TY - CONF
AB - Following the publication of an attack on genome-wide association studies (GWAS) data proposed by Homer et al., considerable attention has been given to developing methods for releasing GWAS data in a privacy-preserving way. Here, we develop an end-to-end differentially private method for solving regression problems with convex penalty functions and selecting the penalty parameters by cross-validation. In particular, we focus on penalized logistic regression with elastic-net regularization, a method widely used to in GWAS analyses to identify disease-causing genes. We show how a differentially private procedure for penalized logistic regression with elastic-net regularization can be applied to the analysis of GWAS data and evaluate our method’s performance.
AU - Yu, Fei
AU - Rybar, Michal
AU - Uhler, Caroline
AU - Fienberg, Stephen
ED - Domingo Ferrer, Josep
ID - 2047
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Differentially-private logistic regression for detecting multiple-SNP association in GWAS databases
VL - 8744
ER -
TY - JOUR
AB - The flow instability and further transition to turbulence in a toroidal pipe (torus) with curvature ratio (tube-to-coiling diameter) 0.049 is investigated experimentally. The flow inside the toroidal pipe is driven by a steel sphere fitted to the inner pipe diameter. The sphere is moved with constant azimuthal velocity from outside the torus by a moving magnet. The experiment is designed to investigate curved pipe flow by optical measurement techniques. Using stereoscopic particle image velocimetry, laser Doppler velocimetry and pressure drop measurements, the flow is measured for Reynolds numbers ranging from 1000 to 15 000. Time- and space-resolved velocity fields are obtained and analysed. The steady axisymmetric basic flow is strongly influenced by centrifugal effects. On an increase of the Reynolds number we find a sequence of bifurcations. For Re=4075±2% a supercritical bifurcation to an oscillatory flow is found in which waves travel in the streamwise direction with a phase velocity slightly faster than the mean flow. The oscillatory flow is superseded by a presumably quasi-periodic flow at a further increase of the Reynolds number before turbulence sets in. The results are found to be compatible, in general, with earlier experimental and numerical investigations on transition to turbulence in helical and curved pipes. However, important aspects of the bifurcation scenario differ considerably.
AU - Kühnen, Jakob
AU - Holzner, Markus
AU - Hof, Björn
AU - Kuhlmann, Hendrik
ID - 2050
JF - Journal of Fluid Mechanics
TI - Experimental investigation of transitional flow in a toroidal pipe
VL - 738
ER -
TY - CONF
AB - A standard technique for solving the parameterized model checking problem is to reduce it to the classic model checking problem of finitely many finite-state systems. This work considers some of the theoretical power and limitations of this technique. We focus on concurrent systems in which processes communicate via pairwise rendezvous, as well as the special cases of disjunctive guards and token passing; specifications are expressed in indexed temporal logic without the next operator; and the underlying network topologies are generated by suitable Monadic Second Order Logic formulas and graph operations. First, we settle the exact computational complexity of the parameterized model checking problem for some of our concurrent systems, and establish new decidability results for others. Second, we consider the cases that model checking the parameterized system can be reduced to model checking some fixed number of processes, the number is known as a cutoff. We provide many cases for when such cutoffs can be computed, establish lower bounds on the size of such cutoffs, and identify cases where no cutoff exists. Third, we consider cases for which the parameterized system is equivalent to a single finite-state system (more precisely a Büchi word automaton), and establish tight bounds on the sizes of such automata.
AU - Aminof, Benjamin
AU - Kotek, Tomer
AU - Rubin, Sacha
AU - Spegni, Francesco
AU - Veith, Helmut
ED - Baldan, Paolo
ED - Gorla, Daniele
ID - 2052
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Parameterized model checking of rendezvous systems
VL - 8704
ER -
TY - CONF
AB - In contrast to the usual understanding of probabilistic systems as stochastic processes, recently these systems have also been regarded as transformers of probabilities. In this paper, we give a natural definition of strong bisimulation for probabilistic systems corresponding to this view that treats probability distributions as first-class citizens. Our definition applies in the same way to discrete systems as well as to systems with uncountable state and action spaces. Several examples demonstrate that our definition refines the understanding of behavioural equivalences of probabilistic systems. In particular, it solves a longstanding open problem concerning the representation of memoryless continuous time by memoryfull continuous time. Finally, we give algorithms for computing this bisimulation not only for finite but also for classes of uncountably infinite systems.
AU - Hermanns, Holger
AU - Krčál, Jan
AU - Kretinsky, Jan
ED - Baldan, Paolo
ED - Gorla, Daniele
ID - 2053
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Probabilistic bisimulation: Naturally on distributions
VL - 8704
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 - JOUR
AB - We consider a continuous-time Markov chain (CTMC) whose state space is partitioned into aggregates, and each aggregate is assigned a probability measure. A sufficient condition for defining a CTMC over the aggregates is presented as a variant of weak lumpability, which also characterizes that the measure over the original process can be recovered from that of the aggregated one. We show how the applicability of de-aggregation depends on the initial distribution. The application section is devoted to illustrate how the developed theory aids in reducing CTMC models of biochemical systems particularly in connection to protein-protein interactions. We assume that the model is written by a biologist in form of site-graph-rewrite rules. Site-graph-rewrite rules compactly express that, often, only a local context of a protein (instead of a full molecular species) needs to be in a certain configuration in order to trigger a reaction event. This observation leads to suitable aggregate Markov chains with smaller state spaces, thereby providing sufficient reduction in computational complexity. This is further exemplified in two case studies: simple unbounded polymerization and early EGFR/insulin crosstalk.
