@article{3772, author = {Barton, Nicholas H}, journal = {PLoS Genetics}, number = {6}, publisher = {Public Library of Science}, title = {{Understanding adaptation in large populations}}, doi = {10.1371/journal.pgen.1000987}, volume = {6}, year = {2010}, } @article{3773, abstract = {If distinct biological species are to coexist in sympatry, they must be reproductively isolated and must exploit different limiting resources. A two-niche Levene model is analysed, in which habitat preference and survival depend on underlying additive traits. The population genetics of preference and viability are equivalent. However, there is a linear trade-off between the chances of settling in either niche, whereas viabilities may be constrained arbitrarily. With a convex trade-off, a sexual population evolves a single generalist genotype, whereas with a concave trade-off, disruptive selection favours maximal variance. A pure habitat preference evolves to global linkage equilibrium if mating occurs in a single pool, but remarkably, evolves to pairwise linkage equilibrium within niches if mating is within those niches--independent of the genetics. With a concave trade-off, the population shifts sharply between a unimodal distribution with high gene flow and a bimodal distribution with strong isolation, as the underlying genetic variance increases. However, these alternative states are only simultaneously stable for a narrow parameter range. A sharp threshold is only seen if survival in the 'wrong' niche is low; otherwise, strong isolation is impossible. Gene flow from divergent demes makes speciation much easier in parapatry than in sympatry.}, author = {Barton, Nicholas H}, journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, number = {1547}, pages = {1825 -- 1840}, publisher = {Royal Society}, title = {{What role does natural selection play in speciation?}}, doi = {10.1098/rstb.2010.0001}, volume = {365}, year = {2010}, } @article{3776, abstract = {The prevalence of recombination in eukaryotes poses one of the most puzzling questions in biology. The most compelling general explanation is that recombination facilitates selection by breaking down the negative associations generated by random drift (i.e. Hill-Robertson interference, HRI). I classify the effects of HRI owing to: deleterious mutation, balancing selection and selective sweeps on: neutral diversity, rates of adaptation and the mutation load. These effects are mediated primarily by the density of deleterious mutations and of selective sweeps. Sequence polymorphism and divergence suggest that these rates may be high enough to cause significant interference even in genomic regions of high recombination. However, neither seems able to generate enough variance in fitness to select strongly for high rates of recombination. It is plausible that spatial and temporal fluctuations in selection generate much more fitness variance, and hence selection for recombination, than can be explained by uniformly deleterious mutations or species-wide selective sweeps.}, author = {Barton, Nicholas H}, journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, number = {1552}, pages = {2559 -- 2569}, publisher = {Royal Society}, title = {{Genetic linkage and natural selection}}, doi = {10.1098/rstb.2010.0106}, volume = {365}, year = {2010}, } @article{3777, abstract = {Under the classical view, selection depends more or less directly on mutation: standing genetic variance is maintained by a balance between selection and mutation, and adaptation is fuelled by new favourable mutations. Recombination is favoured if it breaks negative associations among selected alleles, which interfere with adaptation. Such associations may be generated by negative epistasis, or by random drift (leading to the Hill-Robertson effect). Both deterministic and stochastic explanations depend primarily on the genomic mutation rate, U. This may be large enough to explain high recombination rates in some organisms, but seems unlikely to be so in general. Random drift is a more general source of negative linkage disequilibria, and can cause selection for recombination even in large populations, through the chance loss of new favourable mutations. The rate of species-wide substitutions is much too low to drive this mechanism, but local fluctuations in selection, combined with gene flow, may suffice. These arguments are illustrated by comparing the interaction between good and bad mutations at unlinked loci under the infinitesimal model.