TY - JOUR AB - Let P(t) ∈ ℚ[t] be an irreducible quadratic polynomial and suppose that K is a quartic extension of ℚ containing the roots of P(t). Let N K/ℚ(X) be a full norm form for the extension K/ℚ. We show that the variety P(t) =N K/ℚ(X)≠ 0 satisfies the Hasse principle and weak approximation. The proof uses analytic methods. AU - Timothy Browning AU - Heath-Brown, Roger ID - 243 IS - 5 JF - Geometric and Functional Analysis TI - Quadratic polynomials represented by norm forms VL - 22 ER - TY - CONF AB - We present an algorithm for computing [X, Y], i.e., all homotopy classes of continuous maps X → Y, where X, Y are topological spaces given as finite simplicial complexes, Y is (d - 1)-connected for some d ≥ 2 (for example, Y can be the d-dimensional sphere S d), and dim X ≤ 2d - 2. These conditions on X, Y guarantee that [X, Y] has a natural structure of a finitely generated Abelian group, and the algorithm finds generators and relations for it. We combine several tools and ideas from homotopy theory (such as Postnikov systems, simplicial sets, and obstruction theory) with algorithmic tools from effective algebraic topology (objects with effective homology). We hope that a further extension of the methods developed here will yield an algorithm for computing, in some cases of interest, the ℤ 2-index, which is a quantity playing a prominent role in Borsuk-Ulam style applications of topology in combinatorics and geometry, e.g., in topological lower bounds for the chromatic number of a graph. In a certain range of dimensions, deciding the embeddability of a simplicial complex into ℝ d also amounts to a ℤ 2-index computation. This is the main motivation of our work. We believe that investigating the computational complexity of questions in homotopy theory and similar areas presents a fascinating research area, and we hope that our work may help bridge the cultural gap between algebraic topology and theoretical computer science. AU - Čadek, Martin AU - Marek Krcál AU - Matoušek, Jiří AU - Sergeraert, Francis AU - Vokřínek, Lukáš AU - Uli Wagner ID - 2440 TI - Computing all maps into a sphere ER - TY - JOUR AB - The colored Tverberg theorem asserts that for eve;ry d and r there exists t=t(d,r) such that for every set C ⊂ ℝ d of cardinality (d + 1)t, partitioned into t-point subsets C 1, C 2,...,C d+1 (which we think of as color classes; e. g., the points of C 1 are red, the points of C 2 blue, etc.), there exist r disjoint sets R 1, R 2,...,R r⊆C that are rainbow, meaning that {pipe}R i∩C j{pipe}≤1 for every i,j, and whose convex hulls all have a common point. All known proofs of this theorem are topological. We present a geometric version of a recent beautiful proof by Blagojević, Matschke, and Ziegler, avoiding a direct use of topological methods. The purpose of this de-topologization is to make the proof more concrete and intuitive, and accessible to a wider audience. AU - Matoušek, Jiří AU - Martin Tancer AU - Uli Wagner ID - 2438 IS - 2 JF - Discrete & Computational Geometry TI - A geometric proof of the colored Tverberg theorem VL - 47 ER - TY - JOUR AB - We investigate the solubility of the congruence xy ≡ 1 (mod p), where p is a prime and x, y are restricted to lie in suitable short intervals. Our work relies on a mean value theorem for incomplete Kloosterman sums. AU - Timothy Browning AU - Haynes, Alan K ID - 244 IS - 2 JF - International Journal of Number Theory TI - Incomplete kloosterman sums and multiplicative inverses in short intervals VL - 9 ER - TY - JOUR AB - A Monte Carlo approximation algorithm for the Tukey depth problem in high dimensions is introduced. The algorithm is a generalization of an algorithm presented by Rousseeuw and Struyf (1998) . The performance of this algorithm is studied both analytically and experimentally. AU - Chen, Dan AU - Morin, Pat AU - Uli Wagner ID - 2439 IS - 5 JF - Computational Geometry: Theory and Applications TI - Absolute approximation of Tukey depth: Theory and experiments VL - 46 ER - TY - CONF AB - Eigenvalues associated to graphs are a well-studied subject. In particular the spectra of the adjacency matrix and of the Laplacian of random graphs G(n, p) are known quite precisely. We consider generalizations of these matrices to simplicial complexes of higher dimensions and study their eigenvalues for the Linial-Meshulam model X k(n, p) of random k-dimensional simplicial complexes on n vertices. We show that for p = Ω(log n/n), the eigenvalues of both, the higher-dimensional adjacency matrix and the Laplacian, are a.a.s. sharply concentrated around two values. In a second part of the paper, we discuss a possible higherdimensional analogue of the Discrete Cheeger Inequality. This fundamental inequality expresses a close relationship between the eigenvalues of a graph and its combinatorial expansion properties; in particular, spectral expansion (a large eigenvalue gap) implies edge expansion. Recently, a higher-dimensional analogue of edge expansion for simplicial complexes was introduced by Gromov, and independently by Linial, Meshulam and Wallach and by Newman and Rabinovich. It is natural to ask whether there is a higher-dimensional version of Cheeger's inequality. We show that the most straightforward version of a higher-dimensional Cheeger inequality fails: for every k > 1, there is an infinite family of k-dimensional complexes that are spectrally expanding (there is a large eigenvalue gap for the Laplacian) but not combinatorially expanding. AU - Gundert, Anna AU - Uli Wagner ID - 2441 TI - On Laplacians of random complexes ER - TY - JOUR AB - Constitutive endocytic recycling is a crucial mechanism allowing regulation of the activity of proteins at the plasma membrane and for rapid changes in their localization, as demonstrated in plants for PIN-FORMED (PIN) proteins, the auxin transporters. To identify novel molecular components of endocytic recycling, mainly exocytosis, we designed a PIN1-green fluorescent protein fluorescence imaging-based forward genetic screen for Arabidopsis thaliana mutants that showed increased intracellular accumulation of cargos in response to the trafficking inhibitor brefeldin A (BFA). We identified bex5 (for BFA-visualized exocytic trafficking defective), a novel dominant mutant carrying a missense mutation that disrupts a conserved sequence motif of the small GTPase, RAS GENES FROM RAT BRAINA1b. bex5 displays defects such as enhanced protein accumulation in abnormal BFA compartments, aberrant endosomes, and defective exocytosis and transcytosis. BEX5/RabA1b localizes to trans-Golgi network/early endosomes (TGN/EE) and acts on distinct trafficking processes like those regulated by GTP exchange factors on ADP-ribosylation factors GNOM-LIKE1 and HOPM INTERACTOR7/BFA-VISUALIZED ENDOCYTIC TRAFFICKING DEFECTIVE1, which regulate trafficking at the Golgi apparatus and TGN/EE, respectively. All together, this study identifies Arabidopsis BEX5/RabA1b as a novel regulator of protein trafficking from a TGN/EE compartment to the plasma membrane. AU - Feraru, Elena AU - Feraru, Mugurel Ioan AU - Asaoka, Rin AU - Paciorek, Tomasz AU - De Rycke, Riet M AU - Tanaka, Hirokazu AU - Nakano, Akihiko AU - Jirí Friml ID - 2453 IS - 7 JF - Plant Cell TI - BEX5/RabA1b regulates trans-Golgi network-to-plasma membrane protein trafficking in Arabidopsis VL - 24 ER - TY - JOUR AB - The third EMBO Conference on Plant Molecular Biology, which focused on ‘Plant development and environmental interactions’,was held in May 2012 in Matera, Italy. Here, we review some of the topics and themes that emerged from the various contributions; namely, steering technologies, transcriptional networks and hormonal regulation, small RNAs, cell and tissue polarity, environmental control and natural variation. We intend to provide the reader who might have missed this remarkable event with a glimpse of the recent progress made in this blossoming research field. AU - Beeckman, Tom AU - Friml, Jirí ID - 2456 IS - 20 JF - Development TI - Plant developmental biologists meet on stairways in Matera VL - 139 ER - TY - JOUR AB - Coordinated, subcellular trafficking of proteins is one of the fundamental properties of the multicellular eukaryotic organisms. Trafficking involves a large diversity of compartments, pathways, cargo molecules, and vesicle-sorting events. It is also crucial in regulating the localization and, thus, the activity of various proteins, but the process is still poorly genetically defined in plants. In the past, forward genetics screens had been used to determine the function of genes by searching for a specific morphological phenotype in the organism population in which mutations had been induced chemically or by irradiation. Unfortunately, these straightforward genetic screens turned out to be limited in identifying new regulators of intracellular protein transport, because mutations affecting essential trafficking pathways often lead to lethality. In addition, the use of these approaches has been restricted by functional redundancy among trafficking regulators. Screens for mutants that rely on the observation of changes in the cellular localization or dynamics of fluorescent subcellular markers enable, at least partially, to circumvent these issues. Hence, such image-based screens provide the possibility to identify either alleles with weak effects or components of the subcellular trafficking machinery that have no strong impact on the plant growth. AU - Zwiewka, Marta AU - Friml, Jirí ID - 2459 IS - May JF - Frontiers in Plant Science TI - Fluorescence imaging-based forward genetic screens to identify trafficking regulators in plants VL - 3 ER - TY - JOUR AB - Initiation and successive development of organs induce mechanical stresses at the cellular level. Using the tomato shoot apex, a new study now proposes that mechanical strain regulates the plasma membrane abundance of the PIN1 auxin transporter, thereby reinforcing a positive feed-back loop between growth and auxin accumulation. AU - Li, Hongjiang AU - Friml, Jirí AU - Grunewald, Wim ID - 2458 IS - 16 JF - Current Biology TI - Cell polarity: Stretching prevents developmental cramps VL - 22 ER - TY - JOUR AB - Recently developed pharmacogenetic and optogenetic approaches, with their own advantages and disadvantages, have become indispensable tools in modern neuroscience. Here, we employed a previously described knock-in mouse line (GABA ARγ2 77Ilox) in which the γ2 subunit of the GABA A receptor (GABA AR) was mutated to become zolpidem insensitive (γ2 77I) and used viral vectors to swap γ2 77I with wild-type, zolpidem-sensitive γ2 subunits (γ2 77F). The verification of unaltered density and subcellular distribution of the virally introduced γ2 subunits requires their selective labelling. For this we generated six N- and six C-terminal-tagged γ2 subunits, with which cortical cultures of GABA ARγ2 -/- mice were transduced using lentiviruses. We found that the N-terminal AU1 tag resulted in excellent immunodetection and unimpaired synaptic localization. Unaltered kinetic properties of the AU1-tagged γ2 ( AU1γ2 77F) channels were demonstrated with whole-cell patch-clamp recordings of spontaneous IPSCs from cultured cells. Next, we carried out stereotaxic injections of lenti- and adeno-associated viruses containing Cre-recombinase and the AU1γ2 77F subunit (Cre-2A- AU1γ2 77F) into the neocortex of GABA ARγ2 77Ilox mice. Light microscopic immunofluorescence and electron microscopic freeze-fracture replica immunogold labelling demonstrated the efficient immunodetection of the AU1 tag and the normal enrichment of the AU1γ2 77F subunits in perisomatic GABAergic synapses. In line with this, miniature and action potential-evoked IPSCs whole-cell recorded from transduced cells had unaltered amplitudes, kinetics and restored zolpidem sensitivity. Our results obtained with a wide range of structural and functional verification methods reveal unaltered subcellular distributions and functional properties of γ2 77I and AU1γ2 77F GABA ARs in cortical pyramidal cells. This transgenic-viral pharmacogenetic approach has the advantage that it does not require any extrinsic protein that might endow some unforeseen alterations of the genetically modified cells. In addition, this virus-based approach opens up the possibility of modifying multiple cell types in distinct brain regions and performing alternative recombination-based intersectional genetic manipulations. AU - Sümegi, Máté AU - Fukazawa, Yugo AU - Matsui, Ko AU - Lörincz, Andrea AU - Eyre, Mark D AU - Nusser, Zoltán AU - Ryuichi Shigemoto ID - 2476 IS - 7 JF - Journal of Physiology TI - Virus-mediated swapping of zolpidem-insensitive with zolpidem-sensitive GABA A receptors in cortical pyramidal cells VL - 590 ER - TY - JOUR AB - Background: One of the best-characterized causative factors of Alzheimer's disease (AD) is the generation of amyloid-β peptide (Aβ). AD subjects are at high risk of epileptic seizures accompanied by aberrant neuronal excitability, which in itself enhances Aβ generation. However, the molecular linkage between epileptic seizures and Aβ generation in AD remains unclear. Results: X11 and X11-like (X11L) gene knockout mice suffered from epileptic seizures, along with a malfunction of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Genetic ablation of HCN1 in mice and HCN1 channel blockage in cultured Neuro2a (N2a) cells enhanced Aβ generation. Interestingly, HCN1 levels dramatically decreased in the temporal lobe of cynomolgus monkeys (Macaca fascicularis) during aging and were significantly diminished in the temporal lobe of sporadic AD patients. Conclusion: Because HCN1 associates with amyloid-β precursor protein (APP) and X11/X11L in the brain, genetic deficiency of X11/X11L may induce aberrant HCN1 distribution along with epilepsy. Moreover, the reduction in HCN1 levels in aged primates may contribute to augmented Aβ generation. Taken together, HCN1 is proposed to play an important role in the molecular linkage between epileptic seizures and Aβ generation, and in the aggravation of sporadic AD. AU - Saito, Yuhki AU - Inoue, Tsuyoshi AU - Zhu, Gang AU - Kimura, Naoki AU - Okada, Motohiro AU - Nishimura, Masaki AU - Murayama, Shigeo AU - Kaneko, Sunao AU - Ryuichi Shigemoto AU - Imoto, Keiji AU - Suzuki, Toshiharu ID - 2475 IS - 1 JF - Molecular Neurodegeneration TI - Hyperpolarization-activated cyclic nucleotide gated channels: A potential molecular link between epileptic seizures and Aβ generation in Alzheimer's disease VL - 7 ER - TY - JOUR AB - Dynamic activity of glia has repeatedly been demonstrated, but if such activity