@article{2469, abstract = {Cadherins are transmembrane proteins that mediate cell–cell adhesion in animals. By regulating contact formation and stability, cadherins play a crucial role in tissue morphogenesis and homeostasis. Here, we review the three major unctions of cadherins in cell–cell contact formation and stability. Two of those functions lead to a decrease in interfacial ension at the forming cell–cell contact, thereby promoting contact expansion — first, by providing adhesion tension that lowers interfacial tension at the cell–cell contact, and second, by signaling to the actomyosin cytoskeleton in order to reduce cortex tension and thus interfacial tension at the contact. The third function of cadherins in cell–cell contact formation is to stabilize the contact by resisting mechanical forces that pull on the contact.}, author = {Maître, Jean-Léon and Heisenberg, Carl-Philipp J}, journal = {Current Biology}, number = {14}, pages = {R626 -- R633}, publisher = {Cell Press}, title = {{Three functions of cadherins in cell adhesion}}, doi = {10.1016/j.cub.2013.06.019}, volume = {23}, year = {2013}, } @article{247, abstract = {An improved estimate is provided for the number of Fq-rational points on a geometrically irreducible, projective, cubic hypersurface that is not equal to a cone.}, author = {Timothy Browning}, journal = {Canadian Mathematical Bulletin}, number = {3}, pages = {500 -- 502}, publisher = {Unknown}, title = {{The Lang-Weil estimate for cubic hypersurfaces}}, doi = {10.4153/CMB-2011-177-4}, volume = {56}, year = {2013}, } @article{2473, abstract = {When a mutation with selective advantage s spreads through a panmictic population, it may cause two lineages at a linked locus to coalesce; the probability of coalescence is exp(−2rT), where T∼log(2Ns)/s is the time to fixation, N is the number of haploid individuals, and r is the recombination rate. Population structure delays fixation, and so weakens the effect of a selective sweep. However, favourable alleles spread through a spatially continuous population behind a narrow wavefront; ancestral lineages are confined at the tip of this front, and so coalesce rapidly. In extremely dense populations, coalescence is dominated by rare fluctuations ahead of the front. However, we show that for moderate densities, a simple quasi-deterministic approximation applies: the rate of coalescence within the front is λ∼2g(η)/(ρℓ), where ρ is the population density and is the characteristic scale of the wavefront; g(η) depends only on the strength of random drift, . The net effect of a sweep on coalescence also depends crucially on whether two lineages are ever both within the wavefront at the same time: even in the extreme case when coalescence within the front is instantaneous, the net rate of coalescence may be lower than in a single panmictic population. Sweeps can also have a substantial impact on the rate of gene flow. A single lineage will jump to a new location when it is hit by a sweep, with mean square displacement ; this can be substantial if the species’ range, L, is large, even if the species-wide rate of sweeps per map length, Λ/R, is small. This effect is half as strong in two dimensions. In contrast, the rate of coalescence between lineages, at random locations in space and on the genetic map, is proportional to (c/L)(Λ/R), where c is the wavespeed: thus, on average, one-dimensional structure is likely to reduce coalescence due to sweeps, relative to panmixis. In two dimensions, genes must move along the front before they can coalesce; this process is rapid, being dominated by rare fluctuations. This leads to a dramatically higher rate of coalescence within the wavefront than if lineages simply diffused along the front. Nevertheless, the net rate of coalescence due to a sweep through a two-dimensional population is likely to be lower than it would be with panmixis.