TY - JOUR
AB - We consider sample covariance matrices of the form X∗X, where X is an M×N matrix with independent random entries. We prove the isotropic local Marchenko-Pastur law, i.e. we prove that the resolvent (X∗X−z)−1 converges to a multiple of the identity in the sense of quadratic forms. More precisely, we establish sharp high-probability bounds on the quantity ⟨v,(X∗X−z)−1w⟩−⟨v,w⟩m(z), where m is the Stieltjes transform of the Marchenko-Pastur law and v,w∈CN. We require the logarithms of the dimensions M and N to be comparable. Our result holds down to scales Iz≥N−1+ε and throughout the entire spectrum away from 0. We also prove analogous results for generalized Wigner matrices.
AU - Bloemendal, Alex
AU - Erdös, László
AU - Knowles, Antti
AU - Yau, Horng
AU - Yin, Jun
ID - 2225
JF - Electronic Journal of Probability
SN - 10836489
TI - Isotropic local laws for sample covariance and generalized Wigner matrices
VL - 19
ER -
TY - JOUR
AB - Leaf venation develops complex patterns in angiosperms, but the mechanism underlying this process is largely unknown. To elucidate the molecular mechanisms governing vein pattern formation, we previously isolated vascular network defective (van) mutants that displayed venation discontinuities. Here, we report the phenotypic analysis of van4 mutants, and we identify and characterize the VAN4 gene. Detailed phenotypic analysis shows that van4 mutants are defective in procambium cell differentiation and subsequent vascular cell differentiation. Reduced shoot and root cell growth is observed in van4 mutants, suggesting that VAN4 function is important for cell growth and the establishment of venation continuity. Consistent with these phenotypes, the VAN4 gene is strongly expressed in vascular and meristematic cells. VAN4 encodes a putative TRS120, which is a known guanine nucleotide exchange factor (GEF) for Rab GTPase involved in regulating vesicle transport, and a known tethering factor that determines the specificity of membrane fusion. VAN4 protein localizes at the trans-Golgi network/early endosome (TGN/EE). Aberrant recycling of the auxin efflux carrier PIN proteins is observed in van4 mutants. These results suggest that VAN4-mediated exocytosis at the TGN plays important roles in plant vascular development and cell growth in shoot and root. Our identification of VAN4 as a putative TRS120 shows that Rab GTPases are crucial (in addition to ARF GTPases) for continuous vascular development, and provides further evidence for the importance of vesicle transport in leaf vascular formation.
AU - Naramoto, Satoshi
AU - Nodzyński, Tomasz
AU - Dainobu, Tomoko
AU - Takatsuka, Hirotomo
AU - Okada, Teruyo
AU - Friml, Jirí
AU - Fukuda, Hiroo
ID - 2222
IS - 4
JF - Plant and Cell Physiology
SN - 00320781
TI - VAN4 encodes a putative TRS120 that is required for normal cell growth and vein development in arabidopsis
VL - 55
ER -
TY - JOUR
AB - This work investigates the transition between different traveling helical waves (spirals, SPIs) in the setup of differentially independent rotating cylinders. We use direct numerical simulations to consider an infinite long and periodic Taylor-Couette apparatus with fixed axial periodicity length. We find so-called mixed-cross-spirals (MCSs), that can be seen as nonlinear superpositions of SPIs, to establish stable footbridges connecting SPI states. While bridging the bifurcation branches of SPIs, the corresponding contributions within the MCS vary continuously with the control parameters. Here discussed MCSs presenting footbridge solutions start and end in different SPI branches. Therefore they differ significantly from the already known MCSs that present bypass solutions (Altmeyer and Hoffmann 2010 New J. Phys. 12 113035). The latter start and end in the same SPI branch, while they always bifurcate out of those SPI branches with the larger mode amplitude. Meanwhile, these only appear within the coexisting region of both SPIs. In contrast, the footbridge solutions can also bifurcate out of the minor SPI contribution. We also find they exist in regions where only one of the SPIs contributions exists. In addition, MCS as footbridge solution can appear either stable or unstable. The latter detected transient solutions offer similar spatio-temporal characteristics to the flow establishing stable footbridges. Such transition processes are interesting for pattern-forming systems in general because they accomplish transitions between traveling waves of different azimuthal wave numbers and have not been described in the literature yet.
AU - Altmeyer, Sebastian
ID - 2224
IS - 2
JF - Fluid Dynamics Research
SN - 01695983
TI - On secondary instabilities generating footbridges between spiral vortex flow
VL - 46
ER -
TY - CONF
AB - Recently, Döttling et al. (ASIACRYPT 2012) proposed the first chosen-ciphertext (IND-CCA) secure public-key encryption scheme from the learning parity with noise (LPN) assumption. In this work we give an alternative scheme which is conceptually simpler and more efficient. At the core of our construction is a trapdoor technique originally proposed for lattices by Micciancio and Peikert (EUROCRYPT 2012), which we adapt to the LPN setting. The main technical tool is a new double-trapdoor mechanism, together with a trapdoor switching lemma based on a computational variant of the leftover hash lemma.
AU - Kiltz, Eike
AU - Masny, Daniel
AU - Pietrzak, Krzysztof Z
ID - 2219
SN - 978-364254630-3
TI - Simple chosen-ciphertext security from low noise LPN
VL - 8383
ER -
TY - JOUR
AB - In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications.
AU - De Vos, Marjon
AU - Bollenbach, Mark Tobias
ID - 2220
IS - 4
JF - Chemistry and Biology
SN - 10745521
TI - Suppressive drug interactions between antifungals
VL - 21
ER -
TY - JOUR
AB - A discounted-sum automaton (NDA) is a nondeterministic finite automaton with edge weights, valuing a run by the discounted sum of visited edge weights. More precisely, the weight in the i-th position of the run is divided by λi, where the discount factor λ is a fixed rational number greater than 1. The value of a word is the minimal value of the automaton runs on it. Discounted summation is a common and useful measuring scheme, especially for infinite sequences, reflecting the assumption that earlier weights are more important than later weights. Unfortunately, determinization of NDAs, which is often essential in formal verification, is, in general, not possible. We provide positive news, showing that every NDA with an integral discount factor is determinizable. We complete the picture by proving that the integers characterize exactly the discount factors that guarantee determinizability: for every nonintegral rational discount factor λ, there is a nondeterminizable λ-NDA. We also prove that the class of NDAs with integral discount factors enjoys closure under the algebraic operations min, max, addition, and subtraction, which is not the case for general NDAs nor for deterministic NDAs. For general NDAs, we look into approximate determinization, which is always possible as the influence of a word's suffix decays. We show that the naive approach, of unfolding the automaton computations up to a sufficient level, is doubly exponential in the discount factor. We provide an alternative construction for approximate determinization, which is singly exponential in the discount factor, in the precision, and in the number of states. We also prove matching lower bounds, showing that the exponential dependency on each of these three parameters cannot be avoided. All our results hold equally for automata over finite words and for automata over infinite words.
AU - Boker, Udi
AU - Henzinger, Thomas A
ID - 2233
IS - 1
JF - Logical Methods in Computer Science
SN - 18605974
TI - Exact and approximate determinization of discounted-sum automata
VL - 10
ER -
TY - JOUR
AB - Intracellular electrophysiological recordings provide crucial insights into elementary neuronal signals such as action potentials and synaptic currents. Analyzing and interpreting these signals is essential for a quantitative understanding of neuronal information processing, and requires both fast data visualization and ready access to complex analysis routines. To achieve this goal, we have developed Stimfit, a free software package for cellular neurophysiology with a Python scripting interface and a built-in Python shell. The program supports most standard file formats for cellular neurophysiology and other biomedical signals through the Biosig library. To quantify and interpret the activity of single neurons and communication between neurons, the program includes algorithms to characterize the kinetics of presynaptic action potentials and postsynaptic currents, estimate latencies between pre- and postsynaptic events, and detect spontaneously occurring events. We validate and benchmark these algorithms, give estimation errors, and provide sample use cases, showing that Stimfit represents an efficient, accessible and extensible way to accurately analyze and interpret neuronal signals.
AU - Guzmán, José
AU - Schlögl, Alois
AU - Schmidt Hieber, Christoph
ID - 2230
IS - FEB
JF - Frontiers in Neuroinformatics
SN - 16625196
TI - Stimfit: Quantifying electrophysiological data with Python
VL - 8
ER -
TY - JOUR
AB - Fast-spiking, parvalbumin-expressing GABAergic interneurons, a large proportion of which are basket cells (BCs), have a key role in feedforward and feedback inhibition, gamma oscillations and complex information processing. For these functions, fast propagation of action potentials (APs) from the soma to the presynaptic terminals is important. However, the functional properties of interneuron axons remain elusive. We examined interneuron axons by confocally targeted subcellular patch-clamp recording in rat hippocampal slices. APs were initiated in the proximal axon ∼20 μm from the soma and propagated to the distal axon with high reliability and speed. Subcellular mapping revealed a stepwise increase of Na^+ conductance density from the soma to the proximal axon, followed by a further gradual increase in the distal axon. Active cable modeling and experiments with partial channel block revealed that low axonal Na^+ conductance density was sufficient for reliability, but high Na^+ density was necessary for both speed of propagation and fast-spiking AP phenotype. Our results suggest that a supercritical density of Na^+ channels compensates for the morphological properties of interneuron axons (small segmental diameter, extensive branching and high bouton density), ensuring fast AP propagation and high-frequency repetitive firing.
AU - Hu, Hua
AU - Jonas, Peter M
ID - 2228
IS - 5
JF - Nature Neuroscience
SN - 10976256
TI - A supercritical density of Na^+ channels ensures fast signaling in GABAergic interneuron axons
VL - 17
ER -
TY - JOUR
AB - The distance between Ca^2+ channels and release sensors determines the speed and efficacy of synaptic transmission. Tight "nanodomain" channel-sensor coupling initiates transmitter release at synapses in the mature brain, whereas loose "microdomain" coupling appears restricted to early developmental stages. To probe the coupling configuration at a plastic synapse in the mature central nervous system, we performed paired recordings between mossy fiber terminals and CA3 pyramidal neurons in rat hippocampus. Millimolar concentrations of both the fast Ca^2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane- N,N, N′,N′-tetraacetic acid] and the slow chelator EGTA efficiently suppressed transmitter release, indicating loose coupling between Ca^2+ channels and release sensors. Loose coupling enabled the control of initial release probability by fast endogenous Ca^2+ buffers and the generation of facilitation by buffer saturation. Thus, loose coupling provides the molecular framework for presynaptic plasticity.
AU - Vyleta, Nicholas
AU - Jonas, Peter M
ID - 2229
IS - 6171
JF - Science
SN - 00368075
TI - Loose coupling between Ca^2+ channels and release sensors at a plastic hippocampal synapse
VL - 343
ER -
TY - JOUR
AB - The purpose of this contribution is to summarize and discuss recent advances regarding the onset of turbulence in shear flows. The absence of a clear-cut instability mechanism, the spatio-temporal intermittent character and extremely long lived transients are some of the major difficulties encountered in these flows and have hindered progress towards understanding the transition process. We will show for the case of pipe flow that concepts from nonlinear dynamics and statistical physics can help to explain the onset of turbulence. In particular, the turbulent structures (puffs) observed close to onset are spatially localized chaotic transients and their lifetimes increase super-exponentially with Reynolds number. At the same time fluctuations of individual turbulent puffs can (although very rarely) lead to the nucleation of new puffs. The competition between these two stochastic processes gives rise to a non-equilibrium phase transition where turbulence changes from a super-transient to a sustained state.
AU - Song, Baofang
AU - Hof, Björn
ID - 2232
IS - 2
JF - Journal of Statistical Mechanics Theory and Experiment
SN - 17425468
TI - Deterministic and stochastic aspects of the transition to turbulence
VL - 2014
ER -
TY - JOUR
AB - Based on the measurements of noise in gene expression performed during the past decade, it has become customary to think of gene regulation in terms of a two-state model, where the promoter of a gene can stochastically switch between an ON and an OFF state. As experiments are becoming increasingly precise and the deviations from the two-state model start to be observable, we ask about the experimental signatures of complex multistate promoters, as well as the functional consequences of this additional complexity. In detail, we i), extend the calculations for noise in gene expression to promoters described by state transition diagrams with multiple states, ii), systematically compute the experimentally accessible noise characteristics for these complex promoters, and iii), use information theory to evaluate the channel capacities of complex promoter architectures and compare them with the baseline provided by the two-state model. We find that adding internal states to the promoter generically decreases channel capacity, except in certain cases, three of which (cooperativity, dual-role regulation, promoter cycling) we analyze in detail.
AU - Rieckh, Georg
AU - Tkacik, Gasper
ID - 2231
IS - 5
JF - Biophysical Journal
SN - 00063495
TI - Noise and information transmission in promoters with multiple internal states
VL - 106
ER -
TY - JOUR
AB - Coriolis force effects on shear flows are important in geophysical and astrophysical contexts. We report a study on the linear stability and the transient energy growth of the plane Couette flow with system rotation perpendicular to the shear direction. External rotation causes linear instability. At small rotation rates, the onset of linear instability scales inversely with the rotation rate and the optimal transient growth in the linearly stable region is slightly enhanced ∼Re2. The corresponding optimal initial perturbations are characterized by roll structures inclined in the streamwise direction and are twisted under external rotation. At large rotation rates, the transient growth is significantly inhibited and hence linear stability analysis is a reliable indicator for instability.
