@article{3374,
abstract = {Genetic regulatory networks enable cells to respond to changes in internal and external conditions by dynamically coordinating their gene expression profiles. Our ability to make quantitative measurements in these biochemical circuits has deepened our understanding of what kinds of computations genetic regulatory networks can perform, and with what reliability. These advances have motivated researchers to look for connections between the architecture and function of genetic regulatory networks. Transmitting information between a network's inputs and outputs has been proposed as one such possible measure of function, relevant in certain biological contexts. Here we summarize recent developments in the application of information theory to gene regulatory networks. We first review basic concepts in information theory necessary for understanding recent work. We then discuss the functional complexity of gene regulation, which arises from the molecular nature of the regulatory interactions. We end by reviewing some experiments that support the view that genetic networks responsible for early development of multicellular organisms might be maximizing transmitted 'positional information'.},
author = {Tkacik, Gasper and Walczak, Aleksandra},
journal = {Journal of Physics: Condensed Matter},
number = {15},
publisher = {IOP Publishing Ltd.},
title = {{Information transmission in genetic regulatory networks a review}},
doi = {10.1088/0953-8984/23/15/153102},
volume = {23},
year = {2011},
}
@article{3375,
abstract = {By exploiting an analogy between population genetics and statistical mechanics, we study the evolution of a polygenic trait under stabilizing selection, mutation and genetic drift. This requires us to track only four macroscopic variables, instead of the distribution of all the allele frequencies that influence the trait. These macroscopic variables are the expectations of: the trait mean and its square, the genetic variance, and of a measure of heterozygosity, and are derived from a generating function that is in turn derived by maximizing an entropy measure. These four macroscopics are enough to accurately describe the dynamics of the trait mean and of its genetic variance (and in principle of any other quantity). Unlike previous approaches that were based on an infinite series of moments or cumulants, which had to be truncated arbitrarily, our calculations provide a well-defined approximation procedure. We apply the framework to abrupt and gradual changes in the optimum, as well as to changes in the strength of stabilizing selection. Our approximations are surprisingly accurate, even for systems with as few as five loci. We find that when the effects of drift are included, the expected genetic variance is hardly altered by directional selection, even though it fluctuates in any particular instance. We also find hysteresis, showing that even after averaging over the microscopic variables, the macroscopic trajectories retain a memory of the underlying genetic states.},
author = {de Vladar, Harold and Barton, Nicholas H},
journal = {Journal of the Royal Society Interface},
number = {58},
pages = {720 -- 739},
publisher = {Royal Society of London},
title = {{The statistical mechanics of a polygenic character under stabilizing selection mutation and drift}},
doi = {10.1098/rsif.2010.0438},
volume = {8},
year = {2011},
}
@article{3376,
abstract = {Regulatory conflicts occur when two signals that individually trigger opposite cellular responses are present simultaneously. Here, we investigate regulatory conflicts in the bacterial response to antibiotic combinations. We use an Escherichia coli promoter-GFP library to study the transcriptional response of many promoters to either additive or antagonistic drug pairs at fine two-dimensional (2D) resolution of drug concentration. Surprisingly, we find that this data set can be characterized as a linear sum of only two principal components. Component one, accounting for over 70% of the response, represents the response to growth inhibition by the drugs. Component two describes how regulatory conflicts are resolved. For the additive drug pair, conflicts are resolved by linearly interpolating the single drug responses, while for the antagonistic drug pair, the growth-limiting drug dominates the response. Importantly, for a given drug pair, the same conflict resolution strategy applies to almost all genes. These results provide a recipe for predicting gene expression responses to antibiotic combinations.},
author = {Bollenbach, Mark Tobias and Kishony, Roy},
journal = {Molecular Cell},
number = {4},
pages = {413 -- 425},
publisher = {Cell Press},
title = {{Resolution of gene regulatory conflicts caused by combinations of antibiotics}},
doi = {10.1016/j.molcel.2011.04.016},
volume = {42},
year = {2011},
}
@article{3377,
abstract = {By definition, transverse intersections are stable under in- finitesimal perturbations. Using persistent homology, we ex- tend this notion to sizeable perturbations. Specifically, we assign to each homology class of the intersection its robust- ness, the magnitude of a perturbation necessary to kill it, and prove that robustness is stable. Among the applications of this result is a stable notion of robustness for fixed points of continuous mappings and a statement of stability for con- tours of smooth mappings.},
author = {Edelsbrunner, Herbert and Morozov, Dmitriy and Patel, Amit},
journal = {Foundations of Computational Mathematics},
number = {3},
pages = {345 -- 361},
publisher = {Springer},
title = {{Quantifying transversality by measuring the robustness of intersections}},
doi = {10.1007/s10208-011-9090-8},
volume = {11},
year = {2011},
}
@article{3378,
abstract = {The theory of intersection homology was developed to study the singularities of a topologically stratified space. This paper in- corporates this theory into the already developed framework of persistent homology. We demonstrate that persistent intersec- tion homology gives useful information about the relationship between an embedded stratified space and its singularities. We give, and prove the correctness of, an algorithm for the computa- tion of the persistent intersection homology groups of a filtered simplicial complex equipped with a stratification by subcom- plexes. We also derive, from Poincare ́ Duality, some structural results about persistent intersection homology.},
author = {Bendich, Paul and Harer, John},
journal = {Foundations of Computational Mathematics},
number = {3},
pages = {305 -- 336},
publisher = {Springer},
title = {{Persistent intersection homology}},
doi = {10.1007/s10208-010-9081-1},
volume = {11},
year = {2011},
}
@article{3379,
abstract = {The process of gastrulation is highly conserved across vertebrates on both the genetic and morphological levels, despite great variety in embryonic shape and speed of development. This mechanism spatially separates the germ layers and establishes the organizational foundation for future development. Mesodermal identity is specified in a superficial layer of cells, the epiblast, where cells maintain an epithelioid morphology. These cells involute to join the deeper hypoblast layer where they adopt a migratory, mesenchymal morphology. Expression of a cascade of related transcription factors orchestrates the parallel genetic transition from primitive to mature mesoderm. Although the early and late stages of this process are increasingly well understood, the transition between them has remained largely mysterious. We present here the first high resolution in vivo observations of the blebby transitional morphology of involuting mesodermal cells in a vertebrate embryo. We further demonstrate that the zebrafish spadetail mutation creates a reversible block in the maturation program, stalling cells in the transition state. This mutation creates an ideal system for dissecting the specific properties of cells undergoing the morphological transition of maturing mesoderm, as we demonstrate with a direct measurement of cell–cell adhesion.},
author = {Row, Richard and Maître, Jean-Léon and Martin, Benjamin and Stockinger, Petra and Heisenberg, Carl-Philipp J and Kimelman, David},
journal = {Developmental Biology},
number = {1},
pages = {102 -- 110},
publisher = {Elsevier},
title = {{Completion of the epithelial to mesenchymal transition in zebrafish mesoderm requires Spadetail}},
doi = {10.1016/j.ydbio.2011.03.025},
volume = {354},
year = {2011},
}
@article{3380,
abstract = {Linkage between markers and genes that affect a phenotype of interest may be determined by examining differences in marker allele frequency in the extreme progeny of a cross between two inbred lines. This strategy is usually employed when pooling is used to reduce genotyping costs. When the cross progeny are asexual, the extreme progeny may be selected by multiple generations of asexual reproduction and selection. We analyse this method of measuring phenotype in asexual progeny and examine the changes in marker allele frequency due to selection over many generations. Stochasticity in marker frequency in the selected population arises due to the finite initial population size. We derive the distribution of marker frequency as a result of selection at a single major locus, and show that in order to avoid spurious changes in marker allele frequency in the selected population, the initial population size should be in the low to mid hundreds.},
author = {Logeswaran, Sayanthan and Barton, Nicholas H},
journal = {Genetical Research},
number = {3},
pages = {221 -- 232},
publisher = {Cambridge University Press},
title = {{Mapping Mendelian traits in asexual progeny using changes in marker allele frequency}},
doi = {10.1017/S0016672311000115},
volume = {93},
year = {2011},
}
@article{3381,
abstract = {In this survey, we compare several languages for specifying Markovian population models such as queuing networks and chemical reaction networks. All these languages — matrix descriptions, stochastic Petri nets, stoichiometric equations, stochastic process algebras, and guarded command models — describe continuous-time Markov chains, but they differ according to important properties, such as compositionality, expressiveness and succinctness, executability, and ease of use. Moreover, they provide different support for checking the well-formedness of a model and for analyzing a model.},
author = {Henzinger, Thomas A and Jobstmann, Barbara and Wolf, Verena},
journal = {IJFCS: International Journal of Foundations of Computer Science},
number = {4},
pages = {823 -- 841},
publisher = {World Scientific Publishing},
title = {{Formalisms for specifying Markovian population models}},
doi = {10.1142/S0129054111008441},
volume = {22},
year = {2011},
}
@article{3382,
abstract = {Dynamic tactile sensing is a fundamental ability to recognize materials and objects. However, while humans are born with partially developed dynamic tactile sensing and quickly master this skill, today's robots remain in their infancy. The development of such a sense requires not only better sensors but the right algorithms to deal with these sensors' data as well. For example, when classifying a material based on touch, the data are noisy, high-dimensional, and contain irrelevant signals as well as essential ones. Few classification methods from machine learning can deal with such problems. In this paper, we propose an efficient approach to infer suitable lower dimensional representations of the tactile data. In order to classify materials based on only the sense of touch, these representations are autonomously discovered using visual information of the surfaces during training. However, accurately pairing vision and tactile samples in real-robot applications is a difficult problem. The proposed approach, therefore, works with weak pairings between the modalities. Experiments show that the resulting approach is very robust and yields significantly higher classification performance based on only dynamic tactile sensing.},
author = {Kroemer, Oliver and Lampert, Christoph and Peters, Jan},
journal = {IEEE Transactions on Robotics},
number = {3},
pages = {545 -- 557},
publisher = {IEEE},
title = {{Learning dynamic tactile sensing with robust vision based training}},
doi = {10.1109/TRO.2011.2121130},
volume = {27},
year = {2011},
}
@article{3383,
author = {Heisenberg, Carl-Philipp J},
journal = {FEBS Journal},
number = {S1},
pages = {24 -- 24},
publisher = {Wiley-Blackwell},
title = {{Invited Lectures ‐ Symposia Area}},
doi = {10.1111/j.1742-4658.2011.08136.x},
volume = {278},
year = {2011},
}
@article{3384,
abstract = {Here we introduce a database of calibrated natural images publicly available through an easy-to-use web interface. Using a Nikon D70 digital SLR camera, we acquired about six-megapixel images of Okavango Delta of Botswana, a tropical savanna habitat similar to where the human eye is thought to have evolved. Some sequences of images were captured unsystematically while following a baboon troop, while others were designed to vary a single parameter such as aperture, object distance, time of day or position on the horizon. Images are available in the raw RGB format and in grayscale. Images are also available in units relevant to the physiology of human cone photoreceptors, where pixel values represent the expected number of photoisomerizations per second for cones sensitive to long (L), medium (M) and short (S) wavelengths. This database is distributed under a Creative Commons Attribution-Noncommercial Unported license to facilitate research in computer vision, psychophysics of perception, and visual neuroscience.},
author = {Tkacik, Gasper and Garrigan, Patrick and Ratliff, Charles and Milcinski, Grega and Klein, Jennifer and Seyfarth, Lucia and Sterling, Peter and Brainard, David and Balasubramanian, Vijay},
journal = {PLoS One},
number = {6},
publisher = {Public Library of Science},
title = {{Natural images from the birthplace of the human eye}},
doi = {10.1371/journal.pone.0020409},
volume = {6},
year = {2011},
}
@article{3385,
author = {Sixt, Michael K},
journal = {Immunology Letters},
number = {1},
pages = {32 -- 34},
publisher = {Elsevier},
title = {{Interstitial locomotion of leukocytes}},
doi = {10.1016/j.imlet.2011.02.013},
volume = {138},
year = {2011},
}
@article{3386,
abstract = {Evolutionary theories of ageing predict that life span increases with decreasing extrinsic mortality, and life span variation among queens in ant species seems to corroborate this prediction: queens, which are the only reproductive in a colony, live much longer than queens in multi-queen colonies. The latter often inhabit ephemeral nest sites and accordingly are assumed to experience a higher mortality risk. Yet, all prior studies compared queens from different single- and multi-queen species. Here, we demonstrate an effect of queen number on longevity and fecundity within a single, socially plastic species, where queens experience the similar level of extrinsic mortality. Queens from single- and two-queen colonies had significantly longer lifespan and higher fecundity than queens living in associations of eight queens. As queens also differ neither in morphology nor the mode of colony foundation, our study shows that the social environment itself strongly affects ageing rate.},
author = {Schrempf, Alexandra and Cremer, Sylvia and Heinze, Jürgen},
journal = {Journal of Evolutionary Biology},
number = {7},
pages = {1455 -- 1461},
publisher = {Wiley-Blackwell},
title = {{Social influence on age and reproduction reduced lifespan and fecundity in multi queen ant colonies}},
doi = {10.1111/j.1420-9101.2011.02278.x},
volume = {24},
year = {2011},
}
@article{3387,
