TY - JOUR
AB - The use of optical traps to measure or apply forces on the molecular level requires a precise knowledge of the trapping force field. Close to the trap center, this field is typically approximated as linear in the displacement of the trapped microsphere. However, applications demanding high forces at low laser intensities can probe the light-microsphere interaction beyond the linear regime. Here, we measured the full nonlinear force and displacement response of an optical trap in two dimensions using a dual-beam optical trap setup with back-focal-plane photodetection. We observed a substantial stiffening of the trap beyond the linear regime that depends on microsphere size, in agreement with Mie theory calculations. Surprisingly, we found that the linear detection range for forces exceeds the one for displacement by far. Our approach allows for a complete calibration of an optical trap.
AU - Jahnel, Marcus
AU - Behrndt, Martin
AU - Jannasch, Anita
AU - Schaeffer, Erik
AU - Grill, Stephan
ID - 3373
IS - 7
JF - Optics Letters
TI - Measuring the complete force field of an optical trap
VL - 36
ER -
TY - JOUR
AB - 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'.
AU - Tkacik, Gasper
AU - Walczak, Aleksandra
ID - 3374
IS - 15
JF - Journal of Physics: Condensed Matter
TI - Information transmission in genetic regulatory networks a review
VL - 23
ER -
TY - JOUR
AB - 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.
AU - de Vladar, Harold
AU - Barton, Nicholas H
ID - 3375
IS - 58
JF - Journal of the Royal Society Interface
TI - The statistical mechanics of a polygenic character under stabilizing selection mutation and drift
VL - 8
ER -
TY - JOUR
AB - 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.
AU - Bollenbach, Mark Tobias
AU - Kishony, Roy
ID - 3376
IS - 4
JF - Molecular Cell
TI - Resolution of gene regulatory conflicts caused by combinations of antibiotics
VL - 42
ER -
TY - JOUR
AB - 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.
AU - Edelsbrunner, Herbert
AU - Morozov, Dmitriy
AU - Patel, Amit
ID - 3377
IS - 3
JF - Foundations of Computational Mathematics
TI - Quantifying transversality by measuring the robustness of intersections
VL - 11
ER -
TY - JOUR
AB - 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.
AU - Bendich, Paul
AU - Harer, John
ID - 3378
IS - 3
JF - Foundations of Computational Mathematics
TI - Persistent intersection homology
VL - 11
ER -
TY - JOUR
AB - 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.
AU - Row, Richard
AU - Maître, Jean-Léon
AU - Martin, Benjamin
AU - Stockinger, Petra
AU - Heisenberg, Carl-Philipp J
AU - Kimelman, David
ID - 3379
IS - 1
JF - Developmental Biology
TI - Completion of the epithelial to mesenchymal transition in zebrafish mesoderm requires Spadetail
VL - 354
ER -
TY - JOUR
AB - 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.
AU - Logeswaran, Sayanthan
AU - Barton, Nicholas H
ID - 3380
IS - 3
JF - Genetical Research
TI - Mapping Mendelian traits in asexual progeny using changes in marker allele frequency
VL - 93
ER -
TY - JOUR
AB - 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.
AU - Pavan, Ana
AU - Martins, Felipe
AU - Santos, Fabrício
AU - Ditchfield, Albert
AU - Fernandes Redondo, Rodrigo A
ID - 3771
IS - 3
JF - Biological Journal of the Linnean Society
TI - Patterns of diversification in two species of short-tailed bats (Carollia Gray, 1838): the effects of historical fragmentation of Brazilian rainforests.
VL - 102
ER -
TY - JOUR
AU - Barton, Nicholas H
ID - 3778
IS - 2
JF - Heredity
TI - Estimating linkage disequilibria
VL - 106
ER -
TY - JOUR
AB - 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.
AU - Fasy, Brittany Terese
ID - 3781
IS - 1-2
JF - Acta Sci. Math. (Szeged)
TI - The difference in length of curves in R^n
VL - 77
ER -
TY - JOUR
AB - 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.
AU - Palero, Ferran
AU - Guerao, Guillermo
AU - Clark, Paul
AU - Abello, Pere
ID - 3784
IS - 2
JF - Journal of the Marine Biological Association of the United Kingdom
TI - Scyllarus arctus (Crustacea: Decapoda: Scyllaridae) final stage phyllosoma identified by DNA analysis, with morphological description
VL - 91
ER -
TY - CHAP
AB - 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.
AU - Krens, Gabriel
AU - Heisenberg, Carl-Philipp J
ED - Labouesse, Michel
ID - 3791
T2 - Forces and Tension in Development
TI - Cell sorting in development
VL - 95
ER -
TY - CHAP
AB - 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.
