TY - JOUR AB - We study synthesis of controllers for real-time systems, where the objective is to stay in a given safe set. The problem is solved by obtaining winning strategies in the setting of concurrent two player timed automaton games with safety objectives. To prevent a player from winning by blocking time, we restrict each player to strategies that ensure that the player cannot be responsible for causing a Zeno run. We construct winning strategies for the controller which require access only to (1) the system clocks (thus, controllers which require their own internal infinitely precise clocks are not necessary), and (2) a logarithmic (in the number of clocks) number of memory bits (i.e. a linear number of memory states). Precisely, we show that for safety objectives, a memory of size (3 + lg (| C | + 1)) bits suffices for winning controller strategies, where C is the set of clocks of the timed automaton game, significantly improving the previous known exponential memory states bound. We also settle the open question of whether winning region-based strategies require memory for safety objectives by showing with an example the necessity of memory for such strategies to win for safety objectives. Finally, we show that the decision problem of determining if there exists a receptive player-1 winning strategy for safety objectives is EXPTIME-complete over timed automaton games. AU - Chatterjee, Krishnendu AU - Prabhu, Vinayak ID - 2824 JF - Information and Computation TI - Synthesis of memory-efficient, clock-memory free, and non-Zeno safety controllers for timed systems VL - 228-229 ER - TY - JOUR AB - PIN-FORMED (PIN) proteins localize asymmetrically at the plasma membrane and mediate intercellular polar transport of the plant hormone auxin that is crucial for a multitude of developmental processes in plants. PIN localization is under extensive control by environmental or developmental cues, but mechanisms regulating PIN localization are not fully understood. Here we show that early endosomal components ARF GEF BEN1 and newly identified Sec1/Munc18 family protein BEN2 are involved in distinct steps of early endosomal trafficking. BEN1 and BEN2 are collectively required for polar PIN localization, for their dynamic repolarization, and consequently for auxin activity gradient formation and auxin-related developmental processes including embryonic patterning, organogenesis, and vasculature venation patterning. These results show that early endosomal trafficking is crucial for cell polarity and auxin-dependent regulation of plant architecture. AU - Tanaka, Hirokazu AU - Kitakura, Saeko AU - Rakusová, Hana AU - Uemura, Tomohiro AU - Feraru, Mugurel AU - De Rycke, Riet AU - Robert, Stéphanie AU - Kakimoto, Tatsuo AU - Friml, Jirí ID - 2832 IS - 5 JF - PLoS Genetics TI - Cell polarity and patterning by PIN trafficking through early endosomal compartments in arabidopsis thaliana VL - 9 ER - TY - JOUR AB - We study the complexity of valued constraint satisfaction problems (VCSPs) parametrized by a constraint language, a fixed set of cost functions over a finite domain. An instance of the problem is specified by a sum of cost functions from the language and the goal is to minimize the sum. Under the unique games conjecture, the approximability of finite-valued VCSPs is well understood, see Raghavendra [2008]. However, there is no characterization of finite-valued VCSPs, let alone general-valued VCSPs, that can be solved exactly in polynomial time, thus giving insights from a combinatorial optimization perspective. We consider the case of languages containing all possible unary cost functions. In the case of languages consisting of only {0, ∞}-valued cost functions (i.e., relations), such languages have been called conservative and studied by Bulatov [2003, 2011] and recently by Barto [2011]. Since we study valued languages, we call a language conservative if it contains all finite-valued unary cost functions. The computational complexity of conservative valued languages has been studied by Cohen et al. [2006] for languages over Boolean domains, by Deineko et al. [2008] for {0, 1}-valued languages (a.k.a Max-CSP), and by Takhanov [2010a] for {0, ∞}-valued languages containing all finite-valued unary cost functions (a.k.a. Min-Cost-Hom). We prove a Schaefer-like dichotomy theorem for conservative valued languages: if all cost functions in the language satisfy a certain condition (specified by a complementary combination of STP and MJN multimor-phisms), then any instance can be solved in polynomial time (via a new algorithm developed in this article), otherwise the language is NP-hard. This is the first complete complexity classification of general-valued constraint languages over non-Boolean domains. It is a common phenomenon that complexity classifications of problems over non-Boolean domains are significantly harder than the Boolean cases. The polynomial-time algorithm we present for the tractable cases is a generalization of the submodular minimization problem and a result of Cohen et al. [2008]. Our results generalize previous results by Takhanov [2010a] and (a subset of results) by Cohen et al. [2006] and Deineko et al. [2008]. Moreover, our results do not rely on any computer-assisted search as in Deineko et al. [2008], and provide a powerful tool for proving hardness of finite-valued and general-valued languages. AU - Kolmogorov, Vladimir AU - Živný, Stanislav ID - 2828 IS - 2 JF - Journal of the ACM TI - The complexity of conservative valued CSPs VL - 60 ER - TY - JOUR AB - Laminar-turbulent intermittency is intrinsic to the transitional regime of a wide range of fluid flows including pipe, channel, boundary layer, and Couette flow. In the latter turbulent spots can grow and form continuous stripes, yet in the stripe-normal direction they remain interspersed by laminar fluid. We carry out direct numerical simulations in a long narrow domain and observe that individual turbulent stripes are transient. In agreement with recent observations in pipe flow, we find that turbulence becomes sustained at a distinct critical point once the spatial proliferation outweighs the inherent decaying process. By resolving the asymptotic size distributions close to criticality we can for the first time demonstrate scale invariance at the onset of turbulence. AU - Shi, Liang AU - Avila, Marc AU - Hof, Björn ID - 2829 IS - 20 JF - Physical Review Letters TI - Scale invariance at the onset of turbulence in couette flow VL - 110 ER - TY - JOUR AB - Although the equations governing fluid flow are well known, there are no analytical expressions that describe the complexity of turbulent motion. A recent proposition is that in analogy to low dimensional chaotic systems, turbulence is organized around unstable solutions of the governing equations which provide the building blocks of the disordered dynamics. We report the discovery of periodic solutions which just like intermittent turbulence are spatially localized and show that turbulent transients arise from one such solution branch. AU - Avila, Marc AU - Mellibovsky, Fernando AU - Roland, Nicolas AU - Hof, Björn ID - 2834 IS - 22 JF - Physical Review Letters TI - Streamwise-localized solutions at the onset of turbulence in pipe flow VL - 110 ER - TY - JOUR AB - During development, mechanical forces cause changes in size, shape, number, position, and gene expression of cells. They are therefore integral to any morphogenetic processes. Force generation by actin-myosin networks and force transmission through adhesive complexes are two self-organizing phenomena driving tissue morphogenesis. Coordination and integration of forces by long-range force transmission and mechanosensing of cells within tissues produce large-scale tissue shape changes. Extrinsic mechanical forces also control tissue patterning by modulating cell fate specification and differentiation. Thus, the interplay between tissue mechanics and biochemical signaling orchestrates tissue morphogenesis and patterning in development. AU - Heisenberg, Carl-Philipp J AU - Bellaïche, Yohanns ID - 2833 IS - 5 JF - Cell TI - Forces in tissue morphogenesis and patterning VL - 153 ER - TY - JOUR AU - Moussion, Christine AU - Sixt, Michael K ID - 2830 IS - 5 JF - Immunity TI - A conduit to amplify innate immunity VL - 38 ER - TY - JOUR AB - We outline two approaches to inference of neighbourhood size, N, and dispersal rate, σ2, based on either allele frequencies or on the lengths of sequence blocks that are shared between genomes. Over intermediate timescales (10-100 generations, say), populations that live in two dimensions approach a quasi-equilibrium that is independent of both their local structure and their deeper history. Over such scales, the standardised covariance of allele frequencies (i.e. pairwise FS T) falls with the logarithm of distance, and depends only on neighbourhood size, N, and a 'local scale', κ; the rate of gene flow, σ2, cannot be inferred. We show how spatial correlations can be accounted for, assuming a Gaussian distribution of allele frequencies, giving maximum likelihood estimates of N and κ. Alternatively, inferences can be based on the distribution of the lengths of sequence that are identical between blocks of genomes: long blocks (>0.1 cM, say) tell us about intermediate timescales, over which we assume a quasi-equilibrium. For large neighbourhood size, the distribution of long blocks is given directly by the classical Wright-Malécot formula; this relationship can be used to infer both N and σ2. With small neighbourhood size, there is an appreciable chance that recombinant lineages will coalesce back before escaping into the distant past. For this case, we show that if genomes are sampled from some distance apart, then the distribution of lengths of blocks that are identical in state is geometric, with a mean that depends on N and σ2. AU - Barton, Nicholas H AU - Etheridge, Alison AU - Kelleher, Jerome AU - Véber, Amandine ID - 2842 IS - 1 JF - Theoretical Population Biology TI - Inference in two dimensions: Allele frequencies versus lengths of shared sequence blocks VL - 87 ER - TY - JOUR AB - Individuals with Down syndrome (DS) present important motor deficits that derive from altered motor development of infants and young children. DYRK1A, a candidate gene for DS abnormalities has been implicated in motor function due to its expression in motor nuclei in the adult brain, and its overexpression in DS mouse models leads to hyperactivity and altered motor learning. However, its precise role in the adult motor system, or its possible involvement in postnatal locomotor development has not yet been clarified. During the postnatal period we observed time-specific expression of Dyrk1A in discrete subsets of brainstem nuclei and spinal cord motor neurons. Interestingly, we describe for the first time the presence of Dyrk1A in the presynaptic terminal of the neuromuscular junctions and its axonal transport from the facial nucleus, suggesting a function for Dyrk1A in these structures. Relevant to DS, Dyrk1A overexpression in transgenic mice (TgDyrk1A) produces motor developmental alterations possibly contributing to DS motor phenotypes and modifies the numbers of motor cholinergic neurons, suggesting that the kinase may have a role in the development of the brainstem and spinal cord motor system. AU - Arquè Fuste, Gloria AU - Casanovas, Anna AU - Dierssen, Mara ID - 2838 IS - 1 JF - PLoS One TI - Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: Possible role in Down syndrome VL - 8 ER - TY - JOUR AB - Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues. AU - Weber, Michele AU - Hauschild, Robert AU - Schwarz, Jan AU - Moussion, Christine AU - De Vries, Ingrid AU - Legler, Daniel AU - Luther, Sanjiv AU - Bollenbach, Mark Tobias AU - Sixt, Michael K ID - 2839 IS - 6117 JF - Science TI - Interstitial dendritic cell guidance by haptotactic chemokine gradients VL - 339 ER - TY - JOUR AB - We consider a general class of N × N random matrices whose entries hij are independent up to a symmetry constraint, but not necessarily identically distributed. Our main result is a local semicircle law which improves previous results [17] both in the bulk and at the edge. The error bounds are given in terms of the basic small parameter of the model, maxi,j E|hij|2. As a consequence, we prove the universality of the local n-point correlation functions in the bulk spectrum for a class of matrices whose entries do not have comparable variances, including random band matrices with band width W ≫N1-εn with some εn > 0 and with a negligible mean-field component. In addition, we provide a coherent and pedagogical proof of the local semicircle law, streamlining and strengthening previous arguments from [17, 19, 6]. AU - Erdös, László AU - Knowles, Antti AU - Yau, Horng AU - Yin, Jun ID - 2837 IS - 59 JF - Electronic Journal of Probability TI - The local semicircle law for a general class of random matrices VL - 18 ER - TY - JOUR AB - The phytohormone auxin regulates virtually every aspect of plant development. To identify new genes involved in auxin activity, a genetic screen was performed for Arabidopsis (Arabidopsis thaliana) mutants with altered expression of the auxin-responsive reporter DR5rev:GFP. One of the mutants recovered in the screen, designated as weak auxin response3 (wxr3), exhibits much lower DR5rev:GFP expression when treated with the synthetic auxin 2,4-dichlorophenoxyacetic acid and displays severe defects in root development. The wxr3 mutant decreases polar auxin transport and results in a disruption of the asymmetric auxin distribution. The levels of the auxin transporters AUXIN1 and PIN-FORMED are dramatically reduced in the wxr3 root tip. Molecular analyses demonstrate that WXR3 is ROOT ULTRAVIOLET B-SENSITIVE1 (RUS1), a member of the conserved Domain of Unknown Function647 protein family found in diverse eukaryotic organisms. Our data suggest that RUS1/WXR3 plays an essential role in the regulation of polar auxin transport by maintaining the proper level of auxin transporters on the plasma membrane. AU - Yu, Hong AU - Karampelias, Michael AU - Robert, Stéphanie AU - Peer, Wendy AU - Swarup, Ranjan AU - Ye, Songqing AU - Ge, Lei AU - Cohen, Jerry AU - Murphy, Angus AU - Friml, Jirí AU - Estelle, Mark ID - 2835 IS - 2 JF - Plant Physiology TI - Root ultraviolet b-sensitive1/weak auxin response3 is essential for polar auxin transport in arabidopsis VL - 162 ER - TY - JOUR AB - We study the automatic synthesis of fair non-repudiation protocols, a class of fair exchange protocols, used for digital contract signing. First, we show how to specify the objectives of the participating agents and the trusted third party as path formulas in linear temporal logic and prove that the satisfaction of these objectives imply fairness; a property required of fair exchange