AU - Ganguly, Arnab
AU - Petrov, Tatjana
AU - Koeppl, Heinz
ID - 2056
IS - 3
JF - Journal of Mathematical Biology
TI - Markov chain aggregation and its applications to combinatorial reaction networks
VL - 69
ER -
TY - CONF
AB - In the past few years, a lot of attention has been devoted to multimedia indexing by fusing multimodal informations. Two kinds of fusion schemes are generally considered: The early fusion and the late fusion. We focus on late classifier fusion, where one combines the scores of each modality at the decision level. To tackle this problem, we investigate a recent and elegant well-founded quadratic program named MinCq coming from the machine learning PAC-Bayesian theory. MinCq looks for the weighted combination, over a set of real-valued functions seen as voters, leading to the lowest misclassification rate, while maximizing the voters’ diversity. We propose an extension of MinCq tailored to multimedia indexing. Our method is based on an order-preserving pairwise loss adapted to ranking that allows us to improve Mean Averaged Precision measure while taking into account the diversity of the voters that we want to fuse. We provide evidence that this method is naturally adapted to late fusion procedures and confirm the good behavior of our approach on the challenging PASCAL VOC’07 benchmark.
AU - Morvant, Emilie
AU - Habrard, Amaury
AU - Ayache, Stéphane
ID - 2057
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Majority vote of diverse classifiers for late fusion
VL - 8621
ER -
TY - JOUR
AB - Plant embryogenesis is regulated by differential distribution of the plant hormone auxin. However, the cells establishing these gradients during microspore embryogenesis remain to be identified. For the first time, we describe, using the DR5 or DR5rev reporter gene systems, the GFP- and GUS-based auxin biosensors to monitor auxin during Brassica napus androgenesis at cellular resolution in the initial stages. Our study provides evidence that the distribution of auxin changes during embryo development and depends on the temperature-inducible in vitro culture conditions. For this, microspores (mcs) were induced to embryogenesis by heat treatment and then subjected to genetic modification via Agrobacterium tumefaciens. The duration of high temperature treatment had a significant influence on auxin distribution in isolated and in vitro-cultured microspores and on microspore-derived embryo development. In the “mild” heat-treated (1 day at 32 °C) mcs, auxin localized in a polar way already at the uni-nucleate microspore, which was critical for the initiation of embryos with suspensor-like structure. Assuming a mean mcs radius of 20 μm, endogenous auxin content in a single cell corresponded to concentration of 1.01 μM. In mcs subjected to a prolonged heat (5 days at 32 °C), although auxin concentration increased dozen times, auxin polarization was set up at a few-celled pro-embryos without suspensor. Those embryos were enclosed in the outer wall called the exine. The exine rupture was accompanied by the auxin gradient polarization. Relative quantitative estimation of auxin, using time-lapse imaging, revealed that primordia possess up to 1.3-fold higher amounts than those found in the root apices of transgenic MDEs in the presence of exogenous auxin. Our results show, for the first time, which concentration of endogenous auxin coincides with the first cell division and how the high temperature interplays with auxin, by what affects delay early establishing microspore polarity. Moreover, we present how the local auxin accumulation demonstrates the apical–basal axis formation of the androgenic embryo and directs the axiality of the adult haploid plant.
AU - Dubas, Ewa
AU - Moravčíková, Jana
AU - Libantová, Jana
AU - Matušíková, Ildikó
AU - Benková, Eva
AU - Zur, Iwona
AU - Krzewska, Monika
ID - 2059
IS - 5
JF - Protoplasma
TI - The influence of heat stress on auxin distribution in transgenic B napus microspores and microspore derived embryos
VL - 251
ER -
TY - JOUR
AB - Development of cambium and its activity is important for our knowledge of the mechanism of secondary growth. Arabidopsis thaliana emerges as a good model plant for such a kind of study. Thus, this paper reports on cellular events taking place in the interfascicular regions of inflorescence stems of A. thaliana, leading to the development of interfascicular cambium from differentiated interfascicular parenchyma cells (IPC). These events are as follows: appearance of auxin accumulation, PIN1 gene expression, polar PIN1 protein localization in the basal plasma membrane and periclinal divisions. Distribution of auxin was observed to be higher in differentiating into cambium parenchyma cells compared to cells within the pith and cortex. Expression of PIN1 in IPC was always preceded by auxin accumulation. Basal localization of PIN1 was already established in the cells prior to their periclinal division. These cellular events initiated within parenchyma cells adjacent to the vascular bundles and successively extended from that point towards the middle region of the interfascicular area, located between neighboring vascular bundles. The final consequence of which was the closure of the cambial ring within the stem. Changes in the chemical composition of IPC walls were also detected and included changes of pectic epitopes, xyloglucans (XG) and extensins rich in hydroxyproline (HRGPs). In summary, results presented in this paper describe interfascicular cambium ontogenesis in terms of successive cellular events in the interfascicular regions of inflorescence stems of Arabidopsis.
AU - Mazur, Ewa
AU - Kurczyñska, Ewa
AU - Friml, Jiří
ID - 2061
IS - 5
JF - Protoplasma
TI - Cellular events during interfascicular cambium ontogenesis in inflorescence stems of Arabidopsis
VL - 251
ER -
TY - JOUR
AB - The success story of fast-spiking, parvalbumin-positive (PV+) GABAergic interneurons (GABA, γ-aminobutyric acid) in the mammalian central nervous system is noteworthy. In 1995, the properties of these interneurons were completely unknown. Twenty years later, thanks to the massive use of subcellular patch-clamp techniques, simultaneous multiple-cell recording, optogenetics, in vivo measurements, and computational approaches, our knowledge about PV+ interneurons became more extensive than for several types of pyramidal neurons. These findings have implications beyond the “small world” of basic research on GABAergic cells. For example, the results provide a first proof of principle that neuroscientists might be able to close the gaps between the molecular, cellular, network, and behavioral levels, representing one of the main challenges at the present time. Furthermore, the results may form the basis for PV+ interneurons as therapeutic targets for brain disease in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will be able to use PV+ interneurons for therapeutic purposes.