}, author = {Barton, Nicholas H and Etheridge, Alison and Kelleher, Jerome and Véber, Amandine}, journal = {Theoretical Population Biology}, number = {8}, pages = {75 -- 89}, publisher = {Elsevier}, title = {{Genetic hitch-hiking in spatially extended populations}}, doi = {10.1016/j.tpb.2012.12.001}, volume = {87}, year = {2013}, } @article{2478, abstract = {Despite the pivotal functions of the NMDA receptor (NMDAR) for neural circuit development and synaptic plasticity, the molecular mechanisms underlying the dynamics of NMDAR trafficking are poorly understood. The cell adhesion molecule neuroligin-1 (NL1) modifies NMDAR-dependent synaptic transmission and synaptic plasticity, but it is unclear whether NL1 controls synaptic accumulation or function of the receptors. Here, we provide evidence that NL1 regulates the abundance of NMDARs at postsynaptic sites. This function relies on extracellular, NL1 isoform-specific sequences that facilitate biochemical interactions between NL1 and the NMDAR GluN1 subunit. Our work uncovers NL1 isoform-specific cisinteractions with ionotropic glutamate receptors as a key mechanism for controlling synaptic properties.}, author = {Budreck, Elaine C and Kwon, Oh-Bin and Jung, Jung-Hoon and Baudouin, Stéphane J and Thommen, Albert and Kim, Hye-Sun and Fukazawa, Yugo and Harumi Harada and Tabuchi, Katsuhiko and Ryuichi Shigemoto and Scheiffele, Peter and Kim, Joung-Hun}, journal = {PNAS}, number = {2}, pages = {725 -- 730}, publisher = {National Academy of Sciences}, title = {{Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling}}, doi = {10.1073/pnas.1214718110}, volume = {110}, year = {2013}, } @article{250, abstract = {Châtelet surfaces provide a rich source of geometrically rational surfaces that do not always satisfy the Hasse principle. Restricting attention to a special class of Châtelet surfaces, we investigate the frequency that such counter-examples arise over the rational numbers.}, author = {de la Bretèche, Régis and Timothy Browning}, journal = {Proceedings of the London Mathematical Society}, number = {4}, pages = {1030 -- 1078}, publisher = {Oxford University Press}, title = {{Density of Châtelet surfaces failing the Hasse principle}}, doi = {10.1112/plms/pdt060}, volume = {108}, year = {2013}, } @article{251, abstract = {We study the density of varieties in a certain family which do not satisfy the Hasse principle. This work relies on results recently obtained by Colliot-Thélène [3].}, author = {de la Bretèche, Régis and Timothy Browning}, journal = {Journal de Theorie des Nombres de Bordeaux}, number = {1}, pages = {25 -- 44}, publisher = {Universite de Bordeaux I}, title = {{Counter examples to the Hasse principle among certain coflasque tori}}, doi = {10.5802/jtnb.857}, volume = {26}, year = {2013}, } @inproceedings{2517, abstract = {Traditional formal methods are based on a Boolean satisfaction notion: a reactive system satisfies, or not, a given specification. We generalize formal methods to also address the quality of systems. As an adequate specification formalism we introduce the linear temporal logic LTL[F]. The satisfaction value of an LTL[F] formula is a number between 0 and 1, describing the quality of the satisfaction. The logic generalizes traditional LTL by augmenting it with a (parameterized) set F of arbitrary functions over the interval [0,1]. For example, F may contain the maximum or minimum between the satisfaction values of subformulas, their product, and their average. The classical decision problems in formal methods, such as satisfiability, model checking, and synthesis, are generalized to search and optimization problems in the quantitative setting. For example, model checking asks for the quality in which a specification is satisfied, and synthesis returns a system satisfying the specification with the highest quality. Reasoning about quality gives rise to other natural questions, like the distance between specifications. We formalize these basic questions and study them for LTL[F]. By extending the automata-theoretic approach for LTL to a setting that takes quality into an account, we are able to solve the above problems and show that reasoning about LTL[F] has roughly the same complexity as reasoning about traditional LTL.}, author = {Almagor, Shaull and Boker, Udi and Kupferman, Orna}, location = {Riga, Latvia}, number = {Part 2}, pages = {15 -- 27}, publisher = {Springer}, title = {{Formalizing and reasoning about quality}}, doi = {10.1007/978-3-642-39212-2_3}, volume = {7966}, year = {2013}, } @inproceedings{2518, abstract = {A class of valued constraint satisfaction problems (VCSPs) is characterised by a valued constraint language, a fixed set of cost functions on a finite domain. An instance of the problem is specified by a sum of cost functions from the language with the goal to minimise the sum. We study which classes of finite-valued languages can be solved exactly by the basic linear programming