abstract = {Background: Supertree methods combine overlapping input trees into a larger supertree. Here, I consider split-based supertree methods that first extract the split information of the input trees and subsequently combine this split information into a phylogeny. Well known split-based supertree methods are matrix representation with parsimony and matrix representation with compatibility. Combining input trees on the same taxon set, as in the consensus setting, is a well-studied task and it is thus desirable to generalize consensus methods to supertree methods. Results: Here, three variants of majority-rule (MR) supertrees that generalize majority-rule consensus trees are investigated. I provide simple formulas for computing the respective score for bifurcating input- and supertrees. These score computations, together with a heuristic tree search minmizing the scores, were implemented in the python program PluMiST (Plus- and Minus SuperTrees) available from http://www.cibiv.at/software/ plumist. The different MR methods were tested by simulation and on real data sets. The search heuristic was successful in combining compatible input trees. When combining incompatible input trees, especially one variant, MR(-) supertrees, performed well. Conclusions: The presented framework allows for an efficient score computation of three majority-rule supertree variants and input trees. I combined the score computation with a heuristic search over the supertree space. The implementation was tested by simulation and on real data sets and showed promising results. Especially the MR(-) variant seems to be a reasonable score for supertree reconstruction. Generalizing these computations to multifurcating trees is an open problem, which may be tackled using this framework.},
author = {Kupczok, Anne},
journal = {BMC Evolutionary Biology},
number = {205},
publisher = {BioMed Central},
title = {{Split based computation of majority rule supertrees}},
doi = {10.1186/1471-2148-11-205},
volume = {11},
year = {2011},
}
@article{3388,
abstract = {Background: Fragmentation of terrestrial ecosystems has had detrimental effects on metapopulations of habitat specialists. Maculinea butterflies have been particularly affected because of their specialized lifecycles, requiring both specific food-plants and host-ants. However, the interaction between dispersal, effective population size, and long-term genetic erosion of these endangered butterflies remains unknown. Using non-destructive sampling, we investigated the genetic diversity of the last extant population of M. arion in Denmark, which experienced critically low numbers in the 1980s. Results: Using nine microsatellite markers, we show that the population is genetically impoverished compared to nearby populations in Sweden, but less so than monitoring programs suggested. Ten additional short repeat microsatellites were used to reconstruct changes in genetic diversity and population structure over the last 77 years from museum specimens. We also tested amplification efficiency in such historical samples as a function of repeat length and sample age. Low population numbers in the 1980s did not affect genetic diversity, but considerable turnover of alleles has characterized this population throughout the time-span of our analysis. Conclusions: Our results suggest that M. arion is less sensitive to genetic erosion via population bottlenecks than previously thought, and that managing clusters of high quality habitat may be key for long-term conservation.},
author = {Ugelvig, Line V and Nielsen, Per and Boomsma, Jacobus and Nash, David},
journal = {BMC Evolutionary Biology},
number = {201},
publisher = {BioMed Central},
title = {{Reconstructing eight decades of genetic variation in an isolated Danish population of the large blue butterfly Maculinea arion}},
doi = {10.1186/1471-2148-11-201},
volume = {11},
year = {2011},
}
@article{3389,
abstract = {Kernel canonical correlation analysis (KCCA) is a general technique for subspace learning that incorporates principal components analysis (PCA) and Fisher linear discriminant analysis (LDA) as special cases. By finding directions that maximize correlation, KCCA learns representations that are more closely tied to the underlying process that generates the data and can ignore high-variance noise directions. However, for data where acquisition in one or more modalities is expensive or otherwise limited, KCCA may suffer from small sample effects. We propose to use semi-supervised Laplacian regularization to utilize data that are present in only one modality. This approach is able to find highly correlated directions that also lie along the data manifold, resulting in a more robust estimate of correlated subspaces. Functional magnetic resonance imaging (fMRI) acquired data are naturally amenable to subspace techniques as data are well aligned. fMRI data of the human brain are a particularly interesting candidate. In this study we implemented various supervised and semi-supervised versions of KCCA on human fMRI data, with regression to single and multi-variate labels (corresponding to video content subjects viewed during the image acquisition). In each variate condition, the semi-supervised variants of KCCA performed better than the supervised variants, including a supervised variant with Laplacian regularization. We additionally analyze the weights learned by the regression in order to infer brain regions that are important to different types of visual processing.},
author = {Blaschko, Matthew and Shelton, Jacquelyn and Bartels, Andreas and Lampert, Christoph and Gretton, Arthur},
journal = {Pattern Recognition Letters},
number = {11},
pages = {1572 -- 1583},
publisher = {Elsevier},
title = {{Semi supervised kernel canonical correlation analysis with application to human fMRI}},
doi = {10.1016/j.patrec.2011.02.011},
volume = {32},
year = {2011},
}
@article{3390,
abstract = {What determines the genetic contribution that an individual makes to future generations? With biparental reproduction, each individual leaves a 'pedigree' of descendants, determined by the biparental relationships in the population. The pedigree of an individual constrains the lines of descent of each of its genes. An individual's reproductive value is the expected number of copies of each of its genes that is passed on to distant generations conditional on its pedigree. For the simplest model of biparental reproduction analogous to the Wright-Fisher model, an individual's reproductive value is determined within ~10 generations, independent of population size. Partial selfing and subdivision do not greatly slow this convergence. Our central result is that the probability that a gene will survive is proportional to the reproductive value of the individual that carries it, and that conditional on survival, after a few tens of generations, the distribution of the number of surviving copies is the same for all individuals, whatever their reproductive value. These results can be generalized to the joint distribution of surviving blocks of ancestral genome. Selection on unlinked loci in the genetic background may greatly increase the variance in reproductive value, but the above results nevertheless still hold. The almost linear relationship between survival probability and reproductive value also holds for weakly favored alleles. Thus, the influence of the complex pedigree of descendants on an individual's genetic contribution to the population can be summarized through a single number: its reproductive value.},
author = {Barton, Nicholas H and Etheridge, Alison},
journal = {Genetics},
number = {4},
pages = {953 -- 973},
publisher = {Genetics Society of America},
title = {{The relation between reproductive value and genetic contribution}},
doi = {10.1534/genetics.111.127555},
volume = {188},
year = {2011},
}
@article{3391,
abstract = {Evolutionary biology shares many concepts with statistical physics: both deal with populations, whether of molecules or organisms, and both seek to simplify evolution in very many dimensions. Often, methodologies have undergone parallel and independent development, as with stochastic methods in population genetics. Here, we discuss aspects of population genetics that have embraced methods from physics: non-equilibrium statistical mechanics, travelling waves and Monte-Carlo methods, among others, have been used to study polygenic evolution, rates of adaptation and range expansions. These applications indicate that evolutionary biology can further benefit from interactions with other areas of statistical physics; for example, by following the distribution of paths taken by a population through time},
author = {de Vladar, Harold and Barton, Nicholas H},
journal = {Trends in Ecology and Evolution},
number = {8},
pages = {424 -- 432},
publisher = {Cell Press},
title = {{The contribution of statistical physics to evolutionary biology}},
doi = {10.1016/j.tree.2011.04.002},
volume = {26},
year = {2011},
}
@article{3392,
abstract = {Migrating lymphocytes acquire a polarized phenotype with a leading and a trailing edge, or uropod. Although in vitro experiments in cell lines or activated primary cell cultures have established that Rho-p160 coiled-coil kinase (ROCK)-myosin II-mediated uropod contractility is required for integrin de-adhesion on two-dimensional surfaces and nuclear propulsion through narrow pores in three-dimensional matrices, less is known about the role of these two events during the recirculation of primary, nonactivated lymphocytes. Using pharmacological antagonists of ROCK and myosin II, we report that inhibition of uropod contractility blocked integrin-independent mouse T cell migration through narrow, but not large, pores in vitro. T cell crawling on chemokine-coated endothelial cells under shear was severely impaired by ROCK inhibition, whereas transendothelial migration was only reduced through endothelial cells with high, but not low, barrier properties. Using three-dimensional thick-tissue imaging and dynamic two-photon microscopy of T cell motility in lymphoid tissue, we demonstrated a significant role for uropod contractility in intraluminal crawling and transendothelial migration through lymph node, but not bone marrow, endothelial cells. Finally, we demonstrated that ICAM-1, but not anatomical constraints or integrin-independent interactions, reduced parenchymal motility of inhibitor-treated T cells within the dense lymphoid microenvironment, thus assigning context-dependent roles for uropod contraction during lymphocyte recirculation.},
author = {Soriano, Silvia and Hons, Miroslav and Schumann, Kathrin and Kumar, Varsha and Dennier, Timo and Lyck, Ruth and Sixt, Michael K and Stein, Jens},
journal = {Journal of Immunology},
number = {5},
pages = {2356 -- 2364},
publisher = {American Association of Immunologists},
title = {{In vivo analysis of uropod function during physiological T cell trafficking}},
doi = {10.4049/jimmunol.1100935},
volume = {187},
year = {2011},
}
@article{3393,
abstract = {Unlike unconditionally advantageous “Fisherian” variants that tend to spread throughout a species range once introduced anywhere, “bistable” variants, such as chromosome translocations, have two alternative stable frequencies, absence and (near) fixation. Analogous to populations with Allee effects, bistable variants tend to increase locally only once they become sufficiently common, and their spread depends on their rate of increase averaged over all frequencies. Several proposed manipulations of insect populations, such as using Wolbachia or “engineered underdominance” to suppress vector-borne diseases, produce bistable rather than Fisherian dynamics. We synthesize and extend theoretical analyses concerning three features of their spatial behavior: rate of spread, conditions to initiate spread from a localized introduction, and wave stopping caused by variation in population densities or dispersal rates. Unlike Fisherian variants, bistable variants tend to spread spatially only for particular parameter combinations and initial conditions. Wave initiation requires introduction over an extended region, while subsequent spatial spread is slower than for Fisherian waves and can easily be halted by local spatial inhomogeneities. We present several new results, including robust sufficient conditions to initiate (and stop) spread, using a one-parameter cubic approximation applicable to several models. The results have both basic and applied implications.},
author = {Barton, Nicholas H and Turelli, Michael},
journal = {American Naturalist},
number = {3},
pages = {E48 -- E75},
publisher = {University of Chicago Press},
title = {{Spatial waves of advance with bistable dynamics: Cytoplasmic and genetic analogues of Allee effects}},
doi = {10.1086/661246},
volume = {178},
year = {2011},
}
@article{3394,
abstract = {Random genetic drift shifts clines in space, alters their width, and distorts their shape. Such random fluctuations complicate inferences from cline width and position. Notably, the effect of genetic drift on the expected shape of the cline is opposite to the naive (but quite common) misinterpretation of classic results on the expected cline. While random drift on average broadens the overall cline in expected allele frequency, it narrows the width of any particular cline. The opposing effects arise because locally, drift drives alleles to fixation—but fluctuations in position widen the expected cline. The effect of genetic drift can be predicted from standardized variance in allele frequencies, averaged across the habitat: 〈F〉. A cline maintained by spatially varying selection (step change) is expected to be narrower by a factor of relative to the cline in the absence of drift. The expected cline is broader by the inverse of this factor. In a tension zone maintained by underdominance, the expected cline width is narrower by about 1 – 〈F〉relative to the width in the absence of drift. Individual clines can differ substantially from the expectation, and we give quantitative predictions for the variance in cline position and width. The predictions apply to clines in almost one-dimensional circumstances such as hybrid zones in rivers, deep valleys, or along a coast line and give a guide to what patterns to expect in two dimensions.},
author = {Polechova, Jitka and Barton, Nicholas H},
journal = {Genetics},
number = {1},
pages = {227 -- 235},
publisher = {Genetics Society of America},
title = {{Genetic drift widens the expected cline but narrows the expected cline width}},
doi = {10.1534/genetics.111.129817},
volume = {189},
year = {2011},
}
@article{3395,
abstract = {Defining population structure and genetic diversity levels is of the utmost importance for developing efficient conservation strategies. Overfishing has caused mean annual catches of the European spiny lobster (Palinurus elephas) to decrease alarmingly along its distribution area. In this context, there is a need for comprehensive studies aiming to evaluate the genetic health of the exploited populations. The present study is based on a set of ten nuclear markers amplified in 331 individuals from ten different localities covering most of P. elephas distribution area. Samples from Atlantic and Mediterranean basins showed small but significant differences, indicating that P. elephas populations do not behave as a single panmictic unit but form two partially-overlapping groups. Despite intense overfishing, our dataset did not recover a recent bottleneck signal, and instead showed a large and stable historical effective size. This result could be accounted for by specific life-history traits (reproduction and longevity) and the limitations of molecular markers in covering recent timescales for nontemporal samples. The findings of the present study emphasize the need to integrate information on effective population sizes and life-history parameters when evaluating population connectivity levels from genetic data.},