AU - Shi, Liang
AU - Hof, Björn
AU - Tilgner, Andreas
ID - 2226
IS - 1
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
SN - 15393755
TI - Transient growth of Ekman-Couette flow
VL - 89
ER -
TY - JOUR
AB - The Balkan Peninsula, characterized by high rates of endemism, is recognised as one of the most diverse and species-rich areas of Europe. However, little is known about the origin of Balkan endemics. The present study addresses the phylogenetic position of the Balkan endemic Ranunculus wettsteinii, as well as its taxonomic status and relationship with the widespread R. parnassiifolius, based on nuclear DNA (internal transcribed spacer, ITS) and plastid regions (rpl32-trnL, rps16-trnQ, trnK-matK and ycf6-psbM). Maximum parsimony and Bayesian inference analyses revealed a well-supported clade formed by accessions of R. wettsteinii. Furthermore, our phylogenetic and network analyses supported previous hypotheses of a likely allopolyploid origin for R. wettsteinii between R. montenegrinus and R. parnassiifolius, with the latter as the maternal parent.
AU - Cires Rodriguez, Eduardo
AU - Baltisberger, Matthias
AU - Cuesta, Candela
AU - Vargas, Pablo
AU - Prieto, José
ID - 2227
IS - 1
JF - Organisms Diversity and Evolution
SN - 14396092
TI - Allopolyploid origin of the Balkan endemic Ranunculus wettsteinii (Ranunculaceae) inferred from nuclear and plastid DNA sequences
VL - 14
ER -
TY - JOUR
AB - We study Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) functions. We consider two different objectives, namely, expectation and satisfaction objectives. Given an MDP with κ limit-average functions, in the expectation objective the goal is to maximize the expected limit-average value, and in the satisfaction objective the goal is to maximize the probability of runs such that the limit-average value stays above a given vector. We show that under the expectation objective, in contrast to the case of one limit-average function, both randomization and memory are necessary for strategies even for ε-approximation, and that finite-memory randomized strategies are sufficient for achieving Pareto optimal values. Under the satisfaction objective, in contrast to the case of one limit-average function, infinite memory is necessary for strategies achieving a specific value (i.e. randomized finite-memory strategies are not sufficient), whereas memoryless randomized strategies are sufficient for ε-approximation, for all ε > 0. We further prove that the decision problems for both expectation and satisfaction objectives can be solved in polynomial time and the trade-off curve (Pareto curve) can be ε-approximated in time polynomial in the size of the MDP and 1/ε, and exponential in the number of limit-average functions, for all ε > 0. Our analysis also reveals flaws in previous work for MDPs with multiple mean-payoff functions under the expectation objective, corrects the flaws, and allows us to obtain improved results.
AU - Brázdil, Tomáš
AU - Brožek, Václav
AU - Chatterjee, Krishnendu
AU - Forejt, Vojtěch
AU - Kučera, Antonín
ID - 2234
IS - 1
JF - Logical Methods in Computer Science
SN - 18605974
TI - Markov decision processes with multiple long-run average objectives
VL - 10
ER -
TY - CONF
AB - Consider a joint distribution (X,A) on a set. We show that for any family of distinguishers, there exists a simulator such that 1 no function in can distinguish (X,A) from (X,h(X)) with advantage ε, 2 h is only O(2 3ℓ ε -2) times less efficient than the functions in. For the most interesting settings of the parameters (in particular, the cryptographic case where X has superlogarithmic min-entropy, ε > 0 is negligible and consists of circuits of polynomial size), we can make the simulator h deterministic. As an illustrative application of our theorem, we give a new security proof for the leakage-resilient stream-cipher from Eurocrypt'09. Our proof is simpler and quantitatively much better than the original proof using the dense model theorem, giving meaningful security guarantees if instantiated with a standard blockcipher like AES. Subsequent to this work, Chung, Lui and Pass gave an interactive variant of our main theorem, and used it to investigate weak notions of Zero-Knowledge. Vadhan and Zheng give a more constructive version of our theorem using their new uniform min-max theorem.
AU - Jetchev, Dimitar
AU - Pietrzak, Krzysztof Z
ED - Lindell, Yehuda
ID - 2236
SN - 978-364254241-1
TI - How to fake auxiliary input
VL - 8349
ER -
TY - JOUR
AB - Clathrin-mediated endocytosis is the major mechanism for eukaryotic plasma membrane-based proteome turn-over. In plants, clathrin-mediated endocytosis is essential for physiology and development, but the identification and organization of the machinery operating this process remains largely obscure. Here, we identified an eight-core-component protein complex, the TPLATE complex, essential for plant growth via its role as major adaptor module for clathrin-mediated endocytosis. This complex consists of evolutionarily unique proteins that associate closely with core endocytic elements. The TPLATE complex is recruited as dynamic foci at the plasma membrane preceding recruitment of adaptor protein complex 2, clathrin, and dynamin-related proteins. Reduced function of different complex components severely impaired internalization of assorted endocytic cargoes, demonstrating its pivotal role in clathrin-mediated endocytosis. Taken together, the TPLATE complex is an early endocytic module representing a unique evolutionary plant adaptation of the canonical eukaryotic pathway for clathrin-mediated endocytosis.
AU - Gadeyne, Astrid
AU - Sánchez Rodríguez, Clara
AU - Vanneste, Steffen
AU - Di Rubbo, Simone
AU - Zauber, Henrik
AU - Vanneste, Kevin
AU - Van Leene, Jelle
AU - De Winne, Nancy
AU - Eeckhout, Dominique
AU - Persiau, Geert
AU - Van De Slijke, Eveline
AU - Cannoot, Bernard
AU - Vercruysse, Leen
AU - Mayers, Jonathan
AU - Adamowski, Maciek
AU - Kania, Urszula
AU - Ehrlich, Matthias
AU - Schweighofer, Alois
AU - Ketelaar, Tijs
AU - Maere, Steven
AU - Bednarek, Sebastian
AU - Friml, Jirí
AU - Gevaert, Kris
AU - Witters, Erwin
AU - Russinova, Eugenia
AU - Persson, Staffan
AU - De Jaeger, Geert
AU - Van Damme, Daniël
ID - 2240
IS - 4
JF - Cell
SN - 00928674
TI - The TPLATE adaptor complex drives clathrin-mediated endocytosis in plants
VL - 156
ER -
TY - CONF
AB - The analysis of the energy consumption of software is an important goal for quantitative formal methods. Current methods, using weighted transition systems or energy games, model the energy source as an ideal resource whose status is characterized by one number, namely the amount of remaining energy. Real batteries, however, exhibit behaviors that can deviate substantially from an ideal energy resource. Based on a discretization of a standard continuous battery model, we introduce battery transition systems. In this model, a battery is viewed as consisting of two parts-the available-charge tank and the bound-charge tank. Any charge or discharge is applied to the available-charge tank. Over time, the energy from each tank diffuses to the other tank. Battery transition systems are infinite state systems that, being not well-structured, fall into no decidable class that is known to us. Nonetheless, we are able to prove that the !-regular modelchecking problem is decidable for battery transition systems. We also present a case study on the verification of control programs for energy-constrained semi-autonomous robots.
AU - Boker, Udi
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 2239
IS - 1
SN - 978-145032544-8
TI - Battery transition systems
VL - 49
ER -
TY - JOUR
AB - Emerging infectious diseases (EIDs) pose a risk to human welfare, both directly and indirectly, by affecting managed livestock and wildlife that provide valuable resources and ecosystem services, such as the pollination of crops. Honeybees (Apis mellifera), the prevailing managed insect crop pollinator, suffer from a range of emerging and exotic high-impact pathogens, and population maintenance requires active management by beekeepers to control them. Wild pollinators such as bumblebees (Bombus spp.) are in global decline, one cause of which may be pathogen spillover from managed pollinators like honeybees or commercial colonies of bumblebees. Here we use a combination of infection experiments and landscape-scale field data to show that honeybee EIDs are indeed widespread infectious agents within the pollinator assemblage. The prevalence of deformed wing virus (DWV) and the exotic parasite Nosema ceranae in honeybees and bumblebees is linked; as honeybees have higher DWV prevalence, and sympatric bumblebees and honeybees are infected by the same DWV strains, Apis is the likely source of at least one major EID in wild pollinators. Lessons learned from vertebrates highlight the need for increased pathogen control in managed bee species to maintain wild pollinators, as declines in native pollinators may be caused by interspecies pathogen transmission originating from managed pollinators.
AU - Fürst, Matthias
AU - Mcmahon, Dino
AU - Osborne, Juliet
AU - Paxton, Robert
AU - Brown, Mark
ID - 2235
IS - 7488
JF - Nature
SN - 00280836
TI - Disease associations between honeybees and bumblebees as a threat to wild pollinators
VL - 506
ER -
TY - JOUR
AB - The brain demands high-energy supply and obstruction of blood flow causes rapid deterioration of the healthiness of brain cells. Two major events occur upon ischemia: acidosis and liberation of excess glutamate, which leads to excitotoxicity. However, cellular source of glutamate and its release mechanism upon ischemia remained unknown. Here we show a causal relationship between glial acidosis and neuronal excitotoxicity. As the major cation that flows through channelrhodopsin-2 (ChR2) is proton, this could be regarded as an optogenetic tool for instant intracellular acidification. Optical activation of ChR2 expressed in glial cells led to glial acidification and to release of glutamate. On the other hand, glial alkalization via optogenetic activation of a proton pump, archaerhodopsin (ArchT), led to cessation of glutamate release and to the relief of ischemic brain damage in vivo. Our results suggest that controlling glial pH may be an effective therapeutic strategy for intervention of ischemic brain damage.
AU - Beppu, Kaoru
AU - Sasaki, Takuya
AU - Tanaka, Kenji
AU - Yamanaka, Akihiro
AU - Fukazawa, Yugo
AU - Shigemoto, Ryuichi
AU - Matsui, Ko
ID - 2241
IS - 2
JF - Neuron
SN - 08966273
TI - Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage
VL - 81
ER -
TY - CHAP
AB - Exogenous application of biologically important molecules for plant growth promotion and/or regulation is very common both in plant research and horticulture. Plant hormones such as auxins and cytokinins are classes of compounds which are often applied exogenously. Nevertheless, plants possess a well-established machinery to regulate the active pool of exogenously applied compounds by converting them to metabolites and conjugates. Consequently, it is often very useful to know the in vivo status of applied compounds to connect them with some of the regulatory events in plant developmental processes. The in vivo status of applied compounds can be measured by incubating plants with radiolabeled compounds, followed by extraction, purification, and HPLC metabolic profiling of plant extracts. Recently we have used this method to characterize the intracellularly localized PIN protein, PIN5. Here we explain the method in detail, with a focus on general application.
AU - Simon, Sibu
AU - Skůpa, Petr
AU - Dobrev, Petre
AU - Petrášek, Jan
AU - Zažímalová, Eva
AU - Friml, Jirí
ED - Hicks, Glenn
ED - Robert, Stéphanie
ID - 2245
SN - 10643745
T2 - Plant Chemical Genomics
TI - Analyzing the in vivo status of exogenously applied auxins: A HPLC-based method to characterize the intracellularly localized auxin transporters
VL - 1056
ER -
TY - JOUR
AB - Muller games are played by two players moving a token along a graph; the winner is determined by the set of vertices that occur infinitely often. The central algorithmic problem is to compute the winning regions for the players. Different classes and representations of Muller games lead to problems of varying computational complexity. One such class are parity games; these are of particular significance in computational complexity, as they remain one of the few combinatorial problems known to be in NP ∩ co-NP but not known to be in P. We show that winning regions for a Muller game can be determined from the alternating structure of its traps. To every Muller game we then associate a natural number that we call its trap depth; this parameter measures how complicated the trap structure is. We present algorithms for parity games that run in polynomial time for graphs of bounded trap depth, and in general run in time exponential in the trap depth.
AU - Grinshpun, Andrey
AU - Phalitnonkiat, Pakawat
AU - Rubin, Sasha
AU - Tarfulea, Andrei
ID - 2246
JF - Theoretical Computer Science
SN - 03043975
TI - Alternating traps in Muller and parity games
VL - 521
ER -
TY - JOUR
AB - MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in many cellular pathways. MiRNAs associate with members of the Argonaute protein family and bind to partially complementary sequences on mRNAs and induce translational repression or mRNA decay. Using deep sequencing and Northern blotting, we characterized miRNA expression in wild type and miR-155-deficient dendritic cells (DCs) and macrophages. Analysis of different stimuli (LPS, LDL, eLDL, oxLDL) reveals a direct influence of miR-155 on the expression levels of other miRNAs. For example, miR-455 is negatively regulated in miR-155-deficient cells possibly due to inhibition of the transcription factor C/EBPbeta by miR-155. Based on our comprehensive data sets, we propose a model of hierarchical miRNA expression dominated by miR-155 in DCs and macrophages.