is independent from neuronal activity, glia would not have any role in the information processing in the brain or in the generation of animal behavior. Evidence for neurons communicating with glia is solid, but the signaling pathway leading back from glial-to-neuronal activity was often difficult to study. Here, we introduced a transgenic mouse line in which channelrhodopsin-2, a light-gated cation channel, was expressed in astrocytes. Selective photostimulation of these astrocytes in vivo triggered neuronal activation. Using slice preparations, we show that glial photostimulation leads to release of glutamate, which was sufficient to activate AMPA receptors on Purkinje cells and to induce long-term depression of parallel fiber-to-Purkinje cell synapses through activation of metabotropic glutamate receptors. In contrast to neuronal synaptic vesicular release, glial activation likely causes preferential activation of extrasynaptic receptors that appose glial membrane. Finally, we show that neuronal activation by glial stimulation can lead to perturbation of cerebellar modulated motor behavior. These findings demonstrate that glia can modulate the tone of neuronal activity and behavior. This animal model is expected to be a potentially powerful approach to study the role of glia in brain function. AU - Sasaki, Takuya AU - Beppu, Kaoru AU - Tanaka, Kenji F AU - Fukazawa, Yugo AU - Ryuichi Shigemoto AU - Matsui, Ko ID - 2477 IS - 50 JF - PNAS TI - Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation VL - 109 ER - TY - JOUR AB - Interneurons are critical for neuronal circuit function, but how their dendritic morphologies and membrane properties influence information flow within neuronal circuits is largely unknown. We studied the spatiotemporal profile of synaptic integration and short-term plasticity in dendrites of mature cerebellar stellate cells by combining two-photon guided electrical stimulation, glutamate uncaging, electron microscopy, and modeling. Synaptic activation within thin (0.4 μm) dendrites produced somatic responses that became smaller and slower with increasing distance from the soma, sublinear subthreshold input-output relationships, and a somatodendritic gradient of short-term plasticity. Unlike most studies showing that neurons employ active dendritic mechanisms, we found that passive cable properties of thin dendrites determine the sublinear integration and plasticity gradient, which both result from large dendritic depolarizations that reduce synaptic driving force. These integrative properties allow stellate cells to act as spatiotemporal filters of synaptic input patterns, thereby biasing their output in favor of sparse presynaptic activity. Stellate cells are critical sources of inhibition in the cerebellum, but how their dendrites integrate excitatory synaptic inputs is unknown. Abrahamsson et al. show that thin dendrites and passive membrane properties of SCs promote sublinear synaptic summation and distance-dependent short-term plasticity. AU - Abrahamsson, Therese AU - Cathala, Laurence AU - Matsui, Ko AU - Ryuichi Shigemoto AU - DiGregorio, David A ID - 2474 IS - 6 JF - Neuron TI - Thin dendrites of cerebellar interneurons confer sublinear synaptic integration and a gradient of short-term plasticity VL - 73 ER - TY - JOUR AB - We investigated the temporal and spatial expression of SK2 in the developing mouse hippocampus using molecular and biochemical techniques, quantitative immunogold electron microscopy, and electrophysiology. The mRNA encoding SK2 was expressed in the developing and adult hippocampus. Western blotting and immunohistochemistry showed that SK2 protein increased with age. This was accompanied by a shift in subcellular localization. Early in development (P5), SK2 was predominantly localized to the endoplasmic reticulum in the pyramidal cell layer. But by P30 SK2 was almost exclusively expressed in the dendrites and spines. The level of SK2 at the postsynaptic density (PSD) also increased during development. In the adult, SK2 expression on the spine plasma membrane showed a proximal-to-distal gradient. Consistent with this redistribution and gradient of SK2, the selective SK channel blocker apamin increased evoked excitatory postsynaptic potentials (EPSPs) only in CA1 pyramidal neurons from mice older than P15. However, the effect of apamin on EPSPs was not different between synapses in proximal or distal stratum radiatum or stratum lacunosum-moleculare in adult. These results show a developmental increase and gradient in SK2-containing channel surface expression that underlie their influence on neurotransmission, and that may contribute to increased memory acquisition during early development. AU - Ballesteros-Merino, Carmen AU - Lin, Michael AU - Wu, Wendy W AU - Ferrándiz-Huertas, Clotilde AU - Cabañero, María José AU - Watanabe, Masahiko AU - Fukazawa, Yugo AU - Ryuichi Shigemoto AU - Maylie, James G AU - Adelman, John P AU - Luján, Rafael ID - 2515 IS - 6 JF - Hippocampus TI - Developmental profile of SK2 channel expression and function in CA1 neurons VL - 22 ER - TY - JOUR AB - Visual information must be relayed through the lateral geniculate nucleus before it reaches the visual cortex. However, not all spikes created in the retina lead to postsynaptic spikes and properties of the retinogeniculate synapse contribute to this filtering. To understand the mechanisms underlying this filtering process, we conducted electrophysiology to assess the properties of signal transmission in the Long-Evans rat. We also performed SDS-digested freeze-fracture replica labeling to quantify the receptor and transporter distribution, as well as EM reconstruction to describe the 3D structure. To analyze the impact of transmitter diffusion on the activity of the receptors, simulations were integrated. We identified that a large contributor to the filtering is the marked paired-pulse depression at this synapse, which was intensified by the morphological characteristics of the contacts. The broad presynaptic and postsynaptic contact area restricts transmitter diffusion two dimensionally. Additionally, the presence of multiple closely arranged release sites invites intersynaptic spillover, which causes desensitization of AMPA receptors. The presence of AMPA receptors that slowly recover from desensitization along with the high presynaptic release probability and multivesicular release at each synapse also contribute to the depression. These features contrast with many other synapses where spatiotemporal spread of transmitter is limited by rapid transmitter clearance allowing synapses to operate more independently. We propose that the micrometer-order structure can ultimately affect the visual information processing. AU - Budisantoso, Timotheus AU - Matsui, Ko AU - Kamasawa, Naomi AU - Fukazawa, Yugo AU - Ryuichi Shigemoto ID - 2514 IS - 7 JF - Journal of Neuroscience TI - Mechanisms underlying signal filtering at a multisynapse contact VL - 32 ER - TY - JOUR AB - R-type calcium channels (RTCCs) are well known for their role in synaptic plasticity, but little is known about their subcellular distribution across various neuronal compartments. Using subtype-specific antibodies, we characterized the regional and subcellular localization of Ca v2.3 in mice and rats at both light and electron microscopic levels. Ca v2.3 immunogold particles were found to be predominantly presynaptic in the interpeduncular nucleus, but postsynaptic in other brain regions. Serial section analysis of electron microscopic images from the hippocampal CA1 revealed a higher density of immunogold particles in the dendritic shaft plasma membrane compared with the pyramidal cell somata. However, the labeling densities were not significantly different among the apical, oblique, or basal dendrites. Immunogold particles were also observed over the plasma membrane of dendritic spines, including both synaptic and extrasynaptic sites. Individual spine heads contained <20 immunogold particles, with an average density of ~260 immunoparticles per μm 3 spine head volume, in accordance with the density of RTCCs estimated using calcium imaging (Sabatini and Svoboda, 2000). The Ca v2.3 density was variable among similar-sized spine heads and did not correlate with the density in the parent dendrite, implying that spines are individual calcium compartments operating autonomously from their parent dendrites. AU - Parajuli, Laxmi K AU - Nakajima, Chikako AU - Kulik, Ákos AU - Matsui, Ko AU - Schneider, Toni AU - Ryuichi Shigemoto AU - Fukazawa, Yugo ID - 2689 IS - 39 JF - Journal of Neuroscience TI - Quantitative regional and ultra structural localization of the Ca v2 3 subunit of R type calcium channel in mouse brain VL - 32 ER - TY - JOUR AB - Left-right asymmetry of human brain function has been known for a century, although much of molecular and cellular basis of brain laterality remains to be elusive. Recent studies suggest that hippocampal CA3-CA1 excitatory synapses are asymmetrically arranged, however, the functional implication of the asymmetrical circuitry has not been studied at the behavioral level. In order to address the left-right asymmetry of hippocampal function in behaving mice, we analyzed the performance of "split-brain" mice in the Barnes maze. The "split-brain" mice received ventral hippocampal commissure and corpus callosum transection in addition to deprivation of visual input from one eye. In such mice, the hippocampus in the side of visual deprivation receives sensory-driven input. Better spatial task performance was achieved by the mice which were forced to use the right hippocampus than those which were forced to use the left hippocampus. In two-choice spatial maze, forced usage of left hippocampus resulted in a comparable performance to the right counterpart, suggesting that both hippocampal hemispheres are capable of conducting spatial learning. Therefore, the results obtained from the Barnes maze suggest that the usage of the right hippocampus improves the accuracy of spatial memory. Performance of non-spatial yet hippocampus-dependent tasks (e.g. fear conditioning) was not influenced by the laterality of the hippocampus. AU - Shinohara, Yoshiaki AU - Hosoya, Aki AU - Yamasaki, Nobuyuki AU - Ahmed, Hassan AU - Hattori, Satoko AU - Eguchi, Megumi AU - Yamaguchi, Shun AU - Miyakawa, Tsuyoshi AU - Hirase, Hajime AU - Ryuichi Shigemoto ID - 2687 IS - 2 JF - Hippocampus TI - Right-hemispheric dominance of spatial memory in split-brain mice VL - 22 ER - TY - JOUR AB - To gain insights into structure-function relationship of excitatory synapses, we revisit our quantitative analysis of synaptic AMPAR by highly sensitive freeze-fracture replica labeling in eight different connections. All of these connections showed linear correlation between synapse size and AMPAR number indicating a common intra-synapse-type relationship in CNS synapses. On the contrary, inter-synapse-type relationship is unexpected indicating no correlation between averages of synapse size and AMPAR number. Interestingly, connections with large average synapse size and low AMPAR density showed high variability of AMPAR number and mosaic distribution within the postsynaptic membrane. We propose an idea that these connections may quickly exhibit synaptic plasticity by modifying AMPAR density/number whereas those with high AMPAR density change their efficacy by modifying synapse size. AU - Fukazawa, Yugo AU - Ryuichi Shigemoto ID - 2688 IS - 3 JF - Current Opinion in Neurobiology TI - Intra-synapse-type and inter-synapse-type relationships between synaptic size and AMPAR expression VL - 22 ER - TY - GEN AU - László Erdös ID - 2696 T2 - ArXiv TI - Universality for random matrices and log-gases ER - TY - CONF AU - László Erdös ID - 2700 TI - Lecture notes on quantum Brownian motion VL - 95 ER - TY - CONF AB - We consider Markov decision processes (MDPs) with specifications given as Büchi (liveness) objectives. We consider the problem of computing the set of almost-sure winning vertices from where the objective can be ensured with probability 1. We study for the first time the average case complexity of the classical algorithm for computing the set of almost-sure winning vertices for MDPs with Büchi objectives. Our contributions are as follows: First, we show that for MDPs with constant out-degree the expected number of iterations is at most logarithmic and the average case running time is linear (as compared to the worst case linear number of iterations and quadratic time complexity). Second, for the average case analysis over all MDPs we show that the expected number of iterations is constant and the average case running time is linear (again as compared to the worst case linear number of iterations and quadratic time complexity). Finally we also show that given that all MDPs are equally likely, the probability that the classical algorithm requires more than constant number of iterations is exponentially small. AU - Chatterjee, Krishnendu AU - Joglekar, Manas AU - Shah, Nisarg ID - 2715 TI - Average case analysis of the classical algorithm for Markov decision processes with Büchi objectives VL - 18 ER - TY - CONF AB - Multi-dimensional mean-payoff and energy games provide the mathematical foundation for the quantitative study of reactive systems, and play a central role in the emerging quantitative theory of verification and synthesis. In this work, we study the strategy synthesis problem for games with such multi-dimensional objectives along with a parity condition, a canonical way to express ω-regular conditions. While in general, the winning strategies in such games may require infinite memory, for synthesis the most relevant problem is the construction of a finite-memory winning strategy (if one exists). Our main contributions are as follows. First, we show a tight exponential bound (matching upper and lower bounds) on the memory required for finite-memory winning strategies in both multi-dimensional mean-payoff and energy games along with parity objectives. This significantly improves the triple exponential upper bound for multi energy games (without parity) that could be derived from results in literature for games on VASS (vector addition systems with states). Second, we present an optimal symbolic and incremental algorithm to compute a finite-memory winning strategy (if one exists) in such games. Finally, we give a complete characterization of when finite memory of strategies can be traded off for randomness. In particular, we show that for one-dimension mean-payoff parity games, randomized memoryless strategies are as powerful