TY - JOUR AU - Timothy Browning ID - 253 IS - 1 JF - Mathematika TI - Counting rational points on cubic hypersurfaces: Corrigendum VL - 60 ER - TY - JOUR AB - The group III metabotropic glutamate (mGlu) receptors mGlu7 and mGlu8 are receiving increased attention as potential novel therapeutic targets for anxiety disorders. The effects mediated by these receptors appear to result from a complex interplay of facilitatory and inhibitory actions at different brain sites in the anxiety/fear circuits. To better understand the effect of mGlu7 and mGlu8 receptors on extinction of contextual fear and their critical sites of action in the fear networks, we focused on the amygdala. Direct injection into the basolateral complex of the amygdala of the mGlu7 receptor agonist AMN082 facilitated extinction, whereas the mGlu8 receptor agonist (S)-3,4-DCPG sustained freezing during the extinction acquisition trial. We also determined at the ultrastructural level the synaptic distribution of these receptors in the basal nucleus (BA) and intercalated cell clusters (ITCs) of the amygdala. Both areas are thought to exert key roles in fear extinction. We demonstrate that mGlu7 and mGlu8 receptors are located in different presynaptic terminals forming both asymmetric and symmetric synapses, and that they preferentially target neurons expressing mGlu1α receptors mostly located around ITCs. In addition we show that mGlu7 and mGlu8 receptors were segregated to different inputs to a significant extent. In particular, mGlu7a receptors were primarily onto glutamatergic afferents arising from the BA or midline thalamic nuclei, but not the medial prefrontal cortex (mPFC), as revealed by combined anterograde tracing and pre-embedding electron microscopy. On the other hand, mGlu8a showed a more restricted distribution in the BA and appeared absent from thalamic, mPFC and intrinsic inputs. This segregation of mGlu7 and mGlu8 receptors in different neuronal pathways of the fear circuit might explain the distinct effects on fear extinction training observed with mGlu7 and mGlu8 receptor agonists. AU - Dobi, Alice AU - Sartori, Simone B AU - Busti, Daniela AU - Van Der Putten, Herman V AU - Singewald, Nicolas AU - Ryuichi Shigemoto AU - Ferraguti, Francesco ID - 2692 JF - Neuropharmacology TI - Neural substrates for the distinct effects of presynaptic group III metabotropic glutamate receptors on extinction of contextual fear conditioning in mice VL - 66 ER - TY - JOUR AB - P/Q-type voltage-dependent calcium channels play key roles in transmitter release, integration of dendritic signals, generation of dendritic spikes, and gene expression. High intracellular calcium concentration transient produced by these channels is restricted to tens to hundreds of nanometers from the channels. Therefore, precise localization of these channels along the plasma membrane was long sought to decipher how each neuronal cell function is controlled. Here, we analyzed the distribution of Cav2.1 subunit of the P/Q-type channel using highly sensitive SDS-digested freeze-fracture replica labeling in the rat cerebellar Purkinje cells. The labeling efficiency was such that the number of immunogold particles in each parallel fiber active zone was comparable to that of functional channels calculated from previous reports. Two distinct patterns of Cav2.1 distribution, scattered and clustered, were found in Purkinje cells. The scattered Cav2.1 had a somatodendritic gradient with the density of immunogold particles increasing 2.5-fold from soma to distal dendrites. The other population with 74-fold higher density than the scattered particles was found within clusters of intramembrane particles on the P-face of soma and primary dendrites. Both populations of Cav2.1 were found as early as P3 and increased in the second postnatal week to a mature level. Using double immunogold labeling, we found that virtually all of the Cav2.1 clusters were colocalized with two types of calcium-activated potassium channels, BK and SK2, with the nearest neighbor distance of 40∼nm. Calcium nanodomain created by the opening of Cav2.1 channels likely activates the two channels that limit the extent of depolarization. AU - Indriati, Dwi Wahyu AU - Kamasawa, Naomi AU - Matsui, Ko AU - Meredith, Andrea L AU - Watanabe, Masahiko AU - Ryuichi Shigemoto ID - 2691 IS - 8 JF - Journal of Neuroscience TI - Quantitative localization of Cav2.1 (P/Q-Type) voltage-dependent calcium channels in Purkinje cells: Somatodendritic gradient and distinct somatic coclustering with calcium-activated potassium channels VL - 33 ER - TY - JOUR AB - Establishing the spatiotemporal concentration profile of neurotransmitter following synaptic vesicular release is essential for our understanding of inter-neuronal communication. Such profile is a determinant of synaptic strength, short-term plasticity and inter-synaptic crosstalk. Synaptically released glutamate has been suggested to reach a few millimolar in concentration and last for <1 ms. The synaptic cleft is often conceived as a single concentration compartment, whereas a huge gradient likely exists. Modelling studies have attempted to describe this gradient, but two key parameters, the number of glutamate in a vesicle (NGlu) and its diffusion coefficient (DGlu) in the extracellular space, remained unresolved. To determine this profile, the rat calyx of Held synapse at postnatal day 12-16 was studied where diffusion of glutamate occurs two-dimensionally and where quantification of AMPA receptor distribution on individual postsynaptic specialization on medial nucleus of the trapezoid body principal cells is possible using SDS-digested freeze-fracture