may compete with one another, slowing adaptation. By finding the probability of fixation of a favorable allele in a simple model of a haploid sexual population, we find limits to the rate of adaptive substitution, Λ, that depend on simple parameter combinations. When variance in fitness is low and linkage is loose, the baseline rate of substitution is Λ 0=2NU〈s〉 is the population size, U is the rate of beneficial mutations per genome, and 〈s〉 is their mean selective advantage. Heritable variance ν in log fitness due to unlinked loci reduces Λ by e -4ν under polygamy and e -8ν under monogamy. With a linear genetic map of length R Morgans, interference is yet stronger. We use a scaling argument to show that the density of adaptive substitutions depends on s, N, U, and R only through the baseline density: Λ/R=F(Λ 0/R). Under the approximation that the interference due to different sweeps adds up, we show that Λ/R~(Λ 0/R)/(1+2Λ 0/R), implying that interference prevents the rate of adaptive substitution from exceeding one per centimorgan per 200 generations. Simulations and numerical calculations confirm the scaling argument and confirm the additive approximation for Λ 0/R 1; for higher Λ 0/R, the rate of adaptation grows above R/2, but only very slowly. We also consider the effect of sweeps on neutral diversity and show that, while even occasional sweeps can greatly reduce neutral diversity, this effect saturates as sweeps become more common-diversity can be maintained even in populations experiencing very strong interference. Our results indicate that for some organisms the rate of adaptive substitution may be primarily recombination-limited, depending only weakly on the mutation supply and the strength of selection.
AU - Weissman, Daniel
AU - Barton, Nicholas H
ID - 3131
IS - 6
JF - PLoS Genetics
TI - Limits to the rate of adaptive substitution in sexual populations
VL - 8
ER -
TY - CONF
AB - This note contributes to the point calculus of persistent homology by extending Alexander duality from spaces to real-valued functions. Given a perfect Morse function f: S n+1 →[0, 1 and a decomposition S n+1 = U ∪ V into two (n + 1)-manifolds with common boundary M, we prove elementary relationships between the persistence diagrams of f restricted to U, to V, and to M.
AU - Edelsbrunner, Herbert
AU - Kerber, Michael
ID - 3133
T2 - Proceedings of the twenty-eighth annual symposium on Computational geometry
TI - Alexander duality for functions: The persistent behavior of land and water and shore
ER -
TY - CONF
AB - We introduce consumption games, a model for discrete interactive system with multiple resources that are consumed or reloaded independently. More precisely, a consumption game is a finite-state graph where each transition is labeled by a vector of resource updates, where every update is a non-positive number or ω. The ω updates model the reloading of a given resource. Each vertex belongs either to player □ or player ◇, where the aim of player □ is to play so that the resources are never exhausted. We consider several natural algorithmic problems about consumption games, and show that although these problems are computationally hard in general, they are solvable in polynomial time for every fixed number of resource types (i.e., the dimension of the update vectors) and bounded resource updates.
AU - Brázdil, Brázdil
AU - Chatterjee, Krishnendu
AU - Kučera, Antonín
AU - Novotny, Petr
ID - 3135
TI - Efficient controller synthesis for consumption games with multiple resource types
VL - 7358
ER -
TY - CONF
AB - We propose synchronous interfaces, a new interface theory for discrete-time systems. We use an application to time-triggered scheduling to drive the design choices for our formalism; in particular, additionally to deriving useful mathematical properties, we focus on providing a syntax which is adapted to natural high-level system modeling. As a result, we develop an interface model that relies on a guarded-command based language and is equipped with shared variables and explicit discrete-time clocks. We define all standard interface operations: compatibility checking, composition, refinement, and shared refinement. Apart from the synchronous interface model, the contribution of this paper is the establishment of a formal relation between interface theories and real-time scheduling, where we demonstrate a fully automatic framework for the incremental computation of time-triggered schedules.
AU - Delahaye, Benoît
AU - Fahrenberg, Uli
AU - Henzinger, Thomas A
AU - Legay, Axel
AU - Nickovic, Dejan
ID - 3155
TI - Synchronous interface theories and time triggered scheduling
VL - 7273
ER -
TY - JOUR
AB - Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.