}, author = {Barton, Nicholas H}, journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, number = {1544}, pages = {1281 -- 1294}, publisher = {Royal Society}, title = {{Mutation and the evolution of recombination}}, doi = {10.1098/rstb.2009.0320}, volume = {365}, year = {2010}, } @article{3779, abstract = {Crosses between closely related species give two contrasting results. One result is that species hybrids may be inferior to their parents, for example, being less fertile [1]. The other is that F1 hybrids may display superior performance (heterosis), for example with increased vigour [2]. Although various hypotheses have been proposed to account for these two aspects of hybridisation, their biological basis is still poorly understood [3]. To gain further insights into this issue, we analysed the role that variation in gene expression may play. We took a conserved trait, flower asymmetry in Antirrhinum, and determined the extent to which the underlying regulatory genes varied in expression among closely related species. We show that expression of both genes analysed, CYC and RAD, varies significantly between species because of cis-acting differences. By making a quantitative genotype-phenotype map, using a range of mutant alleles, we demonstrate that the species lie on a plateau in gene expression-morphology space, so that the variation has no detectable phenotypic effect. However, phenotypic differences can be revealed by shifting genotypes off the plateau through genetic crosses. Our results can be readily explained if genomes are free to evolve within an effectively neutral zone in gene expression space. The consequences of this drift will be negligible for individual loci, but when multiple loci across the genome are considered, we show that the variation may have significant effects on phenotype and fitness, causing a significant drift load. By considering these consequences for various gene-expression-fitness landscapes, we conclude that F1 hybrids might be expected to show increased performance with regard to conserved traits, such as basic physiology, but reduced performance with regard to others. Thus, our study provides a new way of explaining how various aspects of hybrid performance may arise through natural variation in gene activity.}, author = {Rosas, Ulises and Barton, Nicholas H and Copsey, Lucy and Barbier De Reuille, Pierre and Coen, Enrico}, journal = {PLoS Biology}, number = {7}, publisher = {Public Library of Science}, title = {{Cryptic variation between species and the basis of hybrid performance}}, doi = {10.1371/journal.pbio.1000429}, volume = {8}, year = {2010}, } @article{3787, abstract = {DNA samples were extracted from ethanol and formalin-fixed decapod crustacean tissue using a new method based on Tetramethylsilane (TMS)-Chelex. It is shown that neither an indigestible matrix of cross-linked protein nor soluble PCR inhibitors impede PCR success when dealing with formalin-fixed material. Instead, amplification success from formalin-fixed tissue appears to depend on the presence of unmodified DNA in the extracted sample. A staining method that facilitates the targeting of samples with a high content of unmodified DNA is provided.}, author = {Palero, Ferran and Hall, Sally and Clark, Paul and Johnston, David and Mackenzie Dodds, Jackie and Thatje, Sven}, journal = {Scientia Marina}, number = {3}, pages = {465 -- 470}, publisher = {Consejo Superior de Investigaciones Científicas}, title = {{DNA extraction from formalin-fixed tissue: new light from the deep sea}}, doi = {10.3989/scimar.2010.74n3465}, volume = {74}, year = {2010}, } @article{3790, abstract = {Cell shape and motility are primarily controlled by cellular mechanics. The attachment of the plasma membrane to the underlying actomyosin cortex has been proposed to be important for cellular processes involving membrane deformation. However, little is known about the actual function of membrane-to-cortex attachment (MCA) in cell protrusion formation and migration, in particular in the context of the developing embryo. Here, we use a multidisciplinary approach to study MCA in zebrafish mesoderm and endoderm (mesendoderm) germ layer progenitor cells, which migrate using a combination of different protrusion types, namely, lamellipodia, filopodia, and blebs, during zebrafish gastrulation. By interfering with the activity of molecules linking the cortex to the membrane and measuring resulting changes in MCA by atomic force microscopy, we show that reducing MCA in mesendoderm progenitors increases the proportion of cellular blebs and reduces the directionality of cell migration. We propose that MCA is a key parameter controlling the relative proportions of different cell protrusion types in mesendoderm progenitors, and thus is key in controlling directed migration during gastrulation.}, author = {Diz Muñoz, Alba and Krieg, Michael and Bergert, Martin and Ibarlucea Benitez, Itziar and Müller, Daniel and Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {PLoS Biology}, number = {11}, publisher = {Public Library of Science}, title = {{Control of directed cell migration in vivo by membrane-to-cortex attachment}}, doi = {10.1371/journal.pbio.1000544}, volume = {8}, year = {2010}, } @inproceedings{3793, abstract = {Recent progress in per-pixel object class labeling of natural images can be attributed to the use of multiple types of image features and sound statistical learning approaches. Within the latter, Conditional Random Fields (CRF) are prominently used for their ability to represent interactions between random variables. Despite their popularity in computer vision, parameter learning for CRFs