replica labelling. To assess the performance of these receptors as glutamate sensors, a kinetic model of the receptors was constructed from outside-out patch recordings. From here, we simulated synaptic responses and compared them with the EPSC recordings. Combinations of NGlu and DGlu with an optimum of 7000 and 0.3 μm2 ms-1 reproduced the data, suggesting slow diffusion. Further simulations showed that a single vesicle does not saturate the synaptic receptors, and that glutamate spillover does not affect the conductance amplitude at this synapse. Using the estimated profile, we also evaluated how the number of multiple vesicle releases at individual active zones affects the amplitude of postsynaptic signals. AU - Budisantoso, Timotheus AU - Harumi Harada AU - Kamasawa, Naomi AU - Fukazawa, Yugo AU - Ryuichi Shigemoto AU - Matsui, Ko ID - 2690 IS - 1 JF - Journal of Physiology TI - Evaluation of glutamate concentration transient in the synaptic cleft of the rat calyx of Held VL - 591 ER - TY - JOUR AB - Inhibitory parvalbumin-containing interneurons (PVIs) control neuronal discharge and support the generation of theta- and gammafrequency oscillations in cortical networks. Fast GABAergic input onto PVIs is crucial for their synchronization and oscillatory entrainment, but the role of metabotropic GABAB receptors (GABABRs) in mediating slow presynaptic and postsynaptic inhibition remains unknown. In this study, we have combined high-resolution immunoelectron microscopy, whole-cell patch-clamp recording, and computational modeling to investigate the subcellular distribution and effects of GABABRs and their postsynaptic effector Kir3 channels in rat hippocampal PVIs. Pre-embedding immunogold labeling revealed that the receptors and channels localize at high levels to the extrasynaptic membrane of parvalbumin-immunoreactive dendrites. Immunoreactivity forGABABRs was also present at lower levels on PVI axon terminals. Whole-cell recordings further showed that synaptically released GABA in response to extracellular stimulation evokes large GABABR-mediated slow IPSCs in perisomatic-targeting (PT) PVIs, but only small or no currents in dendrite-targeting (DT) PVIs. In contrast, paired recordings demonstrated that GABABR activation results in presynaptic inhibition at the output synapses of both PT and DT PVIs, but more strongly in the latter. Finally, computational analysis indicated that GABAB IPSCs can phasically modulate the discharge of PT interneurons at theta frequencies. In summary, our results show that GABABRs differentially mediate slow presynaptic and postsynaptic inhibition in PVIs and can contribute to the dynamic modulation of their activity during oscillations. Furthermore, these data provide evidence for a compartment-specific molecular divergence of hippocampal PVI subtypes, suggesting that activation of GABABRs may shift the balance between perisomatic and dendritic inhibition. AU - Booker, Sam A AU - Gross, Anna AU - Althof, Daniel AU - Ryuichi Shigemoto AU - Bettler, Bernhard AU - Frotscher, Michael AU - Hearing, Matthew C AU - Wickman, Kevin D AU - Watanabe, Masahiko AU - Kulik, Ákos AU - Vida, Imre ID - 2693 IS - 18 JF - Journal of Neuroscience TI - Differential GABAB-receptor-mediated effects in perisomatic- and dendrite-targeting parvalbumin interneurons VL - 33 ER - TY - JOUR AB - We consider non-interacting particles subject to a fixed external potential V and a self-generated magnetic field B. The total energy includes the field energy β∫B2 and we minimize over all particle states and magnetic fields. In the case of spin-1/2 particles this minimization leads to the coupled Maxwell-Pauli system. The parameter β tunes the coupling strength between the field and the particles and it effectively determines the strength of the field. We investigate the stability and the semiclassical asymptotics, h→0, of the total ground state energy E(β,h,V). The relevant parameter measuring the field strength in the semiclassical limit is κ=βh. We are not able to give the exact leading order semiclassical asymptotics uniformly in κ or even for fixed κ. We do however give upper and lower bounds on E with almost matching dependence on κ. In the simultaneous limit h→0 and κ→∞ we show that the standard non-magnetic Weyl asymptotics holds. The same result also holds for the spinless case, i.e. where the Pauli operator is replaced by the Schrödinger operator. AU - Erdös, László AU - Fournais, Søren AU - Solovej, Jan ID - 2698 IS - 6 JF - Journal of the European Mathematical Society TI - Stability and semiclassics in self-generated fields VL - 15 ER - TY - JOUR AB - We consider Hermitian and symmetric random band matrices H = (h xy ) in d⩾1 d ⩾ 1 dimensions. The matrix entries h xy , indexed by x,y∈(Z/LZ)d x , y ∈ ( Z / L Z ) d , are independent, centred random variables with variances sxy=E|hxy|2 s x y = E | h x y | 2 . We assume that s xy is negligible if |x − y| exceeds the band width W. In one dimension we prove that the eigenvectors of H are delocalized if W≫L4/5 W ≫ L 4 / 5 . We also show that the magnitude of the matrix entries |Gxy|2 | G x y | 2 of the resolvent G=G(z)=(H−z)−1 G = G ( z ) = ( H - z ) - 1 is self-averaging and we compute E|Gxy|2 E | G x y | 2 . We show that, as L→∞ L → ∞ and W≫L4/5 W ≫ L 4 / 5 , the behaviour of E|Gxy|2 E | G x y | 2 is governed by a diffusion operator whose diffusion constant we compute. Similar results are obtained in higher dimensions. AU - László Erdös AU - Knowles, Antti AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2697 IS - 1 JF - Communications in Mathematical Physics TI - Delocalization and diffusion profile for random band matrices