AU - Edelsbrunner, Herbert
AU - Kerber, Michael
ED - Calude, Cristian
ED - Rozenberg, Grzegorz
ED - Salomaa, Arto
ID - 3796
T2 - Rainbow of Computer Science
TI - Covering and packing with spheres by diagonal distortion in R^n
VL - 6570
ER -
TY - JOUR
AB - 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.
AU - Henzinger, Thomas A
AU - Jobstmann, Barbara
AU - Wolf, Verena
ID - 3381
IS - 4
JF - IJFCS: International Journal of Foundations of Computer Science
TI - Formalisms for specifying Markovian population models
VL - 22
ER -
TY - JOUR
AB - We consider two-player games played in real time on game structures with clocks where the objectives of players are described using parity conditions. The games are concurrent in that at each turn, both players independently propose a time delay and an action, and the action with the shorter delay is chosen. To prevent a player from winning by blocking time, we restrict each player to play strategies that ensure that the player cannot be responsible for causing a zeno run. First, we present an efficient reduction of these games to turn-based (i.e., not concurrent) finite-state (i.e., untimed) parity games. Our reduction improves the best known complexity for solving timed parity games. Moreover, the rich class of algorithms for classical parity games can now be applied to timed parity games. The states of the resulting game are based on clock regions of the original game, and the state space of the finite game is linear in the size of the region graph. Second, we consider two restricted classes of strategies for the player that represents the controller in a real-time synthesis problem, namely, limit-robust and bounded-robust winning strategies. Using a limit-robust winning strategy, the controller cannot choose an exact real-valued time delay but must allow for some nonzero jitter in each of its actions. If there is a given lower bound on the jitter, then the strategy is bounded-robust winning. We show that exact strategies are more powerful than limit-robust strategies, which are more powerful than bounded-robust winning strategies for any bound. For both kinds of robust strategies, we present efficient reductions to standard timed automaton games. These reductions provide algorithms for the synthesis of robust real-time controllers.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Prabhu, Vinayak
ID - 3315
IS - 4
JF - Logical Methods in Computer Science
TI - Timed parity games: Complexity and robustness
VL - 7
ER -
TY - JOUR
AB - The elevation function on a smoothly embedded 2-manifold in R-3 reflects the multiscale topography of cavities and protrusions as local maxima. The function has been useful in identifying coarse docking configurations for protein pairs. Transporting the concept from the smooth to the piecewise linear category, this paper describes an algorithm for finding all local maxima. While its worst-case running time is the same as of the algorithm used in prior work, its performance in practice is orders of magnitudes superior. We cast light on this improvement by relating the running time to the total absolute Gaussian curvature of the 2-manifold.
AU - Wang, Bei
AU - Edelsbrunner, Herbert
AU - Morozov, Dmitriy
ID - 3965
IS - 2.2
JF - Journal of Experimental Algorithmics
TI - Computing elevation maxima by searching the Gauss sphere
VL - 16
ER -
TY - JOUR
AB - Molecular noise, which arises from the randomness of the discrete events in the cell, significantly influences fundamental biological processes. Discrete-state continuous-time stochastic models (CTMC) can be used to describe such effects, but the calculation of the probabilities of certain events is computationally expensive. We present a comparison of two analysis approaches for CTMC. On one hand, we estimate the probabilities of interest using repeated Gillespie simulation and determine the statistical accuracy that we obtain. On the other hand, we apply a numerical reachability analysis that approximates the probability distributions of the system at several time instances. We use examples of cellular processes to demonstrate the superiority of the reachability analysis if accurate results are required.
AU - Didier, Frédéric
AU - Henzinger, Thomas A
AU - Mateescu, Maria
AU - Wolf, Verena
ID - 3364
IS - 21
JF - Theoretical Computer Science
TI - Approximation of event probabilities in noisy cellular processes
VL - 412
ER -
TY - JOUR
AB - BioSig is an open source software library for biomedical signal processing. The aim of the BioSig project is to foster research in biomedical signal processing by providing free and open source software tools for many different application areas. Some of the areas where BioSig can be employed are neuroinformatics, brain-computer interfaces, neurophysiology, psychology, cardiovascular systems, and sleep research. Moreover, the analysis of biosignals such as the electroencephalogram (EEG), electrocorticogram (ECoG), electrocardiogram (ECG), electrooculogram (EOG), electromyogram (EMG), or respiration signals is a very relevant element of the BioSig project. Specifically, BioSig provides solutions for data acquisition, artifact processing, quality control, feature extraction, classification, modeling, and data visualization, to name a few. In this paper, we highlight several methods to help students and researchers to work more efficiently with biomedical signals.