author = {Palero, Ferran and Abello, Pere and Macpherson, Enrique and Beaumont, Mark and Pascual, Marta},
journal = {Biological Journal of the Linnean Society},
number = {2},
pages = {407 -- 418},
publisher = {Wiley-Blackwell},
title = {{Effect of oceanographic barriers and overfishing on the population genetic structure of the European spiny lobster Palinurus elephas }},
doi = {10.1111/j.1095-8312.2011.01728.x},
volume = {104},
year = {2011},
}
@article{3396,
abstract = {Facial branchiomotor neurons (FBMNs) in zebrafish and mouse embryonic hindbrain undergo a characteristic tangential migration from rhombomere (r) 4, where they are born, to r6/7. Cohesion among neuroepithelial cells (NCs) has been suggested to function in FBMN migration by inhibiting FBMNs positioned in the basal neuroepithelium such that they move apically between NCs towards the midline of the neuroepithelium instead of tangentially along the basal side of the neuroepithelium towards r6/7. However, direct experimental evaluation of this hypothesis is still lacking. Here, we have used a combination of biophysical cell adhesion measurements and high-resolution time-lapse microscopy to determine the role of NC cohesion in FBMN migration. We show that reducing NC cohesion by interfering with Cadherin 2 (Cdh2) activity results in FBMNs positioned at the basal side of the neuroepithelium moving apically towards the neural tube midline instead of tangentially towards r6/7. In embryos with strongly reduced NC cohesion, ectopic apical FBMN movement frequently results in fusion of the bilateral FBMN clusters over the apical midline of the neural tube. By contrast, reducing cohesion among FBMNs by interfering with Contactin 2 (Cntn2) expression in these cells has little effect on apical FBMN movement, but reduces the fusion of the bilateral FBMN clusters in embryos with strongly diminished NC cohesion. These data provide direct experimental evidence that NC cohesion functions in tangential FBMN migration by restricting their apical movement.},
author = {Stockinger, Petra and Heisenberg, Carl-Philipp J and Maître, Jean-Léon},
journal = {Development},
number = {21},
pages = {4673 -- 4683},
publisher = {Company of Biologists},
title = {{Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube}},
doi = {10.1242/dev.071233},
volume = {138},
year = {2011},
}
@article{3397,
abstract = {Recent advances in microscopy techniques and biophysical measurements have provided novel insight into the molecular, cellular and biophysical basis of cell adhesion. However, comparably little is known about a core element of cell–cell adhesion—the energy of adhesion at the cell–cell contact. In this review, we discuss approaches to understand the nature and regulation of adhesion energy, and propose strategies to determine adhesion energy between cells in vitro and in vivo.},
author = {Maître, Jean-Léon and Heisenberg, Carl-Philipp J},
journal = {Current Opinion in Cell Biology},
number = {5},
pages = {508 -- 514},
publisher = {Elsevier},
title = {{The role of adhesion energy in controlling cell-cell contacts}},
doi = {10.1016/j.ceb.2011.07.004},
volume = {23},
year = {2011},
}
@article{3399,
abstract = {Context-dependent adjustment of mating tactics can drastically increase the mating success of behaviourally flexible animals. We used the ant Cardiocondyla obscurior as a model system to study adaptive adjustment of male mating tactics. This species shows a male diphenism of wingless fighter males and peaceful winged males. Whereas the wingless males stay and exclusively mate in the maternal colony, the mating behaviour of winged males is plastic. They copulate with female sexuals in their natal nests early in life but later disperse in search for sexuals outside. In this study, we observed the nest-leaving behaviour of winged males under different conditions and found that they adaptively adjust the timing of their dispersal to the availability of mating partners, as well as the presence, and even the type of competitors in their natal nests. In colonies with virgin female queens winged males stayed longest when they were the only male in the nest. They left earlier when mating partners were not available or when other males were present. In the presence of wingless, locally mating fighter males, winged males dispersed earlier than in the presence of docile, winged competitors. This suggests that C. obscurior males are capable of estimating their local breeding chances and adaptively adjust their dispersal behaviour in both an opportunistic and a risk-sensitive way, thus showing hitherto unknown behavioural plasticity in social insect males.},
author = {Cremer, Sylvia and Schrempf, Alexandra and Heinze, Jürgen},
journal = {PLoS One},
number = {3},
publisher = {Public Library of Science},
title = {{Competition and opportunity shape the reproductive tactics of males in the ant Cardiocondyla obscurior}},
doi = {10.1371/journal.pone.0017323},
volume = {6},
year = {2011},
}
@article{3405,
abstract = {Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and gates non-selective cation channels. The origins of glutamate receptors are not well understood as they differ structurally and functionally from simple bacterial ligand-gated ion channels. Here we report the discovery of an ionotropic glutamate receptor that combines the typical eukaryotic domain architecture with the 'TXVGYG' signature sequence of the selectivity filter found in K+ channels. This receptor exhibits functional properties intermediate between bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.},
author = {Janovjak, Harald L and Sandoz, Guillaume and Isacoff, Ehud},
journal = {Nature Communications},
number = {232},
pages = {1 -- 6},
publisher = {Nature Publishing Group},
title = {{Modern ionotropic glutamate receptor with a K+ selectivity signature sequence}},
doi = {10.1038/ncomms1231},
volume = {2},
year = {2011},
}
@article{3429,
abstract = {Transcription factors are central to sustaining pluripotency, yet little is known about transcription factor dynamics in defining pluripotency in the early mammalian embryo. Here, we establish a fluorescence decay after photoactivation (FDAP) assay to quantitatively study the kinetic behaviour of Oct4, a key transcription factor controlling pre-implantation development in the mouse embryo. FDAP measurements reveal that each cell in a developing embryo shows one of two distinct Oct4 kinetics, before there are any morphologically distinguishable differences or outward signs of lineage patterning. The differences revealed by FDAP are due to differences in the accessibility of Oct4 to its DNA binding sites in the nucleus. Lineage tracing of the cells in the two distinct sub-populations demonstrates that the Oct4 kinetics predict lineages of the early embryo. Cells with slower Oct4 kinetics are more likely to give rise to the pluripotent cell lineage that contributes to the inner cell mass. Those with faster Oct4 kinetics contribute mostly to the extra-embryonic lineage. Our findings identify Oct4 kinetics, rather than differences in total transcription factor expression levels, as a predictive measure of developmental cell lineage patterning in the early mouse embryo.},
author = {Plachta, Nicolas and Bollenbach, Mark Tobias and Pease, Shirley and Fraser, Scott and Pantazis, Periklis},
journal = {Nature Cell Biology},
number = {2},
pages = {117 -- 123},
publisher = {Nature Publishing Group},
title = {{Oct4 kinetics predict cell lineage patterning in the early mammalian embryo}},
doi = {10.1038/ncb2154},
volume = {13},
year = {2011},
}
@article{3505,
abstract = {Cell migration on two-dimensional (2D) substrates follows entirely different rules than cell migration in three-dimensional (3D) environments. This is especially relevant for leukocytes that are able to migrate in the absence of adhesion receptors within the confined geometry of artificial 3D extracellular matrix scaffolds and within the interstitial space in vivo. Here, we describe in detail a simple and economical protocol to visualize dendritic cell migration in 3D collagen scaffolds along chemotactic gradients. This method can be adapted to other cell types and may serve as a physiologically relevant paradigm for the directed locomotion of most amoeboid cells.},
author = {Sixt, Michael K and Lämmermann, Tim},
journal = {Cell Migration},
pages = {149 -- 165},
publisher = {Springer},
title = {{In vitro analysis of chemotactic leukocyte migration in 3D environments}},
doi = {10.1007/978-1-61779-207-6_11},
volume = {769},
year = {2011},
}
@article{3771,
abstract = {The small-sized frugivorous bat Carollia perspicillata is an understory specialist and occurs in a wide range of lowland habitats, tending to be more common in tropical dry or moist forests of South and Central America. Its sister species, Carollia brevicauda, occurs almost exclusively in the Amazon rainforest. A recent phylogeographic study proposed a hypothesis of origin and subsequent diversification for C. perspicillata along the Atlantic coastal forest of Brazil. Additionally, it also found two allopatric clades for C. brevicauda separated by the Amazon Basin. We used cytochrome b gene sequences and a more extensive sampling to test hypotheses related to the origin and diversification of C. perspicillata plus C. brevicauda clade in South America. The results obtained indicate that there are two sympatric evolutionary lineages within each species. In C. perspicillata, one lineage is limited to the Southern Atlantic Forest, whereas the other is widely distributed. Coalescent analysis points to a simultaneous origin for C. perspicillata and C. brevicauda, although no place for the diversification of each species can be firmly suggested. The phylogeographic pattern shown by C. perspicillata is also congruent with the Pleistocene refugia hypothesis as a likely vicariant phenomenon shaping the present distribution of its intraspecific lineages.},
author = {Pavan, Ana and Martins, Felipe and Santos, Fabrício and Ditchfield, Albert and Fernandes Redondo, Rodrigo A},
journal = {Biological Journal of the Linnean Society},
number = {3},
pages = {527 -- 539},
publisher = {Wiley-Blackwell},
title = {{Patterns of diversification in two species of short-tailed bats (Carollia Gray, 1838): the effects of historical fragmentation of Brazilian rainforests.}},
doi = {10.1111/j.1095-8312.2010.01601.x},
volume = {102},
year = {2011},
}
@article{3778,
author = {Barton, Nicholas H},
journal = {Heredity},
number = {2},
pages = {205 -- 206},
publisher = {Nature Publishing Group},
title = {{Estimating linkage disequilibria}},
doi = {10.1038/hdy.2010.67},
volume = {106},
year = {2011},
}
@article{3781,
abstract = {We bound the difference in length of two curves in terms of their total curvatures and the Fréchet distance. The bound is independent of the dimension of the ambient Euclidean space, it improves upon a bound by Cohen-Steiner and Edelsbrunner, and it generalizes a result by Fáry and Chakerian.},
author = {Fasy, Brittany Terese},
journal = {Acta Sci. Math. (Szeged)},
number = {1-2},
pages = {359 -- 367},
publisher = {Szegedi Tudományegyetem},
title = {{The difference in length of curves in R^n}},
volume = {77},
year = {2011},
}
@article{3784,
abstract = {Advanced stages of Scyllarus phyllosoma larvae were collected by demersal trawling during fishery research surveys in the western Mediterranean Sea in 2003–2005. Nucleotide sequence analysis of the mitochondrial 16S rDNA gene allowed the final-stage phyllosoma of Scyllarus arctus to be identified among these larvae. Its morphology is described and illustrated. This constitutes the second complete description of a Scyllaridae phyllosoma with its specific identity being validated by molecular techniques (the first was S. pygmaeus). These results also solved a long lasting taxonomic anomaly of several species assigned to the ancient genus Phyllosoma Leach, 1814. Detailed examination indicated that the final-stage phyllosoma of S. arctus shows closer affinities with the American scyllarid Scyllarus depressus or with the Australian Scyllarus sp. b (sensu Phillips et al., 1981) than to its sympatric species S. pygmaeus.},
author = {Palero, Ferran and Guerao, Guillermo and Clark, Paul and Abello, Pere},
journal = {Journal of the Marine Biological Association of the United Kingdom},
number = {2},
pages = {485 -- 492},
publisher = {Cambridge University Press},
title = {{Scyllarus arctus (Crustacea: Decapoda: Scyllaridae) final stage phyllosoma identified by DNA analysis, with morphological description}},
doi = {10.1017/S0025315410000287},
volume = {91},
year = {2011},
}
@inbook{3796,
abstract = {We address the problem of covering ℝ n with congruent balls, while minimizing the number of balls that contain an average point. Considering the 1-parameter family of lattices defined by stretching or compressing the integer grid in diagonal direction, we give a closed formula for the covering density that depends on the distortion parameter. We observe that our family contains the thinnest lattice coverings in dimensions 2 to 5. We also consider the problem of packing congruent balls in ℝ n , for which we give a closed formula for the packing density as well. Again we observe that our family contains optimal configurations, this time densest packings in dimensions 2 and 3.},
author = {Edelsbrunner, Herbert and Kerber, Michael},
booktitle = {Rainbow of Computer Science},
editor = {Calude, Cristian and Rozenberg, Grzegorz and Salomaa, Arto},
pages = {20 -- 35},
publisher = {Springer},
title = {{Covering and packing with spheres by diagonal distortion in R^n}},
doi = {10.1007/978-3-642-19391-0_2},
volume = {6570},
year = {2011},
}
@inbook{3791,
abstract = {During the development of multicellular organisms, cell fate specification is followed by the sorting of different cell types into distinct domains from where the different tissues and organs are formed. Cell sorting involves both the segregation of a mixed population of cells with different fates and properties into distinct domains, and the active maintenance of their segregated state. Because of its biological importance and apparent resemblance to fluid segregation in physics, cell sorting was extensively studied by both biologists and physicists over the last decades. Different theories were developed that try to explain cell sorting on the basis of the physical properties of the constituent cells. However, only recently the molecular and cellular mechanisms that control the physical properties driving cell sorting, have begun to be unraveled. In this review, we will provide an overview of different cell-sorting processes in development and discuss how these processes can be explained by the different sorting theories, and how these theories in turn can be connected to the molecular and cellular mechanisms driving these processes.},
author = {Krens, Gabriel and Heisenberg, Carl-Philipp J},
booktitle = {Forces and Tension in Development},
editor = {Labouesse, Michel},
pages = {189 -- 213},
publisher = {Elsevier},
title = {{Cell sorting in development}},
doi = {10.1016/B978-0-12-385065-2.00006-2},
volume = {95},
year = {2011},
}
@article{2409,
abstract = {Background: The availability of many gene alignments with overlapping taxon sets raises the question of which strategy is the best to infer species phylogenies from multiple gene information. Methods and programs abound that use the gene alignment in different ways to reconstruct the species tree. In particular, different methods combine the original data at different points along the way from the underlying sequences to the final tree. Accordingly, they are classified into superalignment, supertree and medium-level approaches. Here, we present a simulation study to compare different methods from each of these three approaches.