VL - 323 ER - TY - CONF AB - Even though both population and quantitative genetics, and evolutionary computation, deal with the same questions, they have developed largely independently of each other. I review key results from each field, emphasising those that apply independently of the (usually unknown) relation between genotype and phenotype. The infinitesimal model provides a simple framework for predicting the response of complex traits to selection, which in biology has proved remarkably successful. This allows one to choose the schedule of population sizes and selection intensities that will maximise the response to selection, given that the total number of individuals realised, C = ∑t Nt, is constrained. This argument shows that for an additive trait (i.e., determined by the sum of effects of the genes), the optimum population size and the maximum possible response (i.e., the total change in trait mean) are both proportional to √C. AU - Barton, Nicholas H AU - Paixao, Tiago ID - 2718 T2 - Proceedings of the 15th annual conference on Genetic and evolutionary computation TI - Can quantitative and population genetics help us understand evolutionary computation? ER - TY - JOUR AB - Knowledge of the rate and fitness effects of mutations is essential for understanding the process of evolution. Mutations are inherently difficult to study because they are rare and are frequently eliminated by natural selection. In the ciliate Tetrahymena thermophila, mutations can accumulate in the germline genome without being exposed to selection. We have conducted a mutation accumulation (MA) experiment in this species. Assuming that all mutations are deleterious and have the same effect, we estimate that the deleterious mutation rate per haploid germline genome per generation is U = 0.0047 (95% credible interval: 0.0015, 0.0125), and that germline mutations decrease fitness by s = 11% when expressed in a homozygous state (95% CI: 4.4%, 27%). We also estimate that deleterious mutations are partially recessive on average (h = 0.26; 95% CI: –0.022, 0.62) and that the rate of lethal mutations is <10% of the deleterious mutation rate. Comparisons between the observed evolutionary responses in the germline and somatic genomes and the results from individual-based simulations of MA suggest that the two genomes have similar mutational parameters. These are the first estimates of the deleterious mutation rate and fitness effects from the eukaryotic supergroup Chromalveolata and are within the range of those of other eukaryotes. AU - Long, Hongan AU - Paixao, Tiago AU - Azevedo, Ricardo AU - Zufall, Rebecca ID - 2720 IS - 2 JF - Genetics TI - Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila VL - 195 ER - TY - CONF AB - Prediction of the evolutionary process is a long standing problem both in the theory of evolutionary biology and evolutionary computation (EC). It has long been realized that heritable variation is crucial to both the response to selection and the success of genetic algorithms. However, not all variation contributes in the same way to the response. Quantitative genetics has developed a large body of work trying to estimate and understand how different components of the variance in fitness in the population contribute to the response to selection. We illustrate how to apply some concepts of quantitative genetics to the analysis of genetic algorithms. In particular, we derive estimates for the short term prediction of the response to selection and we use variance decomposition to gain insight on local aspects of the landscape. Finally, we propose a new population based genetic algorithm that uses these methods to improve its operation. AU - Paixao, Tiago AU - Barton, Nicholas H ID - 2719 T2 - Proceedings of the 15th annual conference on Genetic and evolutionary computation TI - A variance decomposition approach to the analysis of genetic algorithms ER - TY - JOUR AB - We consider random n×n matrices of the form (XX*+YY*)^{-1/2}YY*(XX*+YY*)^{-1/2}, where X and Y have independent entries with zero mean and variance one. These matrices are the natural generalization of the Gaussian case, which are known as MANOVA matrices and which have joint eigenvalue density given by the third classical ensemble, the Jacobi ensemble. We show that, away from the spectral edge, the eigenvalue density converges to the limiting density of the Jacobi ensemble even on the shortest possible scales of order 1/n (up to log n factors). This result is the analogue of the local Wigner semicircle law and the local Marchenko-Pastur law for general MANOVA matrices. AU - Erdös, László AU - Farrell, Brendan ID - 2782 IS - 6 JF - Journal of Statistical Physics TI - Local eigenvalue density for general MANOVA matrices VL - 152 ER - TY - JOUR AB - We consider the ensemble of adjacency matrices of Erdős-Rényi random graphs, that is, graphs on N vertices where every edge is chosen independently and with probability p = p(N). We rescale the matrix so that its bulk eigenvalues are of order one. We prove that, as long as pN→∞(with a speed at least logarithmic in N), the density of eigenvalues of the Erdős-Rényi ensemble is given by the Wigner semicircle law for spectral windows of length larger than N-1 (up to logarithmic corrections). As a consequence, all eigenvectors are proved to be completely delocalized in the sense that the ℓ∞-norms of the ℓ2-normalized eigenvectors are at most of order N-1/2 with a very high probability. The estimates in this paper will be used in the companion paper [Spectral statistics of Erdős-Rényi graphs II: Eigenvalue spacing and the extreme eigenvalues (2011) Preprint] to prove the universality