AU - Dueck, Anne
AU - Eichner, Alexander
AU - Sixt, Michael K
AU - Meister, Gunter
ID - 2242
IS - 4
JF - FEBS Letters
SN - 00145793
TI - A miR-155-dependent microRNA hierarchy in dendritic cell maturation and macrophage activation
VL - 588
ER -
TY - JOUR
AB - The genome sequences of new viruses often contain many "orphan" or "taxon-specific" proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as "genus specific" by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virionsd.
AU - Kuchibhatla, Durga
AU - Sherman, Westley
AU - Chung, Betty
AU - Cook, Shelley
AU - Schneider, Georg
AU - Eisenhaber, Birgit
AU - Karlin, David
ID - 2250
IS - 1
JF - Journal of Virology
SN - 0022538X
TI - Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently "orphan" viral proteins
VL - 88
ER -
TY - JOUR
AB - Theta-gamma network oscillations are thought to represent key reference signals for information processing in neuronal ensembles, but the underlying synaptic mechanisms remain unclear. To address this question, we performed whole-cell (WC) patch-clamp recordings from mature hippocampal granule cells (GCs) in vivo in the dentate gyrus of anesthetized and awake rats. GCs in vivo fired action potentials at low frequency, consistent with sparse coding in the dentate gyrus. GCs were exposed to barrages of fast AMPAR-mediated excitatory postsynaptic currents (EPSCs), primarily relayed from the entorhinal cortex, and inhibitory postsynaptic currents (IPSCs), presumably generated by local interneurons. EPSCs exhibited coherence with the field potential predominantly in the theta frequency band, whereas IPSCs showed coherence primarily in the gamma range. Action potentials in GCs were phase locked to network oscillations. Thus, theta-gamma-modulated synaptic currents may provide a framework for sparse temporal coding of information in the dentate gyrus.
AU - Pernia-Andrade, Alejandro
AU - Jonas, Peter M
ID - 2254
IS - 1
JF - Neuron
SN - 08966273
TI - Theta-gamma-modulated synaptic currents in hippocampal granule cells in vivo define a mechanism for network oscillations
VL - 81
ER -
TY - JOUR
AB - Sharp wave/ripple (SWR, 150–250 Hz) hippocampal events have long been postulated to be involved in memory consolidation. However, more recent work has investigated SWRs that occur during active waking behaviour: findings that suggest that SWRs may also play a role in cell assembly strengthening or spatial working memory. Do such theories of SWR function apply to animal learning? This review discusses how general theories linking SWRs to memory-related function may explain circuit mechanisms related to rodent spatial learning and to the associated stabilization of new cognitive maps.
AU - Csicsvari, Jozsef L
AU - Dupret, David
ID - 2251
IS - 1635
JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
SN - 09628436
TI - Sharp wave/ripple network oscillations and learning-associated hippocampal maps
VL - 369
ER -
TY - JOUR
AB - Plant growth is achieved predominantly by cellular elongation, which is thought to be controlled on several levels by apoplastic auxin. Auxin export into the apoplast is achieved by plasma membrane efflux catalysts of the PIN-FORMED (PIN) and ATP-binding cassette protein subfamily B/phosphor- glycoprotein (ABCB/PGP) classes; the latter were shown to depend on interaction with the FKBP42, TWISTED DWARF1 (TWD1). Here by using a transgenic approach in combination with phenotypical, biochemical and cell biological analyses we demonstrate the importance of a putative C-terminal in-plane membrane anchor of TWD1 in the regulation of ABCB-mediated auxin transport. In contrast with dwarfed twd1 loss-of-function alleles, TWD1 gain-of-function lines that lack a putative in-plane membrane anchor (HA-TWD1-Ct) show hypermorphic plant architecture, characterized by enhanced stem length and leaf surface but reduced shoot branching. Greater hypocotyl length is the result of enhanced cell elongation that correlates with reduced polar auxin transport capacity for HA-TWD1-Ct. As a consequence, HA-TWD1-Ct displays higher hypocotyl auxin accumulation, which is shown to result in elevated auxin-induced cell elongation rates. Our data highlight the importance of C-terminal membrane anchoring for TWD1 action, which is required for specific regulation of ABCB-mediated auxin transport. These data support a model in which TWD1 controls lateral ABCB1-mediated export into the apoplast, which is required for auxin-mediated cell elongation.
AU - Bailly, Aurélien
AU - Wang, Bangjun
AU - Zwiewka, Marta
AU - Pollmann, Stephan
AU - Schenck, Daniel
AU - Lüthen, Hartwig
AU - Schulz, Alexander
AU - Friml, Jirí
AU - Geisler, Markus
ID - 2253
IS - 1
JF - Plant Journal
SN - 09607412
TI - Expression of TWISTED DWARF1 lacking its in-plane membrane anchor leads to increased cell elongation and hypermorphic growth
VL - 77
ER -
TY - JOUR
AB - Avian forelimb digit homology remains one of the standard themes in comparative biology and EvoDevo research. In order to resolve the apparent contradictions between embryological and paleontological evidence a variety of hypotheses have been presented in recent years. The proposals range from excluding birds from the dinosaur clade, to assignments of homology by different criteria, or even assuming a hexadactyl tetrapod limb ground state. At present two approaches prevail: the frame shift hypothesis and the pyramid reduction hypothesis. While the former postulates a homeotic shift of digit identities, the latter argues for a gradual bilateral reduction of phalanges and digits. Here we present a new model that integrates elements from both hypotheses with the existing experimental and fossil evidence. We start from the main feature common to both earlier concepts, the initiating ontogenetic event: reduction and loss of the anterior-most digit. It is proposed that a concerted mechanism of molecular regulation and developmental mechanics is capable of shifting the boundaries of hoxD expression in embryonic forelimb buds as well as changing the digit phenotypes. Based on a distinction between positional (topological) and compositional (phenotypic) homology criteria, we argue that the identity of the avian digits is II, III, IV, despite a partially altered phenotype. Finally, we introduce an alternative digit reduction scheme that reconciles the current fossil evidence with the presented molecular-morphogenetic model. Our approach identifies specific experiments that allow to test whether gene expression can be shifted and digit phenotypes can be altered by induced digit loss or digit gain.
AU - Capek, Daniel
AU - Metscher, Brian
AU - Müller, Gerd
ID - 2248
IS - 1
JF - Journal of Experimental Zoology Part B: Molecular and Developmental Evolution
SN - 15525007
TI - Thumbs down: A molecular-morphogenetic approach to avian digit homology
VL - 322
ER -
TY - JOUR
AB - The unfolded protein response (UPR) is a signaling network triggered by overload of protein-folding demand in the endoplasmic reticulum (ER), a condition termed ER stress. The UPR is critical for growth and development; nonetheless, connections between the UPR and other cellular regulatory processes remain largely unknown. Here, we identify a link between the UPR and the phytohormone auxin, a master regulator of plant physiology. We show that ER stress triggers down-regulation of auxin receptors and transporters in Arabidopsis thaliana. We also demonstrate that an Arabidopsis mutant of a conserved ER stress sensor IRE1 exhibits defects in the auxin response and levels. These data not only support that the plant IRE1 is required for auxin homeostasis, they also reveal a species-specific feature of IRE1 in multicellular eukaryotes. Furthermore, by establishing that UPR activation is reduced in mutants of ER-localized auxin transporters, including PIN5, we define a long-neglected biological significance of ER-based auxin regulation. We further examine the functional relationship of IRE1 and PIN5 by showing that an ire1 pin5 triple mutant enhances defects of UPR activation and auxin homeostasis in ire1 or pin5. Our results imply that the plant UPR has evolved a hormone-dependent strategy for coordinating ER function with physiological processes.
AU - Chen, Yani
AU - Aung, Kyaw
AU - Rolčík, Jakub
AU - Walicki, Kathryn
AU - Friml, Jirí
AU - Brandizzí, Federica
ID - 2249
IS - 1
JF - Plant Journal
SN - 09607412
TI - Inter-regulation of the unfolded protein response and auxin signaling
VL - 77
ER -
TY - JOUR
AB - The pattern of inheritance and mechanism of sex determination can have important evolutionary consequences. We studied probabilistic sex determination in the ciliate Tetrahymena thermophila, which was previously shown to cause evolution of skewed sex ratios. We find that the genetic background alters the sex determination patterns of mat alleles in heterozygotes and that allelic interaction can differentially influence the expression probability of the 7 sexes. We quantify the dominance relationships between several mat alleles and find that A-type alleles, which specify sex I, are indeed recessive to B-type alleles, which are unable to specify that sex. Our results provide additional support for the presence of modifier loci and raise implications for the dynamics of sex ratios in populations of T. thermophila.
AU - Phadke, Sujal
AU - Paixao, Tiago
AU - Pham, Tuan
AU - Pham, Stephanie
AU - Zufall, Rebecca
ID - 2252
IS - 1
JF - Journal of Heredity
SN - 00221503
TI - Genetic background alters dominance relationships between mat alleles in the ciliate Tetrahymena Thermophila
VL - 105
ER -
TY - JOUR
AB - To reveal the full potential of human pluripotent stem cells, new methods for rapid, site-specific genomic engineering are needed. Here, we describe a system for precise genetic modification of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We identified a novel human locus, H11, located in a safe, intergenic, transcriptionally active region of chromosome 22, as the recipient site, to provide robust, ubiquitous expression of inserted genes. Recipient cell lines were established by site-specific placement of a ‘landing pad’ cassette carrying attP sites for phiC31 and Bxb1 integrases at the H11 locus by spontaneous or TALEN-assisted homologous recombination. Dual integrase cassette exchange (DICE) mediated by phiC31 and Bxb1 integrases was used to insert genes of interest flanked by phiC31 and Bxb1 attB sites at the H11 locus, replacing the landing pad. This system provided complete control over content, direction and copy number of inserted genes, with a specificity of 100%. A series of genes, including mCherry and various combinations of the neural transcription factors LMX1a, FOXA2 and OTX2, were inserted in recipient cell lines derived from H9 ESC, as well as iPSC lines derived from a Parkinson’s disease patient and a normal sibling control. The DICE system offers rapid, efficient and precise gene insertion in ESC and iPSC and is particularly well suited for repeated modifications of the same locus.
AU - Zhu, Fangfang
AU - Gamboa, Matthew
AU - Farruggio, Alfonso
AU - Hippenmeyer, Simon
AU - Tasic, Bosiljka
AU - Schüle, Birgitt
AU - Chen Tsai, Yanru
AU - Calos, Michele
ID - 2261
IS - 5
JF - Nucleic Acids Research
TI - DICE, an efficient system for iterative genomic editing in human pluripotent stem cells
VL - 42
ER -
TY - CHAP
AB - Coordinated migration of newly-born neurons to their target territories is essential for correct neuronal circuit assembly in the developing brain. Although a cohort of signaling pathways has been implicated in the regulation of cortical projection neuron migration, the precise molecular mechanisms and how a balanced interplay of cell-autonomous and non-autonomous functions of candidate signaling molecules controls the discrete steps in the migration process, are just being revealed. In this chapter, I will focally review recent advances that improved our understanding of the cell-autonomous and possible cell-nonautonomous functions of the evolutionarily conserved LIS1/NDEL1-complex in regulating the sequential steps of cortical projection neuron migration. I will then elaborate on the emerging concept that the Reelin signaling pathway, acts exactly at precise stages in the course of cortical projection neuron migration. Lastly, I will discuss how finely tuned transcriptional programs and downstream effectors govern particular aspects in driving radial migration at discrete stages and how they regulate the precise positioning of cortical projection neurons in the developing cerebral cortex.
AU - Hippenmeyer, Simon
ED - Nguyen, Laurent
ID - 2265
T2 - Cellular and Molecular Control of Neuronal Migration
TI - Molecular pathways controlling the sequential steps of cortical projection neuron migration
VL - 800
ER -
TY - CONF
AB - Energies with high-order non-submodular interactions have been shown to be very useful in vision due to their high modeling power. Optimization of such energies, however, is generally NP-hard. A naive approach that works for small problem instances is exhaustive search, that is, enumeration of all possible labelings of the underlying graph. We propose a general minimization approach for large graphs based on enumeration of labelings of certain small patches.
This partial enumeration technique reduces complex high-order energy formulations to pairwise Constraint Satisfaction Problems with unary costs (uCSP), which can be efficiently solved using standard methods like TRW-S. Our approach outperforms a number of existing state-of-the-art algorithms on well known difficult problems (e.g. curvature regularization, stereo, deconvolution); it gives near global minimum and better speed.
Our main application of interest is curvature regularization. In the context of segmentation, our partial enumeration technique allows to evaluate curvature directly on small patches using a novel integral geometry approach.