protocols. We then show that weak (co-operative) co-synthesis and classical (strictly competitive) co-synthesis fail, whereas assume-guarantee synthesis (AGS) succeeds. We demonstrate the success of AGS as follows: (a) any solution of AGS is attack-free; no subset of participants can violate the objectives of the other participants; (b) the Asokan-Shoup-Waidner certified mail protocol that has known vulnerabilities is not a solution of AGS; (c) the Kremer-Markowitch non-repudiation protocol is a solution of AGS; and (d) AGS presents a new and symmetric fair non-repudiation protocol that is attack-free. To our knowledge this is the first application of synthesis to fair non-repudiation protocols, and our results show how synthesis can both automatically discover vulnerabilities in protocols and generate correct protocols. The solution to AGS can be computed efficiently as the secure equilibrium solution of three-player graph games. AU - Chatterjee, Krishnendu AU - Raman, Vishwanath ID - 2836 IS - 4 JF - Formal Aspects of Computing TI - Assume-guarantee synthesis for digital contract signing VL - 26 ER - TY - JOUR AB - It is known that the entorhinal cortex plays a crucial role in spatial cognition in rodents. Neuroanatomical and electrophysiological data suggest that there is a functional distinction between 2 subregions within the entorhinal cortex, the medial entorhinal cortex (MEC), and the lateral entorhinal cortex (LEC). Rats with MEC or LEC lesions were trained in 2 navigation tasks requiring allothetic (water maze task) or idiothetic (path integration) information processing and 2-object exploration tasks allowing testing of spatial and nonspatial processing of intramaze objects. MEC lesions mildly affected place navigation in the water maze and produced a path integration deficit. They also altered the processing of spatial information in both exploration tasks while sparing the processing of nonspatial information. LEC lesions did not affect navigation abilities in both the water maze and the path integration tasks. They altered spatial and nonspatial processing in the object exploration task but not in the one-trial recognition task. Overall, these results indicate that the MEC is important for spatial processing and path integration. The LEC has some influence on both spatial and nonspatial processes, suggesting that the 2 kinds of information interact at the level of the EC. AU - Van Cauter, Tiffany AU - Camon, Jeremy AU - Alvernhe, Alice AU - Elduayen, Coralie AU - Sargolini, Francesca AU - Save, Étienne ID - 2840 IS - 2 JF - Cerebral Cortex TI - Distinct roles of medial and lateral entorhinal cortex in spatial cognition VL - 23 ER - TY - JOUR AB - In zebrafish early development, blastoderm cells undergo extensive radial intercalations, triggering the spreading of the blastoderm over the yolk cell and thereby initiating embryonic body axis formation. Now reporting in Developmental Cell, Song et al. (2013) demonstrate a critical function for EGF-dependent E-cadherin endocytosis in promoting blastoderm cell intercalations. AU - Morita, Hitoshi AU - Heisenberg, Carl-Philipp J ID - 2841 IS - 6 JF - Developmental Cell TI - Holding on and letting go: Cadherin turnover in cell intercalation VL - 24 ER - TY - JOUR AB - The Red Queen hypothesis proposes that coevolving parasites select for outcrossing in the host. Outcrossing relies on males, which often show lower immune investment due to, for example, sexual selection. Here, we demonstrate that such sex differences in immunity interfere with parasite-mediated selection for outcrossing. Two independent coevolution experiments with Caenorhabditis elegans and its microparasite Bacillus thuringiensis produced decreased yet stable frequencies of outcrossing male hosts. A subsequent systematic analysis verified that male C. elegans suffered from a direct selective disadvantage under parasite pressure (i.e. lower resistance, decreased sexual activity, increased escape behaviour), which can reduce outcrossing and thus male frequencies. At the same time, males offered an indirect selective benefit, because male-mediated outcrossing increased offspring resistance, thus favouring male persistence in the evolving populations. As sex differences in immunity are widespread, such interference of opposing selective constraints is likely of central importance during host adaptation to a coevolving parasite. AU - El Masri, Leila AU - Schulte, Rebecca AU - Timmermeyer, Nadine AU - Thanisch, Stefanie AU - Crummenerl, Lena AU - Jansen, Gunther AU - Michiels, Nico AU - Schulenburg, Hinrich ID - 2846 IS - 4 JF - Ecology Letters TI - Sex differences in host defence interfere with parasite-mediated selection for outcrossing during host-parasite coevolution VL - 16 ER - TY - JOUR AB - As soon as a seed germinates, plant growth relates to gravity to ensure that the root penetrates the soil and the shoot expands aerially. Whereas mechanisms of positive and negative orthogravitropism of primary roots and shoots are relatively well understood [1-3], lateral organs often show more complex growth behavior [4]. Lateral roots (LRs) seemingly suppress positive gravitropic growth and show a defined gravitropic set-point angle (GSA) that allows radial expansion of the root system (plagiotropism) [3, 4]. Despite its eminent importance for root architecture, it so far remains completely unknown how lateral organs partially suppress positive orthogravitropism. Here we show that the phytohormone auxin steers GSA formation and limits positive orthogravitropism in LR. Low and high auxin levels/signaling lead to radial or axial root systems, respectively. At a cellular level, it is the auxin transport-dependent regulation of asymmetric growth in the elongation zone that determines GSA. Our data suggest that strong repression of PIN4/PIN7 and transient PIN3 expression limit auxin redistribution in young LR columella cells. We conclude that PIN activity, by temporally limiting the asymmetric auxin fluxes in the tip of LRs, induces transient, differential growth responses in the elongation zone and, consequently, controls root architecture. AU - Rosquete, Michel AU - Von Wangenheim, Daniel AU - Marhavy, Peter AU - Barbez, Elke AU - Stelzer, Ernst AU - Benková, Eva AU - Maizel, Alexis AU - Kleine Vehn, Jürgen ID - 2844 IS - 9 JF - Current Biology TI - An auxin transport mechanism restricts positive orthogravitropism in lateral roots VL - 23 ER - TY - CONF AB - Mathematical objects can be measured unambiguously, but not so objects from our physical world. Even the total length of tubelike shapes has its difficulties. We introduce a combination of geometric, probabilistic, and topological methods to design a stable length estimate for tube-like shapes; that is: one that is insensitive to small shape changes. AU - Edelsbrunner, Herbert AU - Pausinger, Florian ID - 2843 T2 - 17th IAPR International Conference on Discrete Geometry for Computer Imagery TI - Stable length estimates of tube-like shapes VL - 7749 ER - TY - JOUR AB - At synapses formed between dissociated neurons, about half of all synaptic vesicles are refractory to evoked release, forming the so-called "resting pool." Here, we use optical measurements of vesicular pH to study developmental changes in pool partitioning and vesicle cycling in cultured hippocampal slices. Two-photon imaging of a genetically encoded two-color release sensor (ratio-sypHy) allowed us to perform calibrated measurements at individual Schaffer collateral boutons. Mature boutons released a large fraction of their vesicles during simulated place field activity, and vesicle retrieval rates were 7-fold higher compared to immature boutons. Saturating stimulation mobilized essentially all vesicles at mature synapses. Resting pool formation and a concomitant reduction in evoked release was induced by chronic depolarization but not by acute inhibition of the protein phosphatase calcineurin. We conclude that synapses in CA1 undergo a prominent refinement of vesicle use during early postnatal development that is not recapitulated in dissociated neuronal culture. AU - Rose, Tobias AU - Schönenberger, Philipp AU - Jezek, Karel AU - Oertner, Thomas ID - 2845 IS - 6 JF - Neuron TI - Developmental refinement of vesicle cycling at Schaffer collateral synapses VL - 77 ER - TY - JOUR AB - We consider concurrent games played on graphs. At every round of a game, each player simultaneously and independently selects a move; the moves jointly determine the transition to a successor state. Two basic objectives are the safety objective to stay forever in a given set of states, and its dual, the reachability objective to reach a given set of states. First, we present a simple proof of the fact that in concurrent reachability games, for all ε>0, memoryless ε-optimal strategies exist. A memoryless strategy is independent of the history of plays, and an ε-optimal strategy achieves the objective with probability within ε of the value of the game. In contrast to previous proofs of this fact, our proof is more elementary and more combinatorial. Second, we present a strategy-improvement (a.k.a. policy-iteration) algorithm for concurrent games with reachability objectives. Finally, we present a strategy-improvement algorithm for turn-based stochastic games (where each player selects moves in turns) with safety objectives. Our algorithms yield sequences of player-1 strategies which ensure probabilities of winning that converge monotonically (from below) to the value of the game. © 2012 Elsevier Inc. AU - Chatterjee, Krishnendu AU - De Alfaro, Luca AU - Henzinger, Thomas A ID - 2854 IS - 5 JF - Journal of Computer and System Sciences TI - Strategy improvement for concurrent reachability and turn based stochastic safety games VL - 79 ER - TY - JOUR AB - Recent work emphasizes that the maximum entropy principle provides a bridge between statistical mechanics models for collective behavior in neural networks and experiments on networks of real neurons. Most of this work has focused on capturing the measured correlations among pairs of neurons. Here we suggest an alternative, constructing models that are consistent with the distribution of global network activity, i.e. the probability that K out of N cells in the network generate action potentials in the same small time bin. The inverse problem that we need to solve in constructing the model is analytically tractable, and provides a natural 'thermodynamics' for the network in the limit of large N. We analyze the responses of neurons in a small patch of the retina to naturalistic stimuli, and find that the implied thermodynamics is very close to an unusual critical point, in which the entropy (in proper units) is exactly equal to the energy. © 2013 IOP Publishing Ltd and SISSA Medialab srl. AU - Tkacik, Gasper AU - Marre, Olivier AU - Mora, Thierry AU - Amodei, Dario AU - Berry, Michael AU - Bialek, William ID - 2850 IS - 3 JF - Journal of Statistical Mechanics Theory and Experiment TI - The simplest maximum entropy model for collective behavior in a neural network VL - 2013 ER - TY - JOUR AB - The number of possible activity patterns in a population of neurons grows exponentially with the size of the population. Typical experiments explore only a tiny fraction of the large space of possible activity patterns in the case of populations with more than 10 or 20 neurons. It is thus impossible, in this undersampled regime, to estimate the probabilities with which most of the activity patterns occur. As a result, the corresponding entropy - which is a measure of the computational power of the neural population - cannot be estimated directly. We propose a simple scheme for estimating the entropy in the undersampled regime, which bounds its value from both below and above. The lower bound is the usual 'naive' entropy of the experimental frequencies. The upper bound results from a hybrid approximation of the entropy which makes use of the naive estimate, a maximum entropy fit, and a coverage adjustment. We apply our simple scheme to artificial data, in order to check their accuracy; we also compare its performance to those of several previously defined entropy estimators. We then apply it to actual measurements of neural activity in populations with up to 100 cells. Finally, we discuss the similarities and differences between the proposed simple estimation scheme and various earlier methods. © 2013 IOP Publishing Ltd and SISSA Medialab srl. AU - Berry, Michael AU - Tkacik, Gasper AU - Dubuis, Julien AU - Marre, Olivier AU - Da Silveira, Ravá ID - 2851 IS - 3 JF - Journal of Statistical Mechanics Theory and Experiment TI - A simple method for estimating the entropy of neural activity VL - 2013 ER - TY - JOUR AB - In the vibrant field of optogenetics, optics and genetic targeting are combined to commandeer cellular functions, such as the neuronal action potential, by optically stimulating light-sensitive ion channels expressed in the cell membrane. One broadly applicable manifestation of this approach are covalently attached photochromic tethered ligands (PTLs) that allow activating ligand-gated ion channels with outstanding spatial and temporal resolution. Here, we describe all steps towards the successful development and application of PTL-gated ion channels in cell lines and primary cells. The basis for these experiments forms a combination of molecular modeling, genetic engineering, cell culture, and electrophysiology. The light-gated glutamate receptor (LiGluR), which consists of the PTL-functionalized GluK2 receptor, serves as a model. AU - Szobota, Stephanie AU - Mckenzie, Catherine AU - Janovjak, Harald L ID - 2857 JF - Methods in Molecular Biology TI - Optical control of ligand-gated ion channels VL - 998 ER - TY - JOUR AB - In the hippocampus, cell assemblies forming mnemonic representations of space are thought to arise as a result of changes in functional connections of pyramidal cells. We have found that CA1 interneuron circuits are also reconfigured during goal-oriented spatial learning through modification of inputs from pyramidal cells. As learning progressed, new pyramidal assemblies expressed in theta cycles alternated with previously established ones, and eventually overtook them. The firing patterns of interneurons developed a relationship to new, learning-related assemblies: some interneurons associated their activity with new pyramidal assemblies while some others dissociated from them. These firing associations were explained by changes in the weight of monosynaptic inputs received by interneurons from new pyramidal assemblies, as these predicted the associational changes. Spatial learning thus engages circuit modifications in the hippocampus that incorporate a redistribution of inhibitory activity that might assist in the segregation of competing pyramidal cell assembly patterns in space