@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{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{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{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},
}
@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{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{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{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{3858,
abstract = {We consider two-player zero-sum games on graphs. On the basis of the information available to the players these games can be classified as follows: (a) partial-observation (both players have partial view of the game); (b) one-sided partial-observation (one player has partial-observation and the other player has complete-observation); and (c) complete-observation (both players have com- plete view of the game). We survey the complexity results for the problem of de- ciding the winner in various classes of partial-observation games with ω-regular winning conditions specified as parity objectives. We present a reduction from the class of parity objectives that depend on sequence of states of the game to the sub-class of parity objectives that only depend on the sequence of observations. We also establish that partial-observation acyclic games are PSPACE-complete.},
author = {Chatterjee, Krishnendu and Doyen, Laurent},
editor = {Fermüller, Christian and Voronkov, Andrei},
location = {Yogyakarta, Indonesia},
pages = {1 -- 14},
publisher = {Springer},
title = {{The complexity of partial-observation parity games}},
doi = {10.1007/978-3-642-16242-8_1},
volume = {6397},
year = {2010},
}
@inproceedings{3865,
abstract = {We introduce a technique for debugging multi-threaded C programs and analyzing the impact of source code changes, and its implementation in the prototype tool DIRECT. Our approach uses a combination of source code instrumentation and runtime management. The source code along with a test harness is instrumented to monitor Operating System (OS) and user defined function calls. DIRECT tracks all concurrency control primitives and, optionally, data from the program. DIRECT maintains an abstract global state that combines information from every thread, including the sequence of function calls and concurrency primitives executed. The runtime manager can insert delays, provoking thread inter-leavings that may exhibit bugs that are difficult to reach otherwise. The runtime manager collects an approximation of the reachable state space and uses this approximation to assess the impact of change in a new version of the program.},
author = {Chatterjee, Krishnendu and De Alfaro, Luca and Raman, Vishwanath and Sánchez, César},
editor = {Rosenblum, David and Taenzer, Gabriele},
location = {Paphos, Cyprus},
pages = {293 -- 307},
publisher = {Springer},
title = {{Analyzing the impact of change in multi-threaded programs}},
doi = {10.1007/978-3-642-12029-9_21},
volume = {6013},
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},
}
@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{3860,
abstract = {In mean-payoff games, the objective of the protagonist is to ensure that the limit average of an infinite sequence of numeric weights is nonnegative. In energy games, the objective is to ensure that the running sum of weights is always nonnegative. Generalized mean-payoff and energy games replace individual weights by tuples, and the limit average (resp. running sum) of each coordinate must be (resp. remain) nonnegative. These games have applications in the synthesis of resource-bounded processes with multiple resources. We prove the finite-memory determinacy of generalized energy games and show the inter- reducibility of generalized mean-payoff and energy games for finite-memory strategies. We also improve the computational complexity for solving both classes of games with finite-memory strategies: while the previously best known upper bound was EXPSPACE, and no lower bound was known, we give an optimal coNP-complete bound. For memoryless strategies, we show that the problem of deciding the existence of a winning strategy for the protagonist is NP-complete.},
author = {Chatterjee, Krishnendu and Doyen, Laurent and Henzinger, Thomas A and Raskin, Jean},
location = {Chennai, India},
pages = {505 -- 516},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Generalized mean-payoff and energy games}},
doi = {10.4230/LIPIcs.FSTTCS.2010.505},
volume = {8},
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{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},
}
@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{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},
}
@inproceedings{3866,
abstract = {Systems ought to behave reasonably even in circumstances that are not anticipated in their specifications. We propose a definition of robustness for liveness specifications which prescribes, for any number of environment assumptions that are violated, a minimal number of system guarantees that must still be fulfilled. This notion of robustness can be formulated and realized using a Generalized Reactivity formula. We present an algorithm for synthesizing robust systems from such formulas. For the important special case of Generalized Reactivity formulas of rank 1, our algorithm improves the complexity of [PPS06] for large specifications with a small number of assumptions and guarantees.},
author = {Bloem, Roderick and Chatterjee, Krishnendu and Greimel, Karin and Henzinger, Thomas A and Jobstmann, Barbara},
editor = {Touili, Tayssir and Cook, Byron and Jackson, Paul},
location = {Edinburgh, UK},
pages = {410 -- 424},
publisher = {Springer},
title = {{Robustness in the presence of liveness}},
doi = {10.1007/978-3-642-14295-6_36},
volume = {6174},
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},
}