AU - Olsson, Carl
AU - Ulen, Johannes
AU - Boykov, Yuri
AU - Kolmogorov, Vladimir
ID - 2275
TI - Partial enumeration and curvature regularization
ER -
TY - JOUR
AB - GABAergic inhibitory interneurons control fundamental aspects of neuronal network function. Their functional roles are assumed to be defined by the identity of their input synapses, the architecture of their dendritic tree, the passive and active membrane properties and finally the nature of their postsynaptic targets. Indeed, interneurons display a high degree of morphological and physiological heterogeneity. However, whether their morphological and physiological characteristics are correlated and whether interneuron diversity can be described by a continuum of GABAergic cell types or by distinct classes has remained unclear. Here we perform a detailed morphological and physiological characterization of GABAergic cells in the dentate gyrus, the input region of the hippocampus. To achieve an unbiased and efficient sampling and classification we used knock-in mice expressing the enhanced green fluorescent protein (eGFP) in glutamate decarboxylase 67 (GAD67)-positive neurons and performed cluster analysis. We identified five interneuron classes, each of them characterized by a distinct set of anatomical and physiological parameters. Cross-correlation analysis further revealed a direct relation between morphological and physiological properties indicating that dentate gyrus interneurons fall into functionally distinct classes which may differentially control neuronal network activity.
AU - Hosp, Jonas
AU - Strüber, Michael
AU - Yanagawa, Yuchio
AU - Obata, Kunihiko
AU - Vida, Imre
AU - Jonas, Peter M
AU - Bartos, Marlene
ID - 2285
IS - 2
JF - Hippocampus
TI - Morpho-physiological criteria divide dentate gyrus interneurons into classes
VL - 23
ER -
TY - JOUR
AB - We prove the universality of the β-ensembles with convex analytic potentials and for any β >
0, i.e. we show that the spacing distributions of log-gases at any inverse temperature β coincide with those of the Gaussian β-ensembles.
AU - Erdös, László
AU - Bourgade, Paul
AU - Yau, Horng
ID - 2699
IS - 6
JF - Duke Mathematical Journal
TI - Universality of general β-ensembles
VL - 163
ER -
TY - JOUR
AB - Multi-dimensional mean-payoff and energy games provide the mathematical foundation for the quantitative study of reactive systems, and play a central role in the emerging quantitative theory of verification and synthesis. In this work, we study the strategy synthesis problem for games with such multi-dimensional objectives along with a parity condition, a canonical way to express ω ω -regular conditions. While in general, the winning strategies in such games may require infinite memory, for synthesis the most relevant problem is the construction of a finite-memory winning strategy (if one exists). Our main contributions are as follows. First, we show a tight exponential bound (matching upper and lower bounds) on the memory required for finite-memory winning strategies in both multi-dimensional mean-payoff and energy games along with parity objectives. This significantly improves the triple exponential upper bound for multi energy games (without parity) that could be derived from results in literature for games on vector addition systems with states. Second, we present an optimal symbolic and incremental algorithm to compute a finite-memory winning strategy (if one exists) in such games. Finally, we give a complete characterization of when finite memory of strategies can be traded off for randomness. In particular, we show that for one-dimension mean-payoff parity games, randomized memoryless strategies are as powerful as their pure finite-memory counterparts.
AU - Chatterjee, Krishnendu
AU - Randour, Mickael
AU - Raskin, Jean
ID - 2716
IS - 3-4
JF - Acta Informatica
TI - Strategy synthesis for multi-dimensional quantitative objectives
VL - 51
ER -
TY - JOUR
AB - Motivated by applications in biology, we present an algorithm for estimating the length of tube-like shapes in 3-dimensional Euclidean space. In a first step, we combine the tube formula of Weyl with integral geometric methods to obtain an integral representation of the length, which we approximate using a variant of the Koksma-Hlawka Theorem. In a second step, we use tools from computational topology to decrease the dependence on small perturbations of the shape. We present computational experiments that shed light on the stability and the convergence rate of our algorithm.
AU - Edelsbrunner, Herbert
AU - Pausinger, Florian
ID - 2255
IS - 1
JF - Journal of Mathematical Imaging and Vision
SN - 09249907
TI - Stable length estimates of tube-like shapes
VL - 50
ER -
TY - CONF
AB - Persistent homology is a recent grandchild of homology that has found use in
science and engineering as well as in mathematics. This paper surveys the method as well
as the applications, neglecting completeness in favor of highlighting ideas and directions.
AU - Edelsbrunner, Herbert
AU - Morozovy, Dmitriy
ID - 2905
TI - Persistent homology: Theory and practice
ER -
TY - JOUR
AB - The classical (boolean) notion of refinement for behavioral interfaces of system components is the alternating refinement preorder. In this paper, we define a distance for interfaces, called interface simulation distance. It makes the alternating refinement preorder quantitative by, intuitively, 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, that the distance between two interfaces can be bounded from above and below by distances between abstractions of the two interfaces, and how to synthesize an interface from incompatible requirements. 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 - 1733
IS - 3
JF - Theoretical Computer Science
TI - Interface simulation distances
VL - 560
ER -
TY - JOUR
AB - The computation of the winning set for Büchi objectives in alternating games on graphs is a central problem in computer-aided verification with a large number of applications. The long-standing best known upper bound for solving the problem is Õ(n ⋅ m), where n is the number of vertices and m is the number of edges in the graph. We are the first to break the Õ(n ⋅ m) boundary by presenting a new technique that reduces the running time to O(n2). This bound also leads to O(n2)-time algorithms for computing the set of almost-sure winning vertices for Büchi objectives (1) in alternating games with probabilistic transitions (improving an earlier bound of Õ(n ⋅ m)), (2) in concurrent graph games with constant actions (improving an earlier bound of O(n3)), and (3) in Markov decision processes (improving for m>n4/3 an earlier bound of O(m ⋅ √m)). We then show how to maintain the winning set for Büchi objectives in alternating games under a sequence of edge insertions or a sequence of edge deletions in O(n) amortized time per operation. Our algorithms are the first dynamic algorithms for this problem. We then consider another core graph theoretic problem in verification of probabilistic systems, namely computing the maximal end-component decomposition of a graph. We present two improved static algorithms for the maximal end-component decomposition problem. Our first algorithm is an O(m ⋅ √m)-time algorithm, and our second algorithm is an O(n2)-time algorithm which is obtained using the same technique as for alternating Büchi games. Thus, we obtain an O(min &lcu;m ⋅ √m,n2})-time algorithm improving the long-standing O(n ⋅ m) time bound. Finally, we show how to maintain the maximal end-component decomposition of a graph under a sequence of edge insertions or a sequence of edge deletions in O(n) amortized time per edge deletion, and O(m) worst-case time per edge insertion. Again, our algorithms are the first dynamic algorithms for this problem.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika H
ID - 2141
IS - 3
JF - Journal of the ACM
TI - Efficient and dynamic algorithms for alternating Büchi games and maximal end-component decomposition
VL - 61
ER -
TY - JOUR
AB - Adaptation in the retina is thought to optimize the encoding of natural light signals into sequences of spikes sent to the brain. While adaptive changes in retinal processing to the variations of the mean luminance level and second-order stimulus statistics have been documented before, no such measurements have been performed when higher-order moments of the light distribution change. We therefore measured the ganglion cell responses in the tiger salamander retina to controlled changes in the second (contrast), third (skew) and fourth (kurtosis) moments of the light intensity distribution of spatially uniform temporally independent stimuli. The skew and kurtosis of the stimuli were chosen to cover the range observed in natural scenes. We quantified adaptation in ganglion cells by studying linear-nonlinear models that capture well the retinal encoding properties across all stimuli. We found that the encoding properties of retinal ganglion cells change only marginally when higher-order statistics change, compared to the changes observed in response to the variation in contrast. By analyzing optimal coding in LN-type models, we showed that neurons can maintain a high information rate without large dynamic adaptation to changes in skew or kurtosis. This is because, for uncorrelated stimuli, spatio-temporal summation within the receptive field averages away non-gaussian aspects of the light intensity distribution.
AU - Tkacik, Gasper
AU - Ghosh, Anandamohan
AU - Schneidman, Elad
AU - Segev, Ronen
ID - 3263
IS - 1
JF - PLoS One
TI - Adaptation to changes in higher-order stimulus statistics in the salamander retina
VL - 9
ER -
TY - CONF
AB - We study two-player concurrent games on finite-state graphs played for an infinite number of rounds, where in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine the successor state. The objectives are ω-regular winning conditions specified as parity objectives. We consider the qualitative analysis problems: the computation of the almost-sure and limit-sure winning set of states, where player 1 can ensure to win with probability 1 and with probability arbitrarily close to 1, respectively. In general the almost-sure and limit-sure winning strategies require both infinite-memory as well as infinite-precision (to describe probabilities). While the qualitative analysis problem for concurrent parity games with infinite-memory, infinite-precision randomized strategies was studied before, we study the bounded-rationality problem for qualitative analysis of concurrent parity games, where the strategy set for player 1 is restricted to bounded-resource strategies. In terms of precision, strategies can be deterministic, uniform, finite-precision, or infinite-precision; and in terms of memory, strategies can be memoryless, finite-memory, or infinite-memory. We present a precise and complete characterization of the qualitative winning sets for all combinations of classes of strategies. In particular, we show that uniform memoryless strategies are as powerful as finite-precision infinite-memory strategies, and infinite-precision memoryless strategies are as powerful as infinite-precision finite-memory strategies. We show that the winning sets can be computed in (n2d+3) time, where n is the size of the game structure and 2d is the number of priorities (or colors), and our algorithms are symbolic. The membership problem of whether a state belongs to a winning set can be decided in NP ∩ coNP. Our symbolic algorithms are based on a characterization of the winning sets as μ-calculus formulas, however, our μ-calculus formulas are crucially different from the ones for concurrent parity games (without bounded rationality); and our memoryless witness strategy constructions are significantly different from the infinite-memory witness strategy constructions for concurrent parity games.
AU - Chatterjee, Krishnendu
ED - Baldan, Paolo
ED - Gorla, Daniele
ID - 2054
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Qualitative concurrent parity games: Bounded rationality
VL - 8704
ER -
TY - THES
AB - A variety of developmental and disease related processes depend on epithelial cell sheet spreading. In order to gain insight into the biophysical mechanism(s) underlying the tissue morphogenesis we studied the spreading of an epithelium during the early development of the zebrafish embryo. In zebrafish epiboly the enveloping cell layer (EVL), a simple squamous epithelium, spreads over the yolk cell to completely engulf it at the end of gastrulation. Previous studies have proposed that an actomyosin ring forming within the yolk syncytial layer (YSL) acts as purse string that through constriction along its circumference pulls on the margin of the EVL. Direct biophysical evidence for this hypothesis has however been missing. The aim of the thesis was to understand how the actomyosin ring may generate pulling forces onto the EVL and what cellular mechanism(s) may facilitate the spreading of the epithelium. Using laser ablation to measure cortical tension within the actomyosin ring we found an anisotropic tension distribution, which was highest along the circumference of the ring. However the low degree of anisotropy was incompatible with the actomyosin ring functioning as a purse string only. Additionally, we observed retrograde cortical flow from vegetal parts of the ring into the EVL margin. Interpreting the experimental data using a theoretical distribution that models the tissues as active viscous gels led us to proposen that the actomyosin ring has a twofold contribution to EVL epiboly. It not only acts as a purse string through constriction along its circumference, but in addition constriction along the width of the ring generates pulling forces through friction-resisted cortical flow. Moreover, when rendering the purse string mechanism unproductive EVL epiboly proceeded normally indicating that the flow-friction mechanism is sufficient to drive the process. Aiming to understand what cellular mechanism(s) may facilitate the spreading of the epithelium we found that tension-oriented EVL cell divisions limit tissue anisotropy by releasing tension along the division axis and promote epithelial spreading. Notably, EVL cells undergo ectopic cell fusion in conditions in which oriented-cell division is impaired or the epithelium is mechanically challenged. Taken together our study of EVL epiboly suggests a novel mechanism of force generation for actomyosin rings through friction-resisted cortical flow and highlights the importance of tension-oriented cell divisions in epithelial morphogenesis.
AU - Behrndt, Martin
ID - 1403
TI - Forces driving epithelial spreading in zebrafish epiboly
ER -
TY - JOUR
AB - Receptor tyrosine kinases (RTKs) are a large family of cell surface receptors that sense growth factors and hormones and regulate a variety of cell behaviours in health and disease. Contactless activation of RTKs with spatial and temporal precision is currently not feasible. Here, we generated RTKs that are insensitive to endogenous ligands but can be selectively activated by low-intensity blue light. We screened light-oxygen-voltage (LOV)-sensing domains for their ability to activate RTKs by light-activated dimerization. Incorporation of LOV domains found in aureochrome photoreceptors of stramenopiles resulted in robust activation of the fibroblast growth factor receptor 1 (FGFR1), epidermal growth factor receptor (EGFR) and rearranged during transfection (RET). In human cancer and endothelial cells, light induced cellular signalling with spatial and temporal precision. Furthermore, light faithfully mimicked complex mitogenic and morphogenic cell behaviour induced by growth factors. RTKs under optical control (Opto-RTKs) provide a powerful optogenetic approach to actuate cellular signals and manipulate cell behaviour.