relaxation (BLP). Thapper and Živný showed [20] that if BLP solves the language then the language admits a binary commutative fractional polymorphism. We prove that the converse is also true. This leads to a necessary and a sufficient condition which can be checked in polynomial time for a given language. In contrast, the previous necessary and sufficient condition due to [20] involved infinitely many inequalities. More recently, Thapper and Živný [21] showed (using, in particular, a technique introduced in this paper) that core languages that do not satisfy our condition are NP-hard. Taken together, these results imply that a finite-valued language can either be solved using Linear Programming or is NP-hard.}, author = {Kolmogorov, Vladimir}, location = {Riga, Latvia}, number = {1}, pages = {625 -- 636}, publisher = {Springer}, title = {{The power of linear programming for finite-valued CSPs: A constructive characterization}}, doi = {10.1007/978-3-642-39206-1_53}, volume = {7965}, year = {2013}, } @article{2516, abstract = {We study the problem of object recognition for categories for which we have no training examples, a task also called zero-data or zero-shot learning. This situation has hardly been studied in computer vision research, even though it occurs frequently: the world contains tens of thousands of different object classes and for only few of them image collections have been formed and suitably annotated. To tackle the problem we introduce attribute-based classification: objects are identified based on a high-level description that is phrased in terms of semantic attributes, such as the object's color or shape. Because the identification of each such property transcends the specific learning task at hand, the attribute classifiers can be pre-learned independently, e.g. from existing image datasets unrelated to the current task. Afterwards, new classes can be detected based on their attribute representation, without the need for a new training phase. In this paper we also introduce a new dataset, Animals with Attributes, of over 30,000 images of 50 animal classes, annotated with 85 semantic attributes. Extensive experiments on this and two more datasets show that attribute-based classification indeed is able to categorize images without access to any training images of the target classes.}, author = {Lampert, Christoph and Nickisch, Hannes and Harmeling, Stefan}, journal = {IEEE Transactions on Pattern Analysis and Machine Intelligence}, number = {3}, pages = {453 -- 465}, publisher = {IEEE}, title = {{Attribute-based classification for zero-shot learning of object categories}}, doi = {10.1109/TPAMI.2013.140}, volume = {36}, year = {2013}, } @inproceedings{2520, abstract = {We propose a probabilistic model to infer supervised latent variables in the Hamming space from observed data. Our model allows simultaneous inference of the number of binary latent variables, and their values. The latent variables preserve neighbourhood structure of the data in a sense that objects in the same semantic concept have similar latent values, and objects in different concepts have dissimilar latent values. We formulate the supervised infinite latent variable problem based on an intuitive principle of pulling objects together if they are of the same type, and pushing them apart if they are not. We then combine this principle with a flexible Indian Buffet Process prior on the latent variables. We show that the inferred supervised latent variables can be directly used to perform a nearest neighbour search for the purpose of retrieval. We introduce a new application of dynamically extending hash codes, and show how to effectively couple the structure of the hash codes with continuously growing structure of the neighbourhood preserving infinite latent feature space.}, author = {Quadrianto, Novi and Sharmanska, Viktoriia and Knowles, David and Ghahramani, Zoubin}, booktitle = {Proceedings of the 29th conference uncertainty in Artificial Intelligence}, isbn = {9780974903996}, location = {Bellevue, WA, United States}, pages = {527 -- 536}, publisher = {AUAI Press}, title = {{The supervised IBP: Neighbourhood preserving infinite latent feature models}}, year = {2013}, } @article{253, author = {Timothy Browning}, journal = {Mathematika}, number = {1}, pages = {101 -- 107}, publisher = {Unknown}, title = {{Counting rational points on cubic hypersurfaces: Corrigendum}}, doi = {10.1112/S0025579313000132}, volume = {60}, year = {2013}, } @article{2692, abstract = {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.