TY - CONF
AB - We introduce the idea of using an explicit triangle mesh to track the air/fluid interface in a smoothed particle hydrodynamics (SPH) simulator. Once an initial surface mesh is created, this mesh is carried forward in time using nearby particle velocities to advect the mesh vertices. The mesh connectivity remains mostly unchanged across time-steps; it is only modified locally for topology change events or for the improvement of triangle quality. In order to ensure that the surface mesh does not diverge from the underlying particle simulation, we periodically project the mesh surface onto an implicit surface defined by the physics simulation. The mesh surface gives us several advantages over previous SPH surface tracking techniques. We demonstrate a new method for surface tension calculations that clearly outperforms the state of the art in SPH surface tension for computer graphics. We also demonstrate a method for tracking detailed surface information (like colors) that is less susceptible to numerical diffusion than competing techniques. Finally, our temporally-coherent surface mesh allows us to simulate high-resolution surface wave dynamics without being limited by the particle resolution of the SPH simulation.
AU - Yu, Jihun
AU - Wojtan, Christopher J
AU - Turk, Greg
AU - Yap, Chee
ID - 3123
IS - 2
T2 - Computer Graphics Forum
TI - Explicit mesh surfaces for particle based fluids
VL - 31
ER -
TY - CONF
AB - We consider the problem of inference in a graphical model with binary variables. While in theory it is arguably preferable to compute marginal probabilities, in practice researchers often use MAP inference due to the availability of efficient discrete optimization algorithms. We bridge the gap between the two approaches by introducing the Discrete Marginals technique in which approximate marginals are obtained by minimizing an objective function with unary and pairwise terms over a discretized domain. This allows the use of techniques originally developed for MAP-MRF inference and learning. We explore two ways to set up the objective function - by discretizing the Bethe free energy and by learning it from training data. Experimental results show that for certain types of graphs a learned function can outperform the Bethe approximation. We also establish a link between the Bethe free energy and submodular functions.
AU - Korc, Filip
AU - Kolmogorov, Vladimir
AU - Lampert, Christoph
ID - 3124
TI - Approximating marginals using discrete energy minimization
ER -
TY - CONF
AB - We propose a new learning method to infer a mid-level feature representation that combines the advantage of semantic attribute representations with the higher expressive power of non-semantic features. The idea lies in augmenting an existing attribute-based representation with additional dimensions for which an autoencoder model is coupled with a large-margin principle. This construction allows a smooth transition between the zero-shot regime with no training example, the unsupervised regime with training examples but without class labels, and the supervised regime with training examples and with class labels. The resulting optimization problem can be solved efficiently, because several of the necessity steps have closed-form solutions. Through extensive experiments we show that the augmented representation achieves better results in terms of object categorization accuracy than the semantic representation alone.
AU - Sharmanska, Viktoriia
AU - Quadrianto, Novi
AU - Lampert, Christoph
ID - 3125
IS - PART 5
TI - Augmented attribute representations
VL - 7576
ER -
TY - CONF
AB - In this work we propose a new information-theoretic clustering algorithm that infers cluster memberships by direct optimization of a non-parametric mutual information estimate between data distribution and cluster assignment. Although the optimization objective has a solid theoretical foundation it is hard to optimize. We propose an approximate optimization formulation that leads to an efficient algorithm with low runtime complexity. The algorithm has a single free parameter, the number of clusters to find. We demonstrate superior performance on several synthetic and real datasets.
AU - Müller, Andreas
AU - Nowozin, Sebastian
AU - Lampert, Christoph
ID - 3126
TI - Information theoretic clustering using minimal spanning trees
VL - 7476
ER -
TY - CONF
AB - When searching for characteristic subpatterns in potentially noisy graph data, it appears self-evident that having multiple observations would be better than having just one. However, it turns out that the inconsistencies introduced when different graph instances have different edge sets pose a serious challenge. In this work we address this challenge for the problem of finding maximum weighted cliques.