as their pure finite-memory counterparts. AU - Chatterjee, Krishnendu AU - Randour, Mickael AU - Raskin, Jean-François ED - Koutny, Maciej ED - Ulidowski, Irek ID - 10904 SN - 0302-9743 T2 - CONCUR 2012 - Concurrency Theory TI - Strategy synthesis for multi-dimensional quantitative objectives VL - 7454 ER - TY - JOUR AB - Consider N×N Hermitian or symmetric random matrices H with independent entries, where the distribution of the (i,j) matrix element is given by the probability measure vij with zero expectation and with variance σ ιj 2. We assume that the variances satisfy the normalization condition Σiσij2=1 for all j and that there is a positive constant c such that c≤Nσ ιj 2 ιc -1. We further assume that the probability distributions νij have a uniform subexponential decay. We prove that the Stieltjes transform of the empirical eigenvalue distribution of H is given by the Wigner semicircle law uniformly up to the edges of the spectrum with an error of order (Nη) -1 where η is the imaginary part of the spectral parameter in the Stieltjes transform. There are three corollaries to this strong local semicircle law: (1) Rigidity of eigenvalues: If γj=γj,N denotes the classical location of the j-th eigenvalue under the semicircle law ordered in increasing order, then the j-th eigenvalue λj is close to γj in the sense that for some positive constants C, c P{double-struck}(∃j:|λ j-γ j|≥(logN) CloglogN[min(j,N-j+1)] -1/3N -2/3)≤ C exp[-(logN) cloglogN] for N large enough. (2) The proof of Dyson's conjecture (Dyson, 1962 [15]) which states that the time scale of the Dyson Brownian motion to reach local equilibrium is of order N -1 up to logarithmic corrections. (3) The edge universality holds in the sense that the probability distributions of the largest (and the smallest) eigenvalues of two generalized Wigner ensembles are the same in the large N limit provided that the second moments of the two ensembles are identical. AU - László Erdös AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2770 IS - 3 JF - Advances in Mathematics TI - Rigidity of eigenvalues of generalized Wigner matrices VL - 229 ER - TY - JOUR AB - We present a generalization of the method of the local relaxation flow to establish the universality of local spectral statistics of a broad class of large random matrices. We show that the local distribution of the eigenvalues coincides with the local statistics of the corresponding Gaussian ensemble provided the distribution of the individual matrix element is smooth and the eigenvalues {X J} N j=1 are close to their classical location {y j} N j=1 determined by the limiting density of eigenvalues. Under the scaling where the typical distance between neighboring eigenvalues is of order 1/N, the necessary apriori estimate on the location of eigenvalues requires only to know that E|x j - γ j| 2 ≤ N-1-ε on average. This information can be obtained by well established methods for various matrix ensembles. We demonstrate the method by proving local spectral universality for sample covariance matrices. AU - László Erdös AU - Schlein, Benjamin AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2769 IS - 1 JF - Annales de l'institut Henri Poincare (B) Probability and Statistics TI - The local relaxation flow approach to universality of the local statistics for random matrices VL - 48 ER - TY - JOUR AB - Consider N × N Hermitian or symmetric random matrices H where the distribution of the (i, j) matrix element is given by a probability measure ν ij with a subexponential decay. Let σ ij 2 be the variance for the probability measure ν ij with the normalization property that Σ iσ i,j 2 = 1 for all j. Under essentially the only condition that c ≤ N σ ij 2 ≤ c -1 for some constant c > 0, we prove that, in the limit N → ∞, the eigenvalue spacing statistics of H in the bulk of the spectrum coincide with those of the Gaussian unitary or orthogonal ensemble (GUE or GOE). We also show that for band matrices with bandwidth M the local semicircle law holds to the energy scale M -1. AU - László Erdös AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2767 IS - 1-2 JF - Probability Theory and Related Fields TI - Bulk universality for generalized Wigner matrices VL - 154 ER - TY - JOUR AB - We consider a two dimensional magnetic Schrödinger operator with a spatially stationary random magnetic field. We assume that the magnetic field has a positive lower bound and that it has Fourier modes on arbitrarily short scales. We prove the Wegner estimate at arbitrary energy, i. e. we show that the averaged density of states is finite throughout the whole spectrum. We also prove Anderson localization at the bottom of the spectrum. AU - László Erdös AU - Hasler, David G ID - 2768 IS - 2 JF - Communications in Mathematical Physics TI - Wegner estimate and Anderson localization for random magnetic fields VL - 309 ER - TY - JOUR AB - The Wigner-Dyson-Gaudin-Mehta conjecture asserts that the local eigenvalue statistics of large random matrices exhibit universal behavior depending only on the symmetry class of the matrix ensemble. For invariant matrix models, the eigenvalue distributions are given by a log-gas with potential V and inverse temperature β = 1, 2, 4, corresponding to the orthogonal, unitary and symplectic ensembles. For β ∉ {1, 2, 4}, there is no natural random matrix ensemble behind this model, but the statistical physics interpretation of the log-gas is still valid for all β > 0. The universality conjecture for invariant ensembles asserts that the local eigenvalue statistics are independent of V. In this article, we review our recent solution to the universality conjecture for both invariant and non-invariant ensembles. We will also demonstrate that the local ergodicity of the Dyson Brownian motion is the intrinsic mechanism behind the universality. Furthermore, we review the solution of Dyson's conjecture on the local relaxation time of the Dyson Brownian motion. Related questions such as delocalization of eigenvectors and local version of Wigner's semicircle law will also be discussed. AU - László Erdös AU - Yau, Horng-Tzer ID - 2775 IS - 3 JF - Bulletin of the American Mathematical Society TI - Universality of local spectral statistics of random matrices VL - 49 ER - TY - JOUR AB - We consider a large neutral molecule with total nuclear charge Z in a model with self-generated classical magnetic field and where the kinetic energy of the electrons is treated relativistically. To ensure stability, we assume that Zα < 2/π, where α denotes the fine structure constant. We are interested in the ground state energy in the simultaneous limit Z → ∞, α → 0 such that κ = Zα is fixed. The leading term in the energy asymptotics is independent of κ, it is given by the Thomas-Fermi energy of order Z7/3 and it is unchanged by including the self-generated magnetic field. We prove the first correction term to this energy, the so-called Scott correction of the form S(αZ)Z2. The current paper extends the result of Solovej et al. [Commun. Pure Appl. Math.LXIII, 39-118 (2010)] on the Scott correction for relativistic molecules to include a self-generated magnetic field. Furthermore, we show that the corresponding Scott correction function S, first identified by Solovej et al. [Commun. Pure Appl. Math.LXIII, 39-118 (2010)], is unchanged by including a magnetic field. We also prove new Lieb-Thirring inequalities for the relativistic kinetic energy with magnetic fields. AU - László Erdös AU - Fournais, Søren AU - Solovej, Jan P ID - 2777 IS - 9 JF - Journal of Mathematical Physics TI - Relativistic Scott correction in self-generated magnetic fields VL - 53 ER - TY - JOUR AB - We consider the semiclassical asymptotics of the sum of negative eigenvalues of the three-dimensional Pauli operator with an external potential and a self-generated magnetic field B. We also add the field energy β ∫ B 2 and we minimize over all magnetic fields. The parameter β effectively determines the strength of the field. We consider the weak field regime with βh 2 ≥ const > 0, where h is the semiclassical parameter. For smooth potentials we prove that the semiclassical asymptotics of the total energy is given by the non-magnetic Weyl term to leading order with an error bound that is smaller by a factor h 1+e{open}, i. e. the subleading term vanishes. However for potentials with a Coulomb singularity, the subleading term does not vanish due to the non-semiclassical effect of the singularity. Combined with a multiscale technique, this refined estimate is used in the companion paper (Erdo{double acute}s et al. in Scott correction for large molecules with a self-generated magnetic field, Preprint, 2011) to prove the second order Scott correction to the ground state energy of large atoms and molecules. AU - László Erdös AU - Fournais, Søren AU - Solovej, Jan P ID - 2772 IS - 4 JF - Annales Henri Poincare TI - Second order semiclassics with self generated magnetic fields VL - 13 ER - TY - JOUR AB - We consider the ensemble of adjacency matrices of Erdős-Rényi random graphs, i.e. graphs on N vertices where every edge is chosen independently and with probability p ≡ p(N). We rescale the matrix so that its bulk eigenvalues are of order one. Under the assumption pN≫N2/3 , we prove the universality of eigenvalue distributions both in the bulk and at the edge of the spectrum. More precisely, we prove (1) that the eigenvalue spacing of the Erdős-Rényi graph in the bulk of the spectrum has the same distribution as that of the Gaussian orthogonal ensemble; and (2) that the second largest eigenvalue of the Erdős-Rényi graph has the same distribution as the largest eigenvalue of the Gaussian orthogonal ensemble. As an application of our method, we prove the bulk universality of generalized Wigner matrices under the assumption that the matrix entries have at least 4 + ε moments. AU - László Erdös AU - Knowles, Antti AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2776 IS - 3 JF - Communications in Mathematical Physics TI - Spectral statistics of Erdős-Rényi graphs II: Eigenvalue spacing and the extreme eigenvalues VL - 314 ER - TY - JOUR AB - We consider a large neutral molecule with total nuclear charge Z in non-relativistic quantum mechanics with a self-generated classical electromagnetic field. To ensure stability, we assume that Zα 2 ≤ κ 0 for a sufficiently small κ 0, where α denotes the fine structure constant. We show that, in the simultaneous limit Z → ∞, α → 0 such that κ = Zα 2 is fixed, the ground state energy of the system is given by a two term expansion c 1Z 7/3 + c 2(κ) Z 2 + o(Z 2). The leading term is given by the non-magnetic Thomas-Fermi theory. Our result shows that the magnetic field affects only the second (so-called Scott) term in the expansion. AU - László Erdös AU - Fournais, Søren AU - Solovej, Jan P ID - 2774 IS - 3 JF - Communications in Mathematical Physics TI - Scott correction for large atoms and molecules in a self-generated magnetic field VL - 312 ER - TY - JOUR AB - Recently we proved [3, 4, 6, 7, 9, 10, 11] that the eigenvalue correlation functions of a general class of random matrices converge, weakly with respect to the energy, to the corresponding ones of Gaussian matrices. Tao and Vu [15] gave a proof that for the special case of Hermitian Wigner matrices the convergence can be strengthened to vague convergence at any fixed energy in the bulk. In this article we show that this theorem is an immediate corollary of our earlier results. Indeed, a more general form of this theorem also follows directly from our work [2]. AU - László Erdös AU - Yau, Horng-Tzer ID - 2773 JF - Electronic Journal of Probability TI - A comment on the Wigner-Dyson-Mehta bulk universality conjecture for Wigner matrices VL - 17 ER - TY - JOUR AB - We consider a magnetic Schrödinger operator in two dimensions. The magnetic field is given as the sum of a large and constant magnetic field and a random magnetic field. Moreover, we allow for an additional deterministic potential as well as a magnetic field which are both periodic. We show that the spectrum of this operator is contained in broadened bands around the Landau levels and that the edges of these bands consist of pure point spectrum with exponentially decaying eigenfunctions. The proof is based on a recent Wegner estimate obtained in Erdos and Hasler (Commun. Math. Phys., preprint, arXiv:1012.5185) and a multiscale analysis. AU - László Erdös AU - Hasler, David G ID - 2771 IS - 5 JF - Journal of Statistical Physics TI - Anderson localization at band edges for random magnetic fields VL - 146 ER - TY - JOUR AB - We prove the bulk universality of the β-ensembles with non-convex regular analytic potentials for any β > 0. This removes the convexity assumption appeared in the earlier work [P. Bourgade, L. Erdös, and H.