Results: We observe that superalignment methods usually outperform the other approaches over a wide range of parameters including sparse data and gene-specific evolutionary parameters. In the presence of high incongruency among gene trees, however, other combination methods show better performance than the superalignment approach. Surprisingly, some supertree and medium-level methods exhibit, on average, worse results than a single gene phylogeny with complete taxon information.
Conclusions: For some methods, using the reconstructed gene tree as an estimation of the species tree is superior to the combination of incomplete information. Superalignment usually performs best since it is less susceptible to stochastic error. Supertree methods can outperform superalignment in the presence of gene-tree conflict.},
author = {Kupczok, Anne and Schmidt, Heiko and Von Haeseler, Arndt},
journal = {Algorithms for Molecular Biology},
number = {1},
publisher = {BioMed Central},
title = {{Accuracy of phylogeny reconstruction methods combining overlapping gene data sets }},
doi = {10.1186/1748-7188-5-37},
volume = {5},
year = {2010},
}
@phdthesis{3962,
author = {Pflicke, Holger},
publisher = {IST Austria},
title = {{Dendritic cell migration across basement membranes in the skin}},
year = {2010},
}
@article{4134,
abstract = {All species are restricted in their distribution. Currently, ecological models can only explain such limits if patches vary in quality, leading to asymmetrical dispersal, or if genetic variation is too low at the margins for adaptation. However, population genetic models suggest that the increase in genetic variance resulting from dispersal should allow adaptation to almost any ecological gradient. Clearly therefore, these models miss something that prevents evolution in natural populations. We developed an individual-based simulation to explore stochastic effects in these models. At high carrying capacities, our simulations largely agree with deterministic predictions. However, when carrying capacity is low, the population fails to establish for a wide range of parameter values where adaptation was expected from previous models. Stochastic or transient effects appear critical around the boundaries in parameter space between simulation behaviours. Dispersal, gradient steepness, and population density emerge as key factors determining adaptation on an ecological gradient. },
author = {Bridle, Jon and Polechova, Jitka and Kawata, Masakado and Butlin, Roger},
journal = {Ecology Letters},
number = {4},
pages = {485 -- 494},
publisher = {Wiley-Blackwell},
title = {{Why is adaptation prevented at ecological margins? New insights from individual-based simulations}},
doi = {10.1111/j.1461-0248.2010.01442.x},
volume = {13},
year = {2010},
}
@article{4157,
abstract = {Integrin- and cadherin-mediated adhesion is central for cell and tissue morphogenesis, allowing cells and tissues to change shape without loosing integrity. Studies predominantly in cell culture showed that mechanosensation through adhesion structures is achieved by force-mediated modulation of their molecular composition. The specific molecular composition of adhesion sites in turn determines their signalling activity and dynamic reorganization. Here, we will review how adhesion sites respond to mecanical stimuli, and how spatially and temporally regulated signalling from different adhesion sites controls cell migration and tissue morphogenesis.},
author = {Papusheva, Ekaterina and Heisenberg, Carl-Philipp J},
journal = {EMBO Journal},
number = {16},
pages = {2753 -- 2768},
publisher = {Wiley-Blackwell},
title = {{Spatial organization of adhesion: force-dependent regulation and function in tissue morphogenesis}},
doi = {10.1038/emboj.2010.182},
volume = {29},
year = {2010},
}
@article{4243,
abstract = {We investigate a new model for populations evolving in a spatial continuum. This model can be thought of as a spatial version of the Lambda-Fleming-Viot process. It explicitly incorporates both small scale reproduction events and large scale extinction-recolonisation events. The lineages ancestral to a sample from a population evolving according to this model can be described in terms of a spatial version of the Lambda-coalescent. Using a technique of Evans (1997), we prove existence and uniqueness in law for the model. We then investigate the asymptotic behaviour of the genealogy of a finite number of individuals sampled uniformly at random (or more generally `far enough apart') from a two-dimensional torus of sidelength L as L tends to infinity. Under appropriate conditions (and on a suitable timescale) we can obtain as limiting genealogical processes a Kingman coalescent, a more general Lambda-coalescent or a system of coalescing Brownian motions (with a non-local coalescence mechanism).},
author = {Barton, Nicholas H and Etheridge, Alison and Véber, Amandine},
journal = {Electronic Journal of Probability},
number = {7},
pages = {162 -- 216},
publisher = {Institute of Mathematical Statistics},
title = {{A new model for evolution in a spatial continuum}},
doi = {10.1214/EJP.v15-741},
volume = {15},
year = {2010},
}
@inbook{4339,
abstract = {Mit diesem Buch möchten wir einen Überblick der aktuellen Diskussion zum Thema Bibliothek 2.0 geben und den Stand der tatsächlichen Umsetzung der Web 2.0-Ansätze in deutschsprachigen Bibliotheken beleuchten. An dieser Stelle ist die Frage erlaubt, warum es zu einer Zeit, in der es bereits die ersten "Web 3.0"- Konferenzen gibt, eines Handbuches der Bibliothek 2.0 noch bedarf. Und warum es überhaupt ein deutschsprachiges Handbuch zur Bibliothek 2.0 braucht, wo es doch bereits verschiedenste Publikationen zu diesem Thema aus anderen Ländern, insbesondere des angloamerikanischen Raums gibt. Ist dazu nicht bereits alles gesagt?},
author = {Bergmann, Julia and Danowski, Patrick},
booktitle = {Handbuch Bibliothek 2.0},
editor = {Bergmann, Julia and Danowski, Patrick},
pages = {5 -- 20},
publisher = {De Gruyter},
title = {{Ist Bibliothek 2.0 überhaupt noch relevant? – Eine Einleitung in das Handbuch}},
doi = {10.1515/9783110232103},
year = {2010},
}
@book{4346,
abstract = {With the term "Library 2.0" the editors mean an institution which applies the principles of the Web 2.0 such as openness, re-use, collaboration and interaction in the entire organization. Libraries are extending their service offerings and work processes to include the potential of Web 2.0 technologies. This changes the job description and self-image of librarians. The collective volume offers a complete overview of the topic Library 2.0 and the current state of developments from a technological, sociological, information theoretical and practice-oriented perspective.},
author = {Danowski, Patrick and Bergmann, Julia},
publisher = {De Gruyter},
title = {{Handbuch Bibliothek 2.0}},
year = {2010},
}
@inproceedings{4361,
abstract = {Depth-bounded processes form the most expressive known fragment of the π-calculus for which interesting verification problems are still decidable. In this paper we develop an adequate domain of limits for the well-structured transition systems that are induced by depth-bounded processes. An immediate consequence of our result is that there exists a forward algorithm that decides the covering problem for this class. Unlike backward algorithms, the forward algorithm terminates even if the depth of the process is not known a priori. More importantly, our result suggests a whole spectrum of forward algorithms that enable the effective verification of a large class of mobile systems.},
author = {Wies, Thomas and Zufferey, Damien and Henzinger, Thomas A},
editor = {Ong, Luke},
location = {Paphos, Cyprus},
pages = {94 -- 108},
publisher = {Springer},
title = {{Forward analysis of depth-bounded processes}},
doi = {10.1007/978-3-642-12032-9_8},
volume = {6014},
year = {2010},
}
@inproceedings{4362,
abstract = {Software transactional memories (STMs) promise simple and efficient concurrent programming. Several correctness properties have been proposed for STMs. Based on a bounded conflict graph algorithm for verifying correctness of STMs, we develop TRACER, a tool for runtime verification of STM implementations. The novelty of TRACER lies in the way it combines coarse and precise runtime analyses to guarantee sound and complete verification in an efficient manner. We implement TRACER in the TL2 STM implementation. We evaluate the performance of TRACER on STAMP benchmarks. While a precise runtime verification technique based on conflict graphs results in an average slowdown of 60x, the two-level approach of TRACER performs complete verification with an average slowdown of around 25x across different benchmarks.},
author = {Singh, Vasu},
editor = {Sokolsky, Oleg and Rosu, Grigore and Tilmann, Nikolai and Barringer, Howard and Falcone, Ylies and Finkbeiner, Bernd and Havelund, Klaus and Lee, Insup and Pace, Gordon},
location = {St. Julians, Malta},
pages = {421 -- 435},
publisher = {Springer},
title = {{Runtime verification for software transactional memories}},
doi = {10.1007/978-3-642-16612-9_32},
volume = {6418},
year = {2010},
}
@inproceedings{4369,
abstract = {In this paper we propose a novel technique for constructing timed automata from properties expressed in the logic mtl, under bounded-variability assumptions. We handle full mtl and include all future operators. Our construction is based on separation of the continuous time monitoring of the input sequence and discrete predictions regarding the future. The separation of the continuous from the discrete allows us to determinize our automata in an exponential construction that does not increase the number of clocks. This leads to a doubly exponential construction from mtl to deterministic timed automata, compared with triply exponential using existing approaches. We offer an alternative to the existing approach to linear real-time model checking, which has never been implemented. It further offers a unified framework for model checking, runtime monitoring, and synthesis, in an approach that can reuse tools, implementations, and insights from the discrete setting.},
author = {Nickovic, Dejan and Piterman, Nir},
editor = {Henzinger, Thomas A. and Chatterjee, Krishnendu},
location = {Klosterneuburg, Austria},
pages = {152 -- 167},
publisher = {Springer},
title = {{From MTL to deterministic timed automata}},
doi = {10.1007/978-3-642-15297-9_13},
volume = {6246},
year = {2010},
}
@inproceedings{4378,
abstract = {Techniques such as verification condition generation, predicate abstraction, and expressive type systems reduce software verification to proving formulas in expressive logics. Programs and their specifications often make use of data structures such as sets, multisets, algebraic data types, or graphs. Consequently, formulas generated from verification also involve such data structures. To automate the proofs of such formulas we propose a logic (a “calculus”) of such data structures. We build the calculus by starting from decidable logics of individual data structures, and connecting them through functions and sets, in ways that go beyond the frameworks such as Nelson-Oppen. The result are new decidable logics that can simultaneously specify properties of different kinds of data structures and overcome the limitations of the individual logics. Several of our decidable logics include abstraction functions that map a data structure into its more abstract view (a tree into a multiset, a multiset into a set), into a numerical quantity (the size or the height), or into the truth value of a candidate data structure invariant (sortedness, or the heap property). For algebraic data types, we identify an asymptotic many-to-one condition on the abstraction function that guarantees the existence of a decision procedure. In addition to the combination based on abstraction functions, we can combine multiple data structure theories if they all reduce to the same data structure logic. As an instance of this approach, we describe a decidable logic whose formulas are propositional combinations of formulas in: weak monadic second-order logic of two successors, two-variable logic with counting, multiset algebra with Presburger arithmetic, the Bernays-Schönfinkel-Ramsey class of first-order logic, and the logic of algebraic data types with the set content function. The subformulas in this combination can share common variables that refer to sets of objects along with the common set algebra operations. Such sound and complete combination is possible because the relations on sets definable in the component logics are all expressible in Boolean Algebra with Presburger Arithmetic. Presburger arithmetic and its new extensions play an important role in our decidability results. In several cases, when we combine logics that belong to NP, we can prove the satisfiability for the combined logic is still in NP.},
author = {Kuncak, Viktor and Piskac, Ruzica and Suter, Philippe and Wies, Thomas},
editor = {Barthe, Gilles and Hermenegildo, Manuel},
location = {Madrid, Spain},
pages = {26 -- 44},
publisher = {Springer},
title = {{Building a calculus of data structures}},
doi = {10.1007/978-3-642-11319-2_6},
volume = {5944},
year = {2010},
}
@inproceedings{4380,
abstract = {Cloud computing is an emerging paradigm aimed to offer users pay-per-use computing resources, while leaving the burden of managing the computing infrastructure to the cloud provider. We present a new programming and pricing model that gives the cloud user the flexibility of trading execution speed and price on a per-job basis. We discuss the scheduling and resource management challenges for the cloud provider that arise in the implementation of this model. We argue that techniques from real-time and embedded software can be useful in this context.},
author = {Henzinger, Thomas A and Tomar, Anmol and Singh, Vasu and Wies, Thomas and Zufferey, Damien},
location = {Arizona, USA},
pages = {1 -- 8},
publisher = {ACM},
title = {{A marketplace for cloud resources}},
doi = {10.1145/1879021.1879022},
year = {2010},
}
@inproceedings{4381,