}, author = {Dobi, Alice and Sartori, Simone B and Busti, Daniela and Van Der Putten, Herman V and Singewald, Nicolas and Ryuichi Shigemoto and Ferraguti, Francesco}, journal = {Neuropharmacology}, pages = {274 -- 289}, publisher = {Elsevier}, title = {{Neural substrates for the distinct effects of presynaptic group III metabotropic glutamate receptors on extinction of contextual fear conditioning in mice}}, doi = {10.1016/j.neuropharm.2012.05.025}, volume = {66}, year = {2013}, } @article{2691, abstract = {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.}, author = {Indriati, Dwi Wahyu and Kamasawa, Naomi and Matsui, Ko and Meredith, Andrea L and Watanabe, Masahiko and Ryuichi Shigemoto}, journal = {Journal of Neuroscience}, number = {8}, pages = {3668 -- 3678}, publisher = {Society for Neuroscience}, title = {{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}}, doi = {10.1523/JNEUROSCI.2921-12.2013}, volume = {33}, year = {2013}, } @article{2690, abstract = {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.}, author = {Budisantoso, Timotheus and Harumi Harada and Kamasawa, Naomi and Fukazawa, Yugo and Ryuichi Shigemoto and Matsui, Ko}, journal = {Journal of Physiology}, number = {1}, pages = {219 -- 239}, publisher = {Wiley-Blackwell}, title = {{Evaluation of glutamate concentration transient in the synaptic cleft of the rat calyx of Held}}, doi = {10.1113/jphysiol.2012.241398}, volume = {591}, year = {2013}, } @article{2693, abstract = {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.}, author = {Booker, Sam A and Gross, Anna and Althof, Daniel and Ryuichi Shigemoto and Bettler, Bernhard and Frotscher, Michael and Hearing, Matthew C and Wickman, Kevin D and Watanabe, Masahiko and Kulik, Ákos and Vida, Imre}, journal = {Journal of Neuroscience}, number = {18}, pages = {7961 -- 7974}, publisher = {Society for Neuroscience}, title = {{Differential GABAB-receptor-mediated effects in perisomatic- and dendrite-targeting parvalbumin interneurons}}, doi = {10.1523/JNEUROSCI.1186-12.2013}, volume = {33}, year = {2013}, } @article{2698, abstract = {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.}, author = {Erdös, László and Fournais, Søren and Solovej, Jan}, journal = {Journal of the European Mathematical Society}, number = {6}, pages = {2093 -- 2113}, publisher = {European Mathematical Society}, title = {{Stability and semiclassics in self-generated fields}}, doi = {10.4171/JEMS/416}, volume = {15}, year = {2013}, } @article{2697, abstract = {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.}, author = {László Erdös and Knowles, Antti and Yau, Horng-Tzer and Yin, Jun}, journal = {Communications in Mathematical Physics}, number = {1}, pages = {367 -- 416}, publisher = {Springer}, title = {{Delocalization and diffusion profile for random band matrices}}, doi = {10.1007/s00220-013-1773-3}, volume = {323}, year = {2013}, } @inproceedings{2718, abstract = {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.}, author = {Barton, Nicholas H and Paixao, Tiago}, booktitle = {Proceedings of the 15th annual conference on Genetic and evolutionary computation}, location = {Amsterdam, Netherlands}, pages = {1573 -- 1580}, publisher = {ACM}, title = {{Can quantitative and population genetics help us understand evolutionary computation?}}, doi = {10.1145/2463372.2463568}, year = {2013}, } @article{2720, abstract = {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.}, author = {Long, Hongan and Paixao, Tiago and Azevedo, Ricardo and Zufall, Rebecca}, journal = {Genetics}, number = {2}, pages = {527--540}, publisher = {Genetics Society of America}, title = {{Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila}}, doi = {10.1534/genetics.113.153536}, volume = {195}, year = {2013}, } @inproceedings{2719, abstract = {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.}, author = {Paixao, Tiago and Barton, Nicholas H}, booktitle = {Proceedings of the 15th annual conference on Genetic and evolutionary computation}, location = {Amsterdam, Netherlands}, pages = {845 -- 852}, publisher = {ACM}, title = {{A variance decomposition approach to the analysis of genetic algorithms}}, doi = {10.1145/2463372.2463470}, year = {2013}, } @article{2782, abstract = {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.