-T. Yau, Universality of general β-ensembles, preprint arXiv:0907.5605 (2011)]. The convexity condition enabled us to use the logarithmic Sobolev inequality to estimate events with small probability. The new idea is to introduce a "convexified measure" so that the local statistics are preserved under this convexification. AU - Bourgade, Paul AU - László Erdös AU - Yau, Horng-Tzer ID - 2778 IS - 9 JF - Journal of Mathematical Physics TI - Bulk universality of general β-ensembles with non-convex potential VL - 53 ER - TY - JOUR AB - We consider a two-dimensional magnetic Schrödinger operator on a square lattice with a spatially stationary random magnetic field. We prove Anderson localization near the spectral edges. We use a new approach to establish a Wegner estimate that does not rely on the monotonicity of the energy on the random parameters. AU - László Erdös AU - Hasler, David G ID - 2779 IS - 8 JF - Annales Henri Poincare TI - Wegner estimate for random magnetic Laplacian on ℤ 2 VL - 13 ER - TY - JOUR AB - When a binary fluid demixes under a slow temperature ramp, nucleation, coarsening and sedimentation of droplets lead to an oscillatory evolution of the phase-separating system. The advection of the sedimenting droplets is found to be chaotic. The flow is driven by density differences between two phases. Here, we show how image processing can be combined with particle tracking to resolve droplet size and velocity simultaneously. Droplets are used as tracer particles, and the sedimentation velocity is determined. Taking these effects into account, droplets with radii in the range of 4-40 μm are detected and tracked. Based on these data, we resolve the oscillations in the droplet size distribution that are coupled to the convective flow. AU - Lapp, Tobias AU - Rohloff, Martin AU - Vollmer, Jürgen T AU - Björn Hof ID - 2802 IS - 5 JF - Experiments in Fluids TI - Particle tracking for polydisperse sedimenting droplets in phase separation VL - 52 ER - TY - JOUR AB - Recent numerical studies suggest that in pipe and related shear flows, the region of phase space separating laminar from turbulent motion is organized by a chaotic attractor, called an edge state, which mediates the transition process. We here confirm the existence of the edge state in laboratory experiments. We observe that it governs the dynamics during the decay of turbulence underlining its potential relevance for turbulence control. In addition we unveil two unstable traveling wave solutions underlying the experimental flow fields. This observation corroborates earlier suggestions that unstable solutions organize turbulence and its stability border. AU - de Lózar, Alberto AU - Mellibovsky, Fernando AU - Avila, Marc AU - Björn Hof ID - 2803 IS - 21 JF - Physical Review Letters TI - Edge state in pipe flow experiments VL - 108 ER - TY - JOUR AB - The analysis of the size distribution of droplets condensing on a substrate (breath figures) is a test ground for scaling theories. Here, we show that a faithful description of these distributions must explicitly deal with the growth mechanisms of the droplets. This finding establishes a gateway connecting nucleation and growth of the smallest droplets on surfaces to gross features of the evolution of the droplet size distribution AU - Blaschke, Johannes AU - Lapp, Tobias AU - Björn Hof AU - Vollmer, Jürgen T ID - 2804 IS - 6 JF - Physical Review Letters TI - Breath figures: Nucleation, growth, coalescence, and the size distribution of droplets VL - 109 ER - TY - CONF AB - We study the problem of maximum marginal prediction (MMP) in probabilistic graphical models, a task that occurs, for example, as the Bayes optimal decision rule under a Hamming loss. MMP is typically performed as a two-stage procedure: one estimates each variable's marginal probability and then forms a prediction from the states of maximal probability. In this work we propose a simple yet effective technique for accelerating MMP when inference is sampling-based: instead of the above two-stage procedure we directly estimate the posterior probability of each decision variable. This allows us to identify the point of time when we are sufficiently certain about any individual decision. Whenever this is the case, we dynamically prune the variables we are confident about from the underlying factor graph. Consequently, at any time only samples of variables whose decision is still uncertain need to be created. Experiments in two prototypical scenarios, multi-label classification and image inpainting, show that adaptive sampling can drastically accelerate MMP without sacrificing prediction accuracy. AU - Lampert, Christoph ID - 2825 TI - Dynamic pruning of factor graphs for maximum marginal prediction VL - 1 ER - TY - JOUR AB - We study evolutionary game theory in a setting where individuals learn from each other. We extend the traditional approach by assuming that a population contains individuals with different learning abilities. In particular, we explore the situation where individuals have different search spaces, when attempting to learn the strategies of others. The search space of an individual specifies the set of strategies learnable by that individual. The search space is genetically given and does not change under social evolutionary dynamics. We introduce a general framework and study a specific example in the context of direct reciprocity. For this example, we obtain the counter intuitive result that cooperation can only evolve for intermediate benefit-to-cost ratios, while small and large benefit-to-cost ratios favor defection. Our paper is a step toward making a connection between computational learning theory and evolutionary game dynamics. AU - Chatterjee, Krishnendu AU - Zufferey, Damien AU - Nowak, Martin ID - 2848 JF - Journal of Theoretical Biology TI - Evolutionary game dynamics in populations with different learners VL - 301 ER - TY - JOUR AU - Edelsbrunner, Herbert AU - Strelkova, Nataliya ID - 2849 IS - 6 JF - Russian Mathematical Surveys TI - On the configuration space of Steiner minimal trees VL - 67 ER - TY - JOUR AB - Cytokinin (CK) activity is regulated by the complex interplay of their metabolism, transport, stability and cellular/tissue localization. O-glucosides of zeatin-type CKs are postulated to be storage and/or transport forms. Active CK levels are determined in part by their differential distribution of CK metabolites across different subcellular compartments. We have previously shown that overexpressing chloroplast-localized Zm-p60.1, a maize β-glucosidase capable of releasing active cytokinins from their O- and N3-glucosides, perturbs CK homeostasis in transgenic tobacco. We obtained tobacco (Nicotiana tabacum L., cv Petit Havana SR1) plants overexpressing a recombinant Zm-p60.1 that is targeted to the vacuole. The protein is correctly processed and localized to the vacuole. When grown on medium containing exogenous zeatin, transgenic seedlings rapidly accumulate fresh weight due to ectopic growths at the base of the hypocotyl. The presence of the enzyme in these ectopic structures is shown by histochemical staining. CK quantification reveals that these transgenic seedlings are unable to accumulate zeatin-O-glucoside to levels similar to those observed in the wild type. When crossed with tobacco overexpressing the zeatin-O-glucosyltransferase gene from Phaseolus, the vacuolar variant shows an almost complete reversion in the root elongation assay. This is the first evidence from intact plants that the vacuole is the storage organelle for CK O-glucosides and that they are available to attack by Zm-p60.1. We propose the use of Zm-p60.1 as a robust molecular tool that exploits the reversibility of O-glucosylation and enables delicate manipulations of active CK content at the cellular level. AU - Kiran, Nagavalli S AU - Eva Benková AU - Reková, Alena AU - Dubová, Jaroslava AU - Malbeck, Jiří AU - Palme, Klaus AU - Brzobohatý, Břetislav ID - 2876 JF - Phytochemistry TI - Retargeting a maize β-glucosidase to the vacuole - Evidence from intact plants that zeatin-O-glucoside is stored in the vacuole VL - 79 ER - TY - JOUR AB - Phytohormones are important plant growth regulators that control many developmental processes, such as cell division, cell differentiation, organogenesis and morphogenesis. They regulate a multitude of apparently unrelated physiological processes, often with overlapping roles, and they mutually modulate their effects. These features imply important synergistic and antagonistic interactions between the various plant hormones. Auxin and cytokinin are central hormones involved in the regulation of plant growth and development, including processes determining root architecture, such as root pole establishment during early embryogenesis, root meristem maintenance and lateral root organogenesis. Thus, to control root development both pathways put special demands on the mechanisms that balance their activities and mediate their interactions. Here, we summarize recent knowledge on the role of auxin and cytokinin in the regulation of root architecture with special focus on lateral root organogenesis, discuss the latest findings on the molecular mechanisms of their interactions, and present forward genetic screen as a tool to identify novel molecular components of the auxin and cytokinin crosstalk. AU - Bielach, Agnieszka AU - Duclercq, Jérôme AU - Peter Marhavy AU - Eva Benková ID - 2875 IS - 1595 JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences TI - Genetic approach towards the identification of auxin - cytokinin crosstalk components involved in root development VL - 367 ER - TY - JOUR AB - Phyllotaxis, the regular arrangement of leaves and flowers around the stem, is a key feature of plant architecture. Current models propose that the spatiotemporal regulation of organ initiation is controlled by a positive feedback loop between the plant hormone auxin and its efflux carrier PIN-FORMED1 (PIN1). Consequently, pin1 mutants give rise to naked inflorescence stalks with few or no flowers, indicating that PIN1 plays a crucial role in organ initiation. However, pin1 mutants do produce leaves. In order to understand the regulatory mechanisms controlling leaf initiation in Arabidopsis (Arabidopsis thaliana) rosettes, we have characterized the vegetative pin1 phenotype in detail. We show that although the timing of leaf initiation in vegetative pin1 mutants is variable and divergence angles clearly deviate from the canonical 137° value, leaves are not positioned at random during early developmental stages. Our data further indicate that other PIN proteins are unlikely to explain the persistence of leaf initiation and positioning during pin1 vegetative development. Thus, phyllotaxis appears to be more complex than suggested by current mechanistic models. AU - Guenot, Bernadette AU - Bayer, Emmanuelle AU - Kierzkowski, Daniel AU - Smith, Richard S AU - Mandel, Therese AU - Žádníková, Petra AU - Eva Benková AU - Kuhlemeier, Cris ID - 2878 IS - 4 JF - Plant Physiology TI - Pin1 independent leaf initiation in Arabidopsis VL - 159 ER - TY - JOUR AB - Hormones, such as auxin and cytokinin, are involved in the complex molecular network that regulates the coordinated development of plant organs. Genes controlling ovule patterning have been identified and studied in detail; however, the roles of auxin and cytokinin in ovule development are largely unknown. Here we show that key cytokinin pathway genes, such as isopentenyltransferase and cytokinin receptors, are expressed during ovule development. Also, in a cre1-12 ahk2-2 ahk3-3 triple mutant with severely reduced cytokinin perception, expression of the auxin efflux facilitator PIN-FORMED 1 (PIN1) was severely reduced. In sporocyteless/nozzle (spl/nzz) mutants, which show a similar phenotype to the cre1-12 ahk2-2 ahk3-3 triple mutant, PIN1 expression is also reduced. Treatment with the exogenous cytokinin N6-benzylaminopurine also altered both auxin distribution and patterning of the ovule; this process required the homeodomain transcription factor BELL1 (BEL1). Thus, this article shows that cytokinin regulates ovule development through the regulation of PIN1. Furthermore, the transcription factors BEL1 and SPL/NZZ, previously described as key regulators of ovule development, are needed for the auxin and cytokinin signaling pathways for the correct patterning of the ovule. AU - Bencivenga, Stefano AU - Simonini, Sara AU - Eva Benková AU - Colombo, Lucia ID - 2879 IS - 7 JF - Plant Cell TI - The transcription factors BEL1 and SPL are required for cytokinin and auxin signaling during ovule development in Arabidopsis VL - 24 ER - TY - CONF AB - Quantitative automata are nondeterministic finite automata with edge weights. They value a run by some function from the sequence of visited weights to the reals, and value a word by its minimal/maximal run. They generalize boolean automata, and have gained much attention in recent years. Unfortunately, important automaton classes, such as sum, discounted-sum, and limit-average automata, cannot be determinized. Yet, the quantitative setting provides the potential of approximate determinization. We define approximate determinization with respect to a distance function, and investigate this potential. We show that sum automata cannot be determinized approximately with respect to any distance function. However, restricting to nonnegative weights allows for approximate determinization with respect to some distance functions. Discounted-sum automata allow for approximate determinization, as the influence of a word’s suffix is decaying. However, the naive approach, of unfolding the automaton computations up to a sufficient level, is shown to be doubly exponential in the discount factor. We provide an alternative construction that is singly exponential in the discount factor, in the precision, and in the number of states. We prove matching lower bounds, showing exponential dependency on each of these three parameters. Average and limit-average automata are shown to prohibit approximate determinization with respect to any distance function, and this is the case even for two weights, 0 and 1. AU - Boker, Udi AU - Henzinger, Thomas A ID - 2891 T2 - Leibniz International Proceedings in Informatics TI - Approximate determinization of quantitative automata VL - 18 ER - TY - CONF AB - Systems are often specified using multiple requirements on their behavior. In practice, these requirements can be contradictory. The classical approach to specification, verification, and synthesis demands more detailed specifications that resolve any contradictions in the requirements. These detailed specifications are usually large, cumbersome, and hard to maintain or modify. In contrast, quantitative frameworks allow the formalization of the intuitive idea that what is desired is an implementation that comes "closest" to satisfying the mutually incompatible requirements, according to a measure of fit that can be defined by the requirements engineer. One flexible framework for quantifying how "well" an implementation satisfies a specification is offered by simulation distances that are parameterized by an error model. We introduce this framework, study its properties, and provide an algorithmic solution for the following quantitative synthesis question: given two (or more) behavioral requirements specified by possibly incompatible finite-state machines, and an error model, find the finite-state implementation that minimizes the maximal simulation distance to the given requirements. Furthermore, we generalize the framework to handle infinite alphabets (for example, realvalued domains). We also demonstrate how quantitative specifications based on simulation distances might lead to smaller and easier to modify specifications. Finally, we illustrate our approach using case studies on error correcting codes and scheduler synthesis. AU - Cerny, Pavol AU - Gopi, Sivakanth AU - Henzinger, Thomas A AU - Radhakrishna, Arjun AU - Totla, Nishant ID - 2890 T2 - Proceedings of the tenth ACM international conference on Embedded software TI - Synthesis from incompatible specifications ER - TY - CONF AB - Formal verification aims to improve the quality of hardware and software by detecting errors before they do harm. At the basis of formal verification lies the logical notion of correctness, which purports to capture whether or not a circuit or