has remained difficult, popular approaches being cross-validation and piecewise training. In this work, we propose a simple yet expressive tree-structured CRF based on a recent hierarchical image segmentation method. Our model combines and weights multiple image features within a hierarchical representation and allows simple and efficient globally-optimal learning of ≈ 105 parameters. The tractability of our model allows us to pose and answer some of the open questions regarding parameter learning applying to CRF-based approaches. The key findings for learning CRF models are, from the obvious to the surprising, i) multiple image features always help, ii) the limiting dimension with respect to current models is the amount of training data, iii) piecewise training is competitive, iv) current methods for max-margin training fail for models with many parameters. }, author = {Nowozin, Sebastian and Gehler, Peter and Lampert, Christoph}, location = {Heraklion, Crete, Greece}, pages = {98 -- 111}, publisher = {Springer}, title = {{On parameter learning in CRF-based approaches to object class image segmentation}}, doi = {10.1007/978-3-642-15567-3_8}, volume = {6316}, year = {2010}, } @inbook{3795, abstract = {The (apparent) contour of a smooth mapping from a 2-manifold to the plane, f: M → R2 , is the set of critical values, that is, the image of the points at which the gradients of the two component functions are linearly dependent. Assuming M is compact and orientable and measuring difference with the erosion distance, we prove that the contour is stable.}, author = {Edelsbrunner, Herbert and Morozov, Dmitriy and Patel, Amit}, booktitle = {Topological Data Analysis and Visualization: Theory, Algorithms and Applications}, pages = {27 -- 42}, publisher = {Springer}, title = {{The stability of the apparent contour of an orientable 2-manifold}}, doi = {10.1007/978-3-642-15014-2_3}, year = {2010}, } @article{3831, abstract = {Fast-spiking, parvalbumin-expressing basket cells (BCs) play a key role in feedforward and feedback inhibition in the hippocampus. However, the dendritic mechanisms underlying rapid interneuron recruitment have remained unclear. To quantitatively address this question, we developed detailed passive cable models of BCs in the dentate gyrus based on dual somatic or somatodendritic recordings and complete morphologic reconstructions. Both specific membrane capacitance and axial resistivity were comparable to those of pyramidal neurons, but the average somatodendritic specific membrane resistance (R(m)) was substantially lower in BCs. Furthermore, R(m) was markedly nonuniform, being lowest in soma and proximal dendrites, intermediate in distal dendrites, and highest in the axon. Thus, the somatodendritic gradient of R(m) was the reverse of that in pyramidal neurons. Further computational analysis revealed that these unique cable properties accelerate the time course of synaptic potentials at the soma in response to fast inputs, while boosting the efficacy of slow distal inputs. These properties will facilitate both rapid phasic and efficient tonic activation of BCs in hippocampal microcircuits.}, author = {Norenberg, Anja and Hua Hu and Vida, Imre and Bartos, Marlene and Peter Jonas}, journal = {PNAS}, number = {2}, pages = {894 -- 9}, publisher = {National Academy of Sciences}, title = {{Distinct nonuniform cable properties optimize rapid and efficient activation of fast-spiking GABAergic interneurons}}, doi = {10.1073/pnas.0910716107}, volume = {107}, year = {2010}, } @article{3832, abstract = {A recent paper by von Engelhardt et al. identifies a novel auxiliary subunit of native AMPARs, termedCKAMP44. Unlike other auxiliary subunits, CKAMP44 accelerates desensitization and prolongs recovery from desensitization. CKAMP44 is highly expressed in hippocampal dentate gyrus granule cells and decreases the paired-pulse ratio at perforant path input synapses. Thus, both principal and auxiliary AMPAR subunits control the time course of signaling at glutamatergic synapses.}, author = {Guzmán, José and Jonas, Peter M}, journal = {Neuron}, number = {1}, pages = {8 -- 10}, publisher = {Elsevier}, title = {{Beyond TARPs: The growing list of auxiliary AMPAR subunits}}, doi = {10.1016/j.neuron.2010.04.003}, volume = {66}, year = {2010}, } @article{3834, abstract = {Background The chemical master equation (CME) is a system of ordinary differential equations that describes the evolution of a network of chemical reactions as a stochastic process. Its solution yields the probability density vector of the system at each point in time. Solving the CME numerically is in many cases computationally expensive or even infeasible as the number of reachable states can be very large or infinite. We introduce the sliding window method, which computes an approximate solution of the CME by performing a sequence of local analysis steps. In each step, only a manageable subset of states is considered, representing a "window" into the state space. In subsequent steps, the window follows the direction in which the probability mass