and time. AU - Dupret, David AU - O'Neill, Joseph AU - Csicsvari, Jozsef L ID - 2860 IS - 1 JF - Neuron TI - Dynamic reconfiguration of hippocampal interneuron circuits during spatial learning VL - 78 ER - TY - JOUR AB - Genomic imprinting leads to preferred expression of either the maternal or paternal alleles of a subset of genes. Imprinting is essential for mammalian development, and its deregulation causes many diseases. However, the functional relevance of imprinting at the cellular level is poorly understood for most imprinted genes. We used mosaic analysis with double markers (MADM) in mice to create uniparental disomies (UPDs) and to visualize imprinting effects with single-cell resolution. Although chromosome 12 UPD did not produce detectable phenotypes, chromosome 7 UPD caused highly significant paternal growth dominance in the liver and lung, but not in the brain or heart. A single gene on chromosome 7, encoding the secreted insulin-like growth factor 2 (IGF2), accounts for most of the paternal dominance effect. Mosaic analyses implied additional imprinted loci on chromosome 7 acting cell autonomously to transmit the IGF2 signal. Our study reveals chromosome- and cell-type specificity of genomic imprinting effects. AU - Hippenmeyer, Simon AU - Johnson, Randy AU - Luo, Liqun ID - 2855 IS - 3 JF - Cell Reports TI - Mosaic analysis with double markers reveals cell type specific paternal growth dominance VL - 3 ER - TY - JOUR AB - G protein–coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering of native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized mGluRs (LimGluRs). The light-agonized LimGluR2, on which we focused, was fast, bistable and supported multiple rounds of on/off switching. Light gated two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. We found that the light-antagonized tool LimGluR2-block was able to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalized the optical control to two additional family members: mGluR3 and mGluR6. This system worked in rodent brain slices and in zebrafish in vivo, where we found that mGluR2 modulated the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease. AU - Levitz, Joshua AU - Pantoja, Carlos AU - Gaub, Benjamin AU - Janovjak, Harald L AU - Reiner, Andreas AU - Hoagland, Adam AU - Schoppik, David AU - Kane, Brian AU - Stawski, Philipp AU - Schier, Alexander AU - Trauner, Dirk AU - Isacoff, Ehud ID - 2856 JF - Nature Neuroscience TI - Optical control of metabotropic glutamate receptors VL - 16 ER - TY - JOUR AB - Given a continuous function f:X-R on a topological space, we consider the preimages of intervals and their homology groups and show how to read the ranks of these groups from the extended persistence diagram of f. In addition, we quantify the robustness of the homology classes under perturbations of f using well groups, and we show how to read the ranks of these groups from the same extended persistence diagram. The special case X=R3 has ramifications in the fields of medical imaging and scientific visualization. AU - Bendich, Paul AU - Edelsbrunner, Herbert AU - Morozov, Dmitriy AU - Patel, Amit ID - 2859 IS - 1 JF - Homology, Homotopy and Applications TI - Homology and robustness of level and interlevel sets VL - 15 ER - TY - JOUR AB - Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. For large populations, direct sampling of these distributions is impossible, and so we must rely on constructing appropriate models. We show here that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. We introduce the stimulus-dependent maximum entropy (SDME) model—a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. We find that the SDME model gives a more accurate account of single cell responses and in particular significantly outperforms uncoupled models in reproducing the distributions of population codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like average surprise and information transmission in a neural population. AU - Granot Atedgi, Einat AU - Tkacik, Gasper AU - Segev, Ronen AU - Schneidman, Elad ID - 2863 IS - 3 JF - PLoS Computational Biology TI - Stimulus-dependent maximum entropy models of neural population codes VL - 9 ER - TY - JOUR AB - Motile cilia perform crucial functions during embryonic development and throughout adult life. Development of organs containing motile cilia involves regulation of cilia formation (ciliogenesis) and formation of a luminal space (lumenogenesis) in which cilia generate fluid flows. Control of ciliogenesis and lumenogenesis is not yet fully understood, and it remains unclear whether these processes are coupled. In the zebrafish embryo, lethal giant larvae 2 (lgl2) is expressed prominently in ciliated organs. Lgl proteins are involved in establishing cell polarity and have been implicated in vesicle trafficking. Here, we identified a role for Lgl2 in development of ciliated epithelia in Kupffer's vesicle, which directs left-right asymmetry of the embryo; the otic vesicles, which give rise to the inner ear; and the pronephric ducts of the kidney. Using Kupffer's vesicle as a model ciliated organ, we found that depletion of Lgl2 disrupted lumen formation and reduced cilia number and length. Immunofluorescence and time-lapse imaging of Kupffer's vesicle morphogenesis in Lgl2-deficient embryos suggested cell adhesion defects and revealed loss of the adherens junction component E-cadherin at lateral membranes. Genetic interaction experiments indicate that Lgl2 interacts with Rab11a to regulate E-cadherin and mediate lumen formation that is uncoupled from cilia formation. These results uncover new roles and interactions for Lgl2 that are crucial for both lumenogenesis and ciliogenesis and indicate that these processes are genetically separable in zebrafish. AU - Tay, Hwee AU - Schulze, Sabrina AU - Compagnon, Julien AU - Foley, Fiona AU - Heisenberg, Carl-Philipp J AU - Yost, H Joseph AU - Abdelilah Seyfried, Salim AU - Amack, Jeffrey ID - 2862 IS - 7 JF - Development TI - Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle VL - 140 ER - TY - JOUR AB - We consider a two-parameter family of piecewise linear maps in which the moduli of the two slopes take different values. We provide numerical evidence of the existence of some parameter regions in which the Lyapunov exponent and the topological entropy remain constant. Analytical proof of this phenomenon is also given for certain cases. Surprisingly however, the systems with that property are not conjugate as we prove by using kneading theory. AU - Botella Soler, Vicente AU - Oteo, José AU - Ros, Javier AU - Glendinning, Paul ID - 2861 IS - 12 JF - Journal of Physics A: Mathematical and Theoretical TI - Lyapunov exponent and topological entropy plateaus in piecewise linear maps VL - 46 ER - TY - JOUR AB - Premise of the study: To reach favorable conditions for photosynthesis, seedlings grow upward when deprived of light upon underground germination. To direct their growth, they use their negative gravitropic capacity. Negative gravitropism is under tight control of multiple hormones. • Methods: By counting the number of standing plants in a population or by real time monitoring of the reorientation of gravistimulated seedlings of Arabidopsis thaliana, we evaluated the negative gravitropism of ethylene or brassinosteroid (BR) treated plants. Meta-analysis of transcriptomic data on AUX / IAA genes was gathered, and subsequent mutant analysis was performed. • Key results: Ethylene and BR have opposite effects in regulating shoot gravitropism. Lack of BR enhances gravitropic reorientation in 2-d-old seedlings, whereas ethylene does not. Lack of ethylene signaling results in enhanced BR sensitivity. Ethylene and BRs regulate overlapping sets of AUX / IAA genes. BRs regulate a wider range of auxin signaling components than ethylene. • Conclusions: Upward growth in seedlings depends strongly on the internal hormonal balance. Endogenous ethylene stimulates, whereas BRs reduce negative gravitropism in a manner that depends on the function of different, yet overlapping sets of auxin signaling components. AU - Vandenbussche, Filip AU - Callebert, Pieter AU - Žádníková, Petra AU - Eva Benková AU - Van Der Straeten, Dominique ID - 2877 IS - 1 JF - American Journal of Botany TI - Brassinosteroid control of shoot gravitropism interacts with ethylene and depends on auxin signaling components VL - 100 ER - TY - JOUR AB - Plant architecture is influenced by the polar, cell-to-cell transport of auxin that is primarily provided and regulated by plasma membrane efflux catalysts of the PIN-FORMED and B family of ABC transporter (ABCB) classes. The latter were shown to require the functionality of the FK506 binding protein42 TWISTED DWARF1 (TWD1), although underlying mechanisms are unclear. By genetic manipulation of TWD1 expression, we show here that TWD1 affects shootward root auxin reflux and, thus, downstream developmental traits, such as epidermal twisting and gravitropism of the root. Using immunological assays, we demonstrate a predominant lateral, mainly outward-facing, plasma membrane location for TWD1 in the root epidermis characterized by the lateral marker ABC transporter G36/PLEIOTROPIC DRUG-RESISTANCE8/PENETRATION3. At these epidermal plasma membrane domains, TWD1 colocalizes with nonpolar ABCB1. In planta bioluminescence resonance energy transfer analysis was used to verify specific ABC transporter B1 (ABCB1)-TWD1 interaction. Our data support a model in which TWD1 promotes lateral ABCB-mediated auxin efflux via protein-protein interaction at the plasma membrane, minimizing reflux from the root apoplast into the cytoplasm. AU - Wang, Bangjun AU - Bailly, Aurélien AU - Zwiewk, Marta AU - Henrichs, Sina AU - Azzarello, Elisa AU - Mancuso, Stefano AU - Maeshima, Masayoshi AU - Friml, Jirí AU - Schulz, Alexander AU - Geisler, Markus ID - 2883 IS - 1 JF - Plant Cell TI - Arabidopsis TWISTED DWARF1 functionally interacts with auxin exporter ABCB1 on the root plasma membrane VL - 25 ER - TY - JOUR AB - Lateral root (LR) formation is initiated when pericycle cells accumulate auxin, thereby acquiring founder cell (FC) status and triggering asymmetric cell divisions, giving rise to a new primordium. How this auxin maximum in pericycle cells builds up and remains focused is not understood. We report that the endodermis plays an active role in the regulation of auxin accumulation and is instructive for FCs to progress during the LR initiation (LRI) phase. We describe the functional importance of a PIN3 (PIN-formed) auxin efflux carrier-dependent hormone reflux pathway between overlaying endodermal and pericycle FCs. Disrupting this reflux pathway causes dramatic defects in the progress of FCs towards the next initiation phase. Our data identify an unexpected regulatory function for the endodermis in LRI as part of the fine-tuning mechanism that appears to act as a check point in LR organogenesis after FCs are specified. AU - Marhavy, Peter AU - Vanstraelen, Marleen AU - De Rybel, Bert AU - Zhaojun, Ding AU - Bennett, Malcolm AU - Beeckman, Tom AU - Benková, Eva ID - 2880 IS - 1 JF - EMBO Journal TI - Auxin reflux between the endodermis and pericycle promotes lateral root initiation VL - 32 ER - TY - JOUR AB - Gravitropic bending of plant organs is mediated by an asymmetric signaling of the plant hormone auxin between the upper and lower side of the respective organ. Here, we show that also another plant hormone, gibberellic acid (GA), shows asymmetric action during gravitropic responses. Immunodetection using an antibody against GA and monitoring GA signaling output by downstream degradation of DELLA proteins revealed an asymmetric GA distribution and response with the maximum at the lower side of gravistimulated roots. Genetic or pharmacological manipulation of GA levels or response affects gravity-mediated auxin redistribution and root bending response. The higher GA levels at the lower side of the root correlate with increased amounts of PIN-FORMED2 (PIN2) auxin transporter at the plasma membrane. The observed increase in PIN2 stability is caused by a specific GA effect on trafficking of PIN proteins to lytic vacuoles that presumably occurs downstream of brefeldin A-sensitive endosomes. Our results suggest that asymmetric auxin distribution instructive for gravity-induced differential growth is consolidated by the asymmetric action of GA that stabilizes the PIN-dependent auxin stream along the lower side of gravistimulated roots. AU - Löfke, Christian AU - Zwiewka, Marta AU - Heilmann, Ingo AU - Van Montagu, Marc AU - Teichmann, Thomas AU - Friml, Jirí ID - 2882 IS - 9 JF - PNAS TI - Asymmetric gibberellin signaling regulates vacuolar trafficking of PIN auxin transporters during root gravitropism VL - 110 ER - TY - GEN AB - This volume contains the post-proceedings of the 8th Doctoral Workshop on Mathematical and Engineering Methods in Computer Science, MEMICS 2012, held in Znojmo, Czech Republic, in October, 2012. The 13 thoroughly revised papers were carefully selected out of 31 submissions and are presented together with 6 invited papers. The topics covered by the papers include: computer-aided analysis and verification, applications of game theory in computer science, networks and security, modern trends of graph theory in computer science, electronic systems design and testing, and quantum information processing. ED - Kucera, Antonin ED - Henzinger, Thomas A ED - Nesetril, Jaroslav ED - Vojnar, Tomas ED - Antos, David ID - 2885 TI - Mathematical and Engineering Methods in Computer Science VL - 7721 ER - TY - JOUR AB - The puzzle piece-shaped Arabidopsis leaf pavement cells (PCs) with interdigitated lobes and indents is a good model system to investigate the mechanisms that coordinate cell polarity and shape formation within a tissue. Auxin has been shown to coordinate the interdigitation by activating ROP GTPase-dependent signaling pathways. To identify additional components or mechanisms, we screened for mutants with abnormal PC morphogenesis and found that cytokinin signaling regulates the PC interdigitation pattern. Reduction in cytokinin accumulation and defects in cytokinin signaling (such as in ARR7-over-expressing lines, the ahk3cre1 cytokinin receptor mutant, and the ahp12345 cytokinin signaling mutant) enhanced PC interdigitation, whereas over-production of cytokinin and over-activation of cytokinin signaling in an ARR20 over-expression line delayed or abolished PC interdigitation throughout the cotyledon. Genetic and biochemical analyses suggest that cytokinin signaling acts upstream of ROPs to suppress the formation of interdigitated pattern. Our results provide novel mechanistic understanding of the pathways controlling PC shape and uncover a new role for cytokinin signaling in cell morphogenesis. AU - Hongjiang Li AU - Xu, Tongda AU - Lin, Deshu AU - Wen, Mingzhang