@article{2250, abstract = {The genome sequences of new viruses often contain many "orphan" or "taxon-specific" proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as "genus specific" by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virionsd.}, author = {Kuchibhatla, Durga and Sherman, Westley and Chung, Betty and Cook, Shelley and Schneider, Georg and Eisenhaber, Birgit and Karlin, David}, issn = {0022538X}, journal = {Journal of Virology}, number = {1}, pages = {10 -- 20}, publisher = {ASM}, title = {{Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently "orphan" viral proteins}}, doi = {10.1128/JVI.02595-13}, volume = {88}, year = {2014}, } @article{2251, abstract = {Sharp wave/ripple (SWR, 150–250 Hz) hippocampal events have long been postulated to be involved in memory consolidation. However, more recent work has investigated SWRs that occur during active waking behaviour: findings that suggest that SWRs may also play a role in cell assembly strengthening or spatial working memory. Do such theories of SWR function apply to animal learning? This review discusses how general theories linking SWRs to memory-related function may explain circuit mechanisms related to rodent spatial learning and to the associated stabilization of new cognitive maps.}, author = {Csicsvari, Jozsef L and Dupret, David}, issn = {09628436}, journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, number = {1635}, publisher = {Royal Society, The}, title = {{Sharp wave/ripple network oscillations and learning-associated hippocampal maps}}, doi = {10.1098/rstb.2012.0528}, volume = {369}, year = {2014}, } @article{2252, abstract = {The pattern of inheritance and mechanism of sex determination can have important evolutionary consequences. We studied probabilistic sex determination in the ciliate Tetrahymena thermophila, which was previously shown to cause evolution of skewed sex ratios. We find that the genetic background alters the sex determination patterns of mat alleles in heterozygotes and that allelic interaction can differentially influence the expression probability of the 7 sexes. We quantify the dominance relationships between several mat alleles and find that A-type alleles, which specify sex I, are indeed recessive to B-type alleles, which are unable to specify that sex. Our results provide additional support for the presence of modifier loci and raise implications for the dynamics of sex ratios in populations of T. thermophila.}, author = {Phadke, Sujal and Paixao, Tiago and Pham, Tuan and Pham, Stephanie and Zufall, Rebecca}, issn = {00221503}, journal = {Journal of Heredity}, number = {1}, pages = {130 -- 135}, publisher = {Oxford University Press}, title = {{Genetic background alters dominance relationships between mat alleles in the ciliate Tetrahymena Thermophila}}, doi = {10.1093/jhered/est063}, volume = {105}, year = {2014}, } @article{2253, abstract = {Plant growth is achieved predominantly by cellular elongation, which is thought to be controlled on several levels by apoplastic auxin. Auxin export into the apoplast is achieved by plasma membrane efflux catalysts of the PIN-FORMED (PIN) and ATP-binding cassette protein subfamily B/phosphor- glycoprotein (ABCB/PGP) classes; the latter were shown to depend on interaction with the FKBP42, TWISTED DWARF1 (TWD1). Here by using a transgenic approach in combination with phenotypical, biochemical and cell biological analyses we demonstrate the importance of a putative C-terminal in-plane membrane anchor of TWD1 in the regulation of ABCB-mediated auxin transport. In contrast with dwarfed twd1 loss-of-function alleles, TWD1 gain-of-function lines that lack a putative in-plane membrane anchor (HA-TWD1-Ct) show hypermorphic plant architecture, characterized by enhanced stem length and leaf surface but reduced shoot branching. Greater hypocotyl length is the result of enhanced cell elongation that correlates with reduced polar auxin transport capacity for HA-TWD1-Ct. As a consequence, HA-TWD1-Ct displays higher hypocotyl auxin accumulation, which is shown to result in elevated auxin-induced cell elongation rates. Our data highlight the importance of C-terminal membrane anchoring for TWD1 action, which is required for specific regulation of ABCB-mediated auxin transport. These data support a model in which TWD1 controls lateral ABCB1-mediated export into the apoplast, which is required for auxin-mediated cell elongation.