moves, until the time period of interest has elapsed. We construct the window based on a deterministic approximation of the future behavior of the system by estimating upper and lower bounds on the populations of the chemical species. Results In order to show the effectiveness of our approach, we apply it to several examples previously described in the literature. The experimental results show that the proposed method speeds up the analysis considerably, compared to a global analysis, while still providing high accuracy. Conclusions The sliding window method is a novel approach to address the performance problems of numerical algorithms for the solution of the chemical master equation. The method efficiently approximates the probability distributions at the time points of interest for a variety of chemically reacting systems, including systems for which no upper bound on the population sizes of the chemical species is known a priori.}, author = {Wolf, Verena and Goel, Rushil and Mateescu, Maria and Henzinger, Thomas A}, journal = {BMC Systems Biology}, number = {42}, pages = {1 -- 19}, publisher = {BioMed Central}, title = {{Solving the chemical master equation using sliding windows}}, doi = {10.1186/1752-0509-4-42}, volume = {4}, year = {2010}, } @inproceedings{3838, abstract = {We present a numerical approximation technique for the analysis of continuous-time Markov chains that describe net- works of biochemical reactions and play an important role in the stochastic modeling of biological systems. Our approach is based on the construction of a stochastic hybrid model in which certain discrete random variables of the original Markov chain are approximated by continuous deterministic variables. We compute the solution of the stochastic hybrid model using a numerical algorithm that discretizes time and in each step performs a mutual update of the transient prob- ability distribution of the discrete stochastic variables and the values of the continuous deterministic variables. We im- plemented the algorithm and we demonstrate its usefulness and efficiency on several case studies from systems biology.}, author = {Henzinger, Thomas A and Mateescu, Maria and Mikeev, Linar and Wolf, Verena}, location = {Trento, Italy}, pages = {55 -- 65}, publisher = {Springer}, title = {{Hybrid numerical solution of the chemical master equation}}, doi = {10.1145/1839764.1839772}, year = {2010}, } @inproceedings{3839, abstract = {We present a loop property generation method for loops iterating over multi-dimensional arrays. When used on matrices, our method is able to infer their shapes (also called types), such as upper-triangular, diagonal, etc. To gen- erate loop properties, we first transform a nested loop iterating over a multi- dimensional array into an equivalent collection of unnested loops. Then, we in- fer quantified loop invariants for each unnested loop using a generalization of a recurrence-based invariant generation technique. These loop invariants give us conditions on matrices from which we can derive matrix types automatically us- ing theorem provers. Invariant generation is implemented in the software package Aligator and types are derived by theorem provers and SMT solvers, including Vampire and Z3. When run on the Java matrix package JAMA, our tool was able to infer automatically all matrix types describing the matrix shapes guaranteed by JAMA’s API.}, author = {Henzinger, Thomas A and Hottelier, Thibaud and Kovács, Laura and Voronkov, Andrei}, location = {Madrid, Spain}, pages = {163 -- 179}, publisher = {Springer}, title = {{Invariant and type inference for matrices}}, doi = {10.1007/978-3-642-11319-2_14}, volume = {5944}, year = {2010}, } @article{3842, abstract = {Within systems biology there is an increasing interest in the stochastic behavior of biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous-time Markov chain (CTMC). The uniformization technique is an efficient method to compute probability distributions of a CTMC if the number of states is manageable. However, the size of a CTMC that represents a biochemical reaction network is usually far beyond what is feasible. In this paper we present an on-the-fly variant of uniformization, where we improve the original algorithm at the cost of a small approximation error. By means of several examples, we show that our approach is particularly well-suited for biochemical reaction networks.}, author = {Didier, Frédéric and Henzinger, Thomas A and Mateescu, Maria and Wolf, Verena}, journal = {IET Systems Biology}, number = {6}, pages = {441 -- 452}, publisher = {Institution of Engineering and Technology}, title = {{Fast adaptive uniformization of the chemical master equation}}, doi = {10.1049/iet-syb.2010.0005}, volume = {4}, year = {2010}, } @inproceedings{3845, abstract = {This paper presents Aligators, a tool for the generation of universally quantified array invariants. Aligators leverages recurrence solving and algebraic techniques to carry out inductive reasoning over array content. The Aligators’ loop extraction module allows treatment of multi-path loops by exploiting their commutativity and serializability properties. Our experience in applying Aligators on a collection of loops from open source software projects indicates the applicability of recurrence and algebraic solving techniques for reasoning about arrays.