program behaves as desired. We suggest that the boolean partition into correct and incorrect systems falls short of the practical need to assess the behavior of hardware and software in a more nuanced fashion against multiple criteria. AU - Henzinger, Thomas A ID - 2888 T2 - Conference proceedings MODELS 2012 TI - Quantitative reactive models VL - 7590 ER - TY - CONF AB - In order to enjoy a digital version of the Jordan Curve Theorem, it is common to use the closed topology for the foreground and the open topology for the background of a 2-dimensional binary image. In this paper, we introduce a single topology that enjoys this theorem for all thresholds decomposing a real-valued image into foreground and background. This topology is easy to construct and it generalizes to n-dimensional images. AU - Edelsbrunner, Herbert AU - Symonova, Olga ID - 2903 TI - The adaptive topology of a digital image ER - TY - CONF AB - The classical (boolean) notion of refinement for behavioral interfaces of system components is the alternating refinement preorder. In this paper, we define a quantitative measure for interfaces, called interface simulation distance. It makes the alternating refinement preorder quantitative by, intu- itively, tolerating errors (while counting them) in the alternating simulation game. We show that the interface simulation distance satisfies the triangle inequality, that the distance between two interfaces does not increase under parallel composition with a third interface, and that the distance between two interfaces can be bounded from above and below by distances between abstractions of the two interfaces. We illustrate the framework, and the properties of the distances under composition of interfaces, with two case studies. AU - Cerny, Pavol AU - Chmelik, Martin AU - Henzinger, Thomas A AU - Radhakrishna, Arjun ID - 2916 T2 - Electronic Proceedings in Theoretical Computer Science TI - Interface Simulation Distances VL - 96 ER - TY - JOUR AB - The search for extra-terrestrial intelligence (SETI) has been performed principally as a one-way survey, listening of radio frequencies across the Milky Way and other galaxies. However, scientists have engaged in an active messaging only rarely. This suggests the simple rationale that if other civilizations exist and take a similar approach to ours, namely listening but not broadcasting, the result is a silent universe. A simple game theoretical model, the prisoner's dilemma, explains this situation: each player (civilization) can passively search (defect), or actively search and broadcast (cooperate). In order to maximize the payoff (or, equivalently, minimize the risks) the best strategy is not to broadcast. In fact, the active search has been opposed on the basis that it might be dangerous to expose ourselves. However, most of these ideas have not been based on objective arguments, and ignore accounting of the possible gains and losses. Thus, the question stands: should we perform an active search? I develop a game-theoretical framework where civilizations can be of different types, and explicitly apply it to a situation where societies are either interested in establishing a two-way communication or belligerent and in urge to exploit ours. The framework gives a quantitative solution (a mixed-strategy), which is how frequent we should perform the active SETI. This frequency is roughly proportional to the inverse of the risk, and can be extremely small. However, given the immense amount of stars being scanned, it supports active SETI. The model is compared with simulations, and the possible actions are evaluated through the San Marino scale, measuring the risks of messaging. AU - Vladar, Harold ID - 2917 IS - 1 JF - International Journal of Astrobiology TI - The game of active search for extra terrestrial intelligence Breaking the Great Silence VL - 12 ER - TY - JOUR AB - We have selected problems that may not yet be well known, but have the potential to push the research in interesting directions. In particular, we state problems that do not require specific knowledge outside the standard circle of ideas in discrete geometry. Despite the relatively simple statements, these problems are related to current research and their solutions are likely to require new ideas and approaches. We have chosen problems from different fields to make this short paper attractive to a wide range of specialists. AU - Herbert Edelsbrunner AU - Ivanov, Alexander AU - Karasev, Roman ID - 2911 JF - Automatic Control and Computer Sciences TI - Open problems in discrete and computational geometry VL - in print ER - TY - CONF AB - In this paper we investigate k-submodular functions. This natural family of discrete functions includes submodular and bisubmodular functions as the special cases k = 1 and k = 2 respectively. In particular we generalize the known Min-Max-Theorem for submodular and bisubmodular functions. This theorem asserts that the minimum of the (bi)submodular function can be found by solving a maximization problem over a (bi)submodular polyhedron. We define a k-submodular polyhedron, prove a Min-Max-Theorem for k-submodular functions, and give a greedy algorithm to construct the vertices of the polyhedron. AU - Huber, Anna AU - Kolmogorov, Vladimir ID - 2930 TI - Towards minimizing k-submodular functions VL - 7422 ER - TY - GEN AB - This paper addresses the problem of approximate MAP-MRF inference in general graphical models. Following [36], we consider a family of linear programming relaxations of the problem where each relaxation is specified by a set of nested pairs of factors for which the marginalization constraint needs to be enforced. We develop a generalization of the TRW-S algorithm [9] for this problem, where we use a decomposition into junction chains, monotonic w.r.t. some ordering on the nodes. This generalizes the monotonic chains in [9] in a natural way. We also show how to deal with nested factors in an efficient way. Experiments show an improvement over min-sum diffusion, MPLP and subgradient ascent algorithms on a number of computer vision and natural language processing problems. AU - Kolmogorov, Vladimir AU - Schoenemann, Thomas ID - 2928 T2 - arXiv TI - Generalized sequential tree-reweighted message passing ER - TY - GEN AU - Vladimir Kolmogorov ID - 2929 TI - The power of linear programming for valued CSPs: a constructive characterization ER - TY - CONF AB - Developers building cryptography into security-sensitive applications face a daunting task. Not only must they understand the security guarantees delivered by the constructions they choose, they must also implement and combine them correctly and efficiently. Cryptographic compilers free developers from this task by turning high-level specifications of security goals into efficient implementations. Yet, trusting such tools is hard as they rely on complex mathematical machinery and claim security properties that are subtle and difficult to verify. In this paper we present ZKCrypt, an optimizing cryptographic compiler achieving an unprecedented level of assurance without sacrificing practicality for a comprehensive class of cryptographic protocols, known as Zero-Knowledge Proofs of Knowledge. The pipeline of ZKCrypt integrates purpose-built verified compilers and verifying compilers producing formal proofs in the CertiCrypt framework. By combining the guarantees delivered by each stage, ZKCrypt provides assurance that the output implementation securely realizes the abstract proof goal given as input. We report on the main characteristics of ZKCrypt, highlight new definitions and concepts at its foundations, and illustrate its applicability through a representative example of an anonymous credential system. AU - Almeida, José AU - Barbosa, Manuel AU - Bangerter, Endre AU - Barthe, Gilles AU - Krenn, Stephan AU - Béguelin, Santiago ID - 2937 T2 - Proceedings of the 2012 ACM conference on Computer and communications security TI - Full proof cryptography: Verifiable compilation of efficient zero-knowledge protocols ER - TY - CONF AB - The notion of delays arises naturally in many computational models, such as, in the design of circuits, control systems, and dataflow languages. In this work, we introduce automata with delay blocks (ADBs), extending finite state automata with variable time delay blocks, for deferring individual transition output symbols, in a discrete-time setting. We show that the ADB languages strictly subsume the regular languages, and are incomparable in expressive power to the context-free languages. We show that ADBs are closed under union, concatenation and Kleene star, and under intersection with regular languages, but not closed under complementation and intersection with other ADB languages. We show that the emptiness and the membership problems are decidable in polynomial time for ADBs, whereas the universality problem is undecidable. Finally we consider the linear-time model checking problem, i.e., whether the language of an ADB is contained in a regular language, and show that the model checking problem is PSPACE-complete. Copyright 2012 ACM. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Prabhu, Vinayak ID - 2936 T2 - roceedings of the tenth ACM international conference on Embedded software TI - Finite automata with time delay blocks ER - TY - JOUR AB - Social insects have a very high potential to become invasive pest species. Here, we explore how their social lifestyle and their interaction with parasites may contribute to this invasive success. Similar to solitary species, parasite release followed by the evolution of increased competitive ability can promote establishment of introduced social insect hosts in their introduced range. Genetic bottlenecks during introduction of low numbers of founder individuals decrease the genetic diversity at three levels: the population, the colony and the individual, with the colony level being specific to social insects. Reduced genetic diversity can affect both the individual immune system and the collective colony-level disease defences (social immunity). Still, the dual immune system is likely to make social insects more robust to parasite attack. Changes in social structure from small, family-based, territorially aggressive societies in native populations towards huge networks of cooperating nests (unicoloniality) occur in some invasive social insects, for example, most invasive ants and some termites. Unicoloniality is likely to affect disease dynamics in multiple ways. The free exchange of individuals within the population leads to an increased genetic heterogeneity among individuals of a single nest, thereby decreasing disease transmission. However, the multitude of reproductively active queens per colony buffers the effect of individual diseased queens and their offspring, which may result in a higher level of vertical disease transmission in unicolonial societies. Lastly, unicoloniality provides a competitive advantage over native species, allowing them to quickly become the dominant species in the habitat, which in turn selects for parasite adaptation to this common host genotype and thus eventually a high parasite pressure. Overall, invasions by insect societies are characterized by general features applying to all introduced species, as well as idiosyncrasies that emerge from their social lifestyle. It is important to study these effects in concert to be able to develop efficient management and biocontrol strategies. © 2012 British Ecological Society. AU - Ugelvig, Line V AU - Cremer, Sylvia ID - 2938 IS - 6 JF - Functional Ecology TI - Effects of social immunity and unicoloniality on host parasite interactions in invasive insect societies VL - 26 ER - TY - JOUR AB - In this paper, we present a new approach for establishing correspondences between sparse image features related by an unknown nonrigid mapping and corrupted by clutter and occlusion, such as points extracted from images of different instances of the same object category. We formulate this matching task as an energy minimization problem by defining an elaborate objective function of the appearance and the spatial arrangement of the features. Optimization of this energy is an instance of graph matching, which is in general an NP-hard problem. We describe a novel graph matching optimization technique, which we refer to as dual decomposition (DD), and demonstrate on a variety of examples that this method outperforms existing graph matching algorithms. In the majority of our examples, DD is able to find the global minimum within a minute. The ability to globally optimize the objective allows us to accurately learn the parameters of our matching model from training examples. We show on several matching tasks that our learned model yields results superior to those of state-of-the-art methods. AU - Torresani, Lorenzo AU - Kolmogorov, Vladimir AU - Rother, Carsten ID - 2931 IS - 2 JF - IEEE Transactions on Pattern Analysis and Machine Intelligence TI - A dual decomposition approach to feature correspondence VL - 35 ER - TY - CONF AB - Interface theories provide a formal framework for component-based development of software and hardware which supports the incremental design of systems and the independent implementability of components. These capabilities are ensured through mathematical properties of the parallel composition operator and the refinement relation for components. More recently, a conjunction operation was added to interface theories in order to provide support for handling multiple viewpoints, requirements engineering, and component reuse. Unfortunately, the conjunction operator does not allow independent implementability in general. In this paper, we study conditions that need to be imposed on interface models in order to enforce independent implementability with respect to conjunction. We focus on multiple viewpoint specifications and propose a new compatibility criterion between two interfaces, which we call orthogonality. We show that orthogonal interfaces can be refined separately, while preserving both orthogonality and composability with other interfaces. We illustrate the independent implementability of different viewpoints with a FIFO buffer example. AU - Henzinger, Thomas A AU - Nickovic, Dejan ID - 2942 T2 - Conference proceedings Monterey Workshop 2012 TI - Independent implementability of viewpoints VL - 7539 ER - TY - JOUR AB - We examine whether the Escherichia coli chromosome is folded into a self-adherent nucleoprotein complex, or alternately is a confined but otherwise unconstrained self-avoiding polymer. We address this through