AU - Schlögl, Alois
AU - Vidaurre, Carmen
AU - Sander, Tilmann
ID - 490
JF - Computational Intelligence and Neuroscience
TI - BioSig: The free and open source software library for biomedical signal processing
VL - 2011
ER -
TY - JOUR
AB - In their search for antigens, lymphocytes continuously shuttle among blood vessels, lymph vessels, and lymphatic tissues. Chemokines mediate entry of lymphocytes into lymphatic tissues, and sphingosine 1-phosphate (S1P) promotes localization of lymphocytes to the vasculature. Both signals are sensed through G protein-coupled receptors (GPCRs). Most GPCRs undergo ligand-dependent homologous receptor desensitization, a process that decreases their signaling output after previous exposure to high ligand concentration. Such desensitization can explain why lymphocytes do not take an intermediate position between two signals but rather oscillate between them. The desensitization of S1P receptor 1 (S1PR1) is mediated by GPCR kinase 2 (GRK2). Deletion of GRK2 in lymphocytes compromises desensitization by high vascular S1P concentrations, thereby reducing responsiveness to the chemokine signal and trapping the cells in the vascular compartment. The desensitization kinetics of S1PR1 allows lymphocytes to dynamically shuttle between vasculature and lymphatic tissue, although the positional information in both compartments is static.
AU - Eichner, Alexander
AU - Sixt, Michael K
ID - 491
IS - 198
JF - Science Signaling
TI - Setting the clock for recirculating lymphocytes
VL - 4
ER -
TY - JOUR
AB - Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release.
AU - Vyleta, Nicholas
AU - Smith, Stephen
ID - 469
IS - 12
JF - European Journal of Neuroscience
TI - Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor
VL - 31
ER -
TY - JOUR
AB - Cancer stem cells or cancer initiating cells are believed to contribute to cancer recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with fundamental roles in gene regulation. The role of miRNAs in cancer stem cells is only poorly understood. Here, we report miRNA expression profiles of glioblastoma stem cell-containing CD133 + cell populations. We find that miR-9, miR-9 * (referred to as miR-9/9 *), miR-17 and miR-106b are highly abundant in CD133 + cells. Furthermore, inhibition of miR-9/9 * or miR-17 leads to reduced neurosphere formation and stimulates cell differentiation. Calmodulin-binding transcription activator 1 (CAMTA1) is a putative transcription factor, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA). We identify CAMTA1 as an miR-9/9 * and miR-17 target. CAMTA1 expression leads to reduced neurosphere formation and tumour growth in nude mice, suggesting that CAMTA1 can function as tumour suppressor. Consistently, CAMTA1 and NPPA expression correlate with patient survival. Our findings could provide a basis for novel strategies of glioblastoma therapy.
AU - Schraivogel, Daniel
AU - Weinmann, Lasse
AU - Beier, Dagmar
AU - Tabatabai, Ghazaleh
AU - Eichner, Alexander
AU - Zhu, Jia
AU - Anton, Martina
AU - Sixt, Michael K
AU - Weller, Michael
AU - Beier, Christoph
AU - Meister, Gunter
ID - 518
IS - 20
JF - EMBO Journal
TI - CAMTA1 is a novel tumour suppressor regulated by miR-9/9 * in glioblastoma stem cells
VL - 30
ER -
TY - JOUR
AB - Software transactional memories (STM) are described in the literature with assumptions of sequentially consistent program execution and atomicity of high level operations like read, write, and abort. However, in a realistic setting, processors use relaxed memory models to optimize hardware performance. Moreover, the atomicity of operations depends on the underlying hardware. This paper presents the first approach to verify STMs under relaxed memory models with atomicity of 32 bit loads and stores, and read-modify-write operations. We describe RML, a simple language for expressing concurrent programs. We develop a semantics of RML parametrized by a relaxed memory model. We then present our tool, FOIL, which takes as input the RML description of an STM algorithm restricted to two threads and two variables, and the description of a memory model, and automatically determines the locations of fences, which if inserted, ensure the correctness of the restricted STM algorithm under the given memory model. We use FOIL to verify DSTM, TL2, and McRT STM under the memory models of sequential consistency, total store order, partial store order, and relaxed memory order for two threads and two variables. Finally, we extend the verification results for DSTM and TL2 to an arbitrary number of threads and variables by manually proving that the structural properties of STMs are satisfied at the hardware level of atomicity under the considered relaxed memory models.