AU - Grusch, Michael
AU - Schelch, Karin
AU - Riedler, Robert
AU - Gschaider-Reichhart, Eva
AU - Differ, Christopher
AU - Berger, Walter
AU - Inglés Prieto, Álvaro
AU - Janovjak, Harald L
ID - 2084
IS - 15
JF - EMBO Journal
TI - Spatio-temporally precise activation of engineered receptor tyrosine kinases by light
VL - 33
ER -
TY - JOUR
AB - A robust combiner for hash functions takes two candidate implementations and constructs a hash function which is secure as long as at least one of the candidates is secure. So far, hash function combiners only aim at preserving a single property such as collision-resistance or pseudorandomness. However, when hash functions are used in protocols like TLS they are often required to provide several properties simultaneously. We therefore put forward the notion of robust multi-property combiners and elaborate on different definitions for such combiners. We then propose a combiner that provably preserves (target) collision-resistance, pseudorandomness, and being a secure message authentication code. This combiner satisfies the strongest notion we propose, which requires that the combined function satisfies every security property which is satisfied by at least one of the underlying hash function. If the underlying hash functions have output length n, the combiner has output length 2 n. This basically matches a known lower bound for black-box combiners for collision-resistance only, thus the other properties can be achieved without penalizing the length of the hash values. We then propose a combiner which also preserves the property of being indifferentiable from a random oracle, slightly increasing the output length to 2 n+ω(log n). Moreover, we show how to augment our constructions in order to make them also robust for the one-wayness property, but in this case require an a priory upper bound on the input length.
AU - Fischlin, Marc
AU - Lehmann, Anja
AU - Pietrzak, Krzysztof Z
ID - 2852
IS - 3
JF - Journal of Cryptology
TI - Robust multi-property combiners for hash functions
VL - 27
ER -
TY - CONF
AB - We show that the following algorithmic problem is decidable: given a 2-dimensional simplicial complex, can it be embedded (topologically, or equivalently, piecewise linearly) in ℝ3? By a known reduction, it suffices to decide the embeddability of a given triangulated 3-manifold X into the 3-sphere S3. The main step, which allows us to simplify X and recurse, is in proving that if X can be embedded in S3, then there is also an embedding in which X has a short meridian, i.e., an essential curve in the boundary of X bounding a disk in S3 nX with length bounded by a computable function of the number of tetrahedra of X.
AU - Matoušek, Jiří
AU - Sedgwick, Eric
AU - Tancer, Martin
AU - Wagner, Uli
ID - 2157
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - Embeddability in the 3 sphere is decidable
ER -
TY - JOUR
AB - Invasive alien parasites and pathogens are a growing threat to biodiversity worldwide, which can contribute to the extinction of endemic species. On the Galápagos Islands, the invasive parasitic fly Philornis downsi poses a major threat to the endemic avifauna. Here, we investigated the influence of this parasite on the breeding success of two Darwin's finch species, the warbler finch (Certhidea olivacea) and the sympatric small tree finch (Camarhynchus parvulus), on Santa Cruz Island in 2010 and 2012. While the population of the small tree finch appeared to be stable, the warbler finch has experienced a dramatic decline in population size on Santa Cruz Island since 1997. We aimed to identify whether warbler finches are particularly vulnerable during different stages of the breeding cycle. Contrary to our prediction, breeding success was lower in the small tree finch than in the warbler finch. In both species P. downsi had a strong negative impact on breeding success and our data suggest that heavy rain events also lowered the fledging success. On the one hand parents might be less efficient in compensating their chicks' energy loss due to parasitism as they might be less efficient in foraging on days of heavy rain. On the other hand, intense rainfalls might lead to increased humidity and more rapid cooling of the nests. In the case of the warbler finch we found that the control of invasive plant species with herbicides had a significant additive negative impact on the breeding success. It is very likely that the availability of insects (i.e. food abundance) is lower in such controlled areas, as herbicide usage led to the removal of the entire understory. Predation seems to be a minor factor in brood loss.
AU - Cimadom, Arno
AU - Ulloa, Angel
AU - Meidl, Patrick
AU - Zöttl, Markus
AU - Zöttl, Elisabet
AU - Fessl, Birgit
AU - Nemeth, Erwin
AU - Dvorak, Michael
AU - Cunninghame, Francesca
AU - Tebbich, Sabine
ID - 468
IS - 9
JF - PLoS One
TI - Invasive parasites habitat change and heavy rainfall reduce breeding success in Darwin's finches
VL - 9
ER -
TY - CONF
AB - First cycle games (FCG) are played on a finite graph by two players who push a token along the edges until a vertex is repeated, and a simple cycle is formed. The winner is determined by some fixed property Y of the sequence of labels of the edges (or nodes) forming this cycle. These games are traditionally of interest because of their connection with infinite-duration games such as parity and mean-payoff games. We study the memory requirements for winning strategies of FCGs and certain associated infinite duration games. We exhibit a simple FCG that is not memoryless determined (this corrects a mistake in Memoryless determinacy of parity and mean payoff games: a simple proof by Bj⋯orklund, Sandberg, Vorobyov (2004) that claims that FCGs for which Y is closed under cyclic permutations are memoryless determined). We show that θ (n)! memory (where n is the number of nodes in the graph), which is always sufficient, may be necessary to win some FCGs. On the other hand, we identify easy to check conditions on Y (i.e., Y is closed under cyclic permutations, and both Y and its complement are closed under concatenation) that are sufficient to ensure that the corresponding FCGs and their associated infinite duration games are memoryless determined. We demonstrate that many games considered in the literature, such as mean-payoff, parity, energy, etc., satisfy these conditions. On the complexity side, we show (for efficiently computable Y) that while solving FCGs is in PSPACE, solving some families of FCGs is PSPACE-hard.
AU - Aminof, Benjamin
AU - Rubin, Sasha
ID - 475
T2 - Electronic Proceedings in Theoretical Computer Science, EPTCS
TI - First cycle games
VL - 146
ER -
TY - CONF
AB - In this paper, we introduce planar matchings on directed pseudo-line arrangements, which yield a planar set of pseudo-line segments such that only matching-partners are adjacent. By translating the planar matching problem into a corresponding stable roommates problem we show that such matchings always exist.
Using our new framework, we establish, for the first time, a complete, rigorous definition of weighted straight skeletons, which are based on a so-called wavefront propagation process. We present a generalized and unified approach to treat structural changes in the wavefront that focuses on the restoration of weak planarity by finding planar matchings.
AU - Biedl, Therese
AU - Huber, Stefan
AU - Palfrader, Peter
ID - 10892
SN - 0302-9743
T2 - 25th International Symposium, ISAAC 2014
TI - Planar matchings for weighted straight skeletons
VL - 8889
ER -
TY - JOUR
AB - Energy games belong to a class of turn-based two-player infinite-duration games played on a weighted directed graph. It is one of the rare and intriguing combinatorial problems that lie in NP∩co-NP, but are not known to be in P. The existence of polynomial-time algorithms has been a major open problem for decades and apart from pseudopolynomial algorithms there is no algorithm that solves any non-trivial subclass in polynomial time. In this paper, we give several results based on the weight structures of the graph. First, we identify a notion of penalty and present a polynomial-time algorithm when the penalty is large. Our algorithm is the first polynomial-time algorithm on a large class of weighted graphs. It includes several worst-case instances on which previous algorithms, such as value iteration and random facet algorithms, require at least sub-exponential time. Our main technique is developing the first non-trivial approximation algorithm and showing how to convert it to an exact algorithm. Moreover, we show that in a practical case in verification where weights are clustered around a constant number of values, the energy game problem can be solved in polynomial time. We also show that the problem is still as hard as in general when the clique-width is bounded or the graph is strongly ergodic, suggesting that restricting the graph structure does not necessarily help.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika H
AU - Krinninger, Sebastian
AU - Nanongkai, Danupon
ID - 535
IS - 3
JF - Algorithmica
TI - Polynomial-time algorithms for energy games with special weight structures
VL - 70
ER -
TY - JOUR
AB - Transgenerational effects are broader than only parental relationships. Despite mounting evidence that multigenerational effects alter phenotypic and life-history traits, our understanding of how they combine to determine fitness is not well developed because of the added complexity necessary to study them. Here, we derive a quantitative genetic model of adaptation to an extraordinary new environment by an additive genetic component, phenotypic plasticity, maternal and grandmaternal effects. We show how, at equilibrium, negative maternal and negative grandmaternal effects maximize expected population mean fitness. We define negative transgenerational effects as those that have a negative effect on trait expression in the subsequent generation, that is, they slow, or potentially reverse, the expected evolutionary dynamic. When maternal effects are positive, negative grandmaternal effects are preferred. As expected under Mendelian inheritance, the grandmaternal effects have a lower impact on fitness than the maternal effects, but this dual inheritance model predicts a more complex relationship between maternal and grandmaternal effects to constrain phenotypic variance and so maximize expected population mean fitness in the offspring.
AU - Prizak, Roshan
AU - Ezard, Thomas
AU - Hoyle, Rebecca
ID - 537
IS - 15
JF - Ecology and Evolution
TI - Fitness consequences of maternal and grandmaternal effects
VL - 4
ER -
TY - CONF
AB - We consider two-player zero-sum partial-observation stochastic games on graphs. Based on the information available to the players these games can be classified as follows: (a) general 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) perfect-observation (both players have complete view of the game). The one-sided partial-observation games subsumes the important special case of one-player partial-observation stochastic games (or partial-observation Markov decision processes (POMDPs)). Based on the randomization available for the strategies, (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. We consider all these classes of games with reachability, and parity objectives that can express all ω-regular objectives. The analysis problems are classified into the qualitative analysis that asks for the existence of a strategy that ensures the objective with probability 1; and the quantitative analysis that asks for the existence of a strategy that ensures the objective with probability at least λ (0,1). In this talk we will cover a wide range of results: for perfect-observation games; for POMDPs; for one-sided partial-observation games; and for general partial-observation games.
AU - Chatterjee, Krishnendu
ID - 1903
IS - PART 1
TI - Partial-observation stochastic reachability and parity games
VL - 8634
ER -
TY - JOUR
AB - In two-player finite-state stochastic games of partial observation on graphs, in every state of the graph, the players simultaneously choose an action, and their joint actions determine a probability distribution over the successor states. The game is played for infinitely many rounds and thus the players construct an infinite path in the graph. We consider 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 to 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, (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. Our main results for pure strategies are as follows: (1) For one-sided games with player 2 having perfect 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 almost-sure 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 and present symbolic algorithms that avoid the explicit exponential construction. (2) For one-sided games with player 1 having perfect observation we show that nonelementarymemory 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 nonelementary 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 exhibit serious flaws in previous results of the literature: we show a nonelementary memory lower bound for almost-sure winning whereas an exponential upper bound was previously claimed.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 2211
IS - 2
JF - ACM Transactions on Computational Logic (TOCL)
TI - Partial-observation stochastic games: How to win when belief fails
VL - 15
ER -
TY - JOUR
AB - Recently, there has been an effort to add quantitative objectives to formal verification and synthesis. We introduce and investigate the extension of temporal logics with quantitative atomic assertions. At the heart of quantitative objectives lies the accumulation of values along a computation. It is often the accumulated sum, as with energy objectives, or the accumulated average, as with mean-payoff objectives. We investigate the extension of temporal logics with the prefix-accumulation assertions Sum(v) ≥ c and Avg(v) ≥ c, where v is a numeric (or Boolean) variable of the system, c is a constant rational number, and Sum(v) and Avg(v) denote the accumulated sum and average of the values of v from the beginning of the computation up to the current point in time. We also allow the path-accumulation assertions LimInfAvg(v) ≥ c and LimSupAvg(v) ≥ c, referring to the average value along an entire infinite computation. We study the border of decidability for such quantitative extensions of various temporal logics. In particular, we show that extending the fragment of CTL that has only the EX, EF, AX, and AG temporal modalities with both prefix-accumulation assertions, or extending LTL with both path-accumulation assertions, results in temporal logics whose model-checking problem is decidable. Moreover, the prefix-accumulation assertions may be generalized with "controlled accumulation," allowing, for example, to specify constraints on the average waiting time between a request and a grant. On the negative side, we show that this branching-time logic is, in a sense, the maximal logic with one or both of the prefix-accumulation assertions that permits a decidable model-checking procedure. Extending a temporal logic that has the EG or EU modalities, such as CTL or LTL, makes the problem undecidable.