in vivo visualization, using an inducible GFP fusion to the nucleoid-associated protein Fis to non-specifically decorate the entire chromosome. For a range of different growth conditions, the chromosome is a compact structure that does not fill the volume of the cell, and which moves from the new pole to the cell centre. During rapid growth, chromosome segregation occurs well before cell division, with daughter chromosomes coupled by a thin inter-daughter filament before complete segregation, whereas during slow growth chromosomes stay adjacent until cell division occurs. Image correlation analysis indicates that sub-nucleoid structure is stable on a 1min timescale, comparable to the timescale for redistribution time measured for GFP-Fis after photobleaching. Optical deconvolution and writhe calculation analysis indicate that the nucleoid has a large-scale coiled organization rather than being an amorphous mass. Our observations are consistent with the chromosome having a self-adherent filament organization. AU - Hadizadeh Yazdi, Nastaran AU - Guet, Calin C AU - Johnson, Reid AU - Marko, John ID - 2943 IS - 6 JF - Molecular Microbiology TI - Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions VL - 86 ER - TY - JOUR AU - Dolbilin, Nikolai AU - Edelsbrunner, Herbert AU - Musin, Oleg ID - 2941 IS - 4 JF - Russian Mathematical Surveys TI - On the optimality of functionals over triangulations of Delaunay sets VL - 67 ER - TY - JOUR AB - MicroRNAs (miRNAs) are small noncoding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3′-untranslated region (3′-UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected. AU - Dueck, Anne AU - Ziegler, Christian AU - Eichner, Alexander AU - Berezikov, Eugène AU - Meister, Gunter ID - 2946 IS - 19 JF - Nucleic Acids Research TI - MicroRNAs associated with the different human Argonaute proteins VL - 40 ER - TY - CONF AB - We introduce games with probabilistic uncertainty, a model for controller synthesis in which the controller observes the state through imprecise sensors that provide correct information about the current state with a fixed probability. That is, in each step, the sensors return an observed state, and given the observed state, there is a probability distribution (due to the estimation error) over the actual current state. The controller must base its decision on the observed state (rather than the actual current state, which it does not know). On the other hand, we assume that the environment can perfectly observe the current state. We show that controller synthesis for qualitative ω-regular objectives in our model can be reduced in polynomial time to standard partial-observation stochastic games, and vice-versa. As a consequence we establish the precise decidability frontier for the new class of games, and establish optimal complexity results for all the decidable problems. AU - Chatterjee, Krishnendu AU - Chmelik, Martin AU - Majumdar, Ritankar ID - 2947 TI - Equivalence of games with probabilistic uncertainty and partial observation games VL - 7561 ER - TY - JOUR AB - In search of foreign antigens, lymphocytes recirculate from the blood, through lymph nodes, into lymphatics and back to the blood. Dendritic cells also migrate to lymph nodes for optimal interaction with lymphocytes. This continuous trafficking of immune cells into and out of lymph nodes is essential for immune surveillance of foreign invaders. In this article, we review our current understanding of the functions of high endothelial venules (HEVs), stroma and lymphatics in the entry, positioning and exit of immune cells in lymph nodes during homeostasis, and we highlight the unexpected role of dendritic cells in the control of lymphocyte homing through HEVs. AU - Girard, Jean AU - Moussion, Christine AU - Förster, Reinhold ID - 2945 IS - 11 JF - Nature Reviews Immunology TI - HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes VL - 12 ER - TY - JOUR AU - Dupret, David AU - Csicsvari, Jozsef L ID - 2949 IS - 11 JF - Nature Neuroscience TI - The medial entorhinal cortex keeps Up VL - 15 ER - TY - JOUR AB - Spontaneous postsynaptic currents (PSCs) provide key information about the mechanisms of synaptic transmission and the activity modes of neuronal networks. However, detecting spontaneous PSCs in vitro and in vivo has been challenging, because of the small amplitude, the variable kinetics, and the undefined time of generation of these events. Here, we describe a, to our knowledge, new method for detecting spontaneous synaptic events by deconvolution, using a template that approximates the average time course of spontaneous PSCs. A recorded PSC trace is deconvolved from the template, resulting in a series of delta-like functions. The maxima of these delta-like events are reliably detected, revealing the precise onset times of the spontaneous PSCs. Among all detection methods, the deconvolution-based method has a unique temporal resolution, allowing the detection of individual events in high-frequency bursts. Furthermore, the deconvolution-based method has a high amplitude resolution, because deconvolution can substantially increase the signal/noise ratio. When tested against previously published methods using experimental data, the deconvolution-based method was superior for spontaneous PSCs recorded in vivo. Using the high-resolution deconvolution-based detection algorithm, we show that the frequency of spontaneous excitatory postsynaptic currents in dentate gyrus granule cells is 4.5 times higher in vivo than in vitro. AU - Pernia-Andrade, Alejandro AU - Goswami, Sarit AU - Stickler, Yvonne AU - Fröbe, Ulrich AU - Schlögl, Alois AU - Jonas, Peter M ID - 2954 IS - 7 JF - Biophysical Journal TI - A deconvolution based method with high sensitivity and temporal resolution for detection of spontaneous synaptic currents in vitro and in vivo VL - 103 ER - TY - JOUR AB - Contractile actomyosin rings drive various fundamental morphogenetic processes ranging from cytokinesis to wound healing. Actomyosin rings are generally thought to function by circumferential contraction. Here, we show that the spreading of the enveloping cell layer (EVL) over the yolk cell during zebrafish gastrulation is driven by a contractile actomyosin ring. In contrast to previous suggestions, we find that this ring functions not only by circumferential contraction but also by a flow-friction mechanism. This generates a pulling force through resistance against retrograde actomyosin flow. EVL spreading proceeds normally in situations where circumferential contraction is unproductive, indicating that the flow-friction mechanism is sufficient. Thus, actomyosin rings can function in epithelial morphogenesis through a combination of cable-constriction and flow-friction mechanisms. AU - Behrndt, Martin AU - Salbreux, Guillaume AU - Campinho, Pedro AU - Hauschild, Robert AU - Oswald, Felix AU - Roensch, Julia AU - Grill, Stephan AU - Heisenberg, Carl-Philipp J ID - 2950 IS - 6104 JF - Science TI - Forces driving epithelial spreading in zebrafish gastrulation VL - 338 ER - TY - JOUR AB - Differential cell adhesion and cortex tension are thought to drive cell sorting by controlling cell-cell contact formation. Here, we show that cell adhesion and cortex tension have different mechanical functions in controlling progenitor cell-cell contact formation and sorting during zebrafish gastrulation. Cortex tension controls cell-cell contact expansion by modulating interfacial tension at the contact. By contrast, adhesion has little direct function in contact expansion, but instead is needed to mechanically couple the cortices of adhering cells at their contacts, allowing cortex tension to control contact expansion. The coupling function of adhesion is mediated by E-cadherin and limited by the mechanical anchoring of E-cadherin to the cortex. Thus, cell adhesion provides the mechanical scaffold for cell cortex tension to drive cell sorting during gastrulation. AU - Maître, Jean-Léon AU - Berthoumieux, Hélène AU - Krens, Gabriel AU - Salbreux, Guillaume AU - Julicher, Frank AU - Paluch, Ewa AU - Heisenberg, Carl-Philipp J ID - 2951 IS - 6104 JF - Science TI - Adhesion functions in cell sorting by mechanically coupling the cortices of adhering cells VL - 338 ER - TY - JOUR AB - Body axis elongation represents a common and fundamental morphogenetic process in development. A key mechanism triggering body axis elongation without additional growth is convergent extension (CE), whereby a tissue undergoes simultaneous narrowing and extension. Both collective cell migration and cell intercalation are thought to drive CE and are used to different degrees in various species as they elongate their body axis. Here, we provide an overview of CE as a general strategy for body axis elongation and discuss conserved and divergent mechanisms underlying CE among different species. AU - Tada, Masazumi AU - Heisenberg, Carl-Philipp J ID - 2952 IS - 21 JF - Development TI - Convergent extension Using collective cell migration and cell intercalation to shape embryos VL - 139 ER - TY - JOUR AU - Heisenberg, Carl-Philipp J AU - Fässler, Reinhard ID - 2953 IS - 5 JF - Current Opinion in Cell Biology TI - Cell-cell adhesion and extracellular matrix diversity counts VL - 24 ER - TY - JOUR AB - The activity of hippocampal pyramidal cells reflects both the current position of the animal and information related to its current behavior. Here we investigated whether single hippocampal neurons can encode several independent features defining trials during a memory task. We also tested whether task-related information is represented by partial remapping of the place cell population or, instead, via firing rate modulation of spatially stable place cells. To address these two questions, the activity of hippocampal neurons was recorded in rats performing a conditional discrimination task on a modified T-maze in which the identity of a food reward guided behavior. When the rat was on the central arm of the maze, the firing rate of pyramidal cells changed depending on two independent factors: (1) the identity of the food reward given to the animal and (2) the previous location of the animal on the maze. Importantly, some pyramidal cells encoded information relative to both factors. This trial-type specific and retrospective coding did not interfere with the spatial representation of the maze: hippocampal cells had stable place fields and their theta-phase precession profiles were unaltered during the task, indicating that trial-related information was encoded via rate remapping. During error trials, encoding of both trial-related information and spatial location was impaired. Finally, we found that pyramidal cells also encode trial-related information via rate remapping during the continuous version of the rewarded alternation task without delays. These results suggest that hippocampal neurons can encode several task-related cognitive aspects via rate remapping. AU - Allen, Kevin AU - Rawlins, J Nick AU - Bannerman, David AU - Csicsvari, Jozsef L ID - 2958 IS - 42 JF - Journal of Neuroscience TI - Hippocampal place cells can encode multiple trial-dependent features through rate remapping VL - 32 ER - TY - JOUR AB - We study maximum likelihood estimation in Gaussian graphical models from a geometric point of view. An algebraic elimination criterion allows us to find exact lower bounds on the number of observations needed to ensure that the maximum likelihood estimator (MLE) exists with probability one. This is applied to bipartite graphs, grids and colored graphs. We also study the ML degree, and we present the first instance of a graph for which the MLE exists with probability one, even when the number of observations equals the treewidth. AU - Uhler, Caroline ID - 2959 IS - 1 JF - Annals of Statistics TI - Geometry of maximum likelihood estimation in Gaussian graphical models VL - 40 ER - TY - JOUR AB - Background: The outcome of male-male competition can be predicted from the relative fighting qualities of the opponents, which often depend on their age. In insects, freshly emerged and still sexually inactive males are morphologically indistinct from older, sexually active males. These young inactive males may thus be easy targets for older males if they cannot conceal themselves from their attacks. The ant Cardiocondyla obscurior is characterised by lethal fighting between wingless (" ergatoid" ) males. Here, we analyse for how long young males are defenceless after eclosion, and how early adult males can detect the presence of rival males.Results: We found that old ergatoid males consistently won fights against ergatoid males younger than two days. Old males did not differentiate between different types of unpigmented pupae several days before emergence, but had more frequent contact to ready-to-eclose pupae of female sexuals and winged males than of workers and ergatoid males. In rare cases, old ergatoid males displayed alleviated biting of pigmented ergatoid male pupae shortly before adult eclosion, as well as copulation attempts to dark pupae of female sexuals and winged males. Ergatoid male behaviour may be promoted by a closer similarity of the chemical profile of ready-to-eclose pupae to the profile of adults than that of young pupae several days prior to emergence.Conclusion: Young ergatoid males of C. obscurior would benefit greatly by hiding their identity from older, resident males, as they are highly vulnerable during the first two days of their adult lives. In contrast to the winged males of the same species, which are able to prevent ergatoid male attacks by chemical female mimicry, young ergatoids do not seem to be able to produce a protective chemical profile. Conflicts in male-male competition between ergatoid males of different age thus seem to be resolved in favour of the older males. This might represent selection at the colony level rather than the individual level. © 2012 Cremer et al.; licensee BioMed Central Ltd. AU - Cremer, Sylvia AU - Suefuji, Masaki AU - Schrempf, Alexandra AU - Heinze, Jürgen ID - 2966 JF - BMC Ecology TI - The dynamics of male-male competition in Cardiocondyla obscurior ants VL - 12 ER - TY - JOUR AB - The choice of summary statistics is a crucial step in approximate Bayesian computation (ABC). Since statistics are often not sufficient, this choice involves a trade-off between loss of information and reduction of dimensionality. The latter may increase the efficiency of ABC. Here, we propose an approach for choosing summary statistics based on boosting, a technique from the machine learning literature. We consider