AU - Xie, Mingtang AU - Duclercq, Jérôme AU - Bielach, Agnieszka AU - Kim, Jungmook AU - Reddy, G Venugopala AU - Zuo, Jianru AU - Eva Benková AU - Jirí Friml AU - Guo, Hongwei AU - Yang, Zhenbiao ID - 2881 IS - 2 JF - Cell Research TI - Cytokinin signaling regulates pavement cell morphogenesis in Arabidopsis VL - 23 ER - TY - JOUR 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 - 2884 IS - 2 JF - Medecine Sciences TI - Cell adhesion mechanics of zebrafish gastrulation VL - 29 ER - TY - CONF AB - We focus on the realizability problem of Message Sequence Graphs (MSG), i.e. the problem whether a given MSG specification is correctly distributable among parallel components communicating via messages. This fundamental problem of MSG is known to be undecidable. We introduce a well motivated restricted class of MSG, so called controllable-choice MSG, and show that all its models are realizable and moreover it is decidable whether a given MSG model is a member of this class. In more detail, this class of MSG specifications admits a deadlock-free realization by overloading existing messages with additional bounded control data. We also show that the presented class is the largest known subclass of MSG that allows for deadlock-free realization. AU - Chmelik, Martin AU - Řehák, Vojtěch ID - 2886 TI - Controllable-choice message sequence graphs VL - 7721 ER - TY - JOUR AB - Root system growth and development is highly plastic and is influenced by the surrounding environment. Roots frequently grow in heterogeneous environments that include interactions from neighboring plants and physical impediments in the rhizosphere. To investigate how planting density and physical objects affect root system growth, we grew rice in a transparent gel system in close proximity with another plant or a physical object. Root systems were imaged and reconstructed in three dimensions. Root-root interaction strength was calculated using quantitative metrics that characterize the extent towhich the reconstructed root systems overlap each other. Surprisingly, we found the overlap of root systems of the same genotype was significantly higher than that of root systems of different genotypes. Root systems of the same genotype tended to grow toward each other but those of different genotypes appeared to avoid each other. Shoot separation experiments excluded the possibility of aerial interactions, suggesting root communication. Staggered plantings indicated that interactions likely occur at root tips in close proximity. Recognition of obstacles also occurred through root tips, but through physical contact in a size-dependent manner. These results indicate that root systems use two different forms of communication to recognize objects and alter root architecture: root-root recognition, possibly mediated through root exudates, and root-object recognition mediated by physical contact at the root tips. This finding suggests that root tips act as local sensors that integrate rhizosphere information into global root architectural changes. AU - Fang, Suqin AU - Clark, Randy AU - Zheng, Ying AU - Iyer Pascuzzi, Anjali AU - Weitz, Joshua AU - Kochian, Leon AU - Edelsbrunner, Herbert AU - Liao, Hong AU - Benfey, Philip ID - 2887 IS - 7 JF - PNAS TI - Genotypic recognition and spatial responses by rice roots VL - 110 ER - TY - CONF AB - We introduce the M-modes problem for graphical models: predicting the M label configurations of highest probability that are at the same time local maxima of the probability landscape. M-modes have multiple possible applications: because they are intrinsically diverse, they provide a principled alternative to non-maximum suppression techniques for structured prediction, they can act as codebook vectors for quantizing the configuration space, or they can form component centers for mixture model approximation. We present two algorithms for solving the M-modes problem. The first algorithm solves the problem in polynomial time when the underlying graphical model is a simple chain. The second algorithm solves the problem for junction chains. In synthetic and real dataset, we demonstrate how M-modes can improve the performance of prediction. We also use the generated modes as a tool to understand the topography of the probability distribution of configurations, for example with relation to the training set size and amount of noise in the data. AU - Chen, Chao AU - Kolmogorov, Vladimir AU - Yan, Zhu AU - Metaxas, Dimitris AU - Lampert, Christoph ID - 2901 TI - Computing the M most probable modes of a graphical model VL - 31 ER - TY - JOUR AU - Azevedo, Ricardo B AU - Lohaus, Rolf AU - Tiago Paixao ID - 2900 IS - 5 JF - Evolution & Development TI - Networking networks VL - 10 ER - TY - CONF AB - Motivated by an application in cell biology, we describe an extension of the kinetic data structures framework from Delaunay triangulations to fixed-radius alpha complexes. Our algorithm is implemented using CGAL, following the exact geometric computation paradigm. We report on several techniques to accelerate the computation that turn our implementation applicable to the underlying biological problem. AU - Kerber, Michael AU - Edelsbrunner, Herbert ID - 2906 T2 - 2013 Proceedings of the 15th Workshop on Algorithm Engineering and Experiments TI - 3D kinetic alpha complexes and their implementation ER - TY - JOUR AB - Coalescent simulation has become an indispensable tool in population genetics and many complex evolutionary scenarios have been incorporated into the basic algorithm. Despite many years of intense interest in spatial structure, however, there are no available methods to simulate the ancestry of a sample of genes that occupy a spatial continuum. This is mainly due to the severe technical problems encountered by the classical model of isolation by distance. A recently introduced model solves these technical problems and provides a solid theoretical basis for the study of populations evolving in continuous space. We present a detailed algorithm to simulate the coalescent process in this model, and provide an efficient implementation of a generalised version of this algorithm as a freely available Python module. AU - Kelleher, Jerome AU - Barton, Nicholas H AU - Etheridge, Alison ID - 2910 IS - 7 JF - Bioinformatics TI - Coalescent simulation in continuous space VL - 29 ER - TY - JOUR AB - We survey a class of models for spatially structured populations which we have called spatial Λ-Fleming–Viot processes. They arise from a flexible framework for modelling in which the key innovation is that random genetic drift is driven by a Poisson point process of spatial ‘events’. We demonstrate how this overcomes some of the obstructions to modelling populations which evolve in two- (and higher-) dimensional spatial continua, how its predictions match phenomena observed in data and how it fits with classical models. Finally we outline some directions for future research. AU - Barton, Nicholas H AU - Etheridge, Alison AU - Véber, Amandine ID - 2909 IS - 1 JF - Journal of Statistical Mechanics Theory and Experiment TI - Modelling evolution in a spatial continuum VL - 2013 ER - TY - JOUR AB - Hybridization is an almost inevitable component of speciation, and its study can tell us much about that process. However, hybridization itself may have a negligible influence on the origin of species: on the one hand, universally favoured alleles spread readily across hybrid zones, whilst on the other, spatially heterogeneous selection causes divergence despite gene flow. Thus, narrow hybrid zones or occasional hybridisation may hardly affect the process of divergence. AU - Barton, Nicholas H ID - 2908 IS - 2 JF - Journal of Evolutionary Biology TI - Does hybridisation influence speciation? VL - 26 ER - TY - CHAP AB - Sex and recombination are among the most striking features of the living world, and they play a crucial role in allowing the evolution of complex adaptation. The sharing of genomes through the sexual union of different individuals requires elaborate behavioral and physiological adaptations. At the molecular level, the alignment of two DNA double helices, followed by their precise cutting and rejoining, is an extraordinary feat. Sex and recombination have diverse—and often surprising—evolutionary consequences: distinct sexes, elaborate mating displays, selfish genetic elements, and so on. AU - Barton, Nicholas H ID - 2907 SN - 9780691149776 T2 - The Princeton Guide to Evolution TI - Recombination and sex ER - TY - JOUR AB - The ability of an organism to distinguish between various stimuli is limited by the structure and noise in the population code of its sensory neurons. Here we infer a distance measure on the stimulus space directly from the recorded activity of 100 neurons in the salamander retina. In contrast to previously used measures of stimulus similarity, this "neural metric" tells us how distinguishable a pair of stimulus clips is to the retina, based on the similarity between the induced distributions of population responses. We show that the retinal distance strongly deviates from Euclidean, or any static metric, yet has a simple structure: we identify the stimulus features that the neural population is jointly sensitive to, and show the support-vector-machine- like kernel function relating the stimulus and neural response spaces. We show that the non-Euclidean nature of the retinal distance has important consequences for neural decoding. AU - Tkacik, Gasper AU - Granot Atedgi, Einat AU - Segev, Ronen AU - Schneidman, Elad ID - 2913 IS - 5 JF - Physical Review Letters TI - Retinal metric: a stimulus distance measure derived from population neural responses VL - 110 ER - TY - JOUR AB - Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis. AU - Castanon, Irinka AU - Abrami, Laurence AU - Holtzer, Laurent AU - Heisenberg, Carl-Philipp J AU - Van Der Goot, Françoise AU - González Gaitán, Marcos ID - 2918 IS - 1 JF - Nature Cell Biology TI - Anthrax toxin receptor 2a controls mitotic spindle positioning VL - 15 ER - TY - JOUR AB - The distribution of the phytohormone auxin regulates many aspects of plant development including growth response to gravity. Gravitropic root curvature involves coordinated and asymmetric cell elongation between the lower and upper side of the root, mediated by differential cellular auxin levels. The asymmetry in the auxin distribution is established and maintained by a spatio-temporal regulation of the PIN-FORMED (PIN) auxin transporter activity. We provide novel insights into the complex regulation of PIN abundance and activity during root gravitropism. We show that PIN2 turnover is differentially regulated on the upper and lower side of gravistimulated roots by distinct but partially overlapping auxin feedback mechanisms. In addition to regulating transcription and clathrin-mediated internalization, auxin also controls PIN abundance at the plasma membrane by promoting their vacuolar targeting and degradation. This effect of elevated auxin levels requires the activity of SKP-Cullin-F-box TIR1/AFB (SCF TIR1/AFB)-dependent pathway. Importantly, also suboptimal auxin levels mediate PIN degradation utilizing the same signalling pathway. These feedback mechanisms are functionally important during gravitropic response and ensure fine-tuning of auxin fluxes for maintaining as well as terminating asymmetric growth. AU - Baster, Pawel AU - Robert, Stéphanie AU - Kleine Vehn, Jürgen AU - Vanneste, Steffen AU - Kania, Urszula AU - Grunewald, Wim AU - De Rybel, Bert AU - Beeckman, Tom AU - Friml, Jirí ID - 2919 IS - 2 JF - EMBO Journal TI - SCF^TIR1 AFB-auxin signalling regulates PIN vacuolar trafficking and auxin fluxes during root gravitropism VL - 32 ER - TY - JOUR AB - Cell polarisation in development is a common and fundamental process underlying embryo patterning and morphogenesis, and has been extensively studied over the past years. Our current knowledge of cell polarisation in development is predominantly based on studies that have analysed polarisation of single cells, such as eggs, or cellular aggregates with a stable polarising interface, such as cultured epithelial cells (St Johnston and Ahringer, 2010). However, in embryonic development, particularly of vertebrates, cell polarisation processes often encompass large numbers of cells that are placed within moving and proliferating tissues, and undergo mesenchymal-to-epithelial transitions with a highly complex spatiotemporal choreography. How such intricate cell polarisation processes in embryonic development are achieved has only started to be analysed. By using live imaging of neurulation in the transparent zebrafish embryo, Buckley et al (2012) now describe a novel polarisation strategy by which cells assemble an apical domain in the part of their cell body that intersects with the midline of the forming neural rod. This mechanism, along with the previously described mirror-symmetric divisions (Tawk et al, 2007), is thought to trigger formation of both neural rod midline and lumen. AU - Compagnon, Julien AU - Heisenberg, Carl-Philipp J ID - 2920 IS - 1 JF - EMBO Journal TI - Neurulation coordinating cell polarisation and lumen formation VL - 32 ER - TY - CONF AB - A chain rule for an entropy notion H(.) states that the entropy H(X) of a variable X decreases by at most l if conditioned on an l-bit string A, i.e., H(X|A)>= H(X)-l. More generally, it satisfies a chain rule for conditional entropy if H(X|Y,A)>= H(X|Y)-l. All natural information theoretic entropy notions we are aware of (like Shannon or min-entropy) satisfy some kind of chain rule for conditional entropy. Moreover, many computational entropy notions (like Yao entropy, unpredictability entropy and several variants of HILL entropy) satisfy the chain rule for conditional entropy, though here not only the quantity decreases by l, but also the quality of the entropy decreases exponentially in l. However, for the standard notion of conditional HILL entropy (the computational equivalent of min-entropy) the existence of such a rule was unknown so far. In this paper, we prove that for conditional HILL entropy no meaningful chain rule exists, assuming the existence of one-way permutations: there exist distributions X,Y,A, where A is a distribution over a single bit, but $H(X|Y)>>H(X|Y,A)$, even if we simultaneously allow for a massive degradation in the quality of the entropy. The idea underlying our construction is based on a surprising connection between the chain rule for HILL entropy and deniable encryption. AU - Krenn, Stephan AU - Pietrzak, Krzysztof Z AU - Wadia, Akshay ED - Sahai, Amit ID - 2940 TI - A counterexample to the chain rule for conditional HILL entropy, and what deniable encryption has to do with it VL - 7785 ER - TY - CONF AB - Many visual datasets are traditionally used to analyze the performance of different learning