AU - Hu, Hua
AU - Gan, Jian
AU - Jonas, Peter M
ID - 2062
IS - 6196
JF - Science
TI - Fast-spiking parvalbumin^+ GABAergic interneurons: From cellular design to microcircuit function
VL - 345
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 - JOUR
AB - We examined the synaptic structure, quantity, and distribution of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type glutamate receptors (AMPARs and NMDARs, respectively) in rat cochlear nuclei by a highly sensitive freeze-fracture replica labeling technique. Four excitatory synapses formed by two distinct inputs, auditory nerve (AN) and parallel fibers (PF), on different cell types were analyzed. These excitatory synapse types included AN synapses on bushy cells (AN-BC synapses) and fusiform cells (AN-FC synapses) and PF synapses on FC (PF-FC synapses) and cartwheel cell spines (PF-CwC synapses). Immunogold labeling revealed differences in synaptic structure as well as AMPAR and NMDAR number and/or density in both AN and PF synapses, indicating a target-dependent organization. The immunogold receptor labeling also identified differences in the synaptic organization of FCs based on AN or PF connections, indicating an input-dependent organization in FCs. Among the four excitatory synapse types, the AN-BC synapses were the smallest and had the most densely packed intramembrane particles (IMPs), whereas the PF-CwC synapses were the largest and had sparsely packed IMPs. All four synapse types showed positive correlations between the IMP-cluster area and the AMPAR number, indicating a common intrasynapse-type relationship for glutamatergic synapses. Immunogold particles for AMPARs were distributed over the entire area of individual AN synapses; PF synapses often showed synaptic areas devoid of labeling. The gold-labeling for NMDARs occurred in a mosaic fashion, with less positive correlations between the IMP-cluster area and the NMDAR number. Our observations reveal target- and input-dependent features in the structure, number, and organization of AMPARs and NMDARs in AN and PF synapses.
AU - Rubio, Maía
AU - Fukazawa, Yugo
AU - Kamasawa, Naomi
AU - Clarkson, Cheryl
AU - Molnár, Elek
AU - Shigemoto, Ryuichi
ID - 2064
IS - 18
JF - Journal of Comparative Neurology
TI - Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus
VL - 522
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 - 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 - 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 - 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 - 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
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 - CONF
AB - We define a simple, explicit map sending a morphism f : M → N of pointwise finite dimensional persistence modules to a matching between the barcodes of M and N. Our main result is that, in a precise sense, the quality of this matching is tightly controlled by the lengths of the longest intervals in the barcodes of ker f and coker f . As an immediate corollary, we obtain a new proof of the algebraic stability theorem for persistence barcodes [5, 9], a fundamental result in the theory of persistent homology. In contrast to previous proofs, ours shows explicitly how a δ-interleaving morphism between two persistence modules induces a δ-matching between the barcodes of the two modules. Our main result also specializes to a structure theorem for submodules and quotients of persistence modules. Copyright is held by the owner/author(s).
AU - Bauer, Ulrich
AU - Lesnick, Michael
ID - 2153
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - Induced matchings of barcodes and the algebraic stability of persistence
ER -
TY - JOUR
AB - A result of Boros and Füredi (d = 2) and of Bárány (arbitrary d) asserts that for every d there exists cd > 0 such that for every n-point set P ⊂ ℝd, some point of ℝd is covered by at least (Formula presented.) of the d-simplices spanned by the points of P. The largest possible value of cd has been the subject of ongoing research. Recently Gromov improved the existing lower bounds considerably by introducing a new, topological proof method. We provide an exposition of the combinatorial component of Gromov's approach, in terms accessible to combinatorialists and discrete geometers, and we investigate the limits of his method. In particular, we give tighter bounds on the cofilling profiles for the (n - 1)-simplex. These bounds yield a minor improvement over Gromov's lower bounds on cd for large d, but they also show that the room for further improvement through the cofilling profiles alone is quite small. We also prove a slightly better lower bound for c3 by an approach using an additional structure besides the cofilling profiles. We formulate a combinatorial extremal problem whose solution might perhaps lead to a tight lower bound for cd.
AU - Matoušek, Jiří
AU - Wagner, Uli
ID - 2154
IS - 1
JF - Discrete & Computational Geometry
TI - On Gromov's method of selecting heavily covered points
VL - 52
ER -
TY - CONF
AB - Given a finite set of points in Rn and a positive radius, we study the Čech, Delaunay-Čech, alpha, and wrap complexes as instances of a generalized discrete Morse theory. We prove that the latter three complexes are simple-homotopy equivalent. Our results have applications in topological data analysis and in the reconstruction of shapes from sampled data. Copyright is held by the owner/author(s).
AU - Bauer, Ulrich
AU - Edelsbrunner, Herbert
ID - 2155
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - The morse theory of Čech and Delaunay filtrations
ER -
TY - CONF
AB - We propose a metric for Reeb graphs, called the functional distortion distance. Under this distance, the Reeb graph is stable against small changes of input functions. At the same time, it remains discriminative at differentiating input functions. In particular, the main result is that the functional distortion distance between two Reeb graphs is bounded from below by the bottleneck distance between both the ordinary and extended persistence diagrams for appropriate dimensions. As an application of our results, we analyze a natural simplification scheme for Reeb graphs, and show that persistent features in Reeb graph remains persistent under simplification. Understanding the stability of important features of the Reeb graph under simplification is an interesting problem on its own right, and critical to the practical usage of Reeb graphs. Copyright is held by the owner/author(s).
AU - Bauer, Ulrich
AU - Ge, Xiaoyin
AU - Wang, Yusu
ID - 2156
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - Measuring distance between Reeb graphs
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 - Directional guidance of migrating cells is relatively well explored in the reductionist setting of cell culture experiments. Here spatial gradients of chemical cues as well as gradients of mechanical substrate characteristics prove sufficient to attract single cells as well as their collectives. How such gradients present and act in the context of an organism is far less clear. Here we review recent advances in understanding how guidance cues emerge and operate in the physiological context.