}, author = {Bailly, Aurélien and Wang, Bangjun and Zwiewka, Marta and Pollmann, Stephan and Schenck, Daniel and Lüthen, Hartwig and Schulz, Alexander and Friml, Jirí and Geisler, Markus}, issn = {09607412}, journal = {Plant Journal}, number = {1}, pages = {108 -- 118}, publisher = {Wiley-Blackwell}, title = {{Expression of TWISTED DWARF1 lacking its in-plane membrane anchor leads to increased cell elongation and hypermorphic growth}}, doi = {10.1111/tpj.12369}, volume = {77}, year = {2014}, } @article{2254, abstract = {Theta-gamma network oscillations are thought to represent key reference signals for information processing in neuronal ensembles, but the underlying synaptic mechanisms remain unclear. To address this question, we performed whole-cell (WC) patch-clamp recordings from mature hippocampal granule cells (GCs) in vivo in the dentate gyrus of anesthetized and awake rats. GCs in vivo fired action potentials at low frequency, consistent with sparse coding in the dentate gyrus. GCs were exposed to barrages of fast AMPAR-mediated excitatory postsynaptic currents (EPSCs), primarily relayed from the entorhinal cortex, and inhibitory postsynaptic currents (IPSCs), presumably generated by local interneurons. EPSCs exhibited coherence with the field potential predominantly in the theta frequency band, whereas IPSCs showed coherence primarily in the gamma range. Action potentials in GCs were phase locked to network oscillations. Thus, theta-gamma-modulated synaptic currents may provide a framework for sparse temporal coding of information in the dentate gyrus.}, author = {Pernia-Andrade, Alejandro and Jonas, Peter M}, issn = {08966273}, journal = {Neuron}, number = {1}, pages = {140 -- 152}, publisher = {Elsevier}, title = {{Theta-gamma-modulated synaptic currents in hippocampal granule cells in vivo define a mechanism for network oscillations}}, doi = {10.1016/j.neuron.2013.09.046}, volume = {81}, year = {2014}, } @article{2255, abstract = {Motivated by applications in biology, we present an algorithm for estimating the length of tube-like shapes in 3-dimensional Euclidean space. In a first step, we combine the tube formula of Weyl with integral geometric methods to obtain an integral representation of the length, which we approximate using a variant of the Koksma-Hlawka Theorem. In a second step, we use tools from computational topology to decrease the dependence on small perturbations of the shape. We present computational experiments that shed light on the stability and the convergence rate of our algorithm.}, author = {Edelsbrunner, Herbert and Pausinger, Florian}, issn = {09249907}, journal = {Journal of Mathematical Imaging and Vision}, number = {1}, pages = {164 -- 177}, publisher = {Springer}, title = {{Stable length estimates of tube-like shapes}}, doi = {10.1007/s10851-013-0468-x}, volume = {50}, year = {2014}, } @article{2257, abstract = {Maximum entropy models are the least structured probability distributions that exactly reproduce a chosen set of statistics measured in an interacting network. Here we use this principle to construct probabilistic models which describe the correlated spiking activity of populations of up to 120 neurons in the salamander retina as it responds to natural movies. Already in groups as small as 10 neurons, interactions between spikes can no longer be regarded as small perturbations in an otherwise independent system; for 40 or more neurons pairwise interactions need to be supplemented by a global interaction that controls the distribution of synchrony in the population. Here we show that such “K-pairwise” models—being systematic extensions of the previously used pairwise Ising models—provide an excellent account of the data. We explore the properties of the neural vocabulary by: 1) estimating its entropy, which constrains the population's capacity to represent visual information; 2) classifying activity patterns into a small set of metastable collective modes; 3) showing that the neural codeword ensembles are extremely inhomogenous; 4) demonstrating that the state of individual neurons is highly predictable from the rest of the population, allowing the capacity for error correction.