AU - Guerraoui, Rachid
AU - Henzinger, Thomas A
AU - Singh, Vasu
ID - 531
IS - 3
JF - Formal Methods in System Design
TI - Verification of STM on relaxed memory models
VL - 39
ER -
TY - GEN
AB - Computing the winning set for Büchi objectives in alternating games on graphs is a central problem in computer aided verification with a large number of applications. The long standing best known upper bound for solving the problem is ̃O(n·m), where n is the number of vertices and m is the number of edges in the graph. We are the first to break the ̃O(n·m) boundary by presenting a new technique that reduces the running time to O(n2). This bound also leads to O(n2) time algorithms for computing the set of almost-sure winning vertices for Büchi objectives (1) in alternating games with probabilistic transitions (improving an earlier bound of O(n·m)), (2) in concurrent graph games with constant actions (improving an earlier bound of O(n3)), and (3) in Markov decision processes (improving for m > n4/3 an earlier bound of O(min(m1.5, m·n2/3)). We also show that the same technique can be used to compute the maximal end-component decomposition of a graph in time O(n2), which is an improvement over earlier bounds for m > n4/3. Finally, we show how to maintain the winning set for Büchi objectives in alternating games under a sequence of edge insertions or a sequence of edge deletions in O(n) amortized time per operation. This is the first dynamic algorithm for this problem.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
ID - 5379
SN - 2664-1690
TI - An O(n2) time algorithm for alternating Büchi games
ER -
TY - GEN
AB - We consider 2-player games played on a finite state space for an infinite number of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves inde- pendently and simultaneously; the current state and the two moves determine the successor state. We study concurrent games with ω-regular winning conditions specified as parity objectives. We consider the qualitative analysis problems: the computation of the almost-sure and limit-sure winning set of states, where player 1 can ensure to win with probability 1 and with probability arbitrarily close to 1, respec- tively. In general the almost-sure and limit-sure winning strategies require both infinite-memory as well as infinite-precision (to describe probabilities). We study the bounded-rationality problem for qualitative analysis of concurrent parity games, where the strategy set for player 1 is restricted to bounded-resource strategies. In terms of precision, strategies can be deterministic, uniform, finite-precision or infinite- precision; and in terms of memory, strategies can be memoryless, finite-memory or infinite-memory. We present a precise and complete characterization of the qualitative winning sets for all combinations of classes of strategies. In particular, we show that uniform memoryless strategies are as powerful as finite-precision infinite-memory strategies, and infinite-precision memoryless strategies are as power- ful as infinite-precision finite-memory strategies. We show that the winning sets can be computed in O(n2d+3) time, where n is the size of the game structure and 2d is the number of priorities (or colors), and our algorithms are symbolic. The membership problem of whether a state belongs to a winning set can be decided in NP ∩ coNP. While this complexity is the same as for the simpler class of turn-based parity games, where in each state only one of the two players has a choice of moves, our algorithms, that are obtained by characterization of the winning sets as μ-calculus formulas, are considerably more involved than those for turn-based games.
AU - Chatterjee, Krishnendu
ID - 3338
T2 - arXiv
TI - Bounded rationality in concurrent parity games
ER -
TY - GEN
AB - We present a new decidable logic called TREX for expressing constraints about imperative tree data structures. In particular, TREX supports a transitive closure operator that can express reachability constraints, which often appear in data structure invariants. We show that our logic is closed under weakest precondition computation, which enables its use for automated software verification. We further show that satisfiability of formulas in TREX is decidable in NP. The low complexity makes it an attractive alternative to more expensive logics such as monadic second-order logic (MSOL) over trees, which have been traditionally used for reasoning about tree data structures.
AU - Wies, Thomas
AU - Muñiz, Marco
AU - Kuncak, Viktor
ID - 5383
SN - 2664-1690
TI - On an efficient decision procedure for imperative tree data structures
ER -
TY - CONF
AB - We present a new decidable logic called TREX for expressing constraints about imperative tree data structures. In particular, TREX supports a transitive closure operator that can express reachability constraints, which often appear in data structure invariants. We show that our logic is closed under weakest precondition computation, which enables its use for automated software verification. We further show that satisfiability of formulas in TREX is decidable in NP. The low complexity makes it an attractive alternative to more expensive logics such as monadic second-order logic (MSOL) over trees, which have been traditionally used for reasoning about tree data structures.
AU - Wies, Thomas
AU - Muñiz, Marco
AU - Kuncak, Viktor
ID - 3323
TI - An efficient decision procedure for imperative tree data structures
VL - 6803
ER -
TY - GEN
AB - In two-player finite-state stochastic games of partial obser- vation on graphs, in every state of the graph, the players simultaneously choose an action, and their joint actions determine a probability distri- bution over the successor states. The game is played for infinitely many rounds and thus the players construct an infinite path in the graph. We consider reachability objectives where the first player tries to ensure a target state to be visited almost-surely (i.e., with probability 1) or pos- itively (i.e., with positive probability), no matter the strategy of the second player.