We introduce the concept of most persistent soft-clique. This is subset of vertices, that 1) is almost fully or at least densely connected, 2) occurs in all or almost all graph instances, and 3) has the maximum weight. We present a measure of clique-ness, that essentially counts the number of edge missing to make a subset of vertices into a clique. With this measure, we show that the problem of finding the most persistent soft-clique problem can be cast either as: a) a max-min two person game optimization problem, or b) a min-min soft margin optimization problem. Both formulations lead to the same solution when using a partial Lagrangian method to solve the optimization problems. By experiments on synthetic data and on real social network data, we show that the proposed method is able to reliably find soft cliques in graph data, even if that is distorted by random noise or unreliable observations.
AU - Quadrianto, Novi
AU - Lampert, Christoph
AU - Chen, Chao
ID - 3127
T2 - Proceedings of the 29th International Conference on Machine Learning
TI - The most persistent soft-clique in a set of sampled graphs
ER -
TY - JOUR
AB - We consider two-player zero-sum stochastic games on graphs with ω-regular winning conditions specified as parity objectives. These games have applications in the design and control of reactive systems. We survey the complexity results for the problem of deciding the winner in such games, and in classes of interest obtained as special cases, based on the information and the power of randomization available to the players, on the class of objectives and on the winning mode. On the basis of information, 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 complete view of the game). The one-sided partial-observation games have two important subclasses: the one-player games, known as partial-observation Markov decision processes (POMDPs), and the blind one-player games, known as probabilistic automata. 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. Finally, various classes of games are obtained by restricting the parity objective to a reachability, safety, Büchi, or coBüchi condition. We also consider several winning modes, such as sure-winning (i.e., all outcomes of a strategy have to satisfy the winning condition), almost-sure winning (i.e., winning with probability 1), limit-sure winning (i.e., winning with probability arbitrarily close to 1), and value-threshold winning (i.e., winning with probability at least ν, where ν is a given rational).
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ID - 3128
IS - 2
JF - Formal Methods in System Design
TI - A survey of partial-observation stochastic parity games
VL - 43
ER -
TY - CONF
AB - Let K be a simplicial complex and g the rank of its p-th homology group Hp(K) defined with ℤ2 coefficients. We show that we can compute a basis H of Hp(K) and annotate each p-simplex of K with a binary vector of length g with the following property: the annotations, summed over all p-simplices in any p-cycle z, provide the coordinate vector of the homology class [z] in the basis H. The basis and the annotations for all simplices can be computed in O(n ω ) time, where n is the size of K and ω < 2.376 is a quantity so that two n×n matrices can be multiplied in O(n ω ) time. The precomputed annotations permit answering queries about the independence or the triviality of p-cycles efficiently.
Using annotations of edges in 2-complexes, we derive better algorithms for computing optimal basis and optimal homologous cycles in 1 - dimensional homology. Specifically, for computing an optimal basis of H1(K) , we improve the previously known time complexity from O(n 4) to O(n ω + n 2 g ω − 1). Here n denotes the size of the 2-skeleton of K and g the rank of H1(K) . Computing an optimal cycle homologous to a given 1-cycle is NP-hard even for surfaces and an algorithm taking 2 O(g) nlogn time is known for surfaces. We extend this algorithm to work with arbitrary 2-complexes in O(n ω ) + 2 O(g) n 2logn time using annotations.
AU - Busaryev, Oleksiy
AU - Cabello, Sergio
AU - Chen, Chao
AU - Dey, Tamal
AU - Wang, Yusu
ID - 3129
TI - Annotating simplices with a homology basis and its applications
VL - 7357
ER -
TY - JOUR
AB - Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes.