techniques. The evaluation is usually done within each dataset, therefore it is questionable if such results are a reliable indicator of true generalization ability. We propose here an algorithm to exploit the existing data resources when learning on a new multiclass problem. Our main idea is to identify an image representation that decomposes orthogonally into two subspaces: a part specific to each dataset, and a part generic to, and therefore shared between, all the considered source sets. This allows us to use the generic representation as un-biased reference knowledge for a novel classification task. By casting the method in the multi-view setting, we also make it possible to use different features for different databases. We call the algorithm MUST, Multitask Unaligned Shared knowledge Transfer. Through extensive experiments on five public datasets, we show that MUST consistently improves the cross-datasets generalization performance. AU - Tommasi, Tatiana AU - Quadrianto, Novi AU - Caputo, Barbara AU - Lampert, Christoph ID - 2948 TI - Beyond dataset bias: Multi-task unaligned shared knowledge transfer VL - 7724 ER - TY - CONF AB - Efficient zero-knowledge proofs of knowledge (ZK-PoK) are basic building blocks of many practical cryptographic applications such as identification schemes, group signatures, and secure multiparty computation. Currently, first applications that critically rely on ZK-PoKs are being deployed in the real world. The most prominent example is Direct Anonymous Attestation (DAA), which was adopted by the Trusted Computing Group (TCG) and implemented as one of the functionalities of the cryptographic Trusted Platform Module (TPM) chip. Implementing systems using ZK-PoK turns out to be challenging, since ZK-PoK are, loosely speaking, significantly more complex than standard crypto primitives, such as encryption and signature schemes. As a result, implementation cycles of ZK-PoK are time-consuming and error-prone, in particular for developers with minor or no cryptographic skills. In this paper we report on our ongoing and future research vision with the goal to bring ZK-PoK to practice by making them accessible to crypto and security engineers. To this end we are developing compilers and related tools that support and partially automate the design, implementation, verification and secure implementation of ZK-PoK protocols. AU - Bangerter, Endre AU - Barzan, Stefania AU - Stephan Krenn AU - Sadeghi, Ahmad-Reza AU - Schneider, Thomas AU - Tsay, Joe-Kai ED - Christianson, Bruce ED - Malcolm, James A. ED - Matyas, Vashek ED - Roe, Michael ID - 2973 TI - Bringing Zero-Knowledge Proofs of Knowledge to Practice VL - 7028 ER - TY - JOUR AB - Multithreaded programs coordinate their interaction through synchronization primitives like mutexes and semaphores, which are managed by an OS-provided resource manager. We propose algorithms for the automatic construction of code-aware resource managers for multithreaded embedded applications. Such managers use knowledge about the structure and resource usage (mutex and semaphore usage) of the threads to guarantee deadlock freedom and progress while managing resources in an efficient way. Our algorithms compute managers as winning strategies in certain infinite games, and produce a compact code description of these strategies. We have implemented the algorithms in the tool Cynthesis. Given a multithreaded program in C, the tool produces C code implementing a code-aware resource manager. We show in experiments that Cynthesis produces compact resource managers within a few minutes on a set of embedded benchmarks with up to 6 threads. © 2012 Springer Science+Business Media, LLC. AU - Chatterjee, Krishnendu AU - De Alfaro, Luca AU - Faella, Marco AU - Majumdar, Ritankar AU - Raman, Vishwanath ID - 3116 IS - 2 JF - Formal Methods in System Design TI - Code aware resource management VL - 42 ER - TY - JOUR AB - The fact that a sum of isotropic Gaussian kernels can have more modes than kernels is surprising. Extra (ghost) modes do not exist in ℝ1 and are generally not well studied in higher dimensions. We study a configuration of n+1 Gaussian kernels for which there are exactly n+2 modes. We show that all modes lie on a finite set of lines, which we call axes, and study the restriction of the Gaussian mixture to these axes in order to discover that there are an exponential number of critical points in this configuration. Although the existence of ghost modes remained unknown due to the difficulty of finding examples in ℝ2, we show that the resilience of ghost modes grows like the square root of the dimension. In addition, we exhibit finite configurations of isotropic Gaussian kernels with superlinearly many modes. AU - Edelsbrunner, Herbert AU - Fasy, Brittany Terese AU - Rote, Günter ID - 2815 IS - 4 JF - Discrete & Computational Geometry SN - 0179-5376 TI - Add isotropic Gaussian kernels at own risk: More and more resilient modes in higher dimensions VL - 49 ER - TY - JOUR AB - In this paper, we present the first output-sensitive algorithm to compute the persistence diagram of a filtered simplicial complex. For any Γ > 0, it returns only those homology classes with persistence at least Γ. Instead of the classical reduction via column operations, our algorithm performs rank computations on submatrices of the boundary matrix. For an arbitrary constant δ ∈ (0, 1), the running time is O (C (1 - δ) Γ R d (n) log n), where C (1 - δ) Γ is the number of homology classes with persistence at least (1 - δ) Γ, n is the total number of simplices in the complex, d its dimension, and R d (n) is the complexity of computing the rank of an n × n matrix with O (d n) nonzero entries. Depending on the choice of the rank algorithm, this yields a deterministic O (C (1 - δ) Γ n 2.376) algorithm, an O (C (1 - δ) Γ n 2.28) Las-Vegas algorithm, or an O (C (1 - δ) Γ n 2 + ε{lunate}) Monte-Carlo algorithm for an arbitrary ε{lunate} > 0. The space complexity of the Monte-Carlo version is bounded by O (d n) = O (n log n). AU - Chen, Chao AU - Kerber, Michael ID - 2939 IS - 4 JF - Computational Geometry: Theory and Applications TI - An output sensitive algorithm for persistent homology VL - 46 ER - TY - JOUR AB - Copper-based selenides are attracting increasing interest due to their outstanding optoelectronic and thermoelectric properties. Herein a novel colloidal synthetic route to prepare Cu2SnSe3 nanocrystals with controlled size, shape and composition is presented. The high yield of the developed procedure allowed its up-scaling to the production of grams of colloidal Cu2SnSe3 nanocrystals. These nanocrystals were used as building blocks for the production of Cu2SnSe3 bulk nanostructured materials by spark plasma sintering. The thermoelectric properties of the prepared nanocrystalline Cu2SnSe3 pellets were characterized in the temperature range from 300 to 720 K. The obtained results show the bottom-up production of nanocrystalline materials from solution-processed nanocrystals to be a potentially advantageous alternative to conventional methods of production of efficient thermoelectric materials. AU - Ibáñez, Maria AU - Cadavid, Doris AU - Anselmi Tamburini, Umberto AU - Zamani, Reza AU - Gorsse, Stéphane AU - Li, Wenhua AU - López, Antonio AU - Morante, Joan AU - Arbiol, Jordi AU - Cabot, Andreu ID - 344 IS - 4 JF - Journal of Materials Chemistry A TI - Colloidal synthesis and thermoelectric properties of Cu 2SnSe3 nanocrystals VL - 1 ER - TY - JOUR AB - The presence of organic ligands on the surface of colloidal nanoparticles strongly limits their performance in technological applications where charge carrier transfer/transport plays an important role. We use metal salts, matched with the nanoparticle composition, to eliminate the surface organic ligands without introducing extrinsic impurities in the final nanomaterial. The potential of the simple, general and scalable processes presented here is demonstrated by characterizing the thermoelectric properties of nanostructured Ag2Te produced by the bottom up assembly of Ag2Te nanocrystals. A 6-fold increase of the thermoelectric figure of merit of Ag2Te was obtained when organic ligands were displaced by AgNO3. The same procedure can enhance the performance of nanocrystals and nanocrystal-based devices in a broad range of applications, from photovoltaics and thermoelectrics to catalysis. AU - Cadavid, Doris AU - Ibáñez, Maria AU - Shavel, Alexey AU - Durá, Oscar AU - López De La Torre, Marco AU - Cabot, Andreu ID - 352 IS - 15 JF - Journal of Materials Chemistry A TI - Organic ligand displacement by metal salts to enhance nanoparticle functionality: Thermoelectric properties of Ag inf 2 inf Te VL - 1 ER - TY - JOUR AB - Until recently, to prepare nanocrystals of a new material, scientists searched their shelves for the appropriate molecular precursors, surfactants, and solvents. They then optimized the reaction conditions for the atoms to self-assemble into monodisperse nanocrystals (1). This approach is being replaced by a simpler strategy, in which preformed nanocrystals serve as templates to produce nanoparticles with a different composition through chemical transformation. On page 964 of this issue, Oh et al. (2) report a powerful mechanism that allows the composition of oxide nanoparticles to be transformed in solution and at low temperatures. AU - Ibáñez, Maria AU - Cabot, Andreu ID - 378 IS - 6135 JF - Science TI - All change for nanocrystals VL - 340 ER - TY - JOUR AB - Cells in a developing embryo have no direct way of "measuring" their physical position. Through a variety of processes, however, the expression levels of multiple genes come to be correlated with position, and these expression levels thus form a code for "positional information." We show how to measure this information, in bits, using the gap genes in the Drosophila embryo as an example. Individual genes carry nearly two bits of information, twice as much as expected if the expression patterns consisted only of on/off domains separated by sharp boundaries. Taken together, four gap genes carry enough information to define a cell's location with an error bar of ~1% along the anterior-posterior axis of the embryo. This precision is nearly enough for each cell to have a unique identity, which is the maximum information the system can use, and is nearly constant along the length of the embryo. We argue that this constancy is a signature of optimality in the transmission of information from primary morphogen inputs to the output of the gap gene network. AU - Dubuis, Julien AU - Tkacik, Gasper AU - Wieschaus, Eric AU - Gregor, Thomas AU - Bialek, William ID - 3261 IS - 41 JF - PNAS TI - Positional information, in bits VL - 110 ER - TY - JOUR AB - We report a procedure to prepare highly monodisperse copper telluride nanocubes, nanoplates, and nanorods. The procedure is based on the reaction of a copper salt with trioctylphosphine telluride in the presence of lithium bis(trimethylsilyl)amide and oleylamine. CuTe nanocrystals display a strong near-infrared optical absorption associated with localized surface plasmon resonances. We exploit this plasmon resonance for the design of surface-enhanced Raman scattering sensors for unconventional optical probes. Furthermore, we also report here our preliminary analysis of the use of CuTe nanocrystals as cytotoxic and photothermal agents. AU - Li, Wenhua AU - Zamani, Reza AU - Rivera Gil, Pilar AU - Pelaz, Beatriz AU - Ibáñez, Maria AU - Cadavid, Doris AU - Shavel, Alexey AU - Alvarez Puebla, Ramon AU - Parak, Wolfgang AU - Arbiol, Jordi AU - Cabot, Andreu ID - 331 IS - 19 JF - Journal of the American Chemical Society TI - CuTe nanocrystals: Shape and size control, plasmonic properties, and use as SERS probes and photothermal agents VL - 135 ER - TY - GEN AU - Quadrianto, Novi AU - Lampert, Christoph ED - Dubitzky, Werner ED - Wolkenhauer, Olaf ED - Cho, Kwang ED - Yokota, Hiroki ID - 3321 T2 - Encyclopedia of Systems Biology TI - Kernel based learning VL - 3 ER - TY - JOUR AB - We consider Markov decision processes (MDPs) with Büchi (liveness) objectives. We consider the problem of computing the set of almost-sure winning states from where the objective can be ensured with probability 1. Our contributions are as follows: First, we present the first subquadratic symbolic algorithm to compute the almost-sure winning set for MDPs with Büchi objectives; our algorithm takes O(n · √ m) symbolic steps as compared to the previous known algorithm that takes O(n 2) symbolic steps, where n is the number of states and m is the number of edges of the MDP. In practice MDPs have constant out-degree, and then our symbolic algorithm takes O(n · √ n) symbolic steps, as compared to the previous known O(n 2) symbolic steps algorithm. Second, we present a new algorithm, namely win-lose algorithm, with the following two properties: (a) the algorithm iteratively computes subsets of the almost-sure winning set and its complement, as compared to all previous algorithms that discover the almost-sure winning set upon termination; and (b) requires O(n · √ K) symbolic steps, where K is the maximal number of edges of strongly connected components (scc's) of the MDP. The win-lose algorithm requires symbolic computation of scc's. Third, we improve the algorithm for symbolic scc computation; the previous known algorithm takes linear symbolic steps, and our new algorithm improves the constants associated with the linear number of steps. In the worst case the previous known algorithm takes 5×n symbolic steps, whereas our new algorithm takes 4×n symbolic steps. AU - Chatterjee, Krishnendu AU - Henzinger, Monika H AU - Joglekar, Manas AU - Shah, Nisarg ID - 2831 IS - 3 JF - Formal Methods in System Design TI - Symbolic algorithms for qualitative analysis of Markov decision processes with Büchi objectives VL - 42 ER - TY - JOUR AB - Morphology is a key parameter in the design of novel nanocrystals and nanomaterials with controlled functional properties. Here, we demonstrate the potential of foreign metal ions to tune the morphology of colloidal semiconductor nanoparticles. We illustrate the underlying mechanism by preparing copper selenide nanocubes in the presence of Al ions. We further characterize the plasmonic properties of the obtained nanocrystals and demonstrate their potential as a platform to produce cubic nanoparticles with different composition by cation exchange. © 2013 American Chemical Society. AU - Li, Wenhua AU - Zamani, Reza AU - Ibáñez, Maria AU - Cadavid, Doris AU - Shavel, Alexey AU - Morante, Joan AU - Arbiol, Jordi AU - Cabot, Andreu ID - 342 IS - 12 JF - Journal of the American Chemical Society TI - Metal ions to control the morphology of semiconductor nanoparticles: Copper selenide nanocubes VL - 135 ER - TY - JOUR AB - The bottom-up assembly of nanocrystals provides access to a three-dimensional