abstract = {Cloud computing aims to give users virtually unlimited pay-per-use computing resources without the burden of managing the underlying infrastructure. We claim that, in order to realize the full potential of cloud computing, the user must be presented with a pricing model that offers flexibility at the requirements level, such as a choice between different degrees of execution speed and the cloud provider must be presented with a programming model that offers flexibility at the execution level, such as a choice between different scheduling policies. In such a flexible framework, with each job, the user purchases a virtual computer with the desired speed and cost characteristics, and the cloud provider can optimize the utilization of resources across a stream of jobs from different users. We designed a flexible framework to test our hypothesis, which is called FlexPRICE (Flexible Provisioning of Resources in a Cloud Environment) and works as follows. A user presents a job to the cloud. The cloud finds different schedules to execute the job and presents a set of quotes to the user in terms of price and duration for the execution. The user then chooses a particular quote and the cloud is obliged to execute the job according to the chosen quote. FlexPRICE thus hides the complexity of the actual scheduling decisions from the user, but still provides enough flexibility to meet the users actual demands. We implemented FlexPRICE in a simulator called PRICES that allows us to experiment with our framework. We observe that FlexPRICE provides a wide range of execution options-from fast and expensive to slow and cheap-- for the whole spectrum of data-intensive and computation-intensive jobs. We also observe that the set of quotes computed by FlexPRICE do not vary as the number of simultaneous jobs increases.},
author = {Henzinger, Thomas A and Tomar, Anmol and Singh, Vasu and Wies, Thomas and Zufferey, Damien},
location = {Miami, USA},
pages = {83 -- 90},
publisher = {IEEE},
title = {{FlexPRICE: Flexible provisioning of resources in a cloud environment}},
doi = {10.1109/CLOUD.2010.71},
year = {2010},
}
@inproceedings{4382,
abstract = {Transactional memory (TM) has shown potential to simplify the task of writing concurrent programs. Inspired by classical work on databases, formal definitions of the semantics of TM executions have been proposed. Many of these definitions assumed that accesses to shared data are solely performed through transactions. In practice, due to legacy code and concurrency libraries, transactions in a TM have to share data with non-transactional operations. The semantics of such interaction, while widely discussed by practitioners, lacks a clear formal specification. Those interactions can vary, sometimes in subtle ways, between TM implementations and underlying memory models. We propose a correctness condition for TMs, parametrized opacity, to formally capture the now folklore notion of strong atomicity by stipulating the two following intuitive requirements: first, every transaction appears as if it is executed instantaneously with respect to other transactions and non-transactional operations, and second, non-transactional operations conform to the given underlying memory model. We investigate the inherent cost of implementing parametrized opacity. We first prove that parametrized opacity requires either instrumenting non-transactional operations (for most memory models) or writing to memory by transactions using potentially expensive read-modify-write instructions (such as compare-and-swap). Then, we show that for a class of practical relaxed memory models, parametrized opacity can indeed be implemented with constant-time instrumentation of non-transactional writes and no instrumentation of non-transactional reads. We show that, in practice, parametrizing the notion of correctness allows developing more efficient TM implementations.},
author = {Guerraoui, Rachid and Henzinger, Thomas A and Kapalka, Michal and Singh, Vasu},
location = {Santorini, Greece},
pages = {263 -- 272},
publisher = {ACM},
title = {{Transactions in the jungle}},
doi = {10.1145/1810479.1810529},
year = {2010},
}
@inproceedings{4388,
abstract = {GIST is a tool that (a) solves the qualitative analysis problem of turn-based probabilistic games with ω-regular objectives; and (b) synthesizes reasonable environment assumptions for synthesis of unrealizable specifications. Our tool provides the first and efficient implementations of several reduction-based techniques to solve turn-based probabilistic games, and uses the analysis of turn-based probabilistic games for synthesizing environment assumptions for unrealizable specifications.},
author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Jobstmann, Barbara and Radhakrishna, Arjun},
location = {Edinburgh, UK},
pages = {665 -- 669},
publisher = {Springer},
title = {{GIST: A solver for probabilistic games}},
doi = {10.1007/978-3-642-14295-6_57},
volume = {6174},
year = {2010},
}
@inproceedings{4389,
abstract = {Digital components play a central role in the design of complex embedded systems. These components are interconnected with other, possibly analog, devices and the physical environment. This environment cannot be entirely captured and can provide inaccurate input data to the component. It is thus important for digital components to have a robust behavior, i.e. the presence of a small change in the input sequences should not result in a drastic change in the output sequences. In this paper, we study a notion of robustness for sequential circuits. However, since sequential circuits may have parts that are naturally discontinuous (e.g., digital controllers with switching behavior), we need a flexible framework that accommodates this fact and leaves discontinuous parts of the circuit out from the robustness analysis. As a consequence, we consider sequential circuits that have their input variables partitioned into two disjoint sets: control and disturbance variables. Our contributions are (1) a definition of robustness for sequential circuits as a form of continuity with respect to disturbance variables, (2) the characterization of the exact class of sequential circuits that are robust according to our definition, (3) an algorithm to decide whether a sequential circuit is robust or not.},
author = {Doyen, Laurent and Henzinger, Thomas A and Legay, Axel and Nickovic, Dejan},
pages = {77 -- 84},
publisher = {IEEE},
title = {{Robustness of sequential circuits}},
doi = {10.1109/ACSD.2010.26},
year = {2010},
}
@inproceedings{4390,
abstract = {Concurrent data structures with fine-grained synchronization are notoriously difficult to implement correctly. The difficulty of reasoning about these implementations does not stem from the number of variables or the program size, but rather from the large number of possible interleavings. These implementations are therefore prime candidates for model checking. We introduce an algorithm for verifying linearizability of singly-linked heap-based concurrent data structures. We consider a model consisting of an unbounded heap where each vertex stores an element from an unbounded data domain, with a restricted set of operations for testing and updating pointers and data elements. Our main result is that linearizability is decidable for programs that invoke a fixed number of methods, possibly in parallel. This decidable fragment covers many of the common implementation techniques — fine-grained locking, lazy synchronization, and lock-free synchronization. We also show how the technique can be used to verify optimistic implementations with the help of programmer annotations. We developed a verification tool CoLT and evaluated it on a representative sample of Java implementations of the concurrent set data structure. The tool verified linearizability of a number of implementations, found a known error in a lock-free implementation and proved that the corrected version is linearizable.},
author = {Cerny, Pavol and Radhakrishna, Arjun and Zufferey, Damien and Chaudhuri, Swarat and Alur, Rajeev},
location = {Edinburgh, UK},
pages = {465 -- 479},
publisher = {Springer},
title = {{Model checking of linearizability of concurrent list implementations}},
doi = {10.1007/978-3-642-14295-6_41},
volume = {6174},
year = {2010},
}
@inbook{4392,
abstract = {While a boolean notion of correctness is given by a preorder on systems and properties, a quantitative notion of correctness is defined by a distance function on systems and properties, where the distance between a system and a property provides a measure of “fit” or “desirability.” In this article, we explore several ways how the simulation preorder can be generalized to a distance function. This is done by equipping the classical simulation game between a system and a property with quantitative objectives. In particular, for systems that satisfy a property, a quantitative simulation game can measure the “robustness” of the satisfaction, that is, how much the system can deviate from its nominal behavior while still satisfying the property. For systems that violate a property, a quantitative simulation game can measure the “seriousness” of the violation, that is, how much the property has to be modified so that it is satisfied by the system. These distances can be computed in polynomial time, since the computation reduces to the value problem in limit average games with constant weights. Finally, we demonstrate how the robustness distance can be used to measure how many transmission errors are tolerated by error correcting codes. },
author = {Cerny, Pavol and Henzinger, Thomas A and Radhakrishna, Arjun},
booktitle = {Time For Verification: Essays in Memory of Amir Pnueli},
editor = {Manna, Zohar and Peled, Doron},
pages = {42 -- 60},
publisher = {Springer},
title = {{Quantitative Simulation Games}},
doi = {10.1007/978-3-642-13754-9_3},
volume = {6200},
year = {2010},
}
@inproceedings{4393,
abstract = {Boolean notions of correctness are formalized by preorders on systems. Quantitative measures of correctness can be formalized by real-valued distance functions between systems, where the distance between implementation and specification provides a measure of “fit” or “desirability.” We extend the simulation preorder to the quantitative setting, by making each player of a simulation game pay a certain price for her choices. We use the resulting games with quantitative objectives to define three different simulation distances. The correctness distance measures how much the specification must be changed in order to be satisfied by the implementation. The coverage distance measures how much the implementation restricts the degrees of freedom offered by the specification. The robustness distance measures how much a system can deviate from the implementation description without violating the specification. We consider these distances for safety as well as liveness specifications. The distances can be computed in polynomial time for safety specifications, and for liveness specifications given by weak fairness constraints. We show that the distance functions satisfy the triangle inequality, that the distance between two systems does not increase under parallel composition with a third system, and that the distance between two systems can be bounded from above and below by distances between abstractions of the two systems. These properties suggest that our simulation distances provide an appropriate basis for a quantitative theory of discrete systems. We also demonstrate how the robustness distance can be used to measure how many transmission errors are tolerated by error correcting codes.},
author = {Cerny, Pavol and Henzinger, Thomas A and Radhakrishna, Arjun},
location = {Paris, France},
pages = {235 -- 268},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Simulation distances}},
doi = {10.1007/978-3-642-15375-4_18},
volume = {6269},
year = {2010},
}
@inproceedings{4396,
abstract = {Shape analysis is a promising technique to prove program properties about recursive data structures. The challenge is to automatically determine the data-structure type, and to supply the shape analysis with the necessary information about the data structure. We present a stepwise approach to the selection of instrumentation predicates for a TVLA-based shape analysis, which takes us a step closer towards the fully automatic verification of data structures. The approach uses two techniques to guide the refinement of shape abstractions: (1) during program exploration, an explicit heap analysis collects sample instances of the heap structures, which are used to identify the data structures that are manipulated by the program; and (2) during abstraction refinement along an infeasible error path, we consider different possible heap abstractions and choose the coarsest one that eliminates the infeasible path. We have implemented this combined approach for automatic shape refinement as an extension of the software model checker BLAST. Example programs from a data-structure library that manipulate doubly-linked lists and trees were successfully verified by our tool.},
author = {Beyer, Dirk and Henzinger, Thomas A and Théoduloz, Grégory and Zufferey, Damien},
editor = {Rosenblum, David and Taenzer, Gabriele},
location = {Paphos, Cyprus},
pages = {263 -- 277},
publisher = {Springer},
title = {{Shape refinement through explicit heap analysis}},
doi = {10.1007/978-3-642-12029-9_19},
volume = {6013},
year = {2010},
}
@article{474,
abstract = {Classical models of gene flow fail in three ways: they cannot explain large-scale patterns; they predict much more genetic diversity than is observed; and they assume that loosely linked genetic loci evolve independently. We propose a new model that deals with these problems. Extinction events kill some fraction of individuals in a region. These are replaced by offspring from a small number of parents, drawn from the preexisting population. This model of evolution forwards in time corresponds to a backwards model, in which ancestral lineages jump to a new location if they are hit by an event, and may coalesce with other lineages that are hit by the same event. We derive an expression for the identity in allelic state, and show that, over scales much larger than the largest event, this converges to the classical value derived by Wright and Malécot. However, rare events that cover large areas cause low genetic diversity, large-scale patterns, and correlations in ancestry between unlinked loci.},