of eigenvalue distributions both in the bulk and at the spectral edges under the further restriction that pN »N2/3. AU - László Erdös AU - Knowles, Antti AU - Yau, Horng-Tzer AU - Yin, Jun ID - 2781 IS - 3 B JF - Annals of Probability TI - Spectral statistics of Erdős-Rényi graphs I: Local semicircle law VL - 41 ER - TY - JOUR AB - We consider a general class of random matrices whose entries are centred random variables, independent up to a symmetry constraint. We establish precise high-probability bounds on the averages of arbitrary monomials in the resolvent matrix entries. Our results generalize the previous results of Erdős et al. (Ann Probab, arXiv:1103.1919, 2013; Commun Math Phys, arXiv:1103.3869, 2013; J Combin 1(2):15-85, 2011) which constituted a key step in the proof of the local semicircle law with optimal error bound in mean-field random matrix models. Our bounds apply to random band matrices and improve previous estimates from order 2 to order 4 in the cases relevant to applications. In particular, they lead to a proof of the diffusion approximation for the magnitude of the resolvent of random band matrices. This, in turn, implies new delocalization bounds on the eigenvectors. The applications are presented in a separate paper (Erdős et al., arXiv:1205.5669, 2013). AU - László Erdös AU - Knowles, Antti AU - Yau, Horng-Tzer ID - 2780 IS - 8 JF - Annales Henri Poincare TI - Averaging fluctuations in resolvents of random band matrices VL - 14 ER - TY - CONF AB - We consider several basic problems of algebraic topology, with connections to combinatorial and geometric questions, from the point of view of computational complexity. The extension problem asks, given topological spaces X; Y , a subspace A ⊆ X, and a (continuous) map f : A → Y , whether f can be extended to a map X → Y . For computational purposes, we assume that X and Y are represented as finite simplicial complexes, A is a subcomplex of X, and f is given as a simplicial map. In this generality the problem is undecidable, as follows from Novikov's result from the 1950s on uncomputability of the fundamental group π1(Y ). We thus study the problem under the assumption that, for some k ≥ 2, Y is (k - 1)-connected; informally, this means that Y has \no holes up to dimension k-1" (a basic example of such a Y is the sphere Sk). We prove that, on the one hand, this problem is still undecidable for dimX = 2k. On the other hand, for every fixed k ≥ 2, we obtain an algorithm that solves the extension problem in polynomial time assuming Y (k - 1)-connected and dimX ≤ 2k - 1. For dimX ≤ 2k - 2, the algorithm also provides a classification of all extensions up to homotopy (continuous deformation). This relies on results of our SODA 2012 paper, and the main new ingredient is a machinery of objects with polynomial-time homology, which is a polynomial-time analog of objects with effective homology developed earlier by Sergeraert et al. We also consider the computation of the higher homotopy groups πk(Y ), k ≥ 2, for a 1-connected Y . Their computability was established by Brown in 1957; we show that πk(Y ) can be computed in polynomial time for every fixed k ≥ 2. On the other hand, Anick proved in 1989 that computing πk(Y ) is #P-hard if k is a part of input, where Y is a cell complex with certain rather compact encoding. We strengthen his result to #P-hardness for Y given as a simplicial complex. AU - Čadek, Martin AU - Krcál, Marek AU - Matoušek, Jiří AU - Vokřínek, Lukáš AU - Wagner, Uli ID - 2807 T2 - 45th Annual ACM Symposium on theory of computing TI - Extending continuous maps: Polynomiality and undecidability ER - TY - JOUR AB - In order to establish a reference for analysis of the function of auxin and the auxin biosynthesis regulators SHORT INTERNODE/ STYLISH (SHI/STY) during Physcomitrella patens reproductive development, we have described male (antheridial) and female (archegonial) development in detail, including temporal and positional information of organ initiation. This has allowed us to define discrete stages of organ morphogenesis and to show that reproductive organ development in P. patens is highly organized and that organ phyllotaxis differs between vegetative and reproductive development. Using the PpSHI1 and PpSHI2 reporter and knockout lines, the auxin reporters GmGH3pro:GUS and PpPINApro:GFP-GUS, and the auxin-conjugating transgene PpSHI2pro:IAAL, we could show that the PpSHI genes, and by inference also auxin, play important roles for reproductive organ development in moss. The PpSHI genes are required for the apical opening of the reproductive organs, the final differentiation of the egg cell, and the progression of canal cells into a cell death program. The apical cells of the archegonium, the canal cells, and the egg cell are also sites of auxin responsiveness and are affected by reduced levels of active auxin, suggesting that auxin mediates PpSHI function in the reproductive organs. AU - Landberg, Katarina AU - Pederson, Eric AU - Viaene, Tom AU - Bozorg, Behruz AU - Friml, Jirí AU - Jönsson, Henrik AU - Thelander, Mattias AU - Sundberg, Eva ID - 2808 IS - 3 JF - Plant Physiology TI - The moss physcomitrella patens reproductive organ development is highly organized, affected by the two SHI/STY genes and by the level of active auxin in the SHI/STY expression domain VL - 162 ER - TY - JOUR AB - A novel Taylor-Couette system has been constructed for investigations of transitional as well as high Reynolds number turbulent flows in very large aspect ratios. The flexibility of the setup enables studies of a variety of problems regarding hydrodynamic instabilities and turbulence in rotating flows. The