composition control at the nanoscale not attainable by any other technology. In particular, colloidal nanoheterostructures, with intrinsic multiphase organization, are especially appealing building blocks for the bottom-up production of nanocomposites. In the present work, we use PbTe-PbS as the model material system and thermoelectricity as the paradigmatic application to investigate the potential of the bottom-up assembly of core-shell nanoparticles to produce functional nanocomposites. With this goal in mind, a rapid, high-yield and scalable colloidal synthetic route to prepare grams of PbTe@PbS core-shell nanoparticles with unprecedented narrow size distributions and exceptional composition control is detailed. PbTe@PbS nanoparticles were used as building blocks for the bottom-up production of PbTe-PbS nanocomposites with tuned composition. In such PbTe-PbS nanocomposites, synergistic nanocrystal doping effects result in up to 10-fold higher electrical conductivities than in pure PbTe and PbS nanomaterials. At the same time, the acoustic impedance mismatch between PbTe and PbS phases and a partial phase alloying provide PbTe-PbS nanocomposites with strongly reduced thermal conductivities. As a result, record thermoelectric figures of merit (ZT) of ∼1.1 were obtained from undoped PbTe and PbS phases at 710 K. These high ZT values prove the potential of the proposed processes to produce efficient functional nanomaterials with programmable properties. © 2013 American Chemical Society. AU - Ibáñez, Maria AU - Zamani, Reza AU - Gorsse, Stéphane AU - Fan, Jiandong AU - Ortega, Silvia AU - Cadavid, Doris AU - Morante, Joan AU - Arbiol, Jordi AU - Cabot, Andreu ID - 343 IS - 3 JF - ACS Nano TI - Core shell nanoparticles as building blocks for the bottom-up production of functional nanocomposites: PbTe PbS thermoelectric properties VL - 7 ER - TY - JOUR AB - A multistrategy approach to overcome the main challenges of nanoparticle-based solution-processed Cu2ZnSnSe4 thin film solar cells is presented. We developed an efficient ligand exchange strategy, using an antimony salt, to displace organic ligands from the surface of Cu 2ZnSnS4 nanoparticles. An automated pulsed spray-deposition system was used to deposit the nanoparticles into homogeneous and crack-free films with controlled thickness. After annealing the film in a Se-rich atmosphere, carbon-free and crystalline Cu2ZnSnSe4 absorber layers were obtained. Not only was crystallization promoted by the complete removal of organics, but also Sb itself played a critical role. The Sb-assisted crystal growth is associated with the formation of a Sb-based compound at the grain boundaries, which locally reduces the melting point, thus promoting the film diffusion-limited crystallization. AU - Carrete, Alex AU - Shavel, Alexey AU - Fontané, Xavier AU - Montserrat, Joana AU - Fan, Jiandong AU - Ibáñez, Maria AU - Saucedo, Edgardo AU - Pérez Rodríguez, Alejandro AU - Cabot, Andreu ID - 351 IS - 43 JF - Journal of the American Chemical Society TI - Antimony-based ligand exchange to promote crystallization in spray-deposited Cu2ZnSnSe4 solar cells VL - 135 ER - TY - JOUR AB - We report a procedure to prepare highly monodisperse copper telluride nanocubes, nanoplates, and nanorods. The procedure is based on the reaction of a copper salt with trioctylphosphine telluride in the presence of lithium bis(trimethylsilyl)amide and oleylamine. CuTe nanocrystals display a strong near-infrared optical absorption associated with localized surface plasmon resonances. We exploit this plasmon resonance for the design of surface-enhanced Raman scattering sensors for unconventional optical probes. Furthermore, we also report here our preliminary analysis of the use of CuTe nanocrystals as cytotoxic and photothermal agents. AU - Li, Wenhua AU - Zamani, Reza AU - Rivera Gil, Pilar AU - Pelaz, Beatriz AU - Ibáñez, Maria AU - Cadavid, Doris AU - Shavel, Alexey AU - Alvarez Puebla, Ramon AU - Parak, Wolfgang AU - Arbiol, Jordi AU - Cabot, Andreu ID - 353 IS - 19 JF - Journal of the American Chemical Society TI - CuTe nanocrystals: Shape and size control, plasmonic properties, and use as SERS probes and photothermal agents VL - 135 ER - TY - JOUR AB - The compositional versatility of I2–II–IV–VI4 tetrahedrally-coordinated compounds allows for accommodating their functional properties to numerous technological applications. Among them, Cu2ZnSnSe4 is an emerging photovoltaic material and Cu2CdSnSe4 displays excellent thermoelectric properties. The third compound of this family, Cu2HgSnSe4, remains relatively unexplored. Herein, a synthetic route to produce Cu2HgSnSe4 nanoparticles with narrow size distribution and controlled composition is presented. Cu2HgSnSe4 nanoparticles were subsequently used as building blocks to produce bulk nanocrystalline materials, whose thermoelectric properties were analyzed. A very preliminary adjustment of the material composition yielded Seebeck coefficients up to 160 μV K−1, electrical conductivities close to 104 S m−1 and thermal conductivities down to 0.5 W m−1 K−1. AU - Li, Wenhua AU - Ibáñez, Maria AU - Zamani, Reza AU - García Castelló, Nuria AU - Stéphane, Grosse AU - Cadavid, Doris AU - Prades, Joan AU - Arbiol, Jordi AU - Cabot, Andreu ID - 376 JF - CrystEngComm TI - Cu2HgSnSe4 nanoparticles: synthesis and thermoelectric properties VL - 44 ER - TY - JOUR AB - Understanding the relative importance of heterosis and outbreeding depression over multiple generations is a key question in evolutionary biology and is essential for identifying appropriate genetic sources for population and ecosystem restoration. Here we use 2455 experimental crosses between 12 population pairs of the rare perennial plant Rutidosis leptorrhynchoides (Asteraceae) to investigate the multi-generational (F1, F2, F3) fitness outcomes of inter-population hybridization. We detected no evidence of outbreeding depression, with inter-population hybrids and backcrosses showing either similar fitness or significant heterosis for fitness components across the three generations. Variation in heterosis among population pairs was best explained by characteristics of the foreign source or home population, and was greatest when the source population was large, with high genetic diversity and low inbreeding, and the home population was small and inbred. Our results indicate that the primary consideration for maximizing progeny fitness following population augmentation or restoration is the use of seed from large, genetically diverse populations. AU - Pickup, Melinda AU - Field, David AU - Rowell, David AU - Young, Andrew ID - 450 IS - 1750 JF - Proceedings of the Royal Society of London Series B Biological Sciences TI - Source population characteristics affect heterosis following genetic rescue of fragmented plant populations VL - 280 ER - TY - JOUR AB - Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnant dams to the viral mimic Poly I:C, which triggers an immune response that results in structural, functional, behavioral, and electrophysiological phenotypes in the adult offspring that model those seen in schizophrenia. We used this model to explore the role of synchronization in brain neural networks, a process thought to be dysfunctional in schizophrenia and previously associated with positive, negative, and cognitive symptoms of schizophrenia. Exposure of pregnant dams to Poly I:C on GD15 produced an impairment in long-range neural synchrony in adult offspring between two regions implicated in schizophrenia pathology; the hippocampus and the medial prefrontal cortex (mPFC). This reduction in synchrony was ameliorated by acute doses of the antipsychotic clozapine. MIA animals have previously been shown to have impaired pre-pulse inhibition (PPI), a gold-standard measure of schizophrenia-like deficits in animal models. Our data showed that deficits in synchrony were positively correlated with the impairments in PPI. Subsequent analysis of LFP activity during the PPI response also showed that reduced coupling between the mPFC and the hippocampus following processing of the pre-pulse was associated with reduced PPI. The ability of the MIA intervention to model neurodevelopmental aspects of schizophrenia pathology provides a useful platform from which to investigate the ontogeny of aberrant synchronous processes. Further, the way in which the model expresses translatable deficits such as aberrant synchrony and reduced PPI will allow researchers to explore novel intervention strategies targeted to these changes. AU - Dickerson, Desiree AU - Bilkey, David ID - 476 IS - DEC JF - Frontiers in Behavioral Neuroscience TI - Aberrant neural synchrony in the maternal immune activation model: Using translatable measures to explore targeted interventions VL - 7 ER - TY - JOUR AB - Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure. AU - Wakamoto, Yurichi AU - Dhar, Neraaj AU - Chait, Remy P AU - Schneider, Katrin AU - Signorino Gelo, François AU - Leibler, Stanislas AU - Mckinney, John ID - 499 IS - 6115 JF - Science TI - Dynamic persistence of antibiotic-stressed mycobacteria VL - 339 ER - TY - JOUR AB - Background: Reassortment between the RNA segments encoding haemagglutinin (HA) and neuraminidase (NA), the major antigenic influenza proteins, produces viruses with novel HA and NA subtype combinations and has preceded the emergence of pandemic strains. It has been suggested that productive viral infection requires a balance in the level of functional activity of HA and NA, arising from their closely interacting roles in the viral life cycle, and that this functional balance could be mediated by genetic changes in the HA and NA. Here, we investigate how the selective pressure varies for H7 avian influenza HA on different NA subtype backgrounds. Results: By extending Bayesian stochastic mutational mapping methods to calculate the ratio of the rate of non-synonymous change to the rate of synonymous change (d N/d S), we found the average d N/d S across the avian influenza H7 HA1 region to be significantly greater on an N2 NA subtype background than on an N1, N3 or N7 background. Observed differences in evolutionary rates of H7 HA on different NA subtype backgrounds could not be attributed to underlying differences between avian host species or virus pathogenicity. Examination of d N/d S values for each subtype on a site-by-site basis indicated that the elevated d N/d S on the N2 NA background was a result of increased selection, rather than a relaxation of selective constraint. Conclusions: Our results are consistent with the hypothesis that reassortment exposes influenza HA to significant changes in selective pressure through genetic interactions with NA. Such epistatic effects might be explicitly accounted for in future models of influenza evolution. AU - Ward, Melissa AU - Lycett, Samantha AU - Avila, Dorita AU - Bollback, Jonathan P AU - Leigh Brown, Andrew ID - 500 IS - 1 JF - BMC Evolutionary Biology TI - Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza VL - 13 ER - TY - JOUR AB - All known species of extant tapirs are allopatric: 1 in southeastern Asia and 3 in Central and South America. The fossil record for tapirs, however, is much wider in geographical range, including Europe, Asia, and North and South America, going back to the late Oligocene, making the present distribution a relict of the original one. We here describe a new species of living Tapirus from the Amazon rain forest, the 1st since T. bairdii Gill, 1865, and the 1st new Perissodactyla in more than 100 years, from both morphological and molecular characters. It is shorter in stature than T. terrestris (Linnaeus, 1758) and has distinctive skull morphology, and it is basal to the clade formed by T. terrestris and T. pinchaque (Roulin, 1829). This highlights the unrecognized biodiversity in western Amazonia, where the biota faces increasing threats. Local peoples have long recognized our new species, suggesting a key role for traditional knowledge in understanding the biodiversity of the region. AU - Cozzuol, Mario AU - Clozato, Camila AU - Holanda, Elizete AU - Rodrigues, Flávio AU - Nienow, Samuel AU - De Thoisy, Benoit AU - Fernandes Redondo, Rodrigo A AU - Santos, Fabrício ID - 501 IS - 6 JF - Journal of Mammalogy TI - A new species of tapir from the Amazon VL - 94 ER - TY - JOUR AB - Alkyd resins are polyesters containing unsaturated fatty acids that are used as binding agents in paints and coatings. Chemical drying of these polyesters is based on heavy metal catalyzed cross-linking of the unsaturated fatty acid moieties. Among the heavy-metal catalysts, cobalt complexes are the most effective, yet they have been proven to be carcinogenic. Therefore, strategies to replace the cobalt-based catalyst by environmentally friendlier and less toxic alternatives are under development. Here, we demonstrate for the first time that a laccase-mediator system can effectively replace the heavy-metal catalyst and cross-link alkyd resins. Interestingly, the biocatalytic reaction does not only work in aqueous media, but also in a solid film, where enzyme diffusion is limited. Within the catalytic cycle, the mediator oxidizes the alkyd resin and is regenerated by the laccase, which is uniformly distributed within the drying film as evidenced by confocal laser scanning microscopy. During gradual build-up of molecular weight, there is a concomitant decrease of the oxygen content in the film. A new optical sensor to follow oxygen consumption during the cross-linking reaction was developed and validated with state of the art techniques. A remarkable feature is the low sample amount required, which allows faster screening of new catalysts. AU - Greimel, Katrin AU - Perz, Veronika AU - Koren, Klaus AU - Feola, Roland AU - Temel, Armin AU - Sohar, Christian AU - Herrero Acero, Enrique AU - Klimant, Ingo AU - Guebitz, Georg ID - 505 IS - 2 JF - Green Chemistry TI - Banning toxic heavy-metal catalysts from paints: Enzymatic cross-linking of alkyd resins VL - 15 ER - TY - JOUR AB - Blind signatures allow users to obtain signatures on messages hidden from the signer; moreover, the signer cannot link the resulting message/signature pair to the signing session. This paper presents blind signature schemes, in which the number of interactions between the user and the signer is minimal and whose blind signatures are short. Our schemes are defined over bilinear groups and are proved secure in the common-reference-string model without random oracles and under standard assumptions: CDH and the decision-linear assumption. (We also give variants over asymmetric groups based on similar assumptions.) The blind signatures are Waters signatures, which consist of 2 group elements. Moreover, we instantiate partially blind signatures, where the message consists of a part hidden from the signer and a commonly