AU - Majumdar, Ritankar
AU - Sixt, Michael K
AU - Parent, Carole
ID - 2158
IS - 1
JF - Current Opinion in Cell Biology
TI - New paradigms in the establishment and maintenance of gradients during directed cell migration
VL - 30
ER -
TY - CONF
AB - Transfer learning has received a lot of attention in the machine learning community over the last years, and several effective algorithms have been developed. However, relatively little is known about their theoretical properties, especially in the setting of lifelong learning, where the goal is to transfer information to tasks for which no data have been observed so far. In this work we study lifelong learning from a theoretical perspective. Our main result is a PAC-Bayesian generalization bound that offers a unified view on existing paradigms for transfer learning, such as the transfer of parameters or the transfer of low-dimensional representations. We also use the bound to derive two principled lifelong learning algorithms, and we show that these yield results comparable with existing methods.
AU - Pentina, Anastasia
AU - Lampert, Christoph
ED - Xing, Eric
ED - Jebara, Tony
ID - 2160
TI - A PAC-Bayesian bound for Lifelong Learning
VL - 32
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
TI - Increased grooming after repeated brood care provides sanitary benefits in a clonal ant
VL - 68
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 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 - JOUR
AB - Neuronal ectopia, such as granule cell dispersion (GCD) in temporal lobe epilepsy (TLE), has been assumed to result from a migration defect during development. Indeed, recent studies reported that aberrant migration of neonatal-generated dentate granule cells (GCs) increased the risk to develop epilepsy later in life. On the contrary, in the present study, we show that fully differentiated GCs become motile following the induction of epileptiform activity, resulting in GCD. Hippocampal slice cultures from transgenic mice expressing green fluorescent protein in differentiated, but not in newly generated GCs, were incubated with the glutamate receptor agonist kainate (KA), which induced GC burst activity and GCD. Using real-time microscopy, we observed that KA-exposed, differentiated GCs translocated their cell bodies and changed their dendritic organization. As found in human TLE, KA application was associated with decreased expression of the extracellular matrix protein Reelin, particularly in hilar interneurons. Together these findings suggest that KA-induced motility of differentiated GCs contributes to the development of GCD and establish slice cultures as a model to study neuronal changes induced by epileptiform activity.
AU - Chai, Xuejun
AU - Münzner, Gert
AU - Zhao, Shanting
AU - Tinnes, Stefanie
AU - Kowalski, Janina
AU - Häussler, Ute
AU - Young, Christina
AU - Haas, Carola
AU - Frotscher, Michael
ID - 2164
IS - 8
JF - Cerebral Cortex
TI - Epilepsy-induced motility of differentiated neurons
VL - 24
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 - JOUR
AB - Many species have an essentially continuous distribution in space, in which there are no natural divisions between randomly mating subpopulations. Yet, the standard approach to modelling these populations is to impose an arbitrary grid of demes, adjusting deme sizes and migration rates in an attempt to capture the important features of the population. Such indirect methods are required because of the failure of the classical models of isolation by distance, which have been shown to have major technical flaws. A recently introduced model of extinction and recolonisation in two dimensions solves these technical problems, and provides a rigorous technical foundation for the study of populations evolving in a spatial continuum. The coalescent process for this model is simply stated, but direct simulation is very inefficient for large neighbourhood sizes. We present efficient and exact algorithms to simulate this coalescent process for arbitrary sample sizes and numbers of loci, and analyse these algorithms in detail.
AU - Kelleher, Jerome
AU - Etheridge, Alison
AU - Barton, Nicholas H
ID - 2168
JF - Theoretical Population Biology
TI - Coalescent simulation in continuous space: Algorithms for large neighbourhood size
VL - 95
ER -
TY - JOUR
AU - Barton, Nicholas H
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 2169
IS - 29
JF - PNAS
TI - Diverse forms of selection in evolution and computer science
VL - 111
ER -
TY - JOUR
AB - Short-read sequencing technologies have in principle made it feasible to draw detailed inferences about the recent history of any organism. In practice, however, this remains challenging due to the difficulty of genome assembly in most organisms and the lack of statistical methods powerful enough to discriminate between recent, nonequilibrium histories. We address both the assembly and inference challenges. We develop a bioinformatic pipeline for generating outgroup-rooted alignments of orthologous sequence blocks from de novo low-coverage short-read data for a small number of genomes, and show how such sequence blocks can be used to fit explicit models of population divergence and admixture in a likelihood framework. To illustrate our approach, we reconstruct the Pleistocene history of an oak-feeding insect (the oak gallwasp Biorhiza pallida), which, in common with many other taxa, was restricted during Pleistocene ice ages to a longitudinal series of southern refugia spanning the Western Palaearctic. Our analysis of sequence blocks sampled from a single genome from each of three major glacial refugia reveals support for an unexpected history dominated by recent admixture. Despite the fact that 80% of the genome is affected by admixture during the last glacial cycle, we are able to infer the deeper divergence history of these populations. These inferences are robust to variation in block length, mutation model and the sampling location of individual genomes within refugia. This combination of de novo assembly and numerical likelihood calculation provides a powerful framework for estimating recent population history that can be applied to any organism without the need for prior genetic resources.
AU - Hearn, Jack
AU - Stone, Graham
AU - Bunnefeld, Lynsey
AU - Nicholls, James
AU - Barton, Nicholas H
AU - Lohse, Konrad
ID - 2170
IS - 1
JF - Molecular Ecology
TI - Likelihood-based inference of population history from low-coverage de novo genome assemblies
VL - 23
ER -
TY - CONF
AB - We present LS-CRF, a new method for training cyclic Conditional Random Fields (CRFs) from large datasets that is inspired by classical closed-form expressions for the maximum likelihood parameters of a generative graphical model with tree topology. Training a CRF with LS-CRF requires only solving a set of independent regression problems, each of which can be solved efficiently in closed form or by an iterative solver. This makes LS-CRF orders of magnitude faster than classical CRF training based on probabilistic inference, and at the same time more flexible and easier to implement than other approximate techniques, such as pseudolikelihood or piecewise training. We apply LS-CRF to the task of semantic image segmentation, showing that it achieves on par accuracy to other training techniques at higher speed, thereby allowing efficient CRF training from very large training sets. For example, training a linearly parameterized pairwise CRF on 150,000 images requires less than one hour on a modern workstation.