different types of boosting and compare them to partial least squares regression as an alternative. To mitigate the lack of sufficiency, we also propose an approach for choosing summary statistics locally, in the putative neighborhood of the true parameter value. We study a demographic model motivated by the re-introduction of Alpine ibex (Capra ibex) into the Swiss Alps. The parameters of interest are the mean and standard deviation across microsatellites of the scaled ancestral mutation rate (θanc = 4 Ne u), and the proportion of males obtaining access to matings per breeding season (ω). By simulation, we assess the properties of the posterior distribution obtained with the various methods. According to our criteria, ABC with summary statistics chosen locally via boosting with the L2-loss performs best. Applying that method to the ibex data, we estimate θanc ≈ 1.288, and find that most of the variation across loci of the ancestral mutation rate u is between 7.7×10−4 and 3.5×10−3 per locus per generation. The proportion of males with access to matings is estimated to ω ≈ 0.21, which is in good agreement with recent independent estimates. AU - Aeschbacher, Simon AU - Beaumont, Mark AU - Futschik, Andreas ID - 2962 IS - 3 JF - Genetics TI - A novel approach for choosing summary statistics in approximate Bayesian computation VL - 192 ER - TY - JOUR AB - Dieser Artikel soll die sechs verschiedenen Creative Commons Lizenzen erläutern und ihre Bedeutung im Rahmen des wissenschaftlichen Publizierens und des Open Access erklären (CC-BY, CC-BY-SA, CC-BY-NC, CC-BY-ND, CC-BYNC-SA, CC-BY-NC-ND). AU - Danowski, Patrick ID - 2965 IS - 2 JF - Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen & Bibliothekare TI - Kontext Open Access: Creative Commons VL - 65 ER - TY - JOUR AB - Zebra finches are an ubiquitous model system for the study of vocal learning in animal communication. Their song has been well described, but its possible function(s) in social communication are only partly understood. The so-called ‘directed song’ is a high-intensity, high-performance song given during courtship in close proximity to the female, which is known to mediate mate choice and mating. However, this singing mode constitutes only a fraction of zebra finch males’ prolific song output. Potential communicative functions of their second, ‘undirected’ singing mode remain unresolved in the face of contradicting reports of both facilitating and inhibiting effects of social company on singing. We addressed this issue by experimentally manipulating social contexts in a within-subject design, comparing a solo versus male or female only company condition, each lasting for 24 hours. Males’ total song output was significantly higher when a conspecific was in audible and visible distance than when they were alone. Male and female company had an equally facilitating effect on song output. Our findings thus indicate that singing motivation is facilitated rather than inhibited by social company, suggesting that singing in zebra finches might function both in inter- and intrasexual communication. AU - Jesse, Fabienne AU - Riebel, Katharina ID - 2963 IS - 3 JF - Behavioural Processes TI - Social facilitation of male song by male and female conspecifics in the zebra finch, Taeniopygia guttata VL - 91 ER - TY - CONF AB - We construct a perfectly binding string commitment scheme whose security is based on the learning parity with noise (LPN) assumption, or equivalently, the hardness of decoding random linear codes. Our scheme not only allows for a simple and efficient zero-knowledge proof of knowledge for committed values (essentially a Σ-protocol), but also for such proofs showing any kind of relation amongst committed values, i.e. proving that messages m_0,...,m_u, are such that m_0=C(m_1,...,m_u) for any circuit C. To get soundness which is exponentially small in a security parameter t, and when the zero-knowledge property relies on the LPN problem with secrets of length l, our 3 round protocol has communication complexity O(t|C|l log(l)) and computational complexity of O(t|C|l) bit operations. The hidden constants are small, and the computation consists mostly of computing inner products of bit-vectors. AU - Jain, Abhishek AU - Krenn, Stephan AU - Pietrzak, Krzysztof Z AU - Tentes, Aris ED - Wang, Xiaoyun ED - Sako, Kazue ID - 2974 TI - Commitments and efficient zero knowledge proofs from learning parity with noise VL - 7658 ER - TY - JOUR AB - The coupling between presynaptic Ca^(2+) channels and Ca^(2+) sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca^(2+) channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic opening of presynaptic Ca^(2+) channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca^(2+) concentration and the unselective Ca^(2+) channel blocker Cd^(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ~50%, suggesting that the opening of presynaptic Ca^(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca^(2+) channel blocker ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced mIPSC frequency. Furthermore, both the fast Ca^(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency, suggesting that Ca^(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB_(1) receptor agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca^(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca^(2+) channels may be important for hippocampal information processing. AU - Goswami, Sarit AU - Bucurenciu, Iancu AU - Jonas, Peter M ID - 2969 IS - 41 JF - Journal of Neuroscience TI - Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca^(2+) channels via microdomain coupling VL - 32 ER - TY - JOUR AB - Morphogen gradients regulate the patterning and growth of many tissues, hence a key question is how they are established and maintained during development. Theoretical descriptions have helped to explain how gradient shape is controlled by the rates of morphogen production, spreading and degradation. These effective rates have been measured using fluorescence recovery after photobleaching (FRAP) and photoactivation. To unravel which molecular events determine the effective rates, such tissue-level assays have been combined with genetic analysis, high-resolution assays, and models that take into account interactions with receptors, extracellular components and trafficking. Nevertheless, because of the natural and experimental data variability, and the underlying assumptions of transport models, it remains challenging to conclusively distinguish between cellular mechanisms. AU - Kicheva, Anna AU - Bollenbach, Mark Tobias AU - Wartlick, Ortrud AU - Julicher, Frank AU - Gonzalez Gaitan, Marcos ID - 2970 IS - 6 JF - Current Opinion in Genetics & Development TI - Investigating the principles of morphogen gradient formation: from tissues to cells VL - 22 ER - TY - CONF AB - We study the task of interactive semantic labeling of a segmentation hierarchy. To this end we propose a framework interleaving two components: an automatic labeling step, based on a Conditional Random Field whose dependencies are defined by the inclusion tree of the segmentation hierarchy, and an interaction step that integrates incremental input from a human user. Evaluated on two distinct datasets, the proposed interactive approach efficiently integrates human interventions and illustrates the advantages of structured prediction in an interactive framework. AU - Zankl, Georg AU - Haxhimusa, Yll AU - Ion, Adrian ID - 2971 TI - Interactive labeling of image segmentation hierarchies VL - 7476 ER - TY - JOUR AB - Growth and development are coordinated by an array of intercellular communications. Known plant signaling molecules include phytohormones and hormone peptides. Although both classes can be implicated in the same developmental processes, little is known about the interplay between phytohormone action and peptide signaling within the cellular microenvironment. We show that genes coding for small secretory peptides, designated GOLVEN (GLV), modulate the distribution of the phytohormone auxin. The deregulation of the GLV function impairs the formation of auxin gradients and alters the reorientation of shoots and roots after a gravity stimulus. Specifically, the GLV signal modulates the trafficking dynamics of the auxin efflux carrier PIN-FORMED2 involved in root tropic responses and meristem organization. Our work links the local action of secretory peptides with phytohormone transport. Root growth factor (RGF) or GOLVEN (GLV) secreted peptides have previously been implicated in meristem regulation. Whitford et al. now show that RGF/GLV peptides induce rapid relocalization of the auxin efflux regulator PIN2, regulate auxin gradients, and modulate auxin-dependent root responses to specific stimuli. AU - Whitford, Ryan AU - Fernandez, Ana AU - Tejos, Ricardo AU - Pérez, Amparo Cuéllar AU - Kleine-Vehn, Jürgen AU - Vanneste, Steffen AU - Drozdzecki, Andrzej AU - Leitner, Johannes AU - Abas, Lindy AU - Aerts, Maarten AU - Hoogewijs, Kurt AU - Pawel Baster AU - De Groodt, Ruth AU - Lin, Yao-Cheng AU - Storme, Véronique AU - Van de Peer, Yves AU - Beeckman, Tom AU - Madder, Annemieke AU - Devreese, Bart AU - Luschnig, Christian AU - Jirí Friml AU - Hilson, Pierre ID - 3105 IS - 3 JF - Developmental Cell TI - GOLVEN secretory peptides regulate auxin carrier turnover during plant gravitropic responses VL - 22 ER - TY - JOUR AB - Receptor-mediated endocytosis is an integral part of signal transduction as it mediates signal attenuation and provides spatial and temporal dimensions to signaling events. One of the best-studied leucine-rich repeat receptor-like kinases in plants, BRASSINOSTEROID INSENSITIVE 1 (BRI1), perceives its ligand, the brassinosteroid (BR) hormone, at the cell surface and is constitutively endocytosed. However, the importance of endocytosis for BR signaling remains unclear. Here we developed a bioactive, fluorescent BR analog, Alexa Fluor 647-castasterone (AFCS), and visualized the endocytosis of BRI1-AFCS complexes in living Arabidopsis thaliana cells. Impairment of endocytosis dependent on clathrin and the guanine nucleotide exchange factor for ARF GTPases (ARF-GEF) GNOM enhanced BR signaling by retaining active BRI1-ligand complexes at the plasma membrane. Increasing the trans-Golgi network/early endosome pool of BRI1-BR complexes did not affect BR signaling. Our findings provide what is to our knowledge the first visualization of receptor-ligand complexes in plants and reveal clathrin-and ARF-GEF-dependent endocytic regulation of BR signaling from the plasma membrane. AU - Irani, Niloufer G AU - Di Rubbo, Simone AU - Mylle, Evelien AU - Van Den Begin, Jos AU - Schneider-Pizoń, Joanna AU - Hniliková, Jaroslava AU - Šíša, Miroslav AU - Buyst, Dieter AU - Vilarrasa-Blasi, Josep AU - Szatmári, Anna-Maria AU - Van Damme, Daniël AU - Mishev, Kiril AU - Codreanu, Mirela-Corina AU - Kohout, Ladislav AU - Strnad, Miroslav AU - Caño-Delgado, Ana I AU - Jirí Friml AU - Madder, Annemieke AU - Russinova, Eugenia ID - 3109 IS - 6 JF - Nature Chemical Biology TI - Fluorescent castasterone reveals BRI1 signaling from the plasma membrane VL - 8 ER - TY - JOUR AB - Gradients of the plant hormone auxin, which depend on its active intercellular transport, are crucial for the maintenance of root meristematic activity. This directional transport is largely orchestrated by a complex interaction of specific influx and efflux carriers that mediate the auxin flow into and out of cells, respectively. Besides these transport proteins, plant-specific polyphenolic compounds knownasflavonols have beenshownto act as endogenous regulators of auxin transport. However, only limited information is available on how flavonol synthesis is developmentally regulated. Using reduction-of-function and overexpression approaches in parallel, we demonstrate that the WRKY23 transcription factor is needed for proper root growth and development by stimulating the local biosynthesis of flavonols. The expression of WRKY23 itself is controlled by auxin through the AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 transcriptional response pathway. Our results suggest a model in which WRKY23 is part of a transcriptional feedback loop of auxin on its own transport through local regulation of flavonol biosynthesis. AU - Grunewald, Wim AU - De Smet, Ive AU - Lewis, Daniel R AU - Löfke, Christian AU - Jansen, Leentje AU - Goeminne, Geert AU - Vanden Bossche, Robin AU - Karimi, Mansour AU - De Rybel, Bert AU - Vanholme, Bartel AU - Teichmann, Thomas AU - Boerjan, Wout AU - Van Montagu, Marc C AU - Gheysen, Godelieve AU - Muday, Gloria K AU - Jirí Friml AU - Beeckman, Tom ID - 3104 IS - 5 JF - PNAS TI - Transcription factor WRKY23 assists auxin distribution patterns during Arabidopsis root development through local control on flavonol biosynthesis VL - 109 ER - TY - JOUR AB - The phytohormone auxin acts as a prominent signal, providing, by its local accumulation or depletion in selected cells, a spatial and temporal reference for changes in the developmental program. The distribution of auxin depends on both auxin metabolism (biosynthesis, conjugation and degradation) and cellular auxin transport. We identified in silico a novel putative auxin transport facilitator family, called PIN-LIKES (PILS). Here we illustrate that PILS proteins are required for auxin-dependent regulation of plant growth by determining the cellular sensitivity to auxin. PILS proteins regulate intracellular auxin accumulation at the endoplasmic reticulum and thus auxin availability for nuclear auxin signalling. PILS activity affects the level of endogenous auxin indole-3-acetic acid (IAA), presumably via intracellular accumulation and metabolism. Our findings reveal that the transport machinery to compartmentalize auxin within the cell is of an unexpected molecular complexity and demonstrate this compartmentalization to be functionally important for a number of developmental processes. AU - Barbez, Elke AU - Kubeš, Martin AU - Rolčík, Jakub AU - Béziat, Chloe AU - Pěnčík, Aleš AU - Wang, Bangjun AU - Rosquete, Michel Ruiz AU - Zhu, Jinsheng AU - Dobrev, Petre I AU - Lee, Yuree AU - Zašímalová, Eva AU - Petrášek, Jan AU - Geisler, Markus AU - Jirí Friml AU - Kleine-Vehn, Jürgen ID - 3108 IS - 7396 JF - Nature TI - A novel putative auxin carrier family regulates intracellular auxin homeostasis in plants VL - 485 ER - TY - JOUR AB - Cell polarization via asymmetrical distribution of structures or molecules is essential for diverse cellular functions and development of organisms, but how polarity is developmentally controlled has been poorly