We classify such games according to the information and to the power of randomization available to the players. On the basis of information, the game can be one-sided with either (a) player 1, or (b) player 2 having partial observation (and the other player has perfect observation), or two- sided with (c) both players having partial observation. On the basis of randomization, (a) the players may not be allowed to use randomization (pure strategies), or (b) they may choose a probability distribution over actions but the actual random choice is external and not visible to the player (actions invisible), or (c) they may use full randomization.
Our main results for pure strategies are as follows: (1) For one-sided games with player 2 perfect observation we show that (in contrast to full randomized strategies) belief-based (subset-construction based) strate- gies are not sufficient, and present an exponential upper bound on mem- ory both for almost-sure and positive winning strategies; we show that the problem of deciding the existence of almost-sure and positive winning strategies for player 1 is EXPTIME-complete and present symbolic algo- rithms that avoid the explicit exponential construction. (2) For one-sided games with player 1 perfect observation we show that non-elementary memory is both necessary and sufficient for both almost-sure and posi- tive winning strategies. (3) We show that for the general (two-sided) case finite-memory strategies are sufficient for both positive and almost-sure winning, and at least non-elementary memory is required. We establish the equivalence of the almost-sure winning problems for pure strategies and for randomized strategies with actions invisible. Our equivalence re- sult exhibit serious flaws in previous results in the literature: we show a non-elementary memory lower bound for almost-sure winning whereas an exponential upper bound was previously claimed.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 5381
SN - 2664-1690
TI - Partial-observation stochastic games: How to win when belief fails
ER -
TY - GEN
AB - We consider 2-player games played on a finite state space for an infinite number of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine the successor state. We study concurrent games with ω-regular winning conditions specified as parity objectives. We consider the qualitative analysis problems: the computation of the almost-sure and limit-sure winning set of states, where player 1 can ensure to win with probability 1 and with probability arbitrarily close to 1, respectively. In general the almost-sure and limit-sure winning strategies require both infinite-memory as well as infinite-precision (to describe probabilities). We study the bounded-rationality problem for qualitative analysis of concurrent parity games, where the strategy set for player 1 is restricted to bounded-resource strategies. In terms of precision, strategies can be deterministic, uniform, finite-precision or infinite-precision; and in terms of memory, strategies can be memoryless, finite-memory or infinite-memory. We present a precise and complete characterization of the qualitative winning sets for all combinations of classes of strategies. In particular, we show that uniform memoryless strategies are as powerful as finite-precision infinite-memory strategies, and infinite-precision memoryless strategies are as powerful as infinite-precision finite-memory strategies. We show that the winning sets can be computed in O(n2d+3) time, where n is the size of the game structure and 2d is the number of priorities (or colors), and our algorithms are symbolic. The membership problem of whether a state belongs to a winning set can be decided in NP ∩ coNP. While this complexity is the same as for the simpler class of turn-based parity games, where in each state only one of the two players has a choice of moves, our algorithms,that are obtained by characterization of the winning sets as μ-calculus formulas, are considerably more involved than those for turn-based games.
AU - Chatterjee, Krishnendu
ID - 5380
SN - 2664-1690
TI - Bounded rationality in concurrent parity games
ER -
TY - GEN
AB - We consider two-player stochastic games played on a finite state space for an infinite num- ber of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine a probability distribution over the successor states. We also consider the important special case of turn-based stochastic games where players make moves in turns, rather than concurrently. We study concurrent games with ω-regular winning conditions specified as parity objectives. The value for player 1 for a parity objective is the maximal probability with which the player can guarantee the satisfaction of the objective against all strategies of the opponent. We study the problem of continuity and robustness of the value function in concurrent and turn-based stochastic parity games with respect to imprecision in the transition probabilities. We present quantitative bounds on the difference of the value function (in terms of the imprecision of the transition probabilities) and show the value continuity for structurally equivalent concurrent games (two games are structurally equivalent if the support of the transition func- tion is same and the probabilities differ). We also show robustness of optimal strategies for structurally equivalent turn-based stochastic parity games. Finally we show that the value continuity property breaks without the structurally equivalent assumption (even for Markov chains) and show that our quantitative bound is asymptotically optimal. Hence our results are tight (the assumption is both necessary and sufficient) and optimal (our quantitative bound is asymptotically optimal).