known public part, and schemes achieving perfect blindness. We propose new variants of blind signatures, such as signer-friendly partially blind signatures, where the public part can be chosen by the signer without prior agreement, 3-party blind signatures, as well as blind signatures on multiple aggregated messages provided by independent sources. We also extend Waters signatures to non-binary alphabets by proving a new result on the underlying hash function. AU - Blazy, Olivier AU - Fuchsbauer, Georg AU - Pointcheval, David AU - Vergnaud, Damien ID - 502 IS - 5 JF - Journal of Computer Security TI - Short blind signatures VL - 21 ER - TY - JOUR AB - The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases. AU - Tarazona Santos, Eduardo AU - Machado, Moara AU - Magalhães, Wagner AU - Chen, Renee AU - Lyon, Fernanda AU - Burdett, Laurie AU - Crenshaw, Andrew AU - Fabbri, Cristina AU - Pereira, Latife AU - Pinto, Laelia AU - Fernandes Redondo, Rodrigo A AU - Sestanovich, Ben AU - Yeager, Meredith AU - Chanock, Stephen ID - 508 IS - 9 JF - Molecular Biology and Evolution TI - Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications VL - 30 ER - TY - JOUR AB - Clathrin-mediated endocytosis (CME) regulates many aspects of plant development, including hormone signaling and responses to environmental stresses. Despite the importance of this process, the machinery that regulates CME in plants is largely unknown. In mammals, the heterotetrameric ADAPTOR PROTEIN COMPLEX-2 (AP-2) is required for the formation of clathrin-coated vesicles at the plasma membrane (PM). Although the existence of AP-2 has been predicted in Arabidopsis thaliana, the biochemistry and functionality of the complex is still uncharacterized. Here, we identified all the subunits of the Arabidopsis AP-2 by tandem affinity purification and found that one of the large AP-2 subunits, AP2A1, localized at the PM and interacted with clathrin. Furthermore, endocytosis of the leucine-rich repeat receptor kinase, BRASSINOSTEROID INSENSITIVE1 (BRI1), was shown to depend on AP-2. Knockdown of the two Arabidopsis AP2A genes or overexpression of a dominant-negative version of the medium AP-2 subunit, AP2M, impaired BRI1 endocytosis and enhanced the brassinosteroid signaling. Our data reveal that the CME machinery in Arabidopsis is evolutionarily conserved and that AP-2 functions in receptormediated endocytosis. AU - Di Rubbo, Simone AU - Irani, Niloufer AU - Kim, Soo AU - Xu, Zheng AU - Gadeyne, Astrid AU - Dejonghe, Wim AU - Vanhoutte, Isabelle AU - Persiau, Geert AU - Eeckhout, Dominique AU - Simon, Sibu AU - Song, Kyungyoung AU - Kleine Vehn, Jürgen AU - Friml, Jirí AU - De Jaeger, Geert AU - Van Damme, Daniël AU - Hwang, Inhwan AU - Russinova, Eugenia ID - 509 IS - 8 JF - Plant Cell TI - The clathrin adaptor complex AP-2 mediates endocytosis of brassinosteroid INSENSITIVE1 in arabidopsis VL - 25 ER - TY - JOUR AB - Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4- (4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2-dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs. AU - Kim, Soo AU - Xu, Zheng AU - Song, Kyungyoung AU - Kim, Dae AU - Kang, Hyangju AU - Reichardt, Ilka AU - Sohn, Eun AU - Friml, Jirí AU - Juergens, Gerd AU - Hwang, Inhwan ID - 507 IS - 8 JF - Plant Cell TI - Adaptor protein complex 2-mediated endocytosis is crucial for male reproductive organ development in arabidopsis VL - 25 ER - TY - JOUR AB - The native auxin, indole-3-acetic acid (IAA), is a major regulator of plant growth and development. Its nonuniform distribution between cells and tissues underlies the spatiotemporal coordination of many developmental events and responses to environmental stimuli. The regulation of auxin gradients and the formation of auxin maxima/minima most likely involve the regulation of both metabolic and transport processes. In this article, we have demonstrated that 2-oxindole-3-acetic acid (oxIAA) is a major primary IAA catabolite formed in Arabidopsis thaliana root tissues. OxIAA had little biological activity and was formed rapidly and irreversibly in response to increases in auxin levels. We further showed that there is cell type-specific regulation of oxIAA levels in the Arabidopsis root apex. We propose that oxIAA is an important element in the regulation of output from auxin gradients and, therefore, in the regulation of auxin homeostasis and response mechanisms. AU - Pěnčík, Aleš AU - Simonovik, Biljana AU - Petersson, Sara AU - Henyková, Eva AU - Simon, Sibu AU - Greenham, Kathleen AU - Zhang, Yi AU - Kowalczyk, Mariusz AU - Estelle, Mark AU - Zažímalová, Eva AU - Novák, Ondřej AU - Sandberg, Göran AU - Ljung, Karin ID - 511 IS - 10 JF - Plant Cell TI - Regulation of auxin homeostasis and gradients in Arabidopsis roots through the formation of the indole-3-acetic acid catabolite 2-oxindole-3-acetic acid VL - 25 ER - TY - JOUR AB - In plants, changes in local auxin concentrations can trigger a range of developmental processes as distinct tissues respond differently to the same auxin stimulus. However, little is known about how auxin is interpreted by individual cell types. We performed a transcriptomic analysis of responses to auxin within four distinct tissues of the Arabidopsis thaliana root and demonstrate that different cell types show competence for discrete responses. The majority of auxin‐responsive genes displayed a spatial bias in their induction or repression. The novel data set was used to examine how auxin influences tissue‐specific transcriptional regulation of cell‐identity markers. Additionally, the data were used in combination with spatial expression maps of the root to plot a transcriptomic auxin‐response gradient across the apical and basal meristem. The readout revealed a strong correlation for thousands of genes between the relative response to auxin and expression along the longitudinal axis of the root. This data set and comparative analysis provide a transcriptome‐level spatial breakdown of the response to auxin within an organ where this hormone mediates many aspects of development. AU - Bargmann, Bastiaan AU - Vanneste, Steffen AU - Krouk, Gabriel AU - Nawy, Tal AU - Efroni, Idan AU - Shani, Eilon AU - Choe, Goh AU - Friml, Jirí AU - Bergmann, Dominique AU - Estelle, Mark AU - Birnbaum, Kenneth ID - 516 IS - 1 JF - Molecular Systems Biology TI - A map of cell type‐specific auxin responses VL - 9 ER - TY - JOUR AB - Podoplanin, a mucin-like plasma membrane protein, is expressed by lymphatic endothelial cells and responsible for separation of blood and lymphatic circulation through activation of platelets. Here we show that podoplanin is also expressed by thymic fibroblastic reticular cells (tFRC), a novel thymic medulla stroma cell type associated with thymic conduits, and involved in development of natural regulatory T cells (nTreg). Young mice deficient in podoplanin lack nTreg owing to retardation of CD4+CD25+ thymocytes in the cortex and missing differentiation of Foxp3+ thymocytes in the medulla. This might be due to CCL21 that delocalizes upon deletion of the CCL21-binding podoplanin from medullar tFRC to cortex areas. The animals do not remain devoid of nTreg but generate them delayed within the first month resulting in Th2-biased hypergammaglobulinemia but not in the death-causing autoimmune phenotype of Foxp3-deficient Scurfy mice. AU - Fuertbauer, Elke AU - Zaujec, Jan AU - Uhrin, Pavel AU - Raab, Ingrid AU - Weber, Michele AU - Schachner, Helga AU - Bauer, Miroslav AU - Schütz, Gerhard AU - Binder, Bernd AU - Sixt, Michael K AU - Kerjaschki, Dontscho AU - Stockinger, Hannes ID - 522 IS - 1-2 JF - Immunology Letters TI - Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells VL - 154 ER - TY - CONF AB - We consider two-player games played on weighted directed graphs with mean-payoff and total-payoff objectives, two classical quantitative objectives. While for single-dimensional games the complexity and memory bounds for both objectives coincide, we show that in contrast to multi-dimensional mean-payoff games that are known to be coNP-complete, multi-dimensional total-payoff games are undecidable. We introduce conservative approximations of these objectives, where the payoff is considered over a local finite window sliding along a play, instead of the whole play. For single dimension, we show that (i) if the window size is polynomial, deciding the winner takes polynomial time, and (ii) the existence of a bounded window can be decided in NP ∩ coNP, and is at least as hard as solving mean-payoff games. For multiple dimensions, we show that (i) the problem with fixed window size is EXPTIME-complete, and (ii) there is no primitive-recursive algorithm to decide the existence of a bounded window. AU - Chatterjee, Krishnendu AU - Doyen, Laurent AU - Randour, Mickael AU - Raskin, Jean ID - 2279 TI - Looking at mean-payoff and total-payoff through windows VL - 8172 ER - TY - JOUR AB - Establishment of the embryonic axis foreshadows the main body axis of adults both in plants and in animals, but underlying mechanisms are considered distinct. Plants utilize directional, cell-to-cell transport of the growth hormone auxin [1, 2] to generate an asymmetric auxin response that specifies the embryonic apical-basal axis [3-6]. The auxin flow directionality depends on the polarized subcellular localization of PIN-FORMED (PIN) auxin transporters [7, 8]. It remains unknown which mechanisms and spatial cues guide cell polarization and axis orientation in early embryos. Herein, we provide conceptually novel insights into the formation of embryonic axis in Arabidopsis by identifying a crucial role of localized tryptophan-dependent auxin biosynthesis [9-12]. Local auxin production at the base of young embryos and the accompanying PIN7-mediated auxin flow toward the proembryo are required for the apical auxin response maximum and the specification of apical embryonic structures. Later in embryogenesis, the precisely timed onset of localized apical auxin biosynthesis mediates PIN1 polarization, basal auxin response maximum, and specification of the root pole. Thus, the tight spatiotemporal control of distinct local auxin sources provides a necessary, non-cell-autonomous trigger for the coordinated cell polarization and subsequent apical-basal axis orientation during embryogenesis and, presumably, also for other polarization events during postembryonic plant life [13, 14]. AU - Robert, Hélène AU - Grones, Peter AU - Stepanova, Anna AU - Robles, Linda AU - Lokerse, Annemarie AU - Alonso, Jose AU - Weijers, Dolf AU - Friml, Jirí ID - 528 IS - 24 JF - Current Biology TI - Local auxin sources orient the apical basal axis in arabidopsis embryos VL - 23 ER - TY - JOUR AB - The apical-basal axis of the early plant embryo determines the body plan of the adult organism. To establish a polarized embryonic axis, plants evolved a unique mechanism that involves directional, cell-to-cell transport of the growth regulator auxin. Auxin transport relies on PIN auxin transporters [1], whose polar subcellular localization determines the flow directionality. PIN-mediated auxin transport mediates the spatial and temporal activity of the auxin response machinery [2-7] that contributes to embryo patterning processes, including establishment of the apical (shoot) and basal (root) embryo poles [8]. However, little is known of upstream mechanisms guiding the (re)polarization of auxin fluxes during embryogenesis [9]. Here, we developed a model of plant embryogenesis that correctly generates emergent cell polarities and auxin-mediated sequential initiation of apical-basal axis of plant embryo. The model relies on two precisely localized auxin sources and a feedback between auxin and the polar, subcellular PIN transporter localization. Simulations reproduced PIN polarity and auxin distribution, as well as previously unknown polarization events during early embryogenesis. The spectrum of validated model predictions suggests that our model corresponds to a minimal mechanistic framework for initiation and orientation of the apical-basal axis to guide both embryonic and postembryonic plant development. AU - Wabnik, Krzysztof T AU - Robert, Hélène AU - Smith, Richard AU - Friml, Jirí ID - 527 IS - 24 JF - Current Biology TI - Modeling framework for the establishment of the apical-basal embryonic axis in plants VL - 23 ER - TY - GEN AB - In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics and all relevant statistics. AU - Reiter, Johannes AU - Bozic, Ivana AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 5399 SN - 2664-1690 TI - TTP: Tool for Tumor Progression ER - TY - CONF AB - We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, we establish decidability (with optimal EXPTIME-complete complexity) of the qualitative analysis problems for POMDPs with all parity objectives under finite-memory strategies. We also establish asymptotically optimal (exponential) memory bounds. AU - Chatterjee, Krishnendu AU - Chmelik, Martin AU - Tracol, Mathieu ID - 2295 TI - What is decidable about partially observable Markov decision processes with omega-regular objectives VL - 23 ER - TY - GEN AB - We consider concurrent games played by two-players on a finite state graph, where in every round the players simultaneously choose a move, and the current state along with the joint moves determine the successor state. We study the most fundamental objective for concurrent games, namely, mean-payoff or limit-average objective, where a reward is associated to every transition, and the goal of player 1 is to maximize the long-run average of the rewards, and the objective of player 2 is strictly the opposite (i.e., the games are zero-sum). The path constraint for player 1 could be qualitative, i.e., the mean-payoff is the maximal reward, or arbitrarily close to it; or quantitative, i.e., a given threshold between the minimal and maximal reward. We consider the computation of the almost-sure (resp. positive) winning sets, where player 1 can ensure that the path constraint is satisfied with probability 1 (resp. positive probability). Almost-sure winning with qualitative constraint exactly corresponds to the question whether there exists a strategy to ensure that the payoff is the maximal reward of the game. Our main results for qualitative path constraints are as follows: (1) we establish qualitative determinacy results that show for every state either player 1 has a strategy to ensure almost-sure (resp. positive) winning against all player-2 strategies or player 2 has a spoiling strategy to falsify almost-sure (resp. positive) winning against all player-1 strategies; (2) we present optimal strategy complexity results that precisely characterize the classes of strategies required for almost-sure and positive winning for both players; and (3) we present quadratic time algorithms to compute the almost-sure and the