author = {Barton, Nicholas H and Kelleher, Jerome and Etheridge, Alison},
journal = {Evolution},
number = {9},
pages = {2701 -- 2715},
publisher = {Wiley-Blackwell},
title = {{A new model for extinction and recolonization in two dimensions: Quantifying phylogeography}},
doi = {10.1111/j.1558-5646.2010.01019.x},
volume = {64},
year = {2010},
}
@inproceedings{488,
abstract = {Streaming string transducers [1] define (partial) functions from input strings to output strings. A streaming string transducer makes a single pass through the input string and uses a finite set of variables that range over strings from the output alphabet. At every step, the transducer processes an input symbol, and updates all the variables in parallel using assignments whose right-hand-sides are concatenations of output symbols and variables with the restriction that a variable can be used at most once in a right-hand-side expression. It has been shown that streaming string transducers operating on strings over infinite data domains are of interest in algorithmic verification of list-processing programs, as they lead to PSPACE decision procedures for checking pre/post conditions and for checking semantic equivalence, for a well-defined class of heap-manipulating programs. In order to understand the theoretical expressiveness of streaming transducers, we focus on streaming transducers processing strings over finite alphabets, given the existence of a robust and well-studied class of "regular" transductions for this case. Such regular transductions can be defined either by two-way deterministic finite-state transducers, or using a logical MSO-based characterization. Our main result is that the expressiveness of streaming string transducers coincides exactly with this class of regular transductions. },
author = {Alur, Rajeev and Cerny, Pavol},
location = {Chennai, India},
pages = {1 -- 12},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Expressiveness of streaming string transducers}},
doi = {10.4230/LIPIcs.FSTTCS.2010.1},
volume = {8},
year = {2010},
}
@inproceedings{489,
abstract = {Graph games of infinite length are a natural model for open reactive processes: one player represents the controller, trying to ensure a given specification, and the other represents a hostile environment. The evolution of the system depends on the decisions of both players, supplemented by chance. In this work, we focus on the notion of randomised strategy. More specifically, we show that three natural definitions may lead to very different results: in the most general cases, an almost-surely winning situation may become almost-surely losing if the player is only allowed to use a weaker notion of strategy. In more reasonable settings, translations exist, but they require infinite memory, even in simple cases. Finally, some traditional problems becomes undecidable for the strongest type of strategies.},
author = {Cristau, Julien and David, Claire and Horn, Florian},
booktitle = {Proceedings of GandALF 2010},
location = {Minori, Amalfi Coast, Italy},
pages = {30 -- 39},
publisher = {Open Publishing Association},
title = {{How do we remember the past in randomised strategies? }},
doi = {10.4204/EPTCS.25.7},
volume = {25},
year = {2010},
}
@article{533,
abstract = {Any programming error that can be revealed before compiling a program saves precious time for the programmer. While integrated development environments already do a good job by detecting, e.g., data-flow abnormalities, current static analysis tools suffer from false positives ("noise") or require strong user interaction. We propose to avoid this deficiency by defining a new class of errors. A program fragment is doomed if its execution will inevitably fail, regardless of which state it is started in. We use a formal verification method to identify such errors fully automatically and, most significantly, without producing noise. We report on experiments with a prototype tool.},
author = {Hoenicke, Jochen and Leino, Kari and Podelski, Andreas and Schäf, Martin and Wies, Thomas},
journal = {Formal Methods in System Design},
number = {2-3},
pages = {171 -- 199},
publisher = {Springer},
title = {{Doomed program points}},
doi = {10.1007/s10703-010-0102-0},
volume = {37},
year = {2010},
}
@misc{5388,
abstract = {We present an algorithmic method for the synthesis of concurrent programs that are optimal with respect to quantitative performance measures. The input consists of a sequential sketch, that is, a program that does not contain synchronization constructs, and of a parametric performance model that assigns costs to actions such as locking, context switching, and idling. The quantitative synthesis problem is to automatically introduce synchronization constructs into the sequential sketch so that both correctness is guaranteed and worst-case (or average-case) performance is optimized. Correctness is formalized as race freedom or linearizability.
We show that for worst-case performance, the problem can be modeled
as a 2-player graph game with quantitative (limit-average) objectives, and
for average-case performance, as a 2 1/2 -player graph game (with probabilistic transitions). In both cases, the optimal correct program is derived from an optimal strategy in the corresponding quantitative game. We prove that the respective game problems are computationally expensive (NP-complete), and present several techniques that overcome the theoretical difficulty in cases of concurrent programs of practical interest.
We have implemented a prototype tool and used it for the automatic syn- thesis of programs that access a concurrent list. For certain parameter val- ues, our method automatically synthesizes various classical synchronization schemes for implementing a concurrent list, such as fine-grained locking or a lazy algorithm. For other parameter values, a new, hybrid synchronization style is synthesized, which uses both the lazy approach and coarse-grained locks (instead of standard fine-grained locks). The trade-off occurs because while fine-grained locking tends to decrease the cost that is due to waiting for locks, it increases cache size requirements.},
author = {Chatterjee, Krishnendu and Cerny, Pavol and Henzinger, Thomas A and Radhakrishna, Arjun and Singh, Rohit},
issn = {2664-1690},
pages = {17},
publisher = {IST Austria},
title = {{Quantitative synthesis for concurrent programs}},
doi = {10.15479/AT:IST-2010-0004},
year = {2010},
}
@misc{5389,
abstract = {Boolean notions of correctness are formalized by preorders on systems. Quantitative measures of correctness can be formalized by real-valued distance functions between systems, where the distance between implementation and specification provides a measure of “fit” or “desirability.” We extend the simulation preorder to the quantitative setting, by making each player of a simulation game pay a certain price for her choices. We use the resulting games with quantitative objectives to define three different simulation distances. The correctness distance measures how much the specification must be changed in order to be satisfied by the implementation. The coverage distance measures how much the im- plementation restricts the degrees of freedom offered by the specification. The robustness distance measures how much a system can deviate from the implementation description without violating the specification. We consider these distances for safety as well as liveness specifications. The distances can be computed in polynomial time for safety specifications, and for liveness specifications given by weak fairness constraints. We show that the distance functions satisfy the triangle inequality, that the distance between two systems does not increase under parallel composition with a third system, and that the distance between two systems can be bounded from above and below by distances between abstractions of the two systems. These properties suggest that our simulation distances provide an appropriate basis for a quantitative theory of discrete systems. We also demonstrate how the robustness distance can be used to measure how many transmission errors are tolerated by error correcting codes.},
author = {Cerny, Pavol and Henzinger, Thomas A and Radhakrishna, Arjun},
issn = {2664-1690},
pages = {24},
publisher = {IST Austria},
title = {{Simulation distances}},
doi = {10.15479/AT:IST-2010-0003},
year = {2010},
}
@misc{5390,
abstract = {The class of ω regular languages provide a robust specification language in verification. Every ω-regular condition can be decomposed into a safety part and a liveness part. The liveness part ensures that something good happens “eventually.” Two main strengths of the classical, infinite-limit formulation of liveness are robustness (independence from the granularity of transitions) and simplicity (abstraction of complicated time bounds). However, the classical liveness formulation suffers from the drawback that the time until something good happens may be unbounded. A stronger formulation of liveness, so-called finitary liveness, overcomes this drawback, while still retaining robustness and simplicity. Finitary liveness requires that there exists an unknown, fixed bound b such that something good happens within b transitions. In this work we consider the finitary parity and Streett (fairness) conditions. We present the topological, automata-theoretic and logical characterization of finitary languages defined by finitary parity and Streett conditions. We (a) show that the finitary parity and Streett languages are Σ2-complete; (b) present a complete characterization of the expressive power of various classes of automata with finitary and infinitary conditions (in particular we show that non-deterministic finitary parity and Streett automata cannot be determinized to deterministic finitary parity or Streett automata); and (c) show that the languages defined by non-deterministic finitary parity automata exactly characterize the star-free fragment of ωB-regular languages.},
author = {Chatterjee, Krishnendu and Fijalkow, Nathanaël},
issn = {2664-1690},
pages = {21},
publisher = {IST Austria},
title = {{Topological, automata-theoretic and logical characterization of finitary languages}},
doi = {10.15479/AT:IST-2010-0002},
year = {2010},
}
@misc{5391,
abstract = {Concurrent data structures with fine-grained synchronization are notoriously difficult to implement correctly. The difficulty of reasoning about these implementations does not stem from the number of variables or the program size, but rather from the large number of possible interleavings. These implementations are therefore prime candidates for model checking. We introduce an algorithm for verifying linearizability of singly-linked heap-based concurrent data structures. We consider a model consisting of an unbounded heap where each node consists an element from an unbounded data domain, with a restricted set of operations for testing and updating pointers and data elements. Our main result is that linearizability is decidable for programs that invoke a fixed number of methods, possibly in parallel. This decidable fragment covers many of the common implementation techniques — fine-grained locking, lazy synchronization, and lock-free synchronization. We also show how the technique can be used to verify optimistic implementations with the help of programmer annotations. We developed a verification tool CoLT and evaluated it on a representative sample of Java implementations of the concurrent set data structure. The tool verified linearizability of a number of implementations, found a known error in a lock-free imple- mentation and proved that the corrected version is linearizable.},
author = {Cerny, Pavol and Radhakrishna, Arjun and Zufferey, Damien and Chaudhuri, Swarat and Alur, Rajeev},
issn = {2664-1690},
pages = {27},
publisher = {IST Austria},
title = {{Model checking of linearizability of concurrent list implementations}},
doi = {10.15479/AT:IST-2010-0001},
year = {2010},
}
@article{3303,
abstract = {Biological traits result in part from interactions between different genetic loci. This can lead to sign epistasis, in which a beneficial adaptation involves a combination of individually deleterious or neutral mutations; in this case, a population must cross a “fitness valley” to adapt. Recombination can assist this process by combining mutations from different individuals or retard it by breaking up the adaptive combination. Here, we analyze the simplest fitness valley, in which an adaptation requires one mutation at each of two loci to provide a fitness benefit. We present a theoretical analysis of the effect of recombination on the valley-crossing process across the full spectrum of possible parameter regimes. We find that low recombination rates can speed up valley crossing relative to the asexual case, while higher recombination rates slow down valley crossing, with the transition between the two regimes occurring when the recombination rate between the loci is approximately equal to the selective advantage provided by the adaptation. In large populations, if the recombination rate is high and selection against single mutants is substantial, the time to cross the valley grows exponentially with population size, effectively meaning that the population cannot acquire the adaptation. Recombination at the optimal (low) rate can reduce the valley-crossing time by up to several orders of magnitude relative to that in an asexual population. },
author = {Weissman, Daniel and Feldman, Marcus and Fisher, Daniel},
journal = {Genetics},
number = {4},
pages = {1389 -- 1410},
publisher = {Genetics Society of America},
title = {{The rate of fitness-valley crossing in sexual populations}},
doi = {10.1534/genetics.110.123240},
volume = {186},
year = {2010},
}
@article{3498,
abstract = {Purpose
Calcifying tendinitis is a common condition of the shoulder. In many cases, arthroscopic reduction in the deposit is indicated. The localization of the deposit is sometimes challenging and time-consuming. Pre-operative ultrasound (US)-guided needle placement in the deposit and pre-operative US marking of the deposit at the skin with a ballpoint are described and recommended methods to alleviate the procedure without using ionizing radiation by fluoroscopy.