AU - Boker, Udi
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Kupferman, Orna
ID - 2038
IS - 4
JF - ACM Transactions on Computational Logic (TOCL)
TI - Temporal specifications with accumulative values
VL - 15
ER -
TY - CONF
AB - We study two-player (zero-sum) concurrent mean-payoff games played on a finite-state graph. We focus on the important sub-class of ergodic games where all states are visited infinitely often with probability 1. The algorithmic study of ergodic games was initiated in a seminal work of Hoffman and Karp in 1966, but all basic complexity questions have remained unresolved. Our main results for ergodic games are as follows: We establish (1) an optimal exponential bound on the patience of stationary strategies (where patience of a distribution is the inverse of the smallest positive probability and represents a complexity measure of a stationary strategy); (2) the approximation problem lies in FNP; (3) the approximation problem is at least as hard as the decision problem for simple stochastic games (for which NP ∩ coNP is the long-standing best known bound). We present a variant of the strategy-iteration algorithm by Hoffman and Karp; show that both our algorithm and the classical value-iteration algorithm can approximate the value in exponential time; and identify a subclass where the value-iteration algorithm is a FPTAS. We also show that the exact value can be expressed in the existential theory of the reals, and establish square-root sum hardness for a related class of games.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 2162
IS - Part 2
TI - The complexity of ergodic mean payoff games
VL - 8573
ER -
TY - CONF
AB - We consider two-player partial-observation stochastic games on finitestate graphs where player 1 has partial observation and player 2 has perfect observation. The winning condition we study are ε-regular conditions specified as parity objectives. The qualitative-analysis problem given a partial-observation stochastic game and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). These qualitative-analysis problems are known to be undecidable. However in many applications the relevant question is the existence of finite-memory strategies, and the qualitative-analysis problems under finite-memory strategies was recently shown to be decidable in 2EXPTIME.We improve the complexity and show that the qualitative-analysis problems for partial-observation stochastic parity games under finite-memory strategies are EXPTIME-complete; and also establish optimal (exponential) memory bounds for finite-memory strategies required for qualitative analysis.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Nain, Sumit
AU - Vardi, Moshe
ID - 2213
TI - The complexity of partial-observation stochastic parity games with finite-memory strategies
VL - 8412
ER -
TY - CONF
AB - The theory of graph games is the foundation for modeling and synthesizing reactive processes. In the synthesis of stochastic processes, we use 2 1/2-player games where some transitions of the game graph are controlled by two adversarial players, the System and the Environment, and the other transitions are determined probabilistically. We consider 2 1/2-player games where the objective of the System is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a mean-payoff condition). We establish that the problem of deciding whether the System can ensure that the probability to satisfy the mean-payoff parity objective is at least a given threshold is in NP ∩ coNP, matching the best known bound in the special case of 2-player games (where all transitions are deterministic). We present an algorithm running in time O(d·n2d·MeanGame) to compute the set of almost-sure winning states from which the objective can be ensured with probability 1, where n is the number of states of the game, d the number of priorities of the parity objective, and MeanGame is the complexity to compute the set of almost-sure winning states in 2 1/2-player mean-payoff games. Our results are useful in the synthesis of stochastic reactive systems with both functional requirement (given as a qualitative objective) and performance requirement (given as a quantitative objective).
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Gimbert, Hugo
AU - Oualhadj, Youssouf
ID - 2212
TI - Perfect-information stochastic mean-payoff parity games
VL - 8412
ER -
TY - CONF
AB - The edit distance between two (untimed) traces is the minimum cost of a sequence of edit operations (insertion, deletion, or substitution) needed to transform one trace to the other. Edit distances have been extensively studied in the untimed setting, and form the basis for approximate matching of sequences in different domains such as coding theory, parsing, and speech recognition. In this paper, we lift the study of edit distances from untimed languages to the timed setting. We define an edit distance between timed words which incorporates both the edit distance between the untimed words and the absolute difference in time stamps. Our edit distance between two timed words is computable in polynomial time. Further, we show that the edit distance between a timed word and a timed language generated by a timed automaton, defined as the edit distance between the word and the closest word in the language, is PSPACE-complete. While computing the edit distance between two timed automata is undecidable, we show that the approximate version, where we decide if the edit distance between two timed automata is either less than a given parameter or more than δ away from the parameter, for δ > 0, can be solved in exponential space and is EXPSPACE-hard. Our definitions and techniques can be generalized to the setting of hybrid systems, and analogous decidability results hold for rectangular automata.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Majumdar, Ritankar
ID - 2216
TI - Edit distance for timed automata
ER -
TY - CONF
AB - Model-based testing is a promising technology for black-box software and hardware testing, in which test cases are generated automatically from high-level specifications. Nowadays, systems typically consist of multiple interacting components and, due to their complexity, testing presents a considerable portion of the effort and cost in the design process. Exploiting the compositional structure of system specifications can considerably reduce the effort in model-based testing. Moreover, inferring properties about the system from testing its individual components allows the designer to reduce the amount of integration testing. In this paper, we study compositional properties of the ioco-testing theory. We propose a new approach to composition and hiding operations, inspired by contract-based design and interface theories. These operations preserve behaviors that are compatible under composition and hiding, and prune away incompatible ones. The resulting specification characterizes the input sequences for which the unit testing of components is sufficient to infer the correctness of component integration without the need for further tests. We provide a methodology that uses these results to minimize integration testing effort, but also to detect potential weaknesses in specifications. While we focus on asynchronous models and the ioco conformance relation, the resulting methodology can be applied to a broader class of systems.
AU - Daca, Przemyslaw
AU - Henzinger, Thomas A
AU - Krenn, Willibald
AU - Nickovic, Dejan
ID - 2167
SN - 2159-4848
T2 - IEEE 7th International Conference on Software Testing, Verification and Validation
TI - Compositional specifications for IOCO testing
ER -
TY - GEN
AB - Model-based testing is a promising technology for black-box software and hardware testing, in which test cases are generated automatically from high-level specifications. Nowadays, systems typically consist of multiple interacting components and, due to their complexity, testing presents a considerable portion of the effort and cost in the design process. Exploiting the compositional structure of system specifications can considerably reduce the effort in model-based testing. Moreover, inferring properties about the system from testing its individual components allows the designer to reduce the amount of integration testing.
In this paper, we study compositional properties of the IOCO-testing theory. We propose a new approach to composition and hiding operations, inspired by contract-based design and interface theories. These operations preserve behaviors that are compatible under composition and hiding, and prune away incompatible ones. The resulting specification characterizes the input sequences for which the unit testing of components is sufficient to infer the correctness of component integration without the need for further tests. We provide a methodology that uses these results to minimize integration testing effort, but also to detect potential weaknesses in specifications. While we focus on asynchronous models and the IOCO conformance relation, the resulting methodology can be applied to a broader class of systems.
AU - Daca, Przemyslaw
AU - Henzinger, Thomas A
AU - Krenn, Willibald
AU - Nickovic, Dejan
ID - 5411
SN - 2664-1690
TI - Compositional specifications for IOCO testing
ER -
TY - CONF
AB - We consider Markov decision processes (MDPs) which are a standard model for probabilistic systems.We focus on qualitative properties forMDPs that can express that desired behaviors of the system arise almost-surely (with probability 1) or with positive probability. We introduce a new simulation relation to capture the refinement relation ofMDPs with respect to qualitative properties, and present discrete graph theoretic algorithms with quadratic complexity to compute the simulation relation.We present an automated technique for assume-guarantee style reasoning for compositional analysis ofMDPs with qualitative properties by giving a counterexample guided abstraction-refinement approach to compute our new simulation relation. We have implemented our algorithms and show that the compositional analysis leads to significant improvements.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Daca, Przemyslaw
ID - 2063
TI - CEGAR for qualitative analysis of probabilistic systems
VL - 8559
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) which are a standard model for probabilistic systems. We focus on qualitative properties for MDPs that can express that desired behaviors of the system arise almost-surely (with probability 1) or with positive probability.
We introduce a new simulation relation to capture the refinement relation of MDPs with respect to qualitative properties, and present discrete graph theoretic algorithms with quadratic complexity to compute the simulation relation.
We present an automated technique for assume-guarantee style reasoning for compositional analysis of MDPs with qualitative properties by giving a counter-example guided abstraction-refinement approach to compute our new simulation relation. We have implemented our algorithms and show that the compositional analysis leads to significant improvements.
AU - Chatterjee, Krishnendu
AU - Daca, Przemyslaw
AU - Chmelik, Martin
ID - 5413
SN - 2664-1690
TI - CEGAR for qualitative analysis of probabilistic systems
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) which are a standard model for probabilistic systems. We focus on qualitative properties for MDPs that can express that desired behaviors of the system arise almost-surely (with probability 1) or with positive probability.
We introduce a new simulation relation to capture the refinement relation of MDPs with respect to qualitative properties, and present discrete graph theoretic algorithms with quadratic complexity to compute the simulation relation.
We present an automated technique for assume-guarantee style reasoning for compositional analysis of MDPs with qualitative properties by giving a counter-example guided abstraction-refinement approach to compute our new simulation relation.
We have implemented our algorithms and show that the compositional analysis leads to significant improvements.
AU - Chatterjee, Krishnendu
AU - Daca, Przemyslaw
AU - Chmelik, Martin
ID - 5414
SN - 2664-1690
TI - CEGAR for qualitative analysis of probabilistic systems
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) which are a standard model for probabilistic systems. We focus on qualitative properties for MDPs that can express that desired behaviors of the system arise almost-surely (with probability 1) or with positive probability.
We introduce a new simulation relation to capture the refinement relation of MDPs with respect to qualitative properties, and present discrete graph theoretic algorithms with quadratic complexity to compute the simulation relation.
We present an automated technique for assume-guarantee style reasoning for compositional analysis of MDPs with qualitative properties by giving a counter-example guided abstraction-refinement approach to compute our new simulation relation. We have implemented our algorithms and show that the compositional analysis leads to significant improvements.
AU - Chatterjee, Krishnendu
AU - Daca, Przemyslaw
AU - Chmelik, Martin
ID - 5412
SN - 2664-1690
TI - CEGAR for qualitative analysis of probabilistic systems
ER -
TY - CONF
AB - We consider multi-player graph games with partial-observation and parity objective. While the decision problem for three-player games with a coalition of the first and second players against the third player is undecidable in general, we present a decidability result for partial-observation games where the first and third player are in a coalition against the second player, thus where the second player is adversarial but weaker due to partial-observation. We establish tight complexity bounds in the case where player 1 is less informed than player 2, namely 2-EXPTIME-completeness for parity objectives. The symmetric case of player 1 more informed than player 2 is much more complicated, and we show that already in the case where player 1 has perfect observation, memory of size non-elementary is necessary in general for reachability objectives, and the problem is decidable for safety and reachability objectives. From our results we derive new complexity results for partial-observation stochastic games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 2163
IS - Part 2
T2 - Lecture Notes in Computer Science
TI - Games with a weak adversary
VL - 8573
ER -
TY - GEN
AB - We consider the reachability and shortest path problems on low tree-width graphs, with n nodes, m edges, and tree-width t, on a standard RAM with wordsize W. We use O to hide polynomial factors of the inverse of the Ackermann function. Our main contributions are three fold:
1. For reachability, we present an algorithm that requires O(n·t2·log(n/t)) preprocessing time, O(n·(t·log(n/t))/W) space, and O(t/W) time for pair queries and O((n·t)/W) time for single-source queries. Note that for constant t our algorithm uses O(n·logn) time for preprocessing; and O(n/W) time for single-source queries, which is faster than depth first search/breath first search (after the preprocessing).
2. We present an algorithm for shortest path that requires O(n·t2) preprocessing time, O(n·t) space, and O(t2) time for pair queries and O(n·t) time single-source queries.
3. We give a space versus query time trade-off algorithm for shortest path that, given any constant >0, requires O(n·t2) preprocessing time, O(n·t2) space, and O(n1−·t2) time for pair queries.
Our algorithms improve all existing results, and use very simple data structures.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5419
SN - 2664-1690
TI - Improved algorithms for reachability and shortest path on low tree-width graphs
ER -
TY - CONF
AB - As hybrid systems involve continuous behaviors, they should be evaluated by quantitative methods, rather than qualitative methods. In this paper we adapt a quantitative framework, called model measuring, to the hybrid systems domain. The model-measuring problem asks, given a model M and a specification, what is the maximal distance such that all models within that distance from M satisfy (or violate) the specification. A distance function on models is given as part of the input of the problem. Distances, especially related to continuous behaviors are more natural in the hybrid case than the discrete case. We are interested in distances represented by monotonic hybrid automata, a hybrid counterpart of (discrete) weighted automata, whose recognized timed languages are monotone (w.r.t. inclusion) in the values of parameters.
The contributions of this paper are twofold. First, we give sufficient conditions under which the model-measuring problem can be solved. Second, we discuss the modeling of distances and applications of the model-measuring problem.
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 2217
T2 - Proceedings of the 17th international conference on Hybrid systems: computation and control
TI - Model measuring for hybrid systems
ER -
TY - GEN
AB - We define the model-measuring problem: given a model M and specification φ, what is the maximal distance ρ such that all models M'within distance ρ from M satisfy (or violate)φ. The model measuring problem presupposes a distance function on models. We concentrate on automatic distance functions, which are defined by weighted automata.
The model-measuring problem subsumes several generalizations of the classical model-checking problem, in particular, quantitative model-checking problems that measure the degree of satisfaction of a specification, and robustness problems that measure how much a model can be perturbed without violating the specification.
We show that for automatic distance functions, and ω-regular linear-time and branching-time specifications, the model-measuring problem can be solved.
We use automata-theoretic model-checking methods for model measuring, replacing the emptiness question for standard word and tree automata by the optimal-weight question for the weighted versions of these automata. We consider weighted automata that accumulate weights by maximizing, summing, discounting, and limit averaging.
We give several examples of using the model-measuring problem to compute various notions of robustness and quantitative satisfaction for temporal specifications.