understood. In plants, the asymmetrical distribution of the PIN-FORMED (PIN) proteins involved in the cellular efflux of the quintessential phytohormone auxin plays a central role in developmental patterning, morphogenesis, and differential growth. Recently we showed that auxin promotes cell interdigitation by activating the Rho family ROP GTPases in leaf epidermal pavement cells. Here we found that auxin activation of the ROP2 signaling pathway regulates the asymmetric distribution of PIN1 by inhibiting its endocytosis. ROP2 inhibits PIN1 endocytosis via the accumulation of cortical actin microfilaments induced by the ROP2 effector protein RIC4. Our findings suggest a link between the developmental auxin signal and polar PIN1 distribution via Rho-dependent cytoskeletal reorganization and reveal the conservation of a design principle for cell polarization that is based on Rho GTPase-mediated inhibition of endocytosis. AU - Nagawa, Shingo AU - Xu, Tongda AU - Lin, Deshu AU - Dhonukshe, Pankaj AU - Zhang, Xingxing AU - Jirí Friml AU - Scheres, Ben AU - Fu, Ying AU - Yang, Zhenbiao ID - 3106 IS - 4 JF - PLoS Biology TI - ROP GTPase-dependent actin microfilaments promote PIN1 polarization by localized inhibition of clathrin-dependent endocytosis VL - 10 ER - TY - GEN AU - Vanneste, Steffen AU - Friml, Jirí ID - 3107 IS - 5 T2 - Nature Chemical Biology TI - Plant signaling: Deconstructing auxin sensing VL - 8 ER - TY - CONF AB - We present an approach for artist-directed animation of liquids using multiple levels of control over the simulation, ranging from the overall tracking of desired shapes to highly detailed secondary effects such as dripping streams, separating sheets of fluid, surface waves and ripples. The first portion of our technique is a volume preserving morph that allows the animator to produce a plausible fluid-like motion from a sparse set of control meshes. By rasterizing the resulting control meshes onto the simulation grid, the mesh velocities act as boundary conditions during the projection step of the fluid simulation. We can then blend this motion together with uncontrolled fluid velocities to achieve a more relaxed control over the fluid that captures natural inertial effects. Our method can produce highly detailed liquid surfaces with control over sub-grid details by using a mesh-based surface tracker on top of a coarse grid-based fluid simulation. We can create ripples and waves on the fluid surface attracting the surface mesh to the control mesh with spring-like forces and also by running a wave simulation over the surface mesh. Our video results demonstrate how our control scheme can be used to create animated characters and shapes that are made of water. AU - Raveendran, Karthik AU - Thuerey, Nils AU - Wojtan, Christopher J AU - Turk, Greg ID - 3119 T2 - Proceedings of the ACM SIGGRAPH/Eurographics Symposium on Computer Animation TI - Controlling liquids using meshes ER - TY - JOUR AB - We present a method for recovering a temporally coherent, deforming triangle mesh with arbitrarily changing topology from an incoherent sequence of static closed surfaces. We solve this problem using the surface geometry alone, without any prior information like surface templates or velocity fields. Our system combines a proven strategy for triangle mesh improvement, a robust multi-resolution non-rigid registration routine, and a reliable technique for changing surface mesh topology. We also introduce a novel topological constraint enforcement algorithm to ensure that the output and input always have similar topology. We apply our technique to a series of diverse input data from video reconstructions, physics simulations, and artistic morphs. The structured output of our algorithm allows us to efficiently track information like colors and displacement maps, recover velocity information, and solve PDEs on the mesh as a post process. AU - Bojsen-Hansen, Morten AU - Li, Hao AU - Wojtan, Christopher J ID - 3118 IS - 4 JF - ACM Transactions on Graphics TI - Tracking surfaces with evolving topology VL - 31 ER - TY - JOUR AB - Since Darwin's pioneering research on plant reproductive biology (e.g. Darwin 1877), understanding the mechanisms maintaining the diverse sexual strategies of plants has remained an important challenge for evolutionary biologists. In some species, populations are sexually polymorphic and contain two or more mating morphs (sex phenotypes). Differences in morphology or phenology among the morphs influence patterns of non-random mating. In these populations, negative frequency-dependent selection arising from disassortative (intermorph) mating is usually required for the evolutionary maintenance of sexual polymorphism, but few studies have demonstrated the required patterns of non-random mating. In the current issue of Molecular Ecology, Shang (2012) make an important contribution to our understanding of how disassortative mating influences sex phenotype ratios in Acer pictum subsp. mono (painted maple), a heterodichogamous, deciduous tree of eastern China. They monitored sex expression in 97 adults and used paternity analysis of open-pollinated seed to examine disassortative mating among three sex phenotypes. Using a deterministic 'pollen transfer' model, Shang et al. present convincing evidence that differences in the degree of disassortative mating in progeny arrays of the sex phenotypes can explain their uneven frequencies in the adult population. This study provides a useful example of how the deployment of genetic markers, demographic monitoring and modelling can be integrated to investigate the maintenance of sexual diversity in plants. AU - Field, David AU - Barrett, Spencer ID - 3122 IS - 15 JF - Molecular Ecology TI - Disassortative mating and the maintenance of sexual polymorphism in painted maple VL - 21 ER - TY - JOUR AB - Voltage-activated Ca(2+) channels (VACCs) mediate Ca(2+) influx to trigger action potential-evoked neurotransmitter release, but the mechanism by which Ca(2+) regulates spontaneous transmission is unclear. We found that VACCs are the major physiological triggers for spontaneous release at mouse neocortical inhibitory synapses. Moreover, despite the absence of a synchronizing action potential, we found that spontaneous fusion of a GABA-containing vesicle required the activation of multiple tightly coupled VACCs of variable type. AU - Williams, Courtney AU - Chen, Wenyan AU - Lee, Chia AU - Yaeger, Daniel AU - Vyleta, Nicholas AU - Smith, Stephen ID - 3121 IS - 9 JF - Nature Neuroscience TI - Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA VL - 15 ER - TY - JOUR AB - We introduce a strategy based on Kustin-Miller unprojection that allows us to construct many hundreds of Gorenstein codimension 4 ideals with 9 × 16 resolutions (that is, nine equations and sixteen first syzygies). Our two basic games are called Tom and Jerry; the main application is the biregular construction of most of the anticanonically polarised Mori Fano 3-folds of Altinok's thesis. There are 115 cases whose numerical data (in effect, the Hilbert series) allow a Type I projection. In every case, at least one Tom and one Jerry construction works, providing at least two deformation families of quasismooth Fano 3-folds having the same numerics but different topology. © 2012 Copyright Foundation Compositio Mathematica. AU - Brown, Gavin AU - Kerber, Michael AU - Reid, Miles ID - 3120 IS - 4 JF - Compositio Mathematica TI - Fano 3 folds in codimension 4 Tom and Jerry Part I VL - 148 ER - TY - JOUR AB - We consider the problem of minimizing a function represented as a sum of submodular terms. We assume each term allows an efficient computation of exchange capacities. This holds, for example, for terms depending on a small number of variables, or for certain cardinality-dependent terms. A naive application of submodular minimization algorithms would not exploit the existence of specialized exchange capacity subroutines for individual terms. To overcome this, we cast the problem as a submodular flow (SF) problem in an auxiliary graph in such a way that applying most existing SF algorithms would rely only on these subroutines. We then explore in more detail Iwata's capacity scaling approach for submodular flows (Iwata 1997 [19]). In particular, we show how to improve its complexity in the case when the function contains cardinality-dependent terms. AU - Kolmogorov, Vladimir ID - 3117 IS - 15 JF - Discrete Applied Mathematics TI - Minimizing a sum of submodular functions VL - 160 ER - TY - JOUR AB - In large populations, many beneficial mutations may be simultaneously available and may compete with one another, slowing adaptation. By finding the probability of fixation of a favorable allele in a simple model of a haploid sexual population, we find limits to the rate of adaptive substitution, Λ, that depend on simple parameter combinations. When variance in fitness is low and linkage is loose, the baseline rate of substitution is Λ 0=2NU〈s〉 is the population size, U is the rate of beneficial mutations per genome, and 〈s〉 is their mean selective advantage. Heritable variance ν in log fitness due to unlinked loci reduces Λ by e -4ν under polygamy and e -8ν under monogamy. With a linear genetic map of length R Morgans, interference is yet stronger. We use a scaling argument to show that the density of adaptive substitutions depends on s, N, U, and R only through the baseline density: Λ/R=F(Λ 0/R). Under the approximation that the interference due to different sweeps adds up, we show that Λ/R~(Λ 0/R)/(1+2Λ 0/R), implying that interference prevents the rate of adaptive substitution from exceeding one per centimorgan per 200 generations. Simulations and numerical calculations confirm the scaling argument and confirm the additive approximation for Λ 0/R 1; for higher Λ 0/R, the rate of adaptation grows above R/2, but only very slowly. We also consider the effect of sweeps on neutral diversity and show that, while even occasional sweeps can greatly reduce neutral diversity, this effect saturates as sweeps become more common-diversity can be maintained even in populations experiencing very strong interference. Our results indicate that for some organisms the rate of adaptive substitution may be primarily recombination-limited, depending only weakly on the mutation supply and the strength of selection. AU - Weissman, Daniel AU - Barton, Nicholas H ID - 3131 IS - 6 JF - PLoS Genetics TI - Limits to the rate of adaptive substitution in sexual populations VL - 8 ER - TY - JOUR AB - Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes. AU - Bergmiller, Tobias AU - Ackermann, Martin AU - Silander, Olin ID - 3130 IS - 6 JF - PLoS Genetics TI - Patterns of evolutionary conservation of essential genes correlate with their compensability VL - 8 ER - TY - CONF AB - Continuous-time Markov chains (CTMC) with their rich theory and efficient simulation algorithms have been successfully used in modeling stochastic processes in diverse areas such as computer science, physics, and biology. However, systems that comprise non-instantaneous events cannot be accurately and efficiently modeled with CTMCs. In this paper we define delayed CTMCs, an extension of CTMCs that allows for the specification of a lower bound on the time interval between an event's initiation and its completion, and we propose an algorithm for the computation of their behavior. Our algorithm effectively decomposes the computation into two stages: a pure CTMC governs event initiations while a deterministic process guarantees lower bounds on event completion times. Furthermore, from the nature of delayed CTMCs, we obtain a parallelized version of our algorithm. We use our formalism to model genetic regulatory circuits (biological systems where delayed events are common) and report on the results of our numerical algorithm as run on a cluster. We compare performance and accuracy of our results with results obtained by using pure CTMCs. © 2012 Springer-Verlag. AU - Guet, Calin C AU - Gupta, Ashutosh AU - Henzinger, Thomas A AU - Mateescu, Maria AU - Sezgin, Ali ID - 3136 TI - Delayed continuous time Markov chains for genetic regulatory circuits VL - 7358 ER - TY - CONF AB - We introduce consumption games, a model for discrete interactive system with multiple resources that are consumed or reloaded independently. More precisely, a consumption game is a finite-state graph where each transition is labeled by a vector of resource updates, where every update is a non-positive number or ω. The ω updates model the reloading of a given resource. Each vertex belongs either to player □ or player ◇, where the aim of player □ is to play so that the resources are never exhausted. We consider several natural algorithmic problems about consumption games, and show that although these problems are computationally hard in general, they are solvable in polynomial time for every fixed number of resource types (i.e., the dimension of the update vectors) and bounded resource updates. AU - Brázdil, Brázdil AU - Chatterjee, Krishnendu AU - Kučera, Antonín AU - Novotny, Petr ID - 3135 TI - Efficient controller synthesis for consumption games with multiple resource types VL - 7358 ER - TY - CONF AB - This note contributes to the point calculus of persistent homology by extending Alexander duality from spaces to real-valued functions. Given a perfect Morse function f: S n+1 →[0, 1 and a decomposition S n+1 = U ∪ V into two (n + 1)-manifolds with common boundary M, we prove elementary relationships between the persistence diagrams of f restricted to U, to V, and to M. AU - Edelsbrunner, Herbert AU - Kerber, Michael ID - 3133 T2 - Proceedings of the twenty-eighth annual symposium on Computational geometry TI - Alexander duality for functions: The persistent behavior of land and water and shore ER - TY - CONF AB - It has been an open question whether the sum of finitely many isotropic Gaussian kernels in n ≥ 2 dimensions can have more modes than kernels, until in 2003 Carreira-Perpiñán and Williams exhibited n +1 isotropic Gaussian kernels in ℝ n with n + 2 modes. We give a detailed analysis of this example, showing that it has exponentially many critical points and that the resilience of the extra mode grows like √n. In addition, we exhibit finite configurations of isotropic Gaussian kernels with superlinearly many modes. AU - Edelsbrunner, Herbert AU - Fasy, Brittany AU - Rote, Günter ID - 3134 T2 - Proceedings of the twenty-eighth annual symposium on Computational geometry TI - Add isotropic Gaussian kernels at own risk: More and more resilient modes in higher dimensions ER -