AU - Kolesnikov, Alexander
AU - Guillaumin, Matthieu
AU - Ferrari, Vittorio
AU - Lampert, Christoph
ED - Fleet, David
ED - Pajdla, Tomas
ED - Schiele, Bernt
ED - Tuytelaars, Tinne
ID - 2171
IS - PART 3
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Closed-form approximate CRF training for scalable image segmentation
VL - 8691
ER -
TY - CONF
AB - Fisher Kernels and Deep Learning were two developments with significant impact on large-scale object categorization in the last years. Both approaches were shown to achieve state-of-the-art results on large-scale object categorization datasets, such as ImageNet. Conceptually, however, they are perceived as very different and it is not uncommon for heated debates to spring up when advocates of both paradigms meet at conferences or workshops. In this work, we emphasize the similarities between both architectures rather than their differences and we argue that such a unified view allows us to transfer ideas from one domain to the other. As a concrete example we introduce a method for learning a support vector machine classifier with Fisher kernel at the same time as a task-specific data representation. We reinterpret the setting as a multi-layer feed forward network. Its final layer is the classifier, parameterized by a weight vector, and the two previous layers compute Fisher vectors, parameterized by the coefficients of a Gaussian mixture model. We introduce a gradient descent based learning algorithm that, in contrast to other feature learning techniques, is not just derived from intuition or biological analogy, but has a theoretical justification in the framework of statistical learning theory. Our experiments show that the new training procedure leads to significant improvements in classification accuracy while preserving the modularity and geometric interpretability of a support vector machine setup.
AU - Sydorov, Vladyslav
AU - Sakurada, Mayu
AU - Lampert, Christoph
ID - 2172
T2 - Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition
TI - Deep Fisher Kernels – End to end learning of the Fisher Kernel GMM parameters
ER -
TY - CONF
AB - In this work we introduce a new approach to co-classification, i.e. the task of jointly classifying multiple, otherwise independent, data samples. The method we present, named CoConut, is based on the idea of adding a regularizer in the label space to encode certain priors on the resulting labelings. A regularizer that encourages labelings that are smooth across the test set, for instance, can be seen as a test-time variant of the cluster assumption, which has been proven useful at training time in semi-supervised learning. A regularizer that introduces a preference for certain class proportions can be regarded as a prior distribution on the class labels. CoConut can build on existing classifiers without making any assumptions on how they were obtained and without the need to re-train them. The use of a regularizer adds a new level of flexibility. It allows the integration of potentially new information at test time, even in other modalities than what the classifiers were trained on. We evaluate our framework on six datasets, reporting a clear performance gain in classification accuracy compared to the standard classification setup that predicts labels for each test sample separately.
AU - Khamis, Sameh
AU - Lampert, Christoph
ID - 2173
T2 - Proceedings of the British Machine Vision Conference 2014
TI - CoConut: Co-classification with output space regularization
ER -
TY - JOUR
AB - When polygenic traits are under stabilizing selection, many different combinations of alleles allow close adaptation to the optimum. If alleles have equal effects, all combinations that result in the same deviation from the optimum are equivalent. Furthermore, the genetic variance that is maintained by mutation-selection balance is 2μ/S per locus, where μ is the mutation rate and S the strength of stabilizing selection. In reality, alleles vary in their effects, making the fitness landscape asymmetric and complicating analysis of the equilibria. We show that that the resulting genetic variance depends on the fraction of alleles near fixation, which contribute by 2μ/S, and on the total mutational effects of alleles that are at intermediate frequency. The inpplayfi between stabilizing selection and mutation leads to a sharp transition: alleles with effects smaller than a threshold value of 2 remain polymorphic, whereas those with larger effects are fixed. The genetic load in equilibrium is less than for traits of equal effects, and the fitness equilibria are more similar. We find p the optimum is displaced, alleles with effects close to the threshold value sweep first, and their rate of increase is bounded by Long-term response leads in general to well-adapted traits, unlike the case of equal effects that often end up at a suboptimal fitness peak. However, the particular peaks to which the populations converge are extremely sensitive to the initial states and to the speed of the shift of the optimum trait value.
AU - De Vladar, Harold
AU - Barton, Nicholas H
ID - 2174
IS - 2
JF - Genetics
TI - Stability and response of polygenic traits to stabilizing selection and mutation
VL - 197
ER -
TY - JOUR
AB - The cerebral cortex, the seat of our cognitive abilities, is composed of an intricate network of billions of excitatory projection and inhibitory interneurons. Postmitotic cortical neurons are generated by a diverse set of neural stem cell progenitors within dedicated zones and defined periods of neurogenesis during embryonic development. Disruptions in neurogenesis can lead to alterations in the neuronal cytoarchitecture, which is thought to represent a major underlying cause for several neurological disorders, including microcephaly, autism and epilepsy. Although a number of signaling pathways regulating neurogenesis have been described, the precise cellular and molecular mechanisms regulating the functional neural stem cell properties in cortical neurogenesis remain unclear. Here, we discuss the most up-to-date strategies to monitor the fundamental mechanistic parameters of neuronal progenitor proliferation, and recent advances deciphering the logic and dynamics of neurogenesis.
AU - Postiglione, Maria P
AU - Hippenmeyer, Simon
ID - 2175
IS - 3
JF - Future Neurology
TI - Monitoring neurogenesis in the cerebral cortex: an update
VL - 9
ER -
TY - JOUR
AB - Electron microscopy (EM) allows for the simultaneous visualization of all tissue components at high resolution. However, the extent to which conventional aldehyde fixation and ethanol dehydration of the tissue alter the fine structure of cells and organelles, thereby preventing detection of subtle structural changes induced by an experiment, has remained an issue. Attempts have been made to rapidly freeze tissue to preserve native ultrastructure. Shock-freezing of living tissue under high pressure (high-pressure freezing, HPF) followed by cryosubstitution of the tissue water avoids aldehyde fixation and dehydration in ethanol; the tissue water is immobilized in â ̂1/450 ms, and a close-to-native fine structure of cells, organelles and molecules is preserved. Here we describe a protocol for HPF that is useful to monitor ultrastructural changes associated with functional changes at synapses in the brain but can be applied to many other tissues as well. The procedure requires a high-pressure freezer and takes a minimum of 7 d but can be paused at several points.