positive winning sets, matching the best known bound of the algorithms for much simpler problems (such as reachability objectives). For quantitative constraints we show that a polynomial time solution for the almost-sure or the positive winning set would imply a solution to a long-standing open problem (of solving the value problem of mean-payoff games) that is not known to be in polynomial time. AU - Chatterjee, Krishnendu AU - Ibsen-Jensen, Rasmus ID - 5403 SN - 2664-1690 TI - Qualitative analysis of concurrent mean-payoff games ER - TY - GEN AB - Linearizability requires that the outcome of calls by competing threads to a concurrent data structure is the same as some sequential execution where each thread has exclusive access to the data structure. In an ordered data structure, such as a queue or a stack, linearizability is ensured by requiring threads commit in the order dictated by the sequential semantics of the data structure; e.g., in a concurrent queue implementation a dequeue can only remove the oldest element. In this paper, we investigate the impact of this strict ordering, by comparing what linearizability allows to what existing implementations do. We first give an operational definition for linearizability which allows us to build the most general linearizable implementation as a transition system for any given sequential specification. We then use this operational definition to categorize linearizable implementations based on whether they are bound or free. In a bound implementation, whenever all threads observe the same logical state, the updates to the logical state and the temporal order of commits coincide. All existing queue implementations we know of are bound. We then proceed to present, to the best of our knowledge, the first ever free queue implementation. Our experiments show that free implementations have the potential for better performance by suffering less from contention. AU - Henzinger, Thomas A AU - Sezgin, Ali ID - 5402 SN - 2664-1690 TI - How free is your linearizable concurrent data structure? ER - TY - GEN AB - We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The class of ω-regular languages extends regular languages to infinite strings and provides a robust specification language to express all properties used in verification, and parity objectives are canonical forms to express ω-regular conditions. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satis- fied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, we establish decidability (with optimal complexity) of the qualitative analysis problems for POMDPs with all parity objectives under finite- memory strategies. We establish asymptotically optimal (exponential) memory bounds and EXPTIME- completeness of the qualitative analysis problems under finite-memory strategies for POMDPs with parity objectives. AU - Chatterjee, Krishnendu AU - Chmelik, Martin AU - Tracol, Mathieu ID - 5400 SN - 2664-1690 TI - What is decidable about partially observable Markov decision processes with ω-regular objectives ER - TY - GEN AB - We study finite-state two-player (zero-sum) concurrent mean-payoff games played on a graph. We focus on the important sub-class of ergodic games where all states are visited infinitely often with probability 1. The algorithmic study of ergodic games was initiated in a seminal work of Hoffman and Karp in 1966, but all basic complexity questions have remained unresolved. Our main results for ergodic games are as follows: We establish (1) an optimal exponential bound on the patience of stationary strategies (where patience of a distribution is the inverse of the smallest positive probability and represents a complexity measure of a stationary strategy); (2) the approximation problem lie in FNP; (3) the approximation problem is at least as hard as the decision problem for simple stochastic games (for which NP and coNP is the long-standing best known bound). We show that the exact value can be expressed in the existential theory of the reals, and also establish square-root sum hardness for a related class of games. AU - Chatterjee, Krishnendu AU - Ibsen-Jensen, Rasmus ID - 5404 SN - 2664-1690 TI - The complexity of ergodic games ER - TY - GEN AB - This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the actual initiatives, projects and standards related to the project. It supports the preparation of standards and specifications for the project, which should be considered and followed to ensure interoperability and visibility of the uploaded data. AU - Porsche, Jana ID - 5401 TI - Initiatives and projects related to RD ER - TY - GEN AB - The theory of graph games is the foundation for modeling and synthesizing reactive processes. In the synthesis of stochastic processes, we use 2-1/2-player games where some transitions of the game graph are controlled by two adversarial players, the System and the Environment, and the other transitions are determined probabilistically. We consider 2-1/2-player games where the objective of the System is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a mean-payoff condition). We establish that the problem of deciding whether the System can ensure that the probability to satisfy the mean-payoff parity objective is at least a given threshold is in NP ∩ coNP, matching the best known bound in the special case of 2-player games (where all transitions are deterministic) with only parity objectives, or with only mean-payoff objectives. We present an algorithm running in time O(d · n^{2d}·MeanGame) to compute the set of almost-sure winning states from which the objective can be ensured with probability 1, where n is the number of states of the game, d the number of priorities of the parity objective, and MeanGame is the complexity to compute the set of almost-sure winning states in 2-1/2-player mean-payoff games. Our results are useful in the synthesis of stochastic reactive systems with both functional requirement (given as a qualitative objective) and performance requirement (given as a quantitative objective). AU - Chatterjee, Krishnendu AU - Doyen, Laurent AU - Gimbert, Hugo AU - Oualhadj, Youssouf ID - 5405 SN - 2664-1690 TI - Perfect-information stochastic mean-payoff parity games ER - TY - GEN AB - The edit distance between two (untimed) traces is the minimum cost of a sequence of edit operations (insertion, deletion, or substitution) needed to transform one trace to the other. Edit distances have been extensively studied in the untimed setting, and form the basis for approximate matching of sequences in different domains such as coding theory, parsing, and speech recognition. In this paper, we lift the study of edit distances from untimed languages to the timed setting. We define an edit distance between timed words which incorporates both the edit distance between the untimed words and the absolute difference in timestamps. Our edit distance between two timed words is computable in polynomial time. Further, we show that the edit distance between a timed word and a timed language generated by a timed automaton, defined as the edit distance between the word and the closest word in the language, is PSPACE-complete. While computing the edit distance between two timed automata is undecidable, we show that the approximate version, where we decide if the edit distance between two timed automata is either less than a given parameter or more than delta away from the parameter, for delta>0, can be solved in exponential space and is EXPSPACE-hard. Our definitions and techniques can be generalized to the setting of hybrid systems, and we show analogous decidability results for rectangular automata. AU - Chatterjee, Krishnendu AU - Ibsen-Jensen, Rasmus AU - Majumdar, Rupak ID - 5409 SN - 2664-1690 TI - Edit distance for timed automata ER - TY - CONF AB - We consider the distributed synthesis problem for temporal logic specifications. Traditionally, the problem has been studied for LTL, and the previous results show that the problem is decidable iff there is no information fork in the architecture. We consider the problem for fragments of LTL and our main results are as follows: (1) We show that the problem is undecidable for architectures with information forks even for the fragment of LTL with temporal operators restricted to next and eventually. (2) For specifications restricted to globally along with non-nested next operators, we establish decidability (in EXPSPACE) for star architectures where the processes receive disjoint inputs, whereas we establish undecidability for architectures containing an information fork-meet structure. (3) Finally, we consider LTL without the next operator, and establish decidability (NEXPTIME-complete) for all architectures for a fragment that consists of a set of safety assumptions, and a set of guarantees where each guarantee is a safety, reachability, or liveness condition. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Otop, Jan AU - Pavlogiannis, Andreas ID - 1376 T2 - 13th International Conference on Formal Methods in Computer-Aided Design TI - Distributed synthesis for LTL fragments ER - TY - GEN AB - We consider the distributed synthesis problem fortemporal logic specifications. Traditionally, the problem has been studied for LTL, and the previous results show that the problem is decidable iff there is no information fork in the architecture. We consider the problem for fragments of LTLand our main results are as follows: (1) We show that the problem is undecidable for architectures with information forks even for the fragment of LTL with temporal operators restricted to next and eventually. (2) For specifications restricted to globally along with non-nested next operators, we establish decidability (in EXPSPACE) for star architectures where the processes receive disjoint inputs, whereas we establish undecidability for architectures containing an information fork-meet structure. (3)Finally, we consider LTL without the next operator, and establish decidability (NEXPTIME-complete) for all architectures for a fragment that consists of a set of safety assumptions, and a set of guarantees where each guarantee is a safety, reachability, or liveness condition. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Otop, Jan AU - Pavlogiannis, Andreas ID - 5406 SN - 2664-1690 TI - Distributed synthesis for LTL Fragments ER - TY - GEN AB - We consider two-player partial-observation stochastic games where player 1 has partial observation and player 2 has perfect observation. The winning condition we study are omega-regular conditions specified as parity objectives. The qualitative analysis problem given a partial-observation stochastic game and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, they were shown to be decidable in 2EXPTIME under finite-memory strategies. We improve the complexity and show that the qualitative analysis problems for partial-observation stochastic parity games under finite-memory strategies are EXPTIME-complete; and also establish optimal (exponential) memory bounds for finite-memory strategies required for qualitative analysis. AU - Chatterjee, Krishnendu AU - Doyen, Laurent AU - Nain, Sumit AU - Vardi, Moshe ID - 5408 SN - 2664-1690 TI - The complexity of partial-observation stochastic parity games with finite-memory strategies ER - TY - GEN AB - This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the mandatory features, which need to be fulfilled to provide an institutional repository as a platform and also a service to the scientists at the institute. It also includes optional features, which would be of strong benefit for the scientists and would increase the usage of the repository, and hence the visibility of research at IST Austria. AU - Porsche, Jana ID - 5407 TI - Technical requirements and features ER - TY - GEN AB - Board games, like Tic-Tac-Toe and CONNECT-4, play an important role not only in development of mathematical and logical skills, but also in emotional and social development. In this paper, we address the problem of generating targeted starting positions for such games. This can facilitate new approaches for bringing novice players to mastery, and also leads to discovery of interesting game variants. Our approach generates starting states of varying hardness levels for player 1 in a two-player board game, given rules of the board game, the desired number of steps required for player 1 to win, and the expertise levels of the two players. Our approach leverages symbolic methods and iterative simulation to efficiently search the extremely large state space. We present experimental results that include discovery of states of varying hardness levels for several simple grid-based board games. Also, the presence of such states for standard game variants like Tic-Tac-Toe on board size 4x4 opens up new games to be played that have not been played for ages since the default start state is heavily biased. AU - Ahmed, Umair AU - Chatterjee, Krishnendu AU - Gulwani, Sumit ID - 5410 SN - 2664-1690 TI - Automatic generation of alternative starting positions for traditional board games ER - TY - CONF AB - We define the model-measuring problem: given a model M and specification φ, what is the maximal distance ρ such that all models M′ within distance ρ from M satisfy (or violate) φ. The model measuring problem presupposes a distance function on models. We concentrate on automatic distance functions, which are defined by weighted automata. The model-measuring problem subsumes several generalizations of the classical model-checking problem, in particular, quantitative model-checking problems that measure the degree of satisfaction of a specification, and robustness problems that measure how much a model can be perturbed without violating the specification. We show that for automatic distance functions, and ω-regular linear-time and branching-time specifications, the model-measuring problem can be solved. We use automata-theoretic model-checking methods for model measuring, replacing the emptiness question for standard word and tree automata by the optimal-weight question for the weighted versions of these automata. We consider weighted automata that accumulate weights by maximizing, summing, discounting, and limit averaging. We give several examples of using the model-measuring problem to compute various notions of robustness and quantitative satisfaction for temporal specifications. AU - Henzinger, Thomas A AU - Otop, Jan ID - 2327 TI - From model checking to model measuring VL - 8052 ER - TY - CONF AB - We present two methods of creating two orthogonally-polarized focal points at customizable relative locations. These schemes may be critical for enhancing entanglement sources and other applications. AU - Schmid, David AU - Huang, Ting-Yu AU - Dirks, Radhika AU - Onur Hosten AU - Kwiat, Paul G ID - 590 TI - Polarization dependent focusing ER -