Methods
Intra-operative sonography of the shoulder is introduced as a new method to localize the calcific deposit with high accuracy. After standard arthroscopic buresectomy, the surgeon performs an ultrasound examination under sterile conditions to localize the deposits. A ventral longitudinal US section is recommended, and the upper arm is rotated until the deposit is visible. Subsequently, perpendicular to the skin at the position of the transducer, a needle is introduced under arthroscopic and ultrasound visualization to puncture the deposit.
Results
The presence of snow-white crystals at the tip of the needle proves the exact localization. Consecutively, the curettage can be accomplished. Another intra-operative sonography evaluates possible calcific remnants and the tendon structure.
Conclusion
This new technique may alleviate arthroscopic calcific deposit curettage by visualizing the deposit without using ionizing radiation. Additionally, soft tissue damage due to decreased number of punctures to detect the deposit may be achieved. Both factors may contribute to reduced operation time.},
author = {Sabeti Aschraf, M. and Gonano, C. and Nemecek, E. and Cichocki, Lisa and Schueller Weidekamm, C.},
journal = {Knee Surgery, Sports Traumatology, Arthroscopy},
number = {12},
pages = {1792 -- 1794},
publisher = {Springer},
title = {{Intra-operative ultrasound facilitates the localization of the calcific deposit during arthroscopic treatment of calcifying tendinitis}},
doi = {10.1007/s00167-010-1227-9},
volume = {18},
year = {2010},
}
@article{3604,
abstract = {We investigated temporal changes in hybridization and introgression between native red deer (Cervus elaphus) and invasive Japanese sika (Cervus nippon) on the Kintyre Peninsula, Scotland, over 15 years, through analysis of 1513 samples of deer at 20 microsatellite loci and a mtDNA marker. We found no evidence that either the proportion of recent hybrids, or the levels of introgression had changed over the study period. Nevertheless, in one population where the two species have been in contact since ∼1970, 44% of individuals sampled during the study were hybrids. This suggests that hybridization between these species can proceed fairly rapidly. By analysing the number of alleles that have introgressed from polymorphic red deer into the genetically homogenous sika population, we reconstructed the haplotypes of red deer alleles introduced by backcrossing. Five separate hybridization events could account for all the recently hybridized sika-like individuals found across a large section of the Peninsula. Although we demonstrate that low rates of F1 hybridization can lead to substantial introgression, the progress of hybridization and introgression appears to be unpredictable over the short timescales.},
author = {Senn, Helen and Goodman, Simon and Swanson, Graeme and Barton, Nicholas H and Pemberton, Josephine},
journal = {Molecular Ecology},
number = {5},
pages = {910 -- 924},
publisher = {Wiley-Blackwell},
title = {{Investigating temporal changes in hybridisation and introgression between invasive sika (Cervus nippon) and native red deer (Cervus elaphus) on the Kintyre Peninsula, Scotland}},
doi = {10.1111/j.1365-294X.2009.04497.x},
volume = {19},
year = {2010},
}
@article{3718,
abstract = {Long-term depression (LTD) is a form of synaptic plasticity that may contribute to information storage in the central nervous system. Here we report that LTD can be elicited in layer 5 pyramidal neurons of the rat prefrontal cortex by pairing low frequency stimulation with a modest postsynaptic depolarization. The induction of LTD required the activation of both metabotropic glutamate receptors of the mGlu1 subtype and voltage-sensitive Ca(2+) channels (VSCCs) of the T/R, P/Q and N types, leading to the stimulation of intracellular inositol trisphosphate (IP3) receptors by IP3 and Ca(2+). The subsequent release of Ca(2+) from intracellular stores activated the protein phosphatase cascade involving calcineurin and protein phosphatase 1. The activation of purinergic P2Y(1) receptors blocked LTD. This effect was prevented by P2Y(1) receptor antagonists and was absent in mice lacking P2Y(1) but not P2Y(2) receptors. We also found that activation of P2Y(1) receptors inhibits Ca(2+) transients via VSCCs in the apical dendrites and spines of pyramidal neurons. In addition, we show that the release of ATP under hypoxia is able to inhibit LTD by acting on postsynaptic P2Y(1) receptors. In conclusion, these data suggest that the reduction of Ca(2+) influx via VSCCs caused by the activation of P2Y(1) receptors by ATP is the possible mechanism for the inhibition of LTD in prefrontal cortex.},
author = {Guzmán, José and Schmidt, Hartmut and Franke, Heike and Krügel, Ute and Eilers, Jens and Illes, Peter and Gerevich, Zoltan},
journal = {Neuropharmacology},
number = {6},
pages = {406 -- 415},
publisher = {Elsevier},
title = {{P2Y1 receptors inhibit long-term depression in the prefrontal cortex.}},
doi = {10.1016/j.neuropharm.2010.05.013},
volume = {59},
year = {2010},
}
@inproceedings{3719,
abstract = {The induction of a signaling pathway is characterized by transient complex formation and mutual posttranslational modification of proteins. To faithfully capture this combinatorial process in a math- ematical model is an important challenge in systems biology. Exploiting the limited context on which most binding and modification events are conditioned, attempts have been made to reduce the com- binatorial complexity by quotienting the reachable set of molecular species, into species aggregates while preserving the deterministic semantics of the thermodynamic limit. Recently we proposed a quotienting that also preserves the stochastic semantics and that is complete in the sense that the semantics of individual species can be recovered from the aggregate semantics. In this paper we prove that this quotienting yields a sufficient condition for weak lumpability and that it gives rise to a backward Markov bisimulation between the original and aggregated transition system. We illustrate the framework on a case study of the EGF/insulin receptor crosstalk.},
author = {Feret, Jérôme and Henzinger, Thomas A and Koeppl, Heinz and Petrov, Tatjana},
location = {Jena, Germany},
pages = {142--161},
publisher = {Open Publishing Association},
title = {{Lumpability abstractions of rule-based systems}},
volume = {40},
year = {2010},
}
@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{3774,
abstract = {1. Hybridisation with an invasive species has the potential to alter the phenotype and hence the ecology of a native counterpart. 2. Here data from populations of native red deer Cervus elaphus and invasive sika deer Cervus nippon in Scotland is used to assess the extent to which hybridisation between them is causing phenotypic change. This is done by regression of phenotypic traits against genetic hybrid scores. 3. Hybridisation is causing increases in the body weight of sika-like deer and decreases in the body weight of red-like females. Hybridisation is causing increases in jaw length and increases in incisor arcade breadth in sika-like females. Hybridisation is also causing decreases in incisor arcade breadth in red-like females. 4. There is currently no evidence that hybridisation is causing changes in the kidney fat weight or pregnancy rates of either population. 5. Increased phenotypic similarity between the two species is likely to lead to further hybridisation. The ecological consequences of this are difficult to predict.},
author = {Senn, Helen and Swanson, Graeme and Goodman, Simon and Barton, Nicholas H and Pemberton, Josephine},
journal = {Journal of Animal Ecology},
number = {2},
pages = {414 -- 425},
publisher = {Wiley-Blackwell},
title = {{Phenotypic correlates of hybridisation between red and sika deer (genus Cervus)}},
doi = {10.1111/j.1365-2656.2009.01633.x},
volume = {79},
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},
}
@inproceedings{3782,
abstract = {In cortex surface segmentation, the extracted surface is required to have a particular topology, namely, a two-sphere. We present a new method for removing topology noise of a curve or surface within the level set framework, and thus produce a cortical surface with correct topology. We define a new energy term which quantifies topology noise. We then show how to minimize this term by computing its functional derivative with respect to the level set function. This method differs from existing methods in that it is inherently continuous and not digital; and in the way that our energy directly relates to the topology of the underlying curve or surface, versus existing knot-based measures which are related in a more indirect fashion. The proposed flow is validated empirically.},
author = {Chen, Chao and Freedman, Daniel},
booktitle = { Conference proceedings MCV 2010},
location = {Beijing, China},
pages = {31 -- 42},
publisher = {Springer},
title = {{Topology noise removal for curve and surface evolution}},
doi = {10.1007/978-3-642-18421-5_4},
volume = {6533},
year = {2010},
}
@article{3783,
abstract = {MICROSATELIGHT is a Perl/Tk pipeline with a graphical user interface that facilitates several tasks when scoring microsatellites. It implements new subroutines in R and PERL and takes advantage of features provided by previously developed freeware. MICROSATELIGHT takes raw genotype data and automates the peak identification through PeakScanner. The PeakSelect subroutine assigns peaks to different microsatellite markers according to their multiplex group, fluorochrome type, and size range. After peak selection, binning of alleles can be carried out 1) automatically through AlleloBin or 2) by manual bin definition through Binator. In both cases, several features for quality checking and further binning improvement are provided. The genotype table can then be converted into input files for several population genetics programs through CREATE. Finally, Hardy–Weinberg equilibrium tests and confidence intervals for null allele frequency can be obtained through GENEPOP. MICROSATELIGHT is the only freely available public-domain software that facilitates full multiplex microsatellite scoring, from electropherogram files to user-defined text files to be used with population genetics software. MICROSATELIGHT has been created for the Windows XP operating system and has been successfully tested under Windows 7. It is available at http://sourceforge.net/projects/microsatelight/.},
author = {Palero, Ferran and González Candelas, Fernando and Pascual, Marta},
journal = {Journal of Heredity},
number = {2},
pages = {247 -- 249},
publisher = {Oxford University Press},
title = {{Microsatelight – Pipeline to expedite microsatellite analysis}},
doi = {10.1093/jhered/esq111},
volume = {102},
year = {2010},
}
@article{3785,
abstract = {Most fisheries involving spiny lobsters of the genus Palinurus have been over exploited during the last decades, so there is a raising concern about management decisions for these valuable resources. A total of 13 microsatellite DNA loci recently developed in Palinurus elephas were assayed in order to assess genetic diversity levels in every known species of the genus. Microsatellite markers gave amplifications and showed polymorphism in all species, with gene diversity values varying from 0.65060.077 SD (Palinurus barbarae) to 0.79260.051 SD (Palinurus elephas). Most importantly, when depth distribution was taken into account, shallower waters pecies consistently showed larger historical effective population sizes than their deeper-water counterparts. This could explain why deeper-water species are more sensitive to overfishing, and would indicate that overexploitation may have a larger impact on their long-term genetic diversity.},
author = {Palero, Ferran and Abello, Pere and Macpherson, E. and Matthee, C. and Pascual, Marta},
journal = {Journal of Crustacean Biology},
number = {4},
pages = {658 -- 663},
publisher = {BioOne},
title = {{Genetic diversity levels in fishery-exploited spiny lobsters of the Genus Palinurus (Decapoda: Achelata)}},
doi = {10.1651/09-3192.1},
volume = {30},
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{3788,
abstract = {Cell sorting is a widespread phenomenon pivotal to the early development of multicellular organisms. In vitro cell sorting studies have been instrumental in revealing the cellular properties driving this process. However, these studies have as yet been limited to two-dimensional analysis of three-dimensional cell sorting events. Here we describe a method to record the sorting of primary zebrafish ectoderm and mesoderm germ layer progenitor cells in three dimensions over time, and quantitatively analyze their sorting behavior using an order parameter related to heterotypic interface length. We investigate the cell population size dependence of sorted aggregates and find that the germ layer progenitor cells engulfed in the final configuration display a relationship between total interfacial length and system size according to a simple geometrical argument, subject to a finite-size effect.},
author = {Klopper, Abigail and Krens, Gabriel and Grill, Stephan and Heisenberg, Carl-Philipp J},
journal = {The European Physical Journal E: Soft Matter and Biological Physics},
number = {2},
pages = {99 -- 103},
publisher = {Springer},
title = {{Finite-size corrections to scaling behavior in sorted cell aggregates}},
doi = {10.1140/epje/i2010-10642-y},
volume = {33},
year = {2010},
}
@article{3789,
abstract = {The development of multicellular organisms is dependent on the tight coordination between tissue growth and morphogenesis. The stereotypical orientation of cell divisions has been proposed to be a fundamental mechanism by which proliferating and growing tissues take shape. However, the actual contribution of stereotypical division orientation (SDO) to tissue morphogenesis is unclear. In zebrafish, cell divisions with stereotypical orientation have been implicated in both body-axis elongation and neural rod formation [1, 2], although there is little direct evidence for a critical function of SDO in either of these processes. Here we show that SDO is required for formation of the neural rod midline during neurulation but dispensable for elongation of the body axis during gastrulation. Our data indicate that SDO during both gastrulation and neurulation is dependent on the noncanonical Wnt receptor Frizzled 7 (Fz7) and that interfering with cell division orientation leads to severe defects in neural rod midline formation but not body-axis elongation. These findings suggest a novel function for Fz7-controlled cell division orientation in neural rod midline formation during neurulation. },