inner and outer cylinders and the top and bottom endplates can be rotated independently with rotation rates of up to 30 Hz, thereby covering five orders of magnitude in Reynolds numbers (Re = 101-106). The radius ratio can be easily changed, the highest realized one is η = 0.98 corresponding to an aspect ratio of 260 gap width in the vertical and 300 in the azimuthal direction. For η < 0.98 the aspect ratio can be dynamically changed during measurements and complete transparency in the radial direction over the full length of the cylinders is provided by the usage of a precision glass inner cylinder. The temperatures of both cylinders are controlled independently. Overall this apparatus combines an unmatched variety in geometry, rotation rates, and temperatures, which is provided by a sophisticated high-precision bearing system. Possible applications are accurate studies of the onset of turbulence and spatio-temporal intermittent flow patterns in very large domains, transport processes of turbulence at high Re, the stability of Keplerian flows for different boundary conditions, and studies of baroclinic instabilities. AU - Avila, Kerstin AU - Hof, Björn ID - 2806 IS - 6 JF - Review of Scientific Instruments TI - High-precision Taylor-Couette experiment to study subcritical transitions and the role of boundary conditions and size effects VL - 84 ER - TY - JOUR AB - Transition in shear flows is characterized by localized turbulent regions embedded in the surrounding laminar flow. These so-called turbulent spots or puffs are observed in a variety of shear flows and in certain Reynolds-number regimes, and they are advected by the flow while keeping their characteristic length. We show here for the case of pipe flow that this seemingly passive advection of turbulent puffs involves continuous entrainment and relaminarization of laminar and turbulent fluid across strongly convoluted interfaces. Surprisingly, interface areas are almost two orders of magnitude larger than the pipe cross-section, while local entrainment velocities are much smaller than the mean speed. Even though these velocities were shown to be small and proportional to the Kolmogorov velocity scale (in agreement with a prediction by Corrsin) in a flow without mean shear before, we find that, in pipe flow, local entrainment velocities are about an order of magnitude smaller than this scale. The Lagrangian method used to study the dynamics of the laminar-turbulent interfaces allows accurate determination of the leading and trailing edge speeds. However, to resolve the highly complex interface dynamics requires much higher numerical resolutions than for ordinary turbulent flows. This method also reveals that the volume flux across the leading edge has the same radial dependence but the opposite sign as that across the trailing edge, and it is this symmetry that is responsible for the puff shape remaining constant. AU - Holzner, Markus AU - Song, Baofang AU - Avila, Marc AU - Björn Hof ID - 2805 JF - Journal of Fluid Mechanics TI - Lagrangian approach to laminar-turbulent interfaces in transitional pipe flow VL - 723 ER - TY - JOUR AB - The epistatic interactions that underlie evolutionary constraint have mainly been studied for constant external conditions. However, environmental changes may modulate epistasis and hence affect genetic constraints. Here we investigate genetic constraints in the adaptive evolution of a novel regulatory function in variable environments, using the lac repressor, LacI, as a model system. We have systematically reconstructed mutational trajectories from wild type LacI to three different variants that each exhibit an inverse response to the inducing ligand IPTG, and analyzed the higher-order interactions between genetic and environmental changes. We find epistasis to depend strongly on the environment. As a result, mutational steps essential to inversion but inaccessible by positive selection in one environment, become accessible in another. We present a graphical method to analyze the observed complex higher-order interactions between multiple mutations and environmental change, and show how the interactions can be explained by a combination of mutational effects on allostery and thermodynamic stability. This dependency of genetic constraint on the environment should fundamentally affect evolutionary dynamics and affects the interpretation of phylogenetic data. AU - De Vos, Marjon AU - Poelwijk, Frank AU - Battich, Nico AU - Ndika, Joseph AU - Tans, Sander ID - 2810 IS - 6 JF - PLoS Genetics TI - Environmental dependence of genetic constraint VL - 9 ER - TY - JOUR AB - We study the problem of generating a test sequence that achieves maximal coverage for a reactive system under test. We formulate the problem as a repeated game between the tester and the system, where the system state space is partitioned according to some coverage criterion and the objective of the tester is to maximize the set of partitions (or coverage goals) visited during the game. We show the complexity of the maximal coverage problem for non-deterministic systems is PSPACE-complete, but is NP-complete for deterministic systems. For the special case of non-deterministic systems with a re-initializing "reset" action, which represent running a new test input on a re-initialized system, we show that the complexity is coNP-complete. Our proof technique for reset games uses randomized testing strategies that circumvent the exponentially large memory requirement of deterministic testing strategies. We also discuss the memory requirement for deterministic strategies and extensions of our results to other models, such as pushdown systems