}, author = {Tkacik, Gasper and Marre, Olivier and Amodei, Dario and Schneidman, Elad and Bialek, William and Berry, Michael}, issn = {1553734X}, journal = {PLoS Computational Biology}, number = {1}, publisher = {Public Library of Science}, title = {{Searching for collective behavior in a large network of sensory neurons}}, doi = {10.1371/journal.pcbi.1003408}, volume = {10}, year = {2014}, } @article{2261, abstract = {To reveal the full potential of human pluripotent stem cells, new methods for rapid, site-specific genomic engineering are needed. Here, we describe a system for precise genetic modification of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We identified a novel human locus, H11, located in a safe, intergenic, transcriptionally active region of chromosome 22, as the recipient site, to provide robust, ubiquitous expression of inserted genes. Recipient cell lines were established by site-specific placement of a ‘landing pad’ cassette carrying attP sites for phiC31 and Bxb1 integrases at the H11 locus by spontaneous or TALEN-assisted homologous recombination. Dual integrase cassette exchange (DICE) mediated by phiC31 and Bxb1 integrases was used to insert genes of interest flanked by phiC31 and Bxb1 attB sites at the H11 locus, replacing the landing pad. This system provided complete control over content, direction and copy number of inserted genes, with a specificity of 100%. A series of genes, including mCherry and various combinations of the neural transcription factors LMX1a, FOXA2 and OTX2, were inserted in recipient cell lines derived from H9 ESC, as well as iPSC lines derived from a Parkinson’s disease patient and a normal sibling control. The DICE system offers rapid, efficient and precise gene insertion in ESC and iPSC and is particularly well suited for repeated modifications of the same locus.}, author = {Zhu, Fangfang and Gamboa, Matthew and Farruggio, Alfonso and Hippenmeyer, Simon and Tasic, Bosiljka and Schüle, Birgitt and Chen Tsai, Yanru and Calos, Michele}, journal = {Nucleic Acids Research}, number = {5}, publisher = {Oxford University Press}, title = {{DICE, an efficient system for iterative genomic editing in human pluripotent stem cells}}, doi = {10.1093/nar/gkt1290}, volume = {42}, year = {2014}, } @inbook{2265, abstract = {Coordinated migration of newly-born neurons to their target territories is essential for correct neuronal circuit assembly in the developing brain. Although a cohort of signaling pathways has been implicated in the regulation of cortical projection neuron migration, the precise molecular mechanisms and how a balanced interplay of cell-autonomous and non-autonomous functions of candidate signaling molecules controls the discrete steps in the migration process, are just being revealed. In this chapter, I will focally review recent advances that improved our understanding of the cell-autonomous and possible cell-nonautonomous functions of the evolutionarily conserved LIS1/NDEL1-complex in regulating the sequential steps of cortical projection neuron migration. I will then elaborate on the emerging concept that the Reelin signaling pathway, acts exactly at precise stages in the course of cortical projection neuron migration. Lastly, I will discuss how finely tuned transcriptional programs and downstream effectors govern particular aspects in driving radial migration at discrete stages and how they regulate the precise positioning of cortical projection neurons in the developing cerebral cortex.}, author = {Hippenmeyer, Simon}, booktitle = { Cellular and Molecular Control of Neuronal Migration}, editor = {Nguyen, Laurent}, pages = {1 -- 24}, publisher = {Springer}, title = {{Molecular pathways controlling the sequential steps of cortical projection neuron migration}}, doi = {10.1007/978-94-007-7687-6_1}, volume = {800}, year = {2014}, } @inproceedings{2275, abstract = {Energies with high-order non-submodular interactions have been shown to be very useful in vision due to their high modeling power. Optimization of such energies, however, is generally NP-hard. A naive approach that works for small problem instances is exhaustive search, that is, enumeration of all possible labelings of the underlying graph. We propose a general minimization approach for large graphs based on enumeration of labelings of certain small patches. This partial enumeration technique reduces complex high-order energy formulations to pairwise Constraint Satisfaction Problems with unary costs (uCSP), which can be efficiently solved using standard methods like TRW-S. Our approach outperforms a number of existing state-of-the-art algorithms on well known difficult problems (e.g. curvature regularization, stereo, deconvolution); it gives near global minimum and better speed. Our main application of interest is curvature regularization. In the context of segmentation, our partial enumeration technique allows to evaluate curvature directly on small patches using a novel integral geometry approach. }, author = {Olsson, Carl and