}, author = {Erdös, László and Farrell, Brendan}, journal = {Journal of Statistical Physics}, number = {6}, pages = {1003 -- 1032}, publisher = {Springer}, title = {{Local eigenvalue density for general MANOVA matrices}}, doi = {10.1007/s10955-013-0807-8}, volume = {152}, year = {2013}, } @article{2781, abstract = {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.}, author = {László Erdös and Knowles, Antti and Yau, Horng-Tzer and Yin, Jun}, journal = {Annals of Probability}, number = {3 B}, pages = {2279 -- 2375}, publisher = {Institute of Mathematical Statistics}, title = {{Spectral statistics of Erdős-Rényi graphs I: Local semicircle law}}, doi = {10.1214/11-AOP734}, volume = {41}, year = {2013}, } @article{2780, abstract = {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).}, author = {László Erdös and Knowles, Antti and Yau, Horng-Tzer}, journal = {Annales Henri Poincare}, number = {8}, pages = {1837 -- 1926}, publisher = {Birkhäuser}, title = {{Averaging fluctuations in resolvents of random band matrices}}, doi = {10.1007/s00023-013-0235-y}, volume = {14}, year = {2013}, } @inproceedings{2807, abstract = {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. }, author = {Čadek, Martin and Krcál, Marek and Matoušek, Jiří and Vokřínek, Lukáš and Wagner, Uli}, booktitle = {45th Annual ACM Symposium on theory of computing}, location = {Palo Alto, CA, United States}, pages = {595 -- 604}, publisher = {ACM}, title = {{Extending continuous maps: Polynomiality and undecidability}}, doi = {10.1145/2488608.2488683}, year = {2013}, } @article{2808, abstract = {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.}, author = {Landberg, Katarina and Pederson, Eric and Viaene, Tom and Bozorg, Behruz and Friml, Jirí and Jönsson, Henrik and Thelander, Mattias and Sundberg, Eva}, journal = {Plant Physiology}, number = {3}, pages = {1406 -- 1419}, publisher = {American Society of Plant Biologists}, title = {{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}}, doi = {10.1104/pp.113.214023}, volume = {162}, year = {2013}, } @article{2806, abstract = {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.}, author = {Avila, Kerstin and Hof, Björn}, journal = {Review of Scientific Instruments}, number = {6}, publisher = {American Institute of Physics}, title = {{High-precision Taylor-Couette experiment to study subcritical transitions and the role of boundary conditions and size effects}}, doi = {10.1063/1.4807704}, volume = {84}, year = {2013}, } @article{2805, abstract = {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.}, author = {Holzner, Markus and Song, Baofang and Avila, Marc and Björn Hof}, journal = {Journal of Fluid Mechanics}, pages = {140 -- 162}, publisher = {Cambridge University Press}, title = {{Lagrangian approach to laminar-turbulent interfaces in transitional pipe flow}}, doi = {10.1017/jfm.2013.127}, volume = {723}, year = {2013}, } @article{2810, abstract = {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.}, author = {De Vos, Marjon and Poelwijk, Frank and Battich, Nico and Ndika, Joseph and Tans, Sander}, journal = {PLoS Genetics}, number = {6}, publisher = {Public Library of Science}, title = {{Environmental dependence of genetic constraint}}, doi = {10.1371/journal.pgen.1003580}, volume = {9}, year = {2013}, } @article{2814, abstract = {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.}, author = {Chatterjee, Krishnendu and Alfaro, Luca and Majumdar, Ritankar}, journal = {International Journal of Foundations of Computer Science}, number = {2}, pages = {165 -- 185}, publisher = {World Scientific Publishing}, title = {{The complexity of coverage}}, doi = {10.1142/S0129054113400066}, volume = {24}, year = {2013}, } @article{2811, abstract = {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.}, author = {Avila, Marc and Hof, Björn}, journal = {Physical Review E}, number = {6}, publisher = {American Institute of Physics}, title = {{Nature of laminar-turbulence intermittency in shear flows}}, doi = {10.1103/PhysRevE.87.063012}, volume = {87}, year = {2013}, } @article{2813, abstract = {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.}, author = {Samanta, Devranjan and Dubief, Yves and Holzner, Markus and Schäfer, Christof and Morozov, Alexander and Wagner, Christian and Hof, Björn}, journal = {PNAS}, number = {26}, pages = {10557 -- 10562}, publisher = {National Academy of Sciences}, title = {{Elasto-inertial turbulence}}, doi = {10.1073/pnas.1219666110}, volume = {110}, year = {2013}, } @inproceedings{2812, abstract = {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.