AU - Diaz Jr, Luis
AU - Williams, Richard
AU - Wu, Jian
AU - Kinde, Isaac
AU - Hecht, Joel
AU - Berlin, Jordan
AU - Allen, Benjamin
AU - Božić, Ivana
AU - Reiter, Johannes
AU - Nowak, Martin
AU - Kinzler, Kenneth
AU - Oliner, Kelly
AU - Vogelstein, Bert
ID - 3157
IS - 7404
JF - Nature
TI - The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers
VL - 486
ER -
TY - JOUR
AB - We describe here the development and characterization of a conditionally inducible mouse model expressing Lifeact-GFP, a peptide that reports the dynamics of filamentous actin. We have used this model to study platelets, megakaryocytes and melanoblasts and we provide evidence that Lifeact-GFP is a useful reporter in these cell types ex vivo. In the case of platelets and megakaryocytes, these cells are not transfectable by traditional methods, so conditional activation of Lifeact allows the study of actin dynamics in these cells live. We studied melanoblasts in native skin explants from embryos, allowing the visualization of live actin dynamics during cytokinesis and migration. Our study revealed that melanoblasts lacking the small GTPase Rac1 show a delay in the formation of new pseudopodia following cytokinesis that accounts for the previously reported cytokinesis delay in these cells. Thus, through use of this mouse model, we were able to gain insights into the actin dynamics of cells that could only previously be studied using fixed specimens or following isolation from their native tissue environment.
AU - Schachtner, Hannah
AU - Li, Ang
AU - Stevenson, David
AU - Calaminus, Simon
AU - Thomas, Steven
AU - Watson, Steve
AU - Sixt, Michael K
AU - Wedlich Söldner, Roland
AU - Strathdee, Douglas
AU - Machesky, Laura
ID - 3158
IS - 11-12
JF - European Journal of Cell Biology
TI - Tissue inducible Lifeact expression allows visualization of actin dynamics in vivo and ex vivo
VL - 91
ER -
TY - JOUR
AB - The structure of hierarchical networks in biological and physical systems has long been characterized using the Horton-Strahler ordering scheme. The scheme assigns an integer order to each edge in the network based on the topology of branching such that the order increases from distal parts of the network (e.g., mountain streams or capillaries) to the "root" of the network (e.g., the river outlet or the aorta). However, Horton-Strahler ordering cannot be applied to networks with loops because they they create a contradiction in the edge ordering in terms of which edge precedes another in the hierarchy. Here, we present a generalization of the Horton-Strahler order to weighted planar reticular networks, where weights are assumed to correlate with the importance of network edges, e.g., weights estimated from edge widths may correlate to flow capacity. Our method assigns hierarchical levels not only to edges of the network, but also to its loops, and classifies the edges into reticular edges, which are responsible for loop formation, and tree edges. In addition, we perform a detailed and rigorous theoretical analysis of the sensitivity of the hierarchical levels to weight perturbations. In doing so, we show that the ordering of the reticular edges is more robust to noise in weight estimation than is the ordering of the tree edges. We discuss applications of this generalized Horton-Strahler ordering to the study of leaf venation and other biological networks.
AU - Mileyko, Yuriy
AU - Edelsbrunner, Herbert
AU - Price, Charles
AU - Weitz, Joshua
ID - 3159
IS - 6
JF - PLoS One
TI - Hierarchical ordering of reticular networks
VL - 7
ER -
TY - JOUR
AB - First we note that the best polynomial approximation to vertical bar x vertical bar on the set, which consists of an interval on the positive half-axis and a point on the negative half-axis, can be given by means of the classical Chebyshev polynomials. Then we explore the cases when a solution of the related problem on two intervals can be given in elementary functions.