AU - Studer, Daniel
AU - Zhao, Shanting
AU - Chai, Xuejun
AU - Jonas, Peter M
AU - Graber, Werner
AU - Nestel, Sigrun
AU - Frotscher, Michael
ID - 2176
IS - 6
JF - Nature Protocols
TI - Capture of activity-induced ultrastructural changes at synapses by high-pressure freezing of brain tissue
VL - 9
ER -
TY - CONF
AB - We give evidence for the difficulty of computing Betti numbers of simplicial complexes over a finite field. We do this by reducing the rank computation for sparse matrices with to non-zero entries to computing Betti numbers of simplicial complexes consisting of at most a constant times to simplices. Together with the known reduction in the other direction, this implies that the two problems have the same computational complexity.
AU - Edelsbrunner, Herbert
AU - Parsa, Salman
ID - 2177
T2 - Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms
TI - On the computational complexity of betti numbers reductions from matrix rank
ER -
TY - JOUR
AB - We consider the three-state toric homogeneous Markov chain model (THMC) without loops and initial parameters. At time T, the size of the design matrix is 6 × 3 · 2T-1 and the convex hull of its columns is the model polytope. We study the behavior of this polytope for T ≥ 3 and we show that it is defined by 24 facets for all T ≥ 5. Moreover, we give a complete description of these facets. From this, we deduce that the toric ideal associated with the design matrix is generated by binomials of degree at most 6. Our proof is based on a result due to Sturmfels, who gave a bound on the degree of the generators of a toric ideal, provided the normality of the corresponding toric variety. In our setting, we established the normality of the toric variety associated to the THMC model by studying the geometric properties of the model polytope.
AU - Haws, David
AU - Martin Del Campo Sanchez, Abraham
AU - Takemura, Akimichi
AU - Yoshida, Ruriko
ID - 2178
IS - 1
JF - Beitrage zur Algebra und Geometrie
TI - Markov degree of the three-state toric homogeneous Markov chain model
VL - 55
ER -
TY - JOUR
AB - We extend the proof of the local semicircle law for generalized Wigner matrices given in MR3068390 to the case when the matrix of variances has an eigenvalue -1. In particular, this result provides a short proof of the optimal local Marchenko-Pastur law at the hard edge (i.e. around zero) for sample covariance matrices X*X, where the variances of the entries of X may vary.
AU - Ajanki, Oskari H
AU - Erdös, László
AU - Krüger, Torben H
ID - 2179
JF - Electronic Communications in Probability
TI - Local semicircle law with imprimitive variance matrix
VL - 19
ER -
TY - JOUR
AB - Weighted majority votes allow one to combine the output of several classifiers or voters. MinCq is a recent algorithm for optimizing the weight of each voter based on the minimization of a theoretical bound over the risk of the vote with elegant PAC-Bayesian generalization guarantees. However, while it has demonstrated good performance when combining weak classifiers, MinCq cannot make use of the useful a priori knowledge that one may have when using a mixture of weak and strong voters. In this paper, we propose P-MinCq, an extension of MinCq that can incorporate such knowledge in the form of a constraint over the distribution of the weights, along with general proofs of convergence that stand in the sample compression setting for data-dependent voters. The approach is applied to a vote of k-NN classifiers with a specific modeling of the voters' performance. P-MinCq significantly outperforms the classic k-NN classifier, a symmetric NN and MinCq using the same voters. We show that it is also competitive with LMNN, a popular metric learning algorithm, and that combining both approaches further reduces the error.
AU - Bellet, Aurélien
AU - Habrard, Amaury
AU - Morvant, Emilie
AU - Sebban, Marc
ID - 2180
IS - 1-2
JF - Machine Learning
TI - Learning a priori constrained weighted majority votes
VL - 97
ER -
TY - JOUR
AB - Given topological spaces X,Y, a fundamental problem of algebraic topology is understanding the structure of all continuous maps X→ Y. We consider a computational version, where X,Y are given as finite simplicial complexes, and the goal is to compute [X,Y], that is, all homotopy classes of suchmaps.We solve this problem in the stable range, where for some d ≥ 2, we have dim X ≤ 2d-2 and Y is (d-1)-connected; in particular, Y can be the d-dimensional sphere Sd. The algorithm combines classical tools and ideas from homotopy theory (obstruction theory, Postnikov systems, and simplicial sets) with algorithmic tools from effective algebraic topology (locally effective simplicial sets and objects with effective homology). In contrast, [X,Y] is known to be uncomputable for general X,Y, since for X = S1 it includes a well known undecidable problem: testing triviality of the fundamental group of Y. In follow-up papers, the algorithm is shown to run in polynomial time for d fixed, and extended to other problems, such as the extension problem, where we are given a subspace A ⊂ X and a map A→ Y and ask whether it extends to a map X → Y, or computing the Z2-index-everything in the stable range. Outside the stable range, the extension problem is undecidable.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Matoušek, Jiří
AU - Sergeraert, Francis
AU - Vokřínek, Lukáš
AU - Wagner, Uli
ID - 2184
IS - 3
JF - Journal of the ACM
TI - Computing all maps into a sphere
VL - 61
ER -
TY - CONF
AB - We revisit the classical problem of converting an imperfect source of randomness into a usable cryptographic key. Assume that we have some cryptographic application P that expects a uniformly random m-bit key R and ensures that the best attack (in some complexity class) against P(R) has success probability at most δ. Our goal is to design a key-derivation function (KDF) h that converts any random source X of min-entropy k into a sufficiently "good" key h(X), guaranteeing that P(h(X)) has comparable security δ′ which is 'close' to δ. Seeded randomness extractors provide a generic way to solve this problem for all applications P, with resulting security δ′ = O(δ), provided that we start with entropy k ≥ m + 2 log (1/δ) - O(1). By a result of Radhakrishnan and Ta-Shma, this bound on k (called the "RT-bound") is also known to be tight in general. Unfortunately, in many situations the loss of 2 log (1/δ) bits of entropy is unacceptable. This motivates the study KDFs with less entropy waste by placing some restrictions on the source X or the application P. In this work we obtain the following new