}, author = {Attali, Dominique and Bauer, Ulrich and Devillers, Olivier and Glisse, Marc and Lieutier, André}, booktitle = {Proceedings of the 29th annual symposium on Computational Geometry}, location = {Rio de Janeiro, Brazil}, pages = {117 -- 125}, publisher = {ACM}, title = {{Homological reconstruction and simplification in R3}}, doi = {10.1145/2462356.2462373}, year = {2013}, } @article{2817, abstract = {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.}, author = {Novak, Sebastian and Chatterjee, Krishnendu and Nowak, Martin}, journal = {Journal of Theoretical Biology}, pages = {26 -- 34}, publisher = {Elsevier}, title = {{Density games}}, doi = {10.1016/j.jtbi.2013.05.029}, volume = {334}, year = {2013}, } @inproceedings{2819, abstract = {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. }, author = {Chatterjee, Krishnendu and Prabhu, Vinayak}, booktitle = {Proceedings of the 16th International Conference on Hybrid Systems: Computation and Control}, location = {Philadelphia, PA USA}, pages = {273 -- 282}, publisher = {Springer}, title = {{Quantitative timed simulation functions and refinement metrics for real-time systems}}, doi = {10.1145/2461328.2461370}, volume = {1}, year = {2013}, } @article{2818, abstract = {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.}, author = {Rajan, Kanaka and Marre, Olivier and Tkacik, Gasper}, journal = {Neural Computation}, number = {7}, pages = {1661 -- 1692}, publisher = {MIT Press }, title = {{Learning quadratic receptive fields from neural responses to natural stimuli}}, doi = {10.1162/NECO_a_00463}, volume = {25}, year = {2013}, } @article{2826, abstract = {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.}, author = {Tran Viet, Khanh and Powell, Caldwell and Barathi, Veluchamy and Klemm, Thomas and Maurer Stroh, Sebastian and Limviphuvadh, Vachiranee and Soler, Vincent and Ho, Candice and Yanovitch, Tammy and Schneider, Georg and Li, Yi and Nading, Erica and Metlapally, Ravikanth and Saw, Seang and Goh, Liang and Rozen, Steve and Young, Terri}, journal = {American Journal of Human Genetics}, number = {5}, pages = {820 -- 826}, publisher = {Cell Press}, title = {{Mutations in SCO2 are associated with autosomal-dominant high-grade myopia}}, doi = {10.1016/j.ajhg.2013.04.005}, volume = {92}, year = {2013}, } @article{2822, abstract = {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.}, author = {Topp, Christopher and Iyer Pascuzzi, Anjali and Anderson, Jill and Lee, Cheng and Zurek, Paul and Symonova, Olga and Zheng, Ying and Bucksch, Alexander and Mileyko, Yuriy and Galkovskyi, Taras and Moore, Brad and Harer, John and Edelsbrunner, Herbert and Mitchell Olds, Thomas and Weitz, Joshua and Benfey, Philip}, journal = {PNAS}, number = {18}, pages = {E1695 -- E1704}, publisher = {National Academy of Sciences}, title = {{3D phenotyping and quantitative trait locus mapping identify core regions of the rice genome controlling root architecture}}, doi = {10.1073/pnas.1304354110}, volume = {110}, year = {2013}, } @article{2821, abstract = {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.}, author = {Remy, Estelle and Cabrito, Tânia and Baster, Pawel and Batista, Rita and Teixeira, Miguel and Friml, Jirí and Sá Correia, Isabel and Duque, Paula}, journal = {Plant Cell}, number = {3}, pages = {901 -- 926}, publisher = {American Society of Plant Biologists}, title = {{A major facilitator superfamily transporter plays a dual role in polar auxin transport and drought stress tolerance in Arabidopsis}}, doi = {10.1105/tpc.113.110353}, volume = {25}, year = {2013}, } @article{2827, abstract = {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.}, author = {Du, Yunlong and Tejos, Ricardo and Beck, Martina and Himschoot, Ellie and Li, Hongjiang and Robatzek, Silke and Vanneste, Steffen and Friml, Jirí}, journal = {PNAS}, number = {19}, pages = {7946 -- 7951}, publisher = {National Academy of Sciences}, title = {{Salicylic acid interferes with clathrin-mediated endocytic protein trafficking}}, doi = {10.1073/pnas.1220205110}, volume = {110}, year = {2013}, } @article{2823, abstract = {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.