}, author = {Henzinger, Thomas A and Hottelier, Thibaud and Kovács, Laura and Rybalchenko, Andrey}, location = {Yogyakarta, Indonesia}, pages = {348 -- 356}, publisher = {Springer}, title = {{Aligators for arrays}}, doi = {10.1007/978-3-642-16242-8_25}, volume = {6397}, year = {2010}, } @inproceedings{3847, abstract = {The importance of stochasticity within biological systems has been shown repeatedly during the last years and has raised the need for efficient stochastic tools. We present SABRE, a tool for stochastic analysis of biochemical reaction networks. SABRE implements fast adaptive uniformization (FAU), a direct numerical approximation algorithm for computing transient solutions of biochemical reaction networks. Biochemical reactions networks represent biological systems studied at a molecular level and these reactions can be modeled as transitions of a Markov chain. SABRE accepts as input the formalism of guarded commands, which it interprets either as continuous-time or as discrete-time Markov chains. Besides operating in a stochastic mode, SABRE may also perform a deterministic analysis by directly computing a mean-field approximation of the system under study. We illustrate the different functionalities of SABRE by means of biological case studies.}, author = {Didier, Frédéric and Henzinger, Thomas A and Mateescu, Maria and Wolf, Verena}, location = {Williamsburg, USA}, pages = {193 -- 194}, publisher = {IEEE}, title = {{SABRE: A tool for the stochastic analysis of biochemical reaction networks}}, doi = {10.1109/QEST.2010.33}, year = {2010}, } @inproceedings{3849, abstract = {Using ideas from persistent homology, the robustness of a level set of a real-valued function is defined in terms of the magnitude of the perturbation necessary to kill the classes. Prior work has shown that the homology and robustness information can be read off the extended persistence diagram of the function. This paper extends these results to a non-uniform error model in which perturbations vary in their magnitude across the domain.}, author = {Bendich, Paul and Edelsbrunner, Herbert and Kerber, Michael and Patel, Amit}, location = {Brno, Czech Republic}, pages = {12 -- 23}, publisher = {Springer}, title = {{Persistent homology under non-uniform error}}, doi = {10.1007/978-3-642-15155-2_2}, volume = {6281}, year = {2010}, } @article{385, abstract = {Scanning tunneling spectroscopy studies on high-quality Bi2Te3 crystals exhibit perfect correspondence to angle-resolved photoemission spectroscopy data, hence enabling identification of different regimes measured in the local density of states (LDOS). Oscillations of LDOS near a step are analyzed. Within the main part of the surface band oscillations are strongly damped, supporting the hypothesis of topological protection. At higher energies, as the surface band becomes concave, oscillations appear, dispersing with a wave vector that may result from a hexagonal warping term. }, author = {Alpichshev, Zhanybek and Analytis, James and Chu, Jiunhaw and Fisher, Ian and Chen, Yulin and Shen, Zhixun and Fang, Aiping and Kapitulnik, Aharon}, journal = {Physical Review Letters}, number = {1}, publisher = {American Physical Society}, title = {{STM imaging of electronic waves on the surface of Bi2Te3 Topologically protected surface states and hexagonal warping effects}}, doi = {10.1103/PhysRevLett.104.016401}, volume = {104}, year = {2010}, } @inproceedings{3851, abstract = {Energy parity games are infinite two-player turn-based games played on weighted graphs. The objective of the game combines a (qualitative) parity condition with the (quantitative) requirement that the sum of the weights (i.e., the level of energy in the game) must remain positive. Beside their own interest in the design and synthesis of resource-constrained omega-regular specifications, energy parity games provide one of the simplest model of games with combined qualitative and quantitative objective. Our main results are as follows: (a) exponential memory is sufficient and may be necessary for winning strategies in energy parity games; (b) the problem of deciding the winner in energy parity games can be solved in NP ∩ coNP; and (c) we give an algorithm to solve energy parity by reduction to energy games. We also show that the problem of deciding the winner in energy parity games is polynomially equivalent to the problem of deciding the winner in mean-payoff parity games, which can thus be solved in NP ∩ coNP. As a consequence we also obtain a conceptually simple algorithm to solve mean-payoff parity games.}, author = {Chatterjee, Krishnendu and Doyen, Laurent}, location = {Bordeaux, France}, pages = {599 -- 610}, publisher = {Springer}, title = {{Energy parity games}}, doi = {10.1007/978-3-642-14162-1_50}, volume = {6199}, year = {2010}, }