and timed systems. AU - Chatterjee, Krishnendu AU - Alfaro, Luca AU - Majumdar, Ritankar ID - 2814 IS - 2 JF - International Journal of Foundations of Computer Science TI - The complexity of coverage VL - 24 ER - TY - JOUR AB - In pipe, channel, and boundary layer flows turbulence first occurs intermittently in space and time: at moderate Reynolds numbers domains of disordered turbulent motion are separated by quiescent laminar regions. Based on direct numerical simulations of pipe flow we argue here that the spatial intermittency has its origin in a nearest neighbor interaction between turbulent regions. We further show that in this regime turbulent flows are intrinsically intermittent with a well-defined equilibrium turbulent fraction but without ever assuming a steady pattern. This transition scenario is analogous to that found in simple models such as coupled map lattices. The scaling observed implies that laminar intermissions of the turbulent flow will persist to arbitrarily large Reynolds numbers. AU - Avila, Marc AU - Hof, Björn ID - 2811 IS - 6 JF - Physical Review E TI - Nature of laminar-turbulence intermittency in shear flows VL - 87 ER - TY - JOUR AB - Turbulence is ubiquitous in nature, yet even for the case of ordinary Newtonian fluids like water, our understanding of this phenomenon is limited. Many liquids of practical importance are more complicated (e.g., blood, polymer melts, paints), however; they exhibit elastic as well as viscous characteristics, and the relation between stress and strain is nonlinear. We demonstrate here for a model system of such complex fluids that at high shear rates, turbulence is not simply modified as previously believed but is suppressed and replaced by a different type of disordered motion, elasto-inertial turbulence. Elasto-inertial turbulence is found to occur at much lower Reynolds numbers than Newtonian turbulence, and the dynamical properties differ significantly. The friction scaling observed coincides with the so-called "maximum drag reduction" asymptote, which is exhibited by a wide range of viscoelastic fluids. AU - Samanta, Devranjan AU - Dubief, Yves AU - Holzner, Markus AU - Schäfer, Christof AU - Morozov, Alexander AU - Wagner, Christian AU - Hof, Björn ID - 2813 IS - 26 JF - PNAS TI - Elasto-inertial turbulence VL - 110 ER - TY - CONF AB - We consider the problem of deciding whether the persistent homology group of a simplicial pair (K, L) can be realized as the homology H* (X) of some complex X with L ⊂ X ⊂ K. We show that this problem is NP-complete even if K is embedded in ℝ3. As a consequence, we show that it is NP-hard to simplify level and sublevel sets of scalar functions on S3 within a given tolerance constraint. This problem has relevance to the visualization of medical images by isosurfaces. We also show an implication to the theory of well groups of scalar functions: not every well group can be realized by some level set, and deciding whether a well group can be realized is NP-hard. AU - Attali, Dominique AU - Bauer, Ulrich AU - Devillers, Olivier AU - Glisse, Marc AU - Lieutier, André ID - 2812 T2 - Proceedings of the 29th annual symposium on Computational Geometry TI - Homological reconstruction and simplification in R3 ER - TY - JOUR AB - The basic idea of evolutionary game theory is that payoff determines reproductive rate. Successful individuals have a higher payoff and produce more offspring. But in evolutionary and ecological situations there is not only reproductive rate but also carrying capacity. Individuals may differ in their exposure to density limiting effects. Here we explore an alternative approach to evolutionary game theory by assuming that the payoff from the game determines the carrying capacity of individual phenotypes. Successful strategies are less affected by density limitation (crowding) and reach higher equilibrium abundance. We demonstrate similarities and differences between our framework and the standard replicator equation. Our equation is defined on the positive orthant, instead of the simplex, but has the same equilibrium points as the replicator equation. Linear stability analysis produces the classical conditions for asymptotic stability of pure strategies, but the stability properties of internal equilibria can differ in the two frameworks. For example, in a two-strategy game with an internal equilibrium that is always stable under the replicator equation, the corresponding equilibrium can be unstable in the new framework resulting in a limit cycle. AU - Novak, Sebastian AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 2817 JF - Journal of Theoretical Biology TI - Density games VL - 334 ER - TY - CONF AB - We introduce quantatitive timed refinement metrics and quantitative timed simulation functions, incorporating zenoness checks, for timed systems. These functions assign positive real numbers between zero and infinity which quantify the timing mismatches between two timed systems, amongst non-zeno runs. We quantify timing mismatches in three ways: (1) the maximum timing mismatch that can arise, (2) the "steady-state" maximum timing mismatches, where initial transient timing mismatches are ignored; and (3) the (long-run) average timing mismatches amongst two systems. These three kinds of mismatches constitute three important types of timing differences. Our event times are the global times, measured from the start of the system execution, not just the time durations of individual steps. We present algorithms over timed automata for computing the three quantitative simulation functions to within any desired degree of accuracy. In order to compute the values of the