Ulen, Johannes and Boykov, Yuri and Kolmogorov, Vladimir}, location = {Sydney, Australia}, pages = {2936 -- 2943}, publisher = {IEEE}, title = {{Partial enumeration and curvature regularization}}, doi = {10.1109/ICCV.2013.365}, year = {2014}, } @article{2281, abstract = {We consider two-dimensional Bose-Einstein condensates with attractive interaction, described by the Gross-Pitaevskii functional. Minimizers of this functional exist only if the interaction strength a satisfies {Mathematical expression}, where Q is the unique positive radial solution of {Mathematical expression} in {Mathematical expression}. We present a detailed analysis of the behavior of minimizers as a approaches a*, where all the mass concentrates at a global minimum of the trapping potential.}, author = {Guo, Yujin and Seiringer, Robert}, journal = {Letters in Mathematical Physics}, number = {2}, pages = {141 -- 156}, publisher = {Springer}, title = {{On the mass concentration for Bose-Einstein condensates with attractive interactions}}, doi = {10.1007/s11005-013-0667-9}, volume = {104}, year = {2014}, } @article{2285, abstract = {GABAergic inhibitory interneurons control fundamental aspects of neuronal network function. Their functional roles are assumed to be defined by the identity of their input synapses, the architecture of their dendritic tree, the passive and active membrane properties and finally the nature of their postsynaptic targets. Indeed, interneurons display a high degree of morphological and physiological heterogeneity. However, whether their morphological and physiological characteristics are correlated and whether interneuron diversity can be described by a continuum of GABAergic cell types or by distinct classes has remained unclear. Here we perform a detailed morphological and physiological characterization of GABAergic cells in the dentate gyrus, the input region of the hippocampus. To achieve an unbiased and efficient sampling and classification we used knock-in mice expressing the enhanced green fluorescent protein (eGFP) in glutamate decarboxylase 67 (GAD67)-positive neurons and performed cluster analysis. We identified five interneuron classes, each of them characterized by a distinct set of anatomical and physiological parameters. Cross-correlation analysis further revealed a direct relation between morphological and physiological properties indicating that dentate gyrus interneurons fall into functionally distinct classes which may differentially control neuronal network activity.}, author = {Hosp, Jonas and Strüber, Michael and Yanagawa, Yuchio and Obata, Kunihiko and Vida, Imre and Jonas, Peter M and Bartos, Marlene}, journal = {Hippocampus}, number = {2}, pages = {189 -- 203}, publisher = {Wiley-Blackwell}, title = {{Morpho-physiological criteria divide dentate gyrus interneurons into classes}}, doi = {10.1002/hipo.22214}, volume = {23}, year = {2014}, } @article{2407, abstract = {Two definitions of the effective mass of a particle interacting with a quantum field, such as a polaron, are considered and shown to be equal in models similar to the Fröhlich polaron model. These are: 1. the mass defined by the low momentum energy E(P)≈E(0)+P2/2 M of the translation invariant system constrained to have momentum P and 2. the mass M of a simple particle in an arbitrary slowly varying external potential, V, described by the nonrelativistic Schrödinger equation, whose ground state energy equals that of the combined particle/field system in a bound state in the same V.}, author = {Lieb, Élliott and Seiringer, Robert}, journal = {Journal of Statistical Physics}, number = {1-2}, pages = {51 -- 57}, publisher = {Springer}, title = {{Equivalence of two definitions of the effective mass of a polaron}}, doi = {10.1007/s10955-013-0791-z}, volume = {154}, year = {2014}, } @article{248, abstract = {For any pencil of conics or higher-dimensional quadrics over ℚ, with all degenerate fibres defined over ℚ, we show that the Brauer–Manin obstruction controls weak approximation. The proof is based on the Hasse principle and weak approximation for some special intersections of quadrics over ℚ, which is a consequence of recent advances in additive combinatorics.