positive and negative results in this regard: - Efficient samplability of the source X does not help beat the RT-bound for general applications. This resolves the SRT (samplable RT) conjecture of Dachman-Soled et al. [DGKM12] in the affirmative, and also shows that the existence of computationally-secure extractors beating the RT-bound implies the existence of one-way functions. - We continue in the line of work initiated by Barak et al. [BDK+11] and construct new information-theoretic KDFs which beat the RT-bound for large but restricted classes of applications. Specifically, we design efficient KDFs that work for all unpredictability applications P (e.g., signatures, MACs, one-way functions, etc.) and can either: (1) extract all of the entropy k = m with a very modest security loss δ′ = O(δ·log (1/δ)), or alternatively, (2) achieve essentially optimal security δ′ = O(δ) with a very modest entropy loss k ≥ m + loglog (1/δ). In comparison, the best prior results from [BDK+11] for this class of applications would only guarantee δ′ = O(√δ) when k = m, and would need k ≥ m + log (1/δ) to get δ′ = O(δ). - The weaker bounds of [BDK+11] hold for a larger class of so-called "square- friendly" applications (which includes all unpredictability, but also some important indistinguishability, applications). Unfortunately, we show that these weaker bounds are tight for the larger class of applications. - We abstract out a clean, information-theoretic notion of (k,δ,δ′)- unpredictability extractors, which guarantee "induced" security δ′ for any δ-secure unpredictability application P, and characterize the parameters achievable for such unpredictability extractors. Of independent interest, we also relate this notion to the previously-known notion of (min-entropy) condensers, and improve the state-of-the-art parameters for such condensers.
AU - Dodis, Yevgeniy
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ED - Nguyen, Phong
ED - Oswald, Elisabeth
ID - 2185
TI - Key derivation without entropy waste
VL - 8441
ER -
TY - JOUR
AB - We prove the existence of scattering states for the defocusing cubic Gross-Pitaevskii (GP) hierarchy in ℝ3. Moreover, we show that an exponential energy growth condition commonly used in the well-posedness theory of the GP hierarchy is, in a specific sense, necessary. In fact, we prove that without the latter, there exist initial data for the focusing cubic GP hierarchy for which instantaneous blowup occurs.
AU - Chen, Thomas
AU - Hainzl, Christian
AU - Pavlović, Nataša
AU - Seiringer, Robert
ID - 2186
IS - 7
JF - Letters in Mathematical Physics
TI - On the well-posedness and scattering for the Gross-Pitaevskii hierarchy via quantum de Finetti
VL - 104
ER -
TY - JOUR
AB - Systems should not only be correct but also robust in the sense that they behave reasonably in unexpected situations. This article addresses synthesis of robust reactive systems from temporal specifications. Existing methods allow arbitrary behavior if assumptions in the specification are violated. To overcome this, we define two robustness notions, combine them, and show how to enforce them in synthesis. The first notion applies to safety properties: If safety assumptions are violated temporarily, we require that the system recovers to normal operation with as few errors as possible. The second notion requires that, if liveness assumptions are violated, as many guarantees as possible should be fulfilled nevertheless. We present a synthesis procedure achieving this for the important class of GR(1) specifications, and establish complexity bounds. We also present an implementation of a special case of robustness, and show experimental results.
AU - Bloem, Roderick
AU - Chatterjee, Krishnendu
AU - Greimel, Karin
AU - Henzinger, Thomas A
AU - Hofferek, Georg
AU - Jobstmann, Barbara
AU - Könighofer, Bettina
AU - Könighofer, Robert
ID - 2187
IS - 3-4
JF - Acta Informatica
TI - Synthesizing robust systems
VL - 51
ER -
TY - JOUR
AB - Although plant and animal cells use a similar core mechanism to deliver proteins to the plasma membrane, their different lifestyle, body organization and specific cell structures resulted in the acquisition of regulatory mechanisms that vary in the two kingdoms. In particular, cell polarity regulators do not seem to be conserved, because genes encoding key components are absent in plant genomes. In plants, the broad knowledge on polarity derives from the study of auxin transporters, the PIN-FORMED proteins, in the model plant Arabidopsis thaliana. In animals, much information is provided from the study of polarity in epithelial cells that exhibit basolateral and luminal apical polarities, separated by tight junctions. In this review, we summarize the similarities and differences of the polarization mechanisms between plants and animals and survey the main genetic approaches that have been used to characterize new genes involved in polarity establishment in plants, including the frequently used forward and reverse genetics screens as well as a novel chemical genetics approach that is expected to overcome the limitation of classical genetics methods.
AU - Kania, Urszula
AU - Fendrych, Matyas
AU - Friml, Jiřĺ
ID - 2188
IS - APRIL
JF - Open Biology
TI - Polar delivery in plants; commonalities and differences to animal epithelial cells
VL - 4
ER -
TY - CONF
AB - En apprentissage automatique, nous parlons d'adaptation de domaine lorsque les données de test (cibles) et d'apprentissage (sources) sont générées selon différentes distributions. Nous devons donc développer des algorithmes de classification capables de s'adapter à une nouvelle distribution, pour laquelle aucune information sur les étiquettes n'est disponible. Nous attaquons cette problématique sous l'angle de l'approche PAC-Bayésienne qui se focalise sur l'apprentissage de modèles définis comme des votes de majorité sur un ensemble de fonctions. Dans ce contexte, nous introduisons PV-MinCq une version adaptative de l'algorithme (non adaptatif) MinCq. PV-MinCq suit le principe suivant. Nous transférons les étiquettes sources aux points cibles proches pour ensuite appliquer MinCq sur l'échantillon cible ``auto-étiqueté'' (justifié par une borne théorique). Plus précisément, nous définissons un auto-étiquetage non itératif qui se focalise dans les régions où les distributions marginales source et cible sont les plus similaires. Dans un second temps, nous étudions l'influence de notre auto-étiquetage pour en déduire une procédure de validation des hyperparamètres. Finalement, notre approche montre des résultats empiriques prometteurs.