}, author = {Pickup, Melinda and Wilson, Susie and Freudenberger, David and Nicholls, Nick and Gould, Lori and Hnatiuk, Sarah and Delandre, Jeni}, journal = {Austral Ecology}, number = {3}, pages = {300 -- 312}, publisher = {Wiley-Blackwell}, title = {{Post-fire recovery of revegetated woodland communities in south-eastern Australia}}, doi = {10.1111/j.1442-9993.2012.02404.x}, volume = {38}, year = {2013}, } @article{2824, abstract = {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.}, author = {Chatterjee, Krishnendu and Prabhu, Vinayak}, journal = {Information and Computation}, pages = {83--119}, publisher = {Elsevier}, title = {{Synthesis of memory-efficient, clock-memory free, and non-Zeno safety controllers for timed systems}}, doi = {10.1016/j.ic.2013.04.003}, volume = {228-229}, year = {2013}, } @article{2832, abstract = {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.}, author = {Tanaka, Hirokazu and Kitakura, Saeko and Rakusová, Hana and Uemura, Tomohiro and Feraru, Mugurel and De Rycke, Riet and Robert, Stéphanie and Kakimoto, Tatsuo and Friml, Jirí}, journal = {PLoS Genetics}, number = {5}, publisher = {Public Library of Science}, title = {{Cell polarity and patterning by PIN trafficking through early endosomal compartments in arabidopsis thaliana}}, doi = {10.1371/journal.pgen.1003540}, volume = {9}, year = {2013}, } @article{2828, abstract = {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.}, author = {Kolmogorov, Vladimir and Živný, Stanislav}, journal = {Journal of the ACM}, number = {2}, publisher = {ACM}, title = {{The complexity of conservative valued CSPs}}, doi = {10.1145/2450142.2450146}, volume = {60}, year = {2013}, } @article{2829, abstract = {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.}, author = {Shi, Liang and Avila, Marc and Hof, Björn}, journal = {Physical Review Letters}, number = {20}, publisher = {American Physical Society}, title = {{Scale invariance at the onset of turbulence in couette flow}}, doi = {10.1103/PhysRevLett.110.204502}, volume = {110}, year = {2013}, } @article{2834, abstract = {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.}, author = {Avila, Marc and Mellibovsky, Fernando and Roland, Nicolas and Hof, Björn}, journal = {Physical Review Letters}, number = {22}, publisher = {American Physical Society}, title = {{Streamwise-localized solutions at the onset of turbulence in pipe flow}}, doi = {10.1103/PhysRevLett.110.224502}, volume = {110}, year = {2013}, } @article{2833, abstract = {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.}, author = {Heisenberg, Carl-Philipp J and Bellaïche, Yohanns}, journal = {Cell}, number = {5}, pages = {948 -- 962}, publisher = {Cell Press}, title = {{Forces in tissue morphogenesis and patterning}}, doi = {10.1016/j.cell.2013.05.008}, volume = {153}, year = {2013}, } @article{2830, author = {Moussion, Christine and Sixt, Michael K}, journal = {Immunity}, number = {5}, pages = {853 -- 854}, publisher = {Cell Press}, title = {{A conduit to amplify innate immunity}}, doi = {10.1016/j.immuni.2013.05.005}, volume = {38}, year = {2013}, } @article{2842, abstract = {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.}, author = {Barton, Nicholas H and Etheridge, Alison and Kelleher, Jerome and Véber, Amandine}, journal = {Theoretical Population Biology}, number = {1}, pages = {105 -- 119}, publisher = {Elsevier}, title = {{Inference in two dimensions: Allele frequencies versus lengths of shared sequence blocks}}, doi = {10.1016/j.tpb.2013.03.001}, volume = {87}, year = {2013}, } @article{2838, abstract = {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.}, author = {Arquè Fuste, Gloria and Casanovas, Anna and Dierssen, Mara}, journal = {PLoS One}, number = {1}, publisher = {Public Library of Science}, title = {{Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: Possible role in Down syndrome}}, doi = {10.1371/journal.pone.0054285}, volume = {8}, year = {2013}, } @article{2839, abstract = {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.}, author = {Weber, Michele and Hauschild, Robert and Schwarz, Jan and Moussion, Christine and De Vries, Ingrid and Legler, Daniel and Luther, Sanjiv and Bollenbach, Mark Tobias and Sixt, Michael K}, journal = {Science}, number = {6117}, pages = {328 -- 332}, publisher = {American Association for the Advancement of Science}, title = {{Interstitial dendritic cell guidance by haptotactic chemokine gradients}}, doi = {10.1126/science.1228456}, volume = {339}, year = {2013}, }