AU - Bergmiller, Tobias
AU - Ackermann, Martin
AU - Silander, Olin
ID - 3130
IS - 6
JF - PLoS Genetics
TI - Patterns of evolutionary conservation of essential genes correlate with their compensability
VL - 8
ER -
TY - JOUR
AB - In large populations, many beneficial mutations may be simultaneously available and may compete with one another, slowing adaptation. By finding the probability of fixation of a favorable allele in a simple model of a haploid sexual population, we find limits to the rate of adaptive substitution, Λ, that depend on simple parameter combinations. When variance in fitness is low and linkage is loose, the baseline rate of substitution is Λ 0=2NU〈s〉 is the population size, U is the rate of beneficial mutations per genome, and 〈s〉 is their mean selective advantage. Heritable variance ν in log fitness due to unlinked loci reduces Λ by e -4ν under polygamy and e -8ν under monogamy. With a linear genetic map of length R Morgans, interference is yet stronger. We use a scaling argument to show that the density of adaptive substitutions depends on s, N, U, and R only through the baseline density: Λ/R=F(Λ 0/R). Under the approximation that the interference due to different sweeps adds up, we show that Λ/R~(Λ 0/R)/(1+2Λ 0/R), implying that interference prevents the rate of adaptive substitution from exceeding one per centimorgan per 200 generations. Simulations and numerical calculations confirm the scaling argument and confirm the additive approximation for Λ 0/R 1; for higher Λ 0/R, the rate of adaptation grows above R/2, but only very slowly. We also consider the effect of sweeps on neutral diversity and show that, while even occasional sweeps can greatly reduce neutral diversity, this effect saturates as sweeps become more common-diversity can be maintained even in populations experiencing very strong interference. Our results indicate that for some organisms the rate of adaptive substitution may be primarily recombination-limited, depending only weakly on the mutation supply and the strength of selection.
AU - Weissman, Daniel
AU - Barton, Nicholas H
ID - 3131
IS - 6
JF - PLoS Genetics
TI - Limits to the rate of adaptive substitution in sexual populations
VL - 8
ER -
TY - JOUR
AB - Reproductive division of labour is a characteristic trait of social insects. The dominant reproductive individual, often the queen, uses chemical communication and/or behaviour to maintain her social status. Queens of many social insects communicate their fertility status via cuticle-bound substances. As these substances usually possess a low volatility, their range in queen–worker communication is potentially limited. Here, we investigate the range and impact of behavioural and chemical queen signals on workers of the ant Temnothorax longispinosus. We compared the behaviour and ovary development of workers subjected to three different treatments: workers with direct chemical and physical contact to the queen, those solely under the influence of volatile queen substances and those entirely separated from the queen. In addition to short-ranged queen signals preventing ovary development in workers, we discovered a novel secondary pathway influencing worker behaviour. Workers with no physical contact to the queen, but exposed to volatile substances, started to develop their ovaries, but did not change their behaviour compared to workers in direct contact to the queen. In contrast, workers in queen-separated groups showed both increased ovary development and aggressive dominance interactions. We conclude that T. longispinosus queens influence worker ovary development and behaviour via two independent signals, both ensuring social harmony within the colony.
AU - Konrad, Matthias
AU - Pamminger, Tobias
AU - Foitzik, Susanne
ID - 3132
IS - 8
JF - Naturwissenschaften
TI - Two pathways ensuring social harmony
VL - 99
ER -
TY - CONF
AB - This note contributes to the point calculus of persistent homology by extending Alexander duality from spaces to real-valued functions. Given a perfect Morse function f: S n+1 →[0, 1 and a decomposition S n+1 = U ∪ V into two (n + 1)-manifolds with common boundary M, we prove elementary relationships between the persistence diagrams of f restricted to U, to V, and to M.
AU - Edelsbrunner, Herbert
AU - Kerber, Michael
ID - 3133
T2 - Proceedings of the twenty-eighth annual symposium on Computational geometry
TI - Alexander duality for functions: The persistent behavior of land and water and shore
ER -
TY - CONF
AB - It has been an open question whether the sum of finitely many isotropic Gaussian kernels in n ≥ 2 dimensions can have more modes than kernels, until in 2003 Carreira-Perpiñán and Williams exhibited n +1 isotropic Gaussian kernels in ℝ n with n + 2 modes. We give a detailed analysis of this example, showing that it has exponentially many critical points and that the resilience of the extra mode grows like √n. In addition, we exhibit finite configurations of isotropic Gaussian kernels with superlinearly many modes.
AU - Edelsbrunner, Herbert
AU - Fasy, Brittany
AU - Rote, Günter
ID - 3134
T2 - Proceedings of the twenty-eighth annual symposium on Computational geometry
TI - Add isotropic Gaussian kernels at own risk: More and more resilient modes in higher dimensions
ER -
TY - CONF
AB - We introduce consumption games, a model for discrete interactive system with multiple resources that are consumed or reloaded independently. More precisely, a consumption game is a finite-state graph where each transition is labeled by a vector of resource updates, where every update is a non-positive number or ω. The ω updates model the reloading of a given resource. Each vertex belongs either to player □ or player ◇, where the aim of player □ is to play so that the resources are never exhausted. We consider several natural algorithmic problems about consumption games, and show that although these problems are computationally hard in general, they are solvable in polynomial time for every fixed number of resource types (i.e., the dimension of the update vectors) and bounded resource updates.