AU - Chatterjee, Krishnendu
ID - 5382
SN - 2664-1690
TI - Robustness of structurally equivalent concurrent parity games
ER -
TY - GEN
AB - We consider Markov Decision Processes (MDPs) with mean-payoff parity and energy parity objectives. In system design, the parity objective is used to encode ω-regular specifications, and the mean-payoff and energy objectives can be used to model quantitative resource constraints. The energy condition re- quires that the resource level never drops below 0, and the mean-payoff condi- tion requires that the limit-average value of the resource consumption is within a threshold. While these two (energy and mean-payoff) classical conditions are equivalent for two-player games, we show that they differ for MDPs. We show that the problem of deciding whether a state is almost-sure winning (i.e., winning with probability 1) in energy parity MDPs is in NP ∩ coNP, while for mean- payoff parity MDPs, the problem is solvable in polynomial time, improving a recent PSPACE bound.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 5387
SN - 2664-1690
TI - Energy and mean-payoff parity Markov decision processes
ER -
TY - CONF
AB - There is recently a significant effort to add quantitative objectives to formal verification and synthesis. We introduce and investigate the extension of temporal logics with quantitative atomic assertions, aiming for a general and flexible framework for quantitative-oriented specifications. In the heart of quantitative objectives lies the accumulation of values along a computation. It is either the accumulated summation, as with the energy objectives, or the accumulated average, as with the mean-payoff objectives. We investigate the extension of temporal logics with the prefix-accumulation assertions Sum(v) ≥ c and Avg(v) ≥ c, where v is a numeric variable of the system, c is a constant rational number, and Sum(v) and Avg(v) denote the accumulated sum and average of the values of v from the beginning of the computation up to the current point of time. We also allow the path-accumulation assertions LimInfAvg(v) ≥ c and LimSupAvg(v) ≥ c, referring to the average value along an entire computation. We study the border of decidability for extensions of various temporal logics. In particular, we show that extending the fragment of CTL that has only the EX, EF, AX, and AG temporal modalities by prefix-accumulation assertions and extending LTL with path-accumulation assertions, result in temporal logics whose model-checking problem is decidable. The extended logics allow to significantly extend the currently known energy and mean-payoff objectives. Moreover, the prefix-accumulation assertions may be refined with "controlled-accumulation", allowing, for example, to specify constraints on the average waiting time between a request and a grant. On the negative side, we show that the fragment we point to is, in a sense, the maximal logic whose extension with prefix-accumulation assertions permits a decidable model-checking procedure. Extending a temporal logic that has the EG or EU modalities, and in particular CTL and LTL, makes the problem undecidable.
AU - Boker, Udi
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Kupferman, Orna
ID - 3356
TI - Temporal specifications with accumulative values
ER -
TY - CONF
AB - We consider Markov Decision Processes (MDPs) with mean-payoff parity and energy parity objectives. In system design, the parity objective is used to encode ω-regular specifications, and the mean-payoff and energy objectives can be used to model quantitative resource constraints. The energy condition re- quires that the resource level never drops below 0, and the mean-payoff condi- tion requires that the limit-average value of the resource consumption is within a threshold. While these two (energy and mean-payoff) classical conditions are equivalent for two-player games, we show that they differ for MDPs. We show that the problem of deciding whether a state is almost-sure winning (i.e., winning with probability 1) in energy parity MDPs is in NP ∩ coNP, while for mean- payoff parity MDPs, the problem is solvable in polynomial time, improving a recent PSPACE bound.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 3345
TI - Energy and mean-payoff parity Markov Decision Processes
VL - 6907
ER -
TY - CONF
AB - We introduce TopoCut: a new way to integrate knowledge about topological properties (TPs) into random field image segmentation model. Instead of including TPs as additional constraints during minimization of the energy function, we devise an efficient algorithm for modifying the unary potentials such that the resulting segmentation is guaranteed with the desired properties. Our method is more flexible in the sense that it handles more topology constraints than previous methods, which were only able to enforce pairwise or global connectivity. In particular, our method is very fast, making it for the first time possible to enforce global topological properties in practical image segmentation tasks.