quantitative simulation functions, we use a game theoretic formulation. We introduce two new kinds of objectives for two player games on finite state game graphs: (1) eventual debit-sum level objectives, and (2) average debit-sum level objectives. We present algorithms for computing the optimal values for these objectives for player 1, and then use these algorithms to compute the values of the quantitative timed simulation functions. AU - Chatterjee, Krishnendu AU - Prabhu, Vinayak ID - 2819 T2 - Proceedings of the 16th International Conference on Hybrid Systems: Computation and Control TI - Quantitative timed simulation functions and refinement metrics for real-time systems VL - 1 ER - TY - JOUR AB - Models of neural responses to stimuli with complex spatiotemporal correlation structure often assume that neurons are selective for only a small number of linear projections of a potentially high-dimensional input. In this review, we explore recent modeling approaches where the neural response depends on the quadratic form of the input rather than on its linear projection, that is, the neuron is sensitive to the local covariance structure of the signal preceding the spike. To infer this quadratic dependence in the presence of arbitrary (e.g., naturalistic) stimulus distribution, we review several inference methods, focusing in particular on two information theory–based approaches (maximization of stimulus energy and of noise entropy) and two likelihood-based approaches (Bayesian spike-triggered covariance and extensions of generalized linear models). We analyze the formal relationship between the likelihood-based and information-based approaches to demonstrate how they lead to consistent inference. We demonstrate the practical feasibility of these procedures by using model neurons responding to a flickering variance stimulus. AU - Rajan, Kanaka AU - Marre, Olivier AU - Tkacik, Gasper ID - 2818 IS - 7 JF - Neural Computation TI - Learning quadratic receptive fields from neural responses to natural stimuli VL - 25 ER - TY - JOUR AB - Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than -6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is highly heritable, and to date multiple gene loci have been reported. We performed exome sequencing in 4 individuals from an 11-member family of European descent from the United States. Affected individuals had a mean dioptric spherical equivalent of -22.00 sphere. A premature stop codon mutation c.157C>T (p.Gln53*) cosegregating with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent analyses identified three additional mutations in three highly myopic unrelated individuals (c.341G>A, c.418G>A, and c.776C>T). To determine differential gene expression in a developmental mouse model, we induced myopia by applying a -15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Copper deficiencies have been linked with photoreceptor loss and myopia with increased scleral wall elasticity. Retinal thinning has been reported with an SC02 variant. Human mutation identification with support from an induced myopic animal provides biological insights of myopic development. AU - Tran Viet, Khanh AU - Powell, Caldwell AU - Barathi, Veluchamy AU - Klemm, Thomas AU - Maurer Stroh, Sebastian AU - Limviphuvadh, Vachiranee AU - Soler, Vincent AU - Ho, Candice AU - Yanovitch, Tammy AU - Schneider, Georg AU - Li, Yi AU - Nading, Erica AU - Metlapally, Ravikanth AU - Saw, Seang AU - Goh, Liang AU - Rozen, Steve AU - Young, Terri ID - 2826 IS - 5 JF - American Journal of Human Genetics TI - Mutations in SCO2 are associated with autosomal-dominant high-grade myopia VL - 92 ER - TY - JOUR AB - Identification of genes that control root system architecture in crop plants requires innovations that enable high-throughput and accurate measurements of root system architecture through time. We demonstrate the ability of a semiautomated 3D in vivo imaging and digital phenotyping pipeline to interrogate the quantitative genetic basis of root system growth in a rice biparental mapping population, Bala x Azucena. We phenotyped >1,400 3D root models and >57,000 2D images for a suite of 25 traits that quantified the distribution, shape, extent of exploration, and the intrinsic size of root networks at days 12, 14, and 16 of growth in a gellan gum medium. From these data we identified 89 quantitative trait loci, some of which correspond to those found previously in soil-grown plants, and provide evidence for genetic tradeoffs in root growth allocations, such as between the extent and thoroughness of exploration. We also developed a multivariate method for generating and mapping central root architecture phenotypes and used it to identify five major quantitative trait loci (r2 = 24-37%), two of which were not identified by our univariate analysis. Our imaging and analytical platform provides a means to identify genes with high potential for improving root traits and agronomic qualities of crops. AU - Topp, Christopher AU - Iyer Pascuzzi, Anjali AU - Anderson, Jill AU - Lee, Cheng AU - Zurek, Paul AU - Symonova, Olga AU - Zheng, Ying AU - Bucksch, Alexander AU - Mileyko, Yuriy AU - Galkovskyi, Taras AU - Moore, Brad AU - Harer, John AU - Edelsbrunner, Herbert AU - Mitchell Olds, Thomas AU - Weitz, Joshua AU - Benfey, Philip ID - 2822 IS - 18 JF - PNAS TI - 3D phenotyping and quantitative trait locus mapping identify core regions of the rice genome controlling root architecture VL - 110 ER - TY - JOUR AB - Many key aspects of plant development are regulated by the polarized transport of the phytohormone auxin. Cellular auxin efflux, the rate-limiting step in this process, has been shown to