}, author = {Timothy Browning and Matthiesen, Lilian and Skorobogatov, Alexei N}, journal = {Annals of Mathematics}, number = {1}, pages = {381 -- 402}, publisher = {John Hopkins University Press}, title = {{Rational points on pencils of conics and quadrics with many degenerate fibres}}, doi = {https://doi.org/10.4007/annals.2014.180.1.8}, volume = {180}, year = {2014}, } @article{249, abstract = {A version of the Hardy-Littlewood circle method is developed for number fields K/ℚ and is used to show that nonsingular projective cubic hypersurfaces over K always have a K-rational point when they have dimension at least 8. }, author = {Timothy Browning and Vishe, Pankaj}, journal = {Duke Mathematical Journal}, number = {10}, pages = {1825 -- 1883}, publisher = {Duke University Press}, title = {{Cubic hypersurfaces and a version of the circle method for number fields}}, doi = {10.1215/00127094-2738530}, volume = {163}, year = {2014}, } @article{252, abstract = {For any number field k, upper bounds are established for the number of k-rational points of bounded height on non-singular del Pezzo surfaces defined over k, which are equipped with suitable conic bundle structures over k.}, author = {Timothy Browning and Jones, Michael S}, journal = {Acta Arithmetica}, number = {3}, pages = {271 -- 298}, publisher = {Instytut Matematyczny}, title = {{Counting rational points on del Pezzo surfaces with a conic bundle structure}}, doi = {10.4064/aa163-3-6}, volume = {163}, year = {2014}, } @article{254, abstract = {A new "polynomial sieve" is presented and used to show that almost all integers have at most one representation as a sum of two values of a given polynomial of degree at least 3.}, author = {Timothy Browning}, journal = {International Mathematics Research Notices}, number = {7}, pages = {1987 -- 2019}, publisher = {Oxford University Press}, title = {{The polynomial sieve and equal sums of like polynomials}}, doi = {10.1093/imrn/rnt350}, volume = {2015}, year = {2014}, } @article{255, abstract = {We investigate the Hasse principle for complete intersections cut out by a quadric hypersurface and a cubic hypersurface defined over the rational numbers.}, author = {Browning, Timothy D and Dietmann, Rainer and Heath Brown, Roger}, journal = {Journal of the Institute of Mathematics of Jussieu}, number = {4}, pages = {703 -- 749}, publisher = {Cambridge University Press}, title = {{Rational points on intersections of cubic and quadric hypersurfaces}}, doi = {10.1017/S1474748014000127}, volume = {14}, year = {2014}, } @article{2699, abstract = {We prove the universality of the β-ensembles with convex analytic potentials and for any β > 0, i.e. we show that the spacing distributions of log-gases at any inverse temperature β coincide with those of the Gaussian β-ensembles.}, author = {Erdös, László and Bourgade, Paul and Yau, Horng}, journal = {Duke Mathematical Journal}, number = {6}, pages = {1127 -- 1190}, publisher = {Duke University Press}, title = {{Universality of general β-ensembles}}, doi = {10.1215/00127094-2649752}, volume = {163}, year = {2014}, } @article{2716, abstract = {Multi-dimensional mean-payoff and energy games provide the mathematical foundation for the quantitative study of reactive systems, and play a central role in the emerging quantitative theory of verification and synthesis. In this work, we study the strategy synthesis problem for games with such multi-dimensional objectives along with a parity condition, a canonical way to express ω ω -regular conditions. While in general, the winning strategies in such games may require infinite memory, for synthesis the most relevant problem is the construction of a finite-memory winning strategy (if one exists). Our main contributions are as follows. First, we show a tight exponential bound (matching upper and lower bounds) on the memory required for finite-memory winning strategies in both multi-dimensional mean-payoff and energy games along with parity objectives. This significantly improves the triple exponential upper bound for multi energy games (without parity) that could be derived from results in literature for games on vector addition systems with states. Second, we present an optimal symbolic and incremental algorithm to compute a finite-memory winning strategy (if one exists) in such games. Finally, we give a complete characterization of when finite memory of strategies can be traded off for randomness. In particular, we show that for one-dimension mean-payoff parity games, randomized memoryless strategies are as powerful as their pure finite-memory counterparts.}, author = {Chatterjee, Krishnendu and Randour, Mickael and Raskin, Jean}, journal = {Acta Informatica}, number = {3-4}, pages = {129 -- 163}, publisher = {Springer}, title = {{Strategy synthesis for multi-dimensional quantitative objectives}}, doi = {10.1007/s00236-013-0182-6}, volume = {51}, year = {2014}, }