AU - Chen, Chao
AU - Freedman, Daniel
AU - Lampert, Christoph
ID - 3336
T2 - CVPR: Computer Vision and Pattern Recognition
TI - Enforcing topological constraints in random field image segmentation
ER -
TY - GEN
AB - There is recently a significant effort to add quantitative objectives to formal verification and synthesis. We introduce and investigate the extension of temporal logics with quantitative atomic assertions, aiming for a general and flexible framework for quantitative-oriented specifications. In the heart of quantitative objectives lies the accumulation of values along a computation. It is either the accumulated summation, as with the energy objectives, or the accumulated average, as with the mean-payoff objectives. We investigate the extension of temporal logics with the prefix-accumulation assertions Sum(v) ≥ c and Avg(v) ≥ c, where v is a numeric variable of the system, c is a constant rational number, and Sum(v) and Avg(v) denote the accumulated sum and average of the values of v from the beginning of the computation up to the current point of time. We also allow the path-accumulation assertions LimInfAvg(v) ≥ c and LimSupAvg(v) ≥ c, referring to the average value along an entire computation. We study the border of decidability for extensions of various temporal logics. In particular, we show that extending the fragment of CTL that has only the EX, EF, AX, and AG temporal modalities by prefix-accumulation assertions and extending LTL with path-accumulation assertions, result in temporal logics whose model-checking problem is decidable. The extended logics allow to significantly extend the currently known energy and mean-payoff objectives. Moreover, the prefix-accumulation assertions may be refined with “controlled-accumulation”, allowing, for example, to specify constraints on the average waiting time between a request and a grant. On the negative side, we show that the fragment we point to is, in a sense, the maximal logic whose extension with prefix-accumulation assertions permits a decidable model-checking procedure. Extending a temporal logic that has the EG or EU modalities, and in particular CTL and LTL, makes the problem undecidable.
AU - Boker, Udi
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Kupferman, Orna
ID - 5385
SN - 2664-1690
TI - Temporal specifications with accumulative values
ER -
TY - GEN
AB - We consider probabilistic automata on infinite words with acceptance defined by parity conditions. We consider three qualitative decision problems: (i) the positive decision problem asks whether there is a word that is accepted with positive probability; (ii) the almost decision problem asks whether there is a word that is accepted with probability 1; and (iii) the limit decision problem asks whether for every ε > 0 there is a word that is accepted with probability at least 1 − ε. We unify and generalize several decidability results for probabilistic automata over infinite words, and identify a robust (closed under union and intersection) subclass of probabilistic automata for which all the qualitative decision problems are decidable for parity conditions. We also show that if the input words are restricted to lasso shape words, then the positive and almost problems are decidable for all probabilistic automata with parity conditions.
AU - Chatterjee, Krishnendu
AU - Tracol, Mathieu
ID - 5384
SN - 2664-1690
TI - Decidable problems for probabilistic automata on infinite words
ER -
TY - GEN
AB - We introduce TopoCut: a new way to integrate knowledge about topological properties (TPs) into random field image segmentation model. Instead of including TPs as additional constraints during minimization of the energy function, we devise an efficient algorithm for modifying the unary potentials such that the resulting segmentation is guaranteed with the desired properties. Our method is more flexible in the sense that it handles more topology constraints than previous methods, which were only able to enforce pairwise or global connectivity. In particular, our method is very fast, making it for the first time possible to enforce global topological properties in practical image segmentation tasks.
AU - Chen, Chao
AU - Freedman, Daniel
AU - Lampert, Christoph
ID - 5386
SN - 2664-1690
TI - Enforcing topological constraints in random field image segmentation
ER -
TY - CONF
AB - We present an algorithmic method for the quantitative, performance-aware synthesis of concurrent programs. The input consists of a nondeterministic partial program and of a parametric performance model. The nondeterminism allows the programmer to omit which (if any) synchronization construct is used at a particular program location. The performance model, specified as a weighted automaton, can capture system architectures by assigning different costs to actions such as locking, context switching, and memory and cache accesses. The quantitative synthesis problem is to automatically resolve the nondeterminism of the partial program so that both correctness is guaranteed and performance is optimal. As is standard for shared memory concurrency, correctness is formalized "specification free", in particular as race freedom or deadlock freedom. For worst-case (average-case) performance, we show that the problem can be reduced to 2-player graph games (with probabilistic transitions) with quantitative objectives. While we show, using game-theoretic methods, that the synthesis problem is Nexp-complete, we present an algorithmic method and an implementation that works efficiently for concurrent programs and performance models of practical interest. We have implemented a prototype tool and used it to synthesize finite-state concurrent programs that exhibit different programming patterns, for several performance models representing different architectures.
AU - Cerny, Pavol
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Singh, Rohit
ED - Gopalakrishnan, Ganesh
ED - Qadeer, Shaz
ID - 3366
TI - Quantitative synthesis for concurrent programs
VL - 6806
ER -
TY - JOUR
AB - We report the switching behavior of the full bacterial flagellum system that includes the filament and the motor in wild-type Escherichia coli cells. In sorting the motor behavior by the clockwise bias, we find that the distributions of the clockwise (CW) and counterclockwise (CCW) intervals are either exponential or nonexponential with long tails. At low bias, CW intervals are exponentially distributed and CCW intervals exhibit long tails. At intermediate CW bias (0.5) both CW and CCW intervals are mainly exponentially distributed. A simple model suggests that these two distinct switching behaviors are governed by the presence of signaling noise within the chemotaxis network. Low noise yields exponentially distributed intervals, whereas large noise yields nonexponential behavior with long tails. These drastically different motor statistics may play a role in optimizing bacterial behavior for a wide range of environmental conditions.