rely on the coordinated action of PIN-formed (PIN) and B-type ATP binding cassette (ABCB) carriers. Here, we report that polar auxin transport in the Arabidopsis thaliana root also requires the action of a Major Facilitator Superfamily (MFS) transporter, Zinc-Induced Facilitator-Like 1 (ZIFL1). Sequencing, promoter-reporter, and fluorescent protein fusion experiments indicate that the full-length ZIFL1.1 protein and a truncated splice isoform, ZIFL1.3, localize to the tonoplast of root cells and the plasma membrane of leaf stomatal guard cells, respectively. Using reverse genetics, we show that the ZIFL1.1 transporter regulates various root auxin-related processes, while the ZIFL1.3 isoform mediates drought tolerance by regulating stomatal closure. Auxin transport and immunolocalization assays demonstrate that ZIFL1.1 indirectly modulates cellular auxin efflux during shootward auxin transport at the root tip, likely by regulating plasma membrane PIN2 abundance. Finally, heterologous expression in yeast revealed that ZIFL1.1 and ZIFL1.3 share H+-coupled K+ transport activity. Thus, by determining the subcellular and tissue distribution of two isoforms, alternative splicing dictates a dual function for the ZIFL1 transporter. We propose that this MFS carrier regulates stomatal movements and polar auxin transport by modulating potassium and proton fluxes in Arabidopsis cells. AU - Remy, Estelle AU - Cabrito, Tânia AU - Baster, Pawel AU - Batista, Rita AU - Teixeira, Miguel AU - Friml, Jirí AU - Sá Correia, Isabel AU - Duque, Paula ID - 2821 IS - 3 JF - Plant Cell TI - A major facilitator superfamily transporter plays a dual role in polar auxin transport and drought stress tolerance in Arabidopsis VL - 25 ER - TY - JOUR AB - Removal of cargos from the cell surface via endocytosis is an efficient mechanism to regulate activities of plasma membrane (PM)-resident proteins, such as receptors or transporters. Salicylic acid (SA) is an important plant hormone that is traditionally associated with pathogen defense. Here, we describe an unanticipated effect of SA on subcellular endocytic cycling of proteins. Both exogenous treatments and endogenously enhanced SA levels repressed endocytosis of different PM proteins. The SA effect on endocytosis did not involve transcription or known components of the SA signaling pathway for transcriptional regulation. SA likely targets an endocytic mechanism that involves the coat protein clathrin, because SA interfered with the clathrin incidence at the PM and clathrin-deficient mutants were less sensitive to the impact of SA on the auxin distribution and root bending during the gravitropic response. By contrast, SA did not affect the ligand-induced endocytosis of the FLAGELLIN SENSING2 (FLS2) receptor during pathogen responses. Our data suggest that the established SA impact on transcription in plant immunity and the nontranscriptional effect of SA on clathrin-mediated endocytosis are independent mechanisms by which SA regulates distinct aspects of plant physiology. AU - Du, Yunlong AU - Tejos, Ricardo AU - Beck, Martina AU - Himschoot, Ellie AU - Li, Hongjiang AU - Robatzek, Silke AU - Vanneste, Steffen AU - Friml, Jirí ID - 2827 IS - 19 JF - PNAS TI - Salicylic acid interferes with clathrin-mediated endocytic protein trafficking VL - 110 ER - TY - JOUR AB - The primary goal of restoration is to create self-sustaining ecological communities that are resilient to periodic disturbance. Currently, little is known about how restored communities respond to disturbance events such as fire and how this response compares to remnant vegetation. Following the 2003 fires in south-eastern Australia we examined the post-fire response of revegetation plantings and compared this to remnant vegetation. Ten burnt and 10 unburnt (control) sites were assessed for each of three types of vegetation (direct seeding revegetation, revegetation using nursery seedlings (tubestock) and remnant woodland). Sixty sampling sites were surveyed 6months after fire to quantify the initial survival of mid- and overstorey plant species in each type of vegetation. Three and 5years after fire all sites were resurveyed to assess vegetation structure, species diversity and vigour, as well as indicators of soil function. Overall, revegetation showed high (>60%) post-fire survival, but this varied among species depending on regeneration strategy (obligate seeder or resprouter). The native ground cover, mid- and overstorey in both types of plantings showed rapid recovery of vegetation structure and cover within 3years of fire. This recovery was similar to the burnt remnant woodlands. Non-native (exotic) ground cover initially increased after fire, but was no different in burnt and unburnt sites 5years after fire. Fire had no effect on species richness, but burnt direct seeding sites had reduced species diversity (Simpson's Diversity Index) while diversity was higher in burnt remnant woodlands. Indices of soil function in all types of vegetation had recovered to levels found in unburnt sites 5years after fire. These results indicate that even young revegetation (stands <10years old) showed substantial recovery from disturbance by fire. This suggests that revegetation can provide an important basis for restoring woodland communities in the fire-prone Australian environment. AU - Pickup, Melinda AU - Wilson, Susie AU - Freudenberger, David AU - Nicholls, Nick AU - Gould, Lori AU - Hnatiuk, Sarah AU - Delandre, Jeni ID - 2823 IS - 3 JF - Austral Ecology TI - Post-fire recovery of revegetated woodland communities in south-eastern Australia VL - 38 ER - 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 -