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5417
SN - 2664-1690
TI - From model checking to model measuring
ER -
TY - GEN
AB - As hybrid systems involve continuous behaviors, they should be evaluated by quantitative methods, rather than qualitative methods. In this paper we adapt a quantitative framework, called model measuring, to the hybrid systems domain. The model-measuring problem asks, given a model M and a specification, what is the maximal distance such that all models within that distance from M satisfy (or violate) the specification. A distance function on models is given as part of the input of the problem. Distances, especially related to continuous behaviors are more natural in the hybrid case than the discrete case. We are interested in distances represented by monotonic hybrid automata, a hybrid counterpart of (discrete) weighted automata, whose recognized timed languages are monotone (w.r.t. inclusion) in the values of parameters.The contributions of this paper are twofold. First, we give sufficient conditions under which the model-measuring problem can be solved. Second, we discuss the modeling of distances and applications of the model-measuring problem.
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5416
SN - 2664-1690
TI - Model measuring for hybrid systems
ER -
TY - GEN
AB - We consider multi-player graph games with partial-observation and parity objective. While the decision problem for three-player games with a coalition of the first and second players against the third player is undecidable, we present a decidability result for partial-observation games where the first and third player are in a coalition against the second player, thus where the second player is adversarial but weaker due to partial-observation. We establish tight complexity bounds in the case where player 1 is less informed than player 2, namely 2-EXPTIME-completeness for parity objectives. The symmetric case of player 1 more informed than player 2 is much more complicated, and we show that already in the case where player 1 has perfect observation, memory of size non-elementary is necessary in general for reachability objectives, and the problem is decidable for safety and reachability objectives. Our results have tight connections with partial-observation stochastic games for which we derive new complexity results.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 5418
SN - 2664-1690
TI - Games with a weak adversary
ER -
TY - GEN
AB - We consider concurrent mean-payoff games, a very well-studied class of two-player (player 1 vs player 2) zero-sum games on finite-state graphs where every transition is assigned a reward between 0 and 1, and the payoff function is the long-run average of the rewards. The value is the maximal expected payoff that player 1 can guarantee against all strategies of player 2. We consider the computation of the set of states with value 1 under finite-memory strategies for player 1, and our main results for the problem are as follows: (1) we present a polynomial-time algorithm; (2) we show that whenever there is a finite-memory strategy, there is a stationary strategy that does not need memory at all; and (3) we present an optimal bound (which is double exponential) on the patience of stationary strategies (where patience of a distribution is the inverse of the smallest positive probability and represents a complexity measure of a stationary strategy).
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 5420
SN - 2664-1690
TI - The value 1 problem for concurrent mean-payoff games
ER -
TY - GEN
AB - Notes from the Third Plenary for the Research Data Alliance in Dublin, Ireland on March 26 to 28, 2014 with focus on starting an institutional research data repository.
AU - Porsche, Jana
ID - 5422
TI - Notes from Research Data Alliance Plenary Meeting in Dublin, Ireland
ER -
TY - GEN
AB - We consider partially observable Markov decision processes (POMDPs), that are a standard framework for robotics applications to model uncertainties present in the real world, with temporal logic specifications. All temporal logic specifications in linear-time temporal logic (LTL) can be expressed as parity objectives. We study the qualitative analysis problem for POMDPs with parity objectives that asks whether there is a controller (policy) to ensure that the objective holds with probability 1 (almost-surely). While the qualitative analysis of POMDPs with parity objectives is undecidable, recent results show that when restricted to finite-memory policies the problem is EXPTIME-complete. While the problem is intractable in theory, we present a practical approach to solve the qualitative analysis problem. We designed several heuristics to deal with the exponential complexity, and have used our implementation on a number of well-known POMDP examples for robotics applications. Our results provide the first practical approach to solve the qualitative analysis of robot motion planning with LTL properties in the presence of uncertainty.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Gupta, Raghav
AU - Kanodia, Ayush
ID - 5424
SN - 2664-1690
TI - Qualitative analysis of POMDPs with temporal logic specifications for robotics applications
ER -
TY - GEN
AB - We consider partially observable Markov decision processes (POMDPs), that are a standard framework for robotics applications to model uncertainties present in the real world, with temporal logic specifications. All temporal logic specifications in linear-time temporal logic (LTL) can be expressed as parity objectives. We study the qualitative analysis problem for POMDPs with parity objectives that asks whether there is a controller (policy) to ensure that the objective holds with probability 1 (almost-surely). While the qualitative analysis of POMDPs with parity objectives is undecidable, recent results show that when restricted to finite-memory policies the problem is EXPTIME-complete. While the problem is intractable in theory, we present a practical approach to solve the qualitative analysis problem. We designed several heuristics to deal with the exponential complexity, and have used our implementation on a number of well-known POMDP examples for robotics applications. Our results provide the first practical approach to solve the qualitative analysis of robot motion planning with LTL properties in the presence of uncertainty.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Gupta, Raghav
AU - Kanodia, Ayush
ID - 5426
SN - 2664-1690
TI - Qualitative analysis of POMDPs with temporal logic specifications for robotics applications
ER -
TY - GEN
AB - We present a flexible framework for the automated competitive analysis of on-line scheduling algorithms for firm- deadline real-time tasks based on multi-objective graphs: Given a taskset and an on-line scheduling algorithm specified as a labeled transition system, along with some optional safety, liveness, and/or limit-average constraints for the adversary, we automatically compute the competitive ratio of the algorithm w.r.t. a clairvoyant scheduler. We demonstrate the flexibility and power of our approach by comparing the competitive ratio of several on-line algorithms, including D(over), that have been proposed in the past, for various tasksets. Our experimental results reveal that none of these algorithms is universally optimal, in the sense that there are tasksets where other schedulers provide better performance. Our framework is hence a very useful design tool for selecting optimal algorithms for a given application.
AU - Chatterjee, Krishnendu
AU - Kössler, Alexander
AU - Pavlogiannis, Andreas
AU - Schmid, Ulrich
ID - 5423
SN - 2664-1690
TI - A framework for automated competitive analysis of on-line scheduling of firm-deadline tasks
ER -
TY - GEN
AB - We consider graphs with n nodes together with their tree-decomposition that has b = O ( n ) bags and width t , on the standard RAM computational model with wordsize W = Θ (log n ) . Our contributions are two-fold: Our first contribution is an algorithm that given a graph and its tree-decomposition as input, computes a binary and balanced tree-decomposition of width at most 4 · t + 3 of the graph in O ( b ) time and space, improving a long-standing (from 1992) bound of O ( n · log n ) time for constant treewidth graphs. Our second contribution is on reachability queries for low treewidth graphs. We build on our tree-balancing algorithm and present a data-structure for graph reachability that requires O ( n · t 2 ) preprocessing time, O ( n · t ) space, and O ( d t/ log n e ) time for pair queries, and O ( n · t · log t/ log n ) time for single-source queries. For constant t our data-structure uses O ( n ) time for preprocessing, O (1) time for pair queries, and O ( n/ log n ) time for single-source queries. This is (asymptotically) optimal and is faster than DFS/BFS when answering more than a constant number of single-source queries.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5427
SN - 2664-1690
TI - Optimal tree-decomposition balancing and reachability on low treewidth graphs
ER -
TY - GEN
AB - We consider partially observable Markov decision processes (POMDPs) with a set of target states and every transition is associated with an integer cost. The optimization objective we study asks to minimize the expected total cost till the target set is reached, while ensuring that the target set is reached almost-surely (with probability 1). We show that for integer costs approximating the optimal cost is undecidable. For positive costs, our results are as follows: (i) we establish matching lower and upper bounds for the optimal cost and the bound is double exponential; (ii) we show that the problem of approximating the optimal cost is decidable and present approximation algorithms developing on the existing algorithms for POMDPs with finite-horizon objectives. While the worst-case running time of our algorithm is double exponential, we also present efficient stopping criteria for the algorithm and show experimentally that it performs well in many examples of interest.
AU - Anonymous, 1
AU - Anonymous, 2
AU - Anonymous, 3
AU - Anonymous, 4
ID - 5425
SN - 2664-1690
TI - Optimal cost almost-sure reachability in POMDPs
ER -
TY - GEN
AB - Simulation is an attractive alternative for language inclusion for automata as it is an under-approximation of language inclusion, but usually has much lower complexity. For non-deterministic automata, while language inclusion is PSPACE-complete, simulation can be computed in polynomial time. Simulation has also been extended in two orthogonal directions, namely, (1) fair simulation, for simulation over specified set of infinite runs; and (2) quantitative simulation, for simulation between weighted automata. Again, while fair trace inclusion is PSPACE-complete, fair simulation can be computed in polynomial time. For weighted automata, the (quantitative) language inclusion problem is undecidable for mean-payoff automata and the decidability is open for discounted-sum automata, whereas the (quantitative) simulation reduce to mean-payoff games and discounted-sum games, which admit pseudo-polynomial time algorithms.
In this work, we study (quantitative) simulation for weighted automata with Büchi acceptance conditions, i.e., we generalize fair simulation from non-weighted automata to weighted automata. We show that imposing Büchi acceptance conditions on weighted automata changes many fundamental properties of the simulation games. For example, whereas for mean-payoff and discounted-sum games, the players do not need memory to play optimally; we show in contrast that for simulation games with Büchi acceptance conditions, (i) for mean-payoff objectives, optimal strategies for both players require infinite memory in general, and (ii) for discounted-sum objectives, optimal strategies need not exist for both players. While the simulation games with Büchi acceptance conditions are more complicated (e.g., due to infinite-memory requirements for mean-payoff objectives) as compared to their counterpart without Büchi acceptance conditions, we still present pseudo-polynomial time algorithms to solve simulation games with Büchi acceptance conditions for both weighted mean-payoff and weighted discounted-sum automata.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Velner, Yaron
ID - 5428
SN - 2664-1690
TI - Quantitative fair simulation games
ER -
TY - GEN
AB - Recently there has been a significant effort to add 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, several basic system properties such as average response time cannot be expressed with weighted automata. In this work, we introduce nested weighted automata as a new formalism for expressing important quantitative properties such as average response time. We establish an almost complete decidability picture for the basic decision problems for nested weighted automata, and illustrate its applicability in several domains.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5415
SN - 2664-1690
TI - Nested weighted automata
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. 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 - 5421
SN - 2664-1690
TI - The complexity of evolution on graphs
ER -
TY - JOUR
AB - Maximum entropy models are the least structured probability distributions that exactly reproduce a chosen set of statistics measured in an interacting network. Here we use this principle to construct probabilistic models which describe the correlated spiking activity of populations of up to 120 neurons in the salamander retina as it responds to natural movies. Already in groups as small as 10 neurons, interactions between spikes can no longer be regarded as small perturbations in an otherwise independent system; for 40 or more neurons pairwise interactions need to be supplemented by a global interaction that controls the distribution of synchrony in the population. Here we show that such “K-pairwise” models—being systematic extensions of the previously used pairwise Ising models—provide an excellent account of the data. We explore the properties of the neural vocabulary by: 1) estimating its entropy, which constrains the population's capacity to represent visual information; 2) classifying activity patterns into a small set of metastable collective modes; 3) showing that the neural codeword ensembles are extremely inhomogenous; 4) demonstrating that the state of individual neurons is highly predictable from the rest of the population, allowing the capacity for error correction.
AU - Tkacik, Gasper
AU - Marre, Olivier
AU - Amodei, Dario
AU - Schneidman, Elad
AU - Bialek, William
AU - Berry, Michael
ID - 2257
IS - 1
JF - PLoS Computational Biology
SN - 1553734X
TI - Searching for collective behavior in a large network of sensory neurons
VL - 10
ER -
TY - CHAP
AB - Mechanically coupled cells can generate forces driving cell and tissue morphogenesis during development. Visualization and measuring of these forces is of major importance to better understand the complexity of the biomechanic processes that shape cells and tissues. Here, we describe how UV laser ablation can be utilized to quantitatively assess mechanical tension in different tissues of the developing zebrafish and in cultures of primary germ layer progenitor cells ex vivo.
AU - Smutny, Michael
AU - Behrndt, Martin
AU - Campinho, Pedro
AU - Ruprecht, Verena
AU - Heisenberg, Carl-Philipp J
ED - Nelson, Celeste
ID - 6178
SN - 1064-3745
T2 - Tissue Morphogenesis
TI - UV laser ablation to measure cell and tissue-generated forces in the zebrafish embryo in vivo and ex vivo
VL - 1189
ER -
TY - CONF
AB - Two-player games on graphs provide the theoretical framework for many important problems such as reactive synthesis. While the traditional study of two-player zero-sum games has been extended to multi-player games with several notions of equilibria, they are decidable only for perfect-information games, whereas several applications require imperfect-information games.
In this paper we propose a new notion of equilibria, called doomsday equilibria, which is a strategy profile such that all players satisfy their own objective, and if any coalition of players deviates and violates even one of the players objective, then the objective of every player is violated.