author = {Quesada-Hernández, Elena and Caneparo, Luca and Schneider, Sylvia and Winkler, Sylke and Liebling, Michael and Fraser, Scott and Heisenberg, Carl-Philipp J},
journal = {Current Biology},
number = {21},
pages = {1966 -- 1972},
publisher = {Cell Press},
title = {{Stereotypical cell division orientation controls neural rod midline formation in zebrafish}},
doi = {10.1016/j.cub.2010.10.009},
volume = {20},
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},
}
@article{3792,
abstract = {The yolk syncytial layer (YSL) plays crucial roles in early zebrafish development. The YSL is a transient extra-embryonic syncytial tissue that forms during early cleavage stages and persists until larval stages. During gastrulation, the YSL undergoes highly dynamic movements, which are tightly coordinated with the movements of the overlying germ layer progenitor cells, and has critical functions in cell fate specification and morphogenesis of the early germ layers. Movement coordination between the YSL and blastoderm cells is dependent on contact between these tissues, and is probably required for the patterning and morphogenetic function of the YSL. In this review, we will discuss recent advances in elucidating the molecular and cellular mechanisms underlying the YSL morphogenesis and movement coordination between the YSL and blastoderm during early development.},
author = {Carvalho, Lara and Heisenberg, Carl-Philipp J},
journal = {Trends in Cell Biology},
number = {10},
pages = {586 -- 592},
publisher = {Cell Press},
title = {{The yolk syncytial layer in early, zebrafish development}},
doi = {10.1016/j.tcb.2010.06.009},
volume = {20},
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},
}
@inproceedings{3794,
abstract = {We study the problem of multimodal dimensionality reduction assuming that data samples can be missing at training time, and not all data modalities may be present at application time. Maximum covariance analysis, as a generalization of PCA, has many desirable properties, but its application to practical problems is limited by its need for perfectly paired data. We overcome this limitation by a latent variable approach that allows working with weakly paired data and is still able to efficiently process large datasets using standard numerical routines. The resulting weakly paired maximum covariance analysis often finds better representations than alternative methods, as we show in two exemplary tasks: texture discrimination and transfer learning.},
author = {Lampert, Christoph and Krömer, Oliver},
location = {Heraklion, Crete, Greece},
pages = {566 -- 579},
publisher = {Springer},
title = {{Weakly-paired maximum covariance analysis for multimodal dimensionality reduction and transfer learning}},
doi = {10.1007/978-3-642-15552-9_41},
volume = {6312},
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{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{3833,
author = {Jonas, Peter M and Hefft, Stefan},
journal = {The European Journal of Neuroscience},
number = {7},
pages = {1194 -- 1195},
publisher = {Wiley-Blackwell},
title = {{GABA release at terminals of CCK-interneurons: synchrony, asynchrony and modulation by cannabinoid receptors (commentary on Ali & Todorova)}},
doi = {10.1111/j.1460-9568.2010.07189.x},
volume = {31},
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},
}
@inproceedings{3840,
abstract = {Classical formalizations of systems and properties are boolean: given a system and a property, the property is either true or false of the system. Correspondingly, classical methods for system analysis determine the truth value of a property, preferably giving a proof if the property is true, and a counterexample if the property is false; classical methods for system synthesis construct a system for which a property is true; classical methods for system transformation, composition, and abstraction aim to preserve the truth of properties. The boolean view is prevalent even if the system, the property, or both refer to numerical quantities, such as the times or probabilities of events. For example, a timed automaton either satisfies or violates a formula of a real-time logic; a stochastic process either satisfies or violates a formula of a probabilistic logic. The classical black-and-white view partitions the world into "correct" and "incorrect" systems, offering few nuances. In reality, of several systems that satisfy a property in the boolean sense, often some are more desirable than others, and of the many systems that violate a property, usually some are less objectionable than others. For instance, among the systems that satisfy the response property that every request be granted, we may prefer systems that grant requests quickly (the quicker, the better), or we may prefer systems that issue few unnecessary grants (the fewer, the better); and among the systems that violate the response property, we may prefer systems that serve many initial requests (the more, the better), or we may prefer systems that serve many requests in the long run (the greater the fraction of served to unserved requests, the better). Formally, while a boolean notion of correctness is given by a preorder on systems and properties, a quantitative notion of correctness is defined by a directed metric on systems and properties, where the distance between a system and a property provides a measure of "fit" or "desirability." There are many ways how such distances can be defined. In a linear-time framework, one assigns numerical values to individual behaviors before assigning values to systems and properties, which are sets of behaviors. For example, the value of a single behavior may be a discounted value, which is largely determined by a prefix of the behavior, e.g., by the number of requests that are granted before the first request that is not granted; or a limit value, which is independent of any finite prefix. A limit value may be an average, such as the average response time over an infinite sequence of requests and grants, or a supremum, such as the worst-case response time. Similarly, the value of a set of behaviors may be an extremum or an average across the values of all behaviors in the set: in this way one can measure the worst of all possible average-case response times, or the average of all possible worst-case response times, etc. Accordingly, the distance between two sets of behaviors may be defined as the worst or average difference between the values of corresponding behaviors. In summary, we propagate replacing boolean specifications for the correctness of systems with quantitative measures for the desirability of systems. In quantitative analysis, the aim is to compute the distance between a system and a property (or between two systems, or two properties); in quantitative synthesis, the objective is to construct a system that has minimal distance from a given property. Multiple quantitative measures can be prioritized (e.g., combined lexicographically into a single measure) or studied along the Pareto curve. Quantitative transformations, compositions, and abstractions of systems are useful if they allow us to bound the induced change in distance from a property. We present some initial results in some of these directions. We also give some potential applications, which not only generalize tradiditional correctness concerns in the functional, timed, and probabilistic domains, but also capture such system measures as resource use, performance, cost, reliability, and robustness.},
author = {Henzinger, Thomas A},
location = {Madrid, Spain},
number = {1},
pages = {157 -- 158},
publisher = {ACM},
title = {{From boolean to quantitative notions of correctness}},
doi = {10.1145/1706299.1706319},
volume = {45},
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{3848,
abstract = {We define the robustness of a level set homology class of a function f:XR as the magnitude of a perturbation necessary to kill the class. Casting this notion into a group theoretic framework, we compute the robustness for each class, using a connection to extended persistent homology. The special case X=R3 has ramifications in medical imaging and scientific visualization.},
author = {Bendich, Paul and Edelsbrunner, Herbert and Morozov, Dmitriy and Patel, Amit},
location = {Liverpool, UK},
pages = {1 -- 10},
publisher = {Springer},
title = {{The robustness of level sets}},
doi = {10.1007/978-3-642-15775-2_1},
volume = {6346},
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},
}
@inproceedings{3850,
abstract = {Given a polygonal shape Q with n vertices, can it be expressed, up to a tolerance ε in Hausdorff distance, as the Minkowski sum of another polygonal shape with a disk of fixed radius? If it does, we also seek a preferably simple solution shape P;P’s offset constitutes an accurate, vertex-reduced, and smoothened approximation of Q. We give a decision algorithm for fixed radius in O(nlogn) time that handles any polygonal shape. For convex shapes, the complexity drops to O(n), which is also the time required to compute a solution shape P with at most one more vertex than a vertex-minimal one.},
author = {Berberich, Eric and Halperin, Dan and Kerber, Michael and Pogalnikova, Roza},
location = {Dortmund, Germany},
pages = {12 -- 23},
publisher = {TU Dortmund},
title = {{Polygonal reconstruction from approximate offsets}},
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},
}
@inproceedings{3852,
abstract = {We introduce two-level discounted games played by two players on a perfect-information stochastic game graph. The upper level game is a discounted game and the lower level game is an undiscounted reachability game. Two-level games model hierarchical and sequential decision making under uncertainty across different time scales. We show the existence of pure memoryless optimal strategies for both players and an ordered field property for such games. We show that if there is only one player (Markov decision processes), then the values can be computed in polynomial time. It follows that whether the value of a player is equal to a given rational constant in two-level discounted games can be decided in NP intersected coNP. We also give an alternate strategy improvement algorithm to compute the value. },
author = {Chatterjee, Krishnendu and Majumdar, Ritankar},
location = {Minori, Italy},
pages = {22 -- 29},
publisher = {EPTCS},
title = {{Discounting in games across time scales}},
doi = {10.4204/EPTCS.25.6},
volume = {25},
year = {2010},
}
@inproceedings{3853,
abstract = {Quantitative languages are an extension of boolean languages that assign to each word a real number. Mean-payoff automata are finite automata with numerical weights on transitions that assign to each infinite path the long-run average of the transition weights. When the mode of branching of the automaton is deterministic, nondeterministic, or alternating, the corresponding class of quantitative languages is not robust as it is not closed under the pointwise operations of max, min, sum, and numerical complement. Nondeterministic and alternating mean-payoff automata are not decidable either, as the quantitative generalization of the problems of universality and language inclusion is undecidable. We introduce a new class of quantitative languages, defined by mean-payoff automaton expressions, which is robust and decidable: it is closed under the four pointwise operations, and we show that all decision problems are decidable for this class. Mean-payoff automaton expressions subsume deterministic meanpayoff automata, and we show that they have expressive power incomparable to nondeterministic and alternating mean-payoff automata. We also present for the first time an algorithm to compute distance between two quantitative languages, and in our case the quantitative languages are given as mean-payoff automaton expressions.},
author = {Chatterjee, Krishnendu and Doyen, Laurent and Edelsbrunner, Herbert and Henzinger, Thomas A and Rannou, Philippe},
location = {Paris, France},
pages = {269 -- 283},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Mean-payoff automaton expressions}},
doi = {10.1007/978-3-642-15375-4_19},
volume = {6269},
year = {2010},
}
@inproceedings{3854,
abstract = {Graph games of infinite length provide a natural model for open reactive systems: one player (Eve) represents the controller and the other player (Adam) represents the environment. The evolution of the system depends on the decisions of both players. The specification for the system is usually given as an ω-regular language L over paths and Eve’s goal is to ensure that the play belongs to L irrespective of Adam’s behaviour. The classical notion of winning strategies fails to capture several interesting scenarios. For example, strong fairness (Streett) conditions are specified by a number of request-grant pairs and require every pair that is requested infinitely often to be granted infinitely often: Eve might win just by preventing Adam from making any new request, but a “better” strategy would allow Adam to make as many requests as possible and still ensure fairness. To address such questions, we introduce the notion of obliging games, where Eve has to ensure a strong condition Φ, while always allowing Adam to satisfy a weak condition Ψ. We present a linear time reduction of obliging games with two Muller conditions Φ and Ψ to classical Muller games. We consider obliging Streett games and show they are co-NP complete, and show a natural quantitative optimisation problem for obliging Streett games is in FNP. We also show how obliging games can provide new and interesting semantics for multi-player games.},
author = {Chatterjee, Krishnendu and Horn, Florian and Löding, Christof},
location = {Paris, France},
pages = {284 -- 296},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Obliging games}},
doi = {10.1007/978-3-642-15375-4_20},
volume = {6269},
year = {2010},
}