AU - Pausinger, Florian
ID - 6588
IS - 1
JF - Journal of Mathematical Physics, Analysis, Geometry
SN - 1812-9471
TI - Elementary solutions of the Bernstein problem on two intervals
VL - 8
ER -
TY - CONF
AB - Software model checking, as an undecidable problem, has three possible outcomes: (1) the program satisfies the specification, (2) the program does not satisfy the specification, and (3) the model checker fails. The third outcome usually manifests itself in a space-out, time-out, or one component of the verification tool giving up; in all of these failing cases, significant computation is performed by the verification tool before the failure, but no result is reported. We propose to reformulate the model-checking problem as follows, in order to have the verification tool report a summary of the performed work even in case of failure: given a program and a specification, the model checker returns a condition Ψ - usually a state predicate - such that the program satisfies the specification under the condition Ψ - that is, as long as the program does not leave the states in which Ψ is satisfied. In our experiments, we investigated as one major application of conditional model checking the sequential combination of model checkers with information passing. We give the condition that one model checker produces, as input to a second conditional model checker, such that the verification problem for the second is restricted to the part of the state space that is not covered by the condition, i.e., the second model checker works on the problems that the first model checker could not solve. Our experiments demonstrate that repeated application of conditional model checkers, passing information from one model checker to the next, can significantly improve the verification results and performance, i.e., we can now verify programs that we could not verify before.
AU - Beyer, Dirk
AU - Henzinger, Thomas A
AU - Keremoglu, Mehmet
AU - Wendler, Philipp
ID - 1384
T2 - Proceedings of the ACM SIGSOFT 20th International Symposium on the Foundations of Software Engineering
TI - Conditional model checking: A technique to pass information between verifiers
ER -
TY - JOUR
AB - Some inflammatory stimuli trigger activation of the NLRP3 inflammasome by inducing efflux of cellular potassium. Loss of cellular potassium is known to potently suppress protein synthesis, leading us to test whether the inhibition of protein synthesis itself serves as an activating signal for the NLRP3 inflammasome. Murine bone marrow-derived macrophages, either primed by LPS or unprimed, were exposed to a panel of inhibitors of ribosomal function: ricin, cycloheximide, puromycin, pactamycin, and anisomycin. Macrophages were also exposed to nigericin, ATP, monosodium urate (MSU), and poly I:C. Synthesis of pro-IL-ß and release of IL-1ß from cells in response to these agents was detected by immunoblotting and ELISA. Release of intracellular potassium was measured by mass spectrometry. Inhibition of translation by each of the tested translation inhibitors led to processing of IL-1ß, which was released from cells. Processing and release of IL-1ß was reduced or absent from cells deficient in NLRP3, ASC, or caspase-1, demonstrating the role of the NLRP3 inflammasome. Despite the inability of these inhibitors to trigger efflux of intracellular potassium, the addition of high extracellular potassium suppressed activation of the NLRP3 inflammasome. MSU and double-stranded RNA, which are known to activate the NLRP3 inflammasome, also substantially inhibited protein translation, supporting a close association between inhibition of translation and inflammasome activation. These data demonstrate that translational inhibition itself constitutes a heretofore-unrecognized mechanism underlying IL-1ß dependent inflammatory signaling and that other physical, chemical, or pathogen-associated agents that impair translation may lead to IL-1ß-dependent inflammation through activation of the NLRP3 inflammasome. For agents that inhibit translation through decreased cellular potassium, the application of high extracellular potassium restores protein translation and suppresses activation of the NLRP inflammasome. For agents that inhibit translation through mechanisms that do not involve loss of potassium, high extracellular potassium suppresses IL-1ß processing through a mechanism that remains undefined.
AU - Vyleta, Meghan
AU - Wong, John
AU - Magun, Bruce
ID - 3161
IS - 5
JF - PLoS One
TI - Suppression of ribosomal function triggers innate immune signaling through activation of the NLRP3 inflammasome
VL - 7
ER -
TY - CONF
AB - Given a dense-time real-valued signal and a parameterized temporal logic formula with both magnitude and timing parameters, we compute the subset of the parameter space that renders the formula satisfied by the trace. We provide two preliminary implementations, one which follows the exact semantics and attempts to compute the validity domain by quantifier elimination in linear arithmetics and one which conducts adaptive search in the parameter space.