AU - Morvant, Emilie
ID - 2189
TI - Adaptation de domaine de vote de majorité par auto-étiquetage non itératif
VL - 1
ER -
TY - CONF
AB - We present a new algorithm to construct a (generalized) deterministic Rabin automaton for an LTL formula φ. The automaton is the product of a master automaton and an array of slave automata, one for each G-subformula of φ. The slave automaton for G ψ is in charge of recognizing whether FG ψ holds. As opposed to standard determinization procedures, the states of all our automata have a clear logical structure, which allows for various optimizations. Our construction subsumes former algorithms for fragments of LTL. Experimental results show improvement in the sizes of the resulting automata compared to existing methods.
AU - Esparza, Javier
AU - Kretinsky, Jan
ID - 2190
TI - From LTL to deterministic automata: A safraless compositional approach
VL - 8559
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 - 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 - 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 - JOUR
AB - A hallmark of immune cell trafficking is directional guidance via gradients of soluble or surface bound chemokines. Vascular endothelial cells produce, transport and deposit either their own chemokines or chemokines produced by the underlying stroma. Endothelial heparan sulfate (HS) was suggested to be a critical scaffold for these chemokine pools, but it is unclear how steep chemokine gradients are sustained between the lumenal and ablumenal aspects of blood vessels. Addressing this question by semi-quantitative immunostaining of HS moieties around blood vessels with a pan anti-HS IgM mAb, we found a striking HS enrichment in the basal lamina of resting and inflamed post capillary skin venules, as well as in high endothelial venules (HEVs) of lymph nodes. Staining of skin vessels with a glycocalyx probe further suggested that their lumenal glycocalyx contains much lower HS density than their basolateral extracellular matrix (ECM). This polarized HS pattern was observed also in isolated resting and inflamed microvascular dermal cells. Notably, progressive skin inflammation resulted in massive ECM deposition and in further HS enrichment around skin post capillary venules and their associated pericytes. Inflammation-dependent HS enrichment was not compromised in mice deficient in the main HS degrading enzyme, heparanase. Our results suggest that the blood vasculature patterns steep gradients of HS scaffolds between their lumenal and basolateral endothelial aspects, and that inflammatory processes can further enrich the HS content nearby inflamed vessels. We propose that chemokine gradients between the lumenal and ablumenal sides of vessels could be favored by these sharp HS scaffold gradients.
AU - Stoler Barak, Liat
AU - Moussion, Christine
AU - Shezen, Elias
AU - Hatzav, Miki
AU - Sixt, Michael K
AU - Alon, Ronen
ID - 2214
IS - 1
JF - PLoS One
TI - Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects
VL - 9
ER -
TY - JOUR
AB - Homologous recombination is crucial for genome stability and for genetic exchange. Although our knowledge of the principle steps in recombination and its machinery is well advanced, homology search, the critical step of exploring the genome for homologous sequences to enable recombination, has remained mostly enigmatic. However, recent methodological advances have provided considerable new insights into this fundamental step in recombination that can be integrated into a mechanistic model. These advances emphasize the importance of genomic proximity and nuclear organization for homology search and the critical role of homology search mediators in this process. They also aid our understanding of how homology search might lead to unwanted and potentially disease-promoting recombination events.
AU - Renkawitz, Jörg
AU - Lademann, Claudio
AU - Jentsch, Stefan
ID - 2215
IS - 6
JF - Nature Reviews Molecular Cell Biology
TI - Mechanisms and principles of homology search during recombination
VL - 15
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 - 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 - 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 - 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 - Correct positioning of membrane proteins is an essential process in eukaryotic organisms. The plant hormone auxin is distributed through intercellular transport and triggers various cellular responses. Auxin transporters of the PIN-FORMED (PIN) family localize asymmetrically at the plasma membrane (PM) and mediate the directional transport of auxin between cells. A fungal toxin, brefeldin A (BFA), inhibits a subset of guanine nucleotide exchange factors for ADP-ribosylation factor small GTPases (ARF GEFs) including GNOM, which plays a major role in localization of PIN1 predominantly to the basal side of the PM. The Arabidopsis genome encodes 19 ARF-related putative GTPases. However, ARF components involved in PIN1 localization have been genetically poorly defined. Using a fluorescence imaging-based forward genetic approach, we identified an Arabidopsis mutant, bfa-visualized exocytic trafficking defective1 (bex1), in which PM localization of PIN1-green fluorescent protein (GFP) as well as development is hypersensitive to BFA. We found that in bex1 a member of the ARF1 gene family, ARF1A1C, was mutated. ARF1A1C localizes to the trans-Golgi network/early endosome and Golgi apparatus, acts synergistically to BEN1/MIN7 ARF GEF and is important for PIN recycling to the PM. Consistent with the developmental importance of PIN proteins, functional interference with ARF1 resulted in an impaired auxin response gradient and various developmental defects including embryonic patterning defects and growth arrest. Our results show that ARF1A1C is essential for recycling of PIN auxin transporters and for various auxin-dependent developmental processes.
AU - Tanaka, Hirokazu
AU - Nodzyński, Tomasz
AU - Kitakura, Saeko
AU - Feraru, Mugurel
AU - Sasabe, Michiko
AU - Ishikawa, Tomomi
AU - Kleine Vehn, Jürgen
AU - Kakimoto, Tatsuo
AU - Friml, Jirí
ID - 2223
IS - 4
JF - Plant and Cell Physiology
SN - 00320781
TI - BEX1/ARF1A1C is required for BFA-sensitive recycling of PIN auxin transporters and auxin-mediated 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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
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 - 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 - 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 - 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 - 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 - 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 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 - 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 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 - 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 - 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 -