We present algorithms and complexity results for deciding the existence of doomsday equilibria for various classes of ω-regular objectives, both for imperfect-information games, and for perfect-information games.We provide optimal complexity bounds for imperfect-information games, and in most cases for perfect-information games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Filiot, Emmanuel
AU - Raskin, Jean-François
ID - 10885
SN - 0302-9743
T2 - VMCAI 2014: Verification, Model Checking, and Abstract Interpretation
TI - Doomsday equilibria for omega-regular games
VL - 8318
ER -
TY - BOOK
AB - This monograph presents a short course in computational geometry and topology. In the first part the book covers Voronoi diagrams and Delaunay triangulations, then it presents the theory of alpha complexes which play a crucial role in biology. The central part of the book is the homology theory and their computation, including the theory of persistence which is indispensable for applications, e.g. shape reconstruction. The target audience comprises researchers and practitioners in mathematics, biology, neuroscience and computer science, but the book may also be beneficial to graduate students of these fields.
AU - Edelsbrunner, Herbert
ID - 6853
SN - 2191-530X
TI - A Short Course in Computational Geometry and Topology
ER -
TY - GEN
AU - Huszár, Kristóf
AU - Rolinek, Michal
ID - 7038
TI - Playful Math - An introduction to mathematical games
ER -
TY - CONF
AB - Many questions concerning models in quantum mechanics require a detailed analysis of the spectrum of the corresponding Hamiltonian, a linear operator on a suitable Hilbert space. Of particular relevance for an understanding of the low-temperature properties of a system is the structure of the excitation spectrum, which is the part of the spectrum close to the spectral bottom. We present recent progress on this question for bosonic many-body quantum systems with weak two-body interactions. Such system are currently of great interest, due to their experimental realization in ultra-cold atomic gases. We investigate the accuracy of the Bogoliubov approximations, which predicts that the low-energy spectrum is made up of sums of elementary excitations, with linear dispersion law at low momentum. The latter property is crucial for the superfluid behavior the system.
AU - Seiringer, Robert
ID - 8044
SN - 9788961058063
T2 - Proceeding of the International Congress of Mathematicans
TI - Structure of the excitation spectrum for many-body quantum systems
VL - 3
ER -
TY - JOUR
AB - Antibiotics affect bacterial cell physiology at many levels. Rather than just compensating for the direct cellular defects caused by the drug, bacteria respond to antibiotics by changing their morphology, macromolecular composition, metabolism, gene expression and possibly even their mutation rate. Inevitably, these processes affect each other, resulting in a complex response with changes in the expression of numerous genes. Genome‐wide approaches can thus help in gaining a comprehensive understanding of bacterial responses to antibiotics. In addition, a combination of experimental and theoretical approaches is needed for identifying general principles that underlie these responses. Here, we review recent progress in our understanding of bacterial responses to antibiotics and their combinations, focusing on effects at the levels of growth rate and gene expression. We concentrate on studies performed in controlled laboratory conditions, which combine promising experimental techniques with quantitative data analysis and mathematical modeling. While these basic research approaches are not immediately applicable in the clinic, uncovering the principles and mechanisms underlying bacterial responses to antibiotics may, in the long term, contribute to the development of new treatment strategies to cope with and prevent the rise of resistant pathogenic bacteria.
AU - Mitosch, Karin
AU - Bollenbach, Tobias
ID - 2001
IS - 6
JF - Environmental Microbiology Reports
TI - Bacterial responses to antibiotics and their combinations
VL - 6
ER -
TY - CONF
AB - NMAC is a mode of operation which turns a fixed input-length keyed hash function f into a variable input-length function. A practical single-key variant of NMAC called HMAC is a very popular and widely deployed message authentication code (MAC). Security proofs and attacks for NMAC can typically be lifted to HMAC. NMAC was introduced by Bellare, Canetti and Krawczyk [Crypto'96], who proved it to be a secure pseudorandom function (PRF), and thus also a MAC, assuming that (1) f is a PRF and (2) the function we get when cascading f is weakly collision-resistant. Unfortunately, HMAC is typically instantiated with cryptographic hash functions like MD5 or SHA-1 for which (2) has been found to be wrong. To restore the provable guarantees for NMAC, Bellare [Crypto'06] showed its security based solely on the assumption that f is a PRF, albeit via a non-uniform reduction. - Our first contribution is a simpler and uniform proof for this fact: If f is an ε-secure PRF (against q queries) and a δ-non-adaptively secure PRF (against q queries), then NMAC f is an (ε+ℓqδ)-secure PRF against q queries of length at most ℓ blocks each. - We then show that this ε+ℓqδ bound is basically tight. For the most interesting case where ℓqδ ≥ ε we prove this by constructing an f for which an attack with advantage ℓqδ exists. This also violates the bound O(ℓε) on the PRF-security of NMAC recently claimed by Koblitz and Menezes. - Finally, we analyze the PRF-security of a modification of NMAC called NI [An and Bellare, Crypto'99] that differs mainly by using a compression function with an additional keying input. This avoids the constant rekeying on multi-block messages in NMAC and allows for a security proof starting by the standard switch from a PRF to a random function, followed by an information-theoretic analysis. We carry out such an analysis, obtaining a tight ℓq2/2 c bound for this step, improving over the trivial bound of ℓ2q2/2c. The proof borrows combinatorial techniques originally developed for proving the security of CBC-MAC [Bellare et al., Crypto'05].
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Rybar, Michal
ED - Garay, Juan
ED - Gennaro, Rosario
ID - 2082
IS - 1
TI - The exact PRF-security of NMAC and HMAC
VL - 8616
ER -
TY - JOUR
AB - Kupffer's vesicle (KV) is the zebrafish organ of laterality, patterning the embryo along its left-right (LR) axis. Regional differences in cell shape within the lumen-lining KV epithelium are essential for its LR patterning function. However, the processes by which KV cells acquire their characteristic shapes are largely unknown. Here, we show that the notochord induces regional differences in cell shape within KV by triggering extracellular matrix (ECM) accumulation adjacent to anterior-dorsal (AD) regions of KV. This localized ECM deposition restricts apical expansion of lumen-lining epithelial cells in AD regions of KV during lumen growth. Our study provides mechanistic insight into the processes by which KV translates global embryonic patterning into regional cell shape differences required for its LR symmetry-breaking function.
AU - Compagnon, Julien
AU - Barone, Vanessa
AU - Rajshekar, Srivarsha
AU - Kottmeier, Rita
AU - Pranjic-Ferscha, Kornelija
AU - Behrndt, Martin
AU - Heisenberg, Carl-Philipp J
ID - 1912
IS - 6
JF - Developmental Cell
TI - The notochord breaks bilateral symmetry by controlling cell shapes in the Zebrafish laterality organ
VL - 31
ER -
TY - JOUR
AB - Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment.
AU - Lagator, Mato
AU - Morgan, Andrew
AU - Neve, Paul
AU - Colegrave, Nick
ID - 2083
IS - 8
JF - Evolution
TI - Role of sex and migration in adaptation to sink environments
VL - 68
ER -
TY - GEN
AB - Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment.
AU - Lagator, Mato
AU - Morgan, Andrew
AU - Neve, Paul
AU - Colegrave, Nick
ID - 9747
TI - Data from: Role of sex and migration in adaptation to sink environments
ER -
TY - JOUR
AB - Pathogens may gain a fitness advantage through manipulation of the behaviour of their hosts. Likewise, host behavioural changes can be a defence mechanism, counteracting the impact of pathogens on host fitness. We apply harmonic radar technology to characterize the impact of an emerging pathogen - Nosema ceranae (Microsporidia) - on honeybee (Apis mellifera) flight and orientation performance in the field. Honeybees are the most important commercial pollinators. Emerging diseases have been proposed to play a prominent role in colony decline, partly through sub-lethal behavioural manipulation of their hosts. We found that homing success was significantly reduced in diseased (65.8%) versus healthy foragers (92.5%). Although lost bees had significantly reduced continuous flight times and prolonged resting times, other flight characteristics and navigational abilities showed no significant difference between infected and non-infected bees. Our results suggest that infected bees express normal flight characteristics but are constrained in their homing ability, potentially compromising the colony by reducing its resource inputs, but also counteracting the intra-colony spread of infection. We provide the first high-resolution analysis of sub-lethal effects of an emerging disease on insect flight behaviour. The potential causes and the implications for both host and parasite are discussed.
AU - Wolf, Stephan
AU - Mcmahon, Dino
AU - Lim, Ka
AU - Pull, Christopher
AU - Clark, Suzanne
AU - Paxton, Robert
AU - Osborne, Juliet
ID - 2086
IS - 8
JF - PLoS One
TI - So near and yet so far: Harmonic radar reveals reduced homing ability of Nosema infected honeybees
VL - 9
ER -
TY - GEN
AB - Detailed description of the experimental prodedures, data analyses and additional statistical analyses of the results.
AU - Wolf, Stephan
AU - Mcmahon, Dino
AU - Lim, Ka
AU - Pull, Christopher
AU - Clark, Suzanne
AU - Paxton, Robert
AU - Osborne, Juliet
ID - 9888
TI - Supporting information
ER -
TY - JOUR
AB - We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.
AU - Lovrics, Anna
AU - Gao, Yu
AU - Juhász, Bianka
AU - Bock, István
AU - Byrne, Helen
AU - Dinnyés, András
AU - Kovács, Krisztián
ID - 2004
IS - 11
JF - PLoS One
TI - Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord
VL - 9
ER -
TY - GEN
AU - Lovrics, Anna
AU - Gao, Yu
AU - Juhász, Bianka
AU - Bock, István
AU - Byrne, Helen M.
AU - Dinnyés, András
AU - Kovács, Krisztián
ID - 9722
TI - Transition probability between TF expression states when Dbx2 inhibits Nkx2.2
ER -
TY - JOUR
AB - A fundamental question in biology is the following: what is the time scale that is needed for evolutionary innovations? There are many results that characterize single steps in terms of the fixation time of new mutants arising in populations of certain size and structure. But here we ask a different question, which is concerned with the much longer time scale of evolutionary trajectories: how long does it take for a population exploring a fitness landscape to find target sequences that encode new biological functions? Our key variable is the length, (Formula presented.) of the genetic sequence that undergoes adaptation. In computer science there is a crucial distinction between problems that require algorithms which take polynomial or exponential time. The latter are considered to be intractable. Here we develop a theoretical approach that allows us to estimate the time of evolution as function of (Formula presented.) We show that adaptation on many fitness landscapes takes time that is exponential in (Formula presented.) even if there are broad selection gradients and many targets uniformly distributed in sequence space. These negative results lead us to search for specific mechanisms that allow evolution to work on polynomial time scales. We study a regeneration process and show that it enables evolution to work in polynomial time.
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Adlam, Ben
AU - Nowak, Martin
ID - 2039
IS - 9
JF - PLoS Computational Biology
TI - The time scale of evolutionary innovation
VL - 10
ER -
TY - JOUR
AB - Repeated pathogen exposure is a common threat in colonies of social insects, posing selection pressures on colony members to respond with improved disease-defense performance. We here tested whether experience gained by repeated tending of low-level fungus-exposed (Metarhizium robertsii) larvae may alter the performance of sanitary brood care in the clonal ant, Platythyrea punctata. We trained ants individually over nine consecutive trials to either sham-treated or fungus-exposed larvae. We then compared the larval grooming behavior of naive and trained ants and measured how effectively they removed infectious fungal conidiospores from the fungus-exposed larvae. We found that the ants changed the duration of larval grooming in response to both, larval treatment and their level of experience: (1) sham-treated larvae received longer grooming than the fungus-exposed larvae and (2) trained ants performed less self-grooming but longer larval grooming than naive ants, which was true for both, ants trained to fungus-exposed and also to sham-treated larvae. Ants that groomed the fungus-exposed larvae for longer periods removed a higher number of fungal conidiospores from the surface of the fungus-exposed larvae. As experienced ants performed longer larval grooming, they were more effective in fungal removal, thus making them better caretakers under pathogen attack of the colony. By studying this clonal ant, we can thus conclude that even in the absence of genetic variation between colony members, differences in experience levels of brood care may affect performance of sanitary brood care in social insects.
AU - Westhus, Claudia
AU - Ugelvig, Line V
AU - Tourdot, Edouard
AU - Heinze, Jürgen
AU - Doums, Claudie
AU - Cremer, Sylvia
ID - 2161
IS - 10
JF - Behavioral Ecology and Sociobiology
SN - 0340-5443
TI - Increased grooming after repeated brood care provides sanitary benefits in a clonal ant
VL - 68
ER -
TY - JOUR
AB - In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments.
AU - Lagator, Mato
AU - Colegrave, Nick
AU - Neve, Paul
ID - 2036
IS - 1794
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses
VL - 281
ER -
TY - GEN
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 - 9740
TI - Data from: Anti-pathogen protection versus survival costs mediated by an ectosymbiont in an ant host
ER -
TY - GEN
AB - In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments.
AU - Lagator, Mato
AU - Colegrave, Nick
AU - Neve, Paul
ID - 9741
TI - Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses
ER -
TY - GEN
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Adlam, Ben
AU - Novak, Martin
ID - 9739
TI - Detailed proofs for “The time scale of evolutionary innovation”
ER -