AU - Asarin, Eugene
AU - Donzé, Alexandre
AU - Maler, Oded
AU - Nickovic, Dejan
ID - 3162
TI - Parametric identification of temporal properties
VL - 7186
ER -
TY - JOUR
AB - There is evidence that the genetic code was established prior to the existence of proteins, when metabolism was powered by ribozymes. Also, early proto-organisms had to rely on simple anaerobic bioenergetic processes. In this work I propose that amino acid fermentation powered metabolism in the RNA world, and that this was facilitated by proto-adapters, the precursors of the tRNAs. Amino acids were used as carbon sources rather than as catalytic or structural elements. In modern bacteria, amino acid fermentation is known as the Stickland reaction. This pathway involves two amino acids: the first undergoes oxidative deamination, and the second acts as an electron acceptor through reductive deamination. This redox reaction results in two keto acids that are employed to synthesise ATP via substrate-level phosphorylation. The Stickland reaction is the basic bioenergetic pathway of some bacteria of the genus Clostridium. Two other facts support Stickland fermentation in the RNA world. First, several Stickland amino acid pairs are synthesised in abiotic amino acid synthesis. This suggests that amino acids that could be used as an energy substrate were freely available. Second, anticodons that have complementary sequences often correspond to amino acids that form Stickland pairs. The main hypothesis of this paper is that pairs of complementary proto-adapters were assigned to Stickland amino acids pairs. There are signatures of this hypothesis in the genetic code. Furthermore, it is argued that the proto-adapters formed double strands that brought amino acid pairs into proximity to facilitate their mutual redox reaction, structurally constraining the anticodon pairs that are assigned to these amino acid pairs. Significance tests which randomise the code are performed to study the extent of the variability of the energetic (ATP) yield. Random assignments can lead to a substantial yield of ATP and maintain enough variability, thus selection can act and refine the assignments into a proto-code that optimises the energetic yield. Monte Carlo simulations are performed to evaluate the establishment of these simple proto-codes, based on amino acid substitutions and codon swapping. In all cases, donor amino acids are assigned to anticodons composed of U+G, and have low redundancy (1-2 codons), whereas acceptor amino acids are assigned to the the remaining codons. These bioenergetic and structural constraints allow for a metabolic role for amino acids before their co-option as catalyst cofactors. Reviewers: this article was reviewed by Prof. William Martin, Prof. Eors Szathmary (nominated by Dr. Gaspar Jekely) and Dr. Adam Kun (nominated by Dr. Sandor Pongor)
AU - Vladar, Harold
ID - 3166
JF - Biology Direct
TI - Amino acid fermentation at the origin of the genetic code
VL - 7
ER -
TY - JOUR
AB - Due to the omnipresent risk of epidemics, insect societies have evolved sophisticated disease defences at the individual and colony level. An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathogen. We tested whether such social immunisation in Lasius ants against the entomopathogenic fungus Metarhizium anisopliae is based on active upregulation of the immune system of nestmates following contact to an infectious individual or passive protection via transfer of immune effectors among group members—that is, active versus passive immunisation. We found no evidence for involvement of passive immunisation via transfer of antimicrobials among colony members. Instead, intensive allogrooming behaviour between naive and pathogen-exposed ants before fungal conidia firmly attached to their cuticle suggested passage of the pathogen from the exposed individuals to their nestmates. By tracing fluorescence-labelled conidia we indeed detected frequent pathogen transfer to the nestmates, where they caused low-level infections as revealed by growth of small numbers of fungal colony forming units from their dissected body content. These infections rarely led to death, but instead promoted an enhanced ability to inhibit fungal growth and an active upregulation of immune genes involved in antifungal defences (defensin and prophenoloxidase, PPO). Contrarily, there was no upregulation of the gene cathepsin L, which is associated with antibacterial and antiviral defences, and we found no increased antibacterial activity of nestmates of fungus-exposed ants. This indicates that social immunisation after fungal exposure is specific, similar to recent findings for individual-level immune priming in invertebrates. Epidemiological modeling further suggests that active social immunisation is adaptive, as it leads to faster elimination of the disease and lower death rates than passive immunisation. Interestingly, humans have also utilised the protective effect of low-level infections to fight smallpox by intentional transfer of low pathogen doses (“variolation” or “inoculation”).
AU - Konrad, Matthias
AU - Vyleta, Meghan
AU - Theis, Fabian
AU - Stock, Miriam
AU - Tragust, Simon
AU - Klatt, Martina
AU - Drescher, Verena
AU - Marr, Carsten
AU - Ugelvig, Line V
AU - Cremer, Sylvia
ID - 3242
IS - 4
JF - PLoS Biology
TI - Social transfer of pathogenic fungus promotes active immunisation in ant colonies
VL - 10
ER -