AU - Park, Heungwon
AU - Oikonomou, Panos
AU - Guet, Calin C
AU - Cluzel, Philippe
ID - 6496
IS - 10
JF - Biophysical Journal
SN - 0006-3495
TI - Noise underlies switching behavior of the bacterial flagellum
VL - 101
ER -
TY - JOUR
AB - 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.
AU - Kupczok, Anne
AU - Schmidt, Heiko
AU - Von Haeseler, Arndt
ID - 2409
IS - 1
JF - Algorithms for Molecular Biology
TI - Accuracy of phylogeny reconstruction methods combining overlapping gene data sets
VL - 5
ER -
TY - JOUR
AB - 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.
AU - Weissman, Daniel
AU - Feldman, Marcus
AU - Fisher, Daniel
ID - 3303
IS - 4
JF - Genetics
TI - The rate of fitness-valley crossing in sexual populations
VL - 186
ER -
TY - JOUR
AB - Weighted automata are nondeterministic automata with numerical weights on transitions. They can define quantitative languages L that assign to each word w a real number L(w). In the case of infinite words, the value of a run is naturally computed as the maximum, limsup, liminf, limit-average, or discounted-sum of the transition weights. The value of a word w is the supremum of the values of the runs over w. We study expressiveness and closure questions about these quantitative languages. We first show that the set of words with value greater than a threshold can be omega-regular for deterministic limit-average and discounted-sum automata, while this set is always omega-regular when the threshold is isolated (i.e., some neighborhood around the threshold contains no word). In the latter case, we prove that the omega-regular language is robust against small perturbations of the transition weights. We next consider automata with transition weights 0 or 1 and show that they are as expressive as general weighted automata in the limit-average case, but not in the discounted-sum case. Third, for quantitative languages L-1 and L-2, we consider the operations max(L-1, L-2), min(L-1, L-2), and 1 - L-1, which generalize the boolean operations on languages, as well as the sum L-1 + L-2. We establish the closure properties of all classes of quantitative languages with respect to these four operations.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ID - 3867
IS - 3
JF - Logical Methods in Computer Science
TI - Expressiveness and closure properties for quantitative languages
VL - 6
ER -
TY - CONF
AB - 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.
AU - Feret, Jérôme
AU - Henzinger, Thomas A
AU - Koeppl, Heinz
AU - Petrov, Tatjana
ID - 3719
TI - Lumpability abstractions of rule-based systems
VL - 40
ER -
TY - JOUR
AU - Barton, Nicholas H
ID - 3772
IS - 6
JF - PLoS Genetics
TI - Understanding adaptation in large populations
VL - 6
ER -
TY - JOUR
AB - 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.
AU - Barton, Nicholas H
ID - 3773
IS - 1547
JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
TI - What role does natural selection play in speciation?
VL - 365
ER -
TY - JOUR
AB - 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.
AU - Senn, Helen
AU - Swanson, Graeme
AU - Goodman, Simon
AU - Barton, Nicholas H
AU - Pemberton, Josephine
ID - 3774
IS - 2
JF - Journal of Animal Ecology
TI - Phenotypic correlates of hybridisation between red and sika deer (genus Cervus)
VL - 79
ER -
TY - JOUR
AB - 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.
AU - Barton, Nicholas H
ID - 3776
IS - 1552
JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
TI - Genetic linkage and natural selection
VL - 365
ER -
TY - JOUR
AB - 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.
AU - Barton, Nicholas H
ID - 3777
IS - 1544
JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
TI - Mutation and the evolution of recombination
VL - 365
ER -
TY - JOUR
AB - 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.
AU - Rosas, Ulises
AU - Barton, Nicholas H
AU - Copsey, Lucy
AU - Barbier De Reuille, Pierre
AU - Coen, Enrico
ID - 3779
IS - 7
JF - PLoS Biology
TI - Cryptic variation between species and the basis of hybrid performance
VL - 8
ER -
TY - CONF
AB - 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.
AU - Chen, Chao
AU - Freedman, Daniel
ID - 3782
T2 - Conference proceedings MCV 2010
TI - Topology noise removal for curve and surface evolution
VL - 6533
ER -