AU - Brázdil, Brázdil
AU - Chatterjee, Krishnendu
AU - Kučera, Antonín
AU - Novotny, Petr
ID - 3135
TI - Efficient controller synthesis for consumption games with multiple resource types
VL - 7358
ER -
TY - CONF
AB - Continuous-time Markov chains (CTMC) with their rich theory and efficient simulation algorithms have been successfully used in modeling stochastic processes in diverse areas such as computer science, physics, and biology. However, systems that comprise non-instantaneous events cannot be accurately and efficiently modeled with CTMCs. In this paper we define delayed CTMCs, an extension of CTMCs that allows for the specification of a lower bound on the time interval between an event's initiation and its completion, and we propose an algorithm for the computation of their behavior. Our algorithm effectively decomposes the computation into two stages: a pure CTMC governs event initiations while a deterministic process guarantees lower bounds on event completion times. Furthermore, from the nature of delayed CTMCs, we obtain a parallelized version of our algorithm. We use our formalism to model genetic regulatory circuits (biological systems where delayed events are common) and report on the results of our numerical algorithm as run on a cluster. We compare performance and accuracy of our results with results obtained by using pure CTMCs. © 2012 Springer-Verlag.
AU - Guet, Calin C
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
AU - Mateescu, Maria
AU - Sezgin, Ali
ID - 3136
TI - Delayed continuous time Markov chains for genetic regulatory circuits
VL - 7358
ER -
TY - CONF
AB - We propose synchronous interfaces, a new interface theory for discrete-time systems. We use an application to time-triggered scheduling to drive the design choices for our formalism; in particular, additionally to deriving useful mathematical properties, we focus on providing a syntax which is adapted to natural high-level system modeling. As a result, we develop an interface model that relies on a guarded-command based language and is equipped with shared variables and explicit discrete-time clocks. We define all standard interface operations: compatibility checking, composition, refinement, and shared refinement. Apart from the synchronous interface model, the contribution of this paper is the establishment of a formal relation between interface theories and real-time scheduling, where we demonstrate a fully automatic framework for the incremental computation of time-triggered schedules.
AU - Delahaye, Benoît
AU - Fahrenberg, Uli
AU - Henzinger, Thomas A
AU - Legay, Axel
AU - Nickovic, Dejan
ID - 3155
TI - Synchronous interface theories and time triggered scheduling
VL - 7273
ER -
TY - JOUR
AB - Dispersal is crucial for gene flow and often determines the long-term stability of meta-populations, particularly in rare species with specialized life cycles. Such species are often foci of conservation efforts because they suffer disproportionally from degradation and fragmentation of their habitat. However, detailed knowledge of effective gene flow through dispersal is often missing, so that conservation strategies have to be based on mark-recapture observations that are suspected to be poor predictors of long-distance dispersal. These constraints have been especially severe in the study of butterfly populations, where microsatellite markers have been difficult to develop. We used eight microsatellite markers to analyse genetic population structure of the Large Blue butterfly Maculinea arion in Sweden. During recent decades, this species has become an icon of insect conservation after massive decline throughout Europe and extinction in Britain followed by reintroduction of a seed population from the Swedish island of Öland. We find that populations are highly structured genetically, but that gene flow occurs over distances 15 times longer than the maximum distance recorded from mark-recapture studies, which can only be explained by maximum dispersal distances at least twice as large as previously accepted. However, we also find evidence that gaps between sites with suitable habitat exceeding ∼ 20 km induce genetic erosion that can be detected from bottleneck analyses. Although further work is needed, our results suggest that M. arion can maintain fully functional metapopulations when they consist of optimal habitat patches that are no further apart than ∼10 km.
AU - Ugelvig, Line V
AU - Andersen, Anne
AU - Boomsma, Jacobus
AU - Nash, David
ID - 3156
IS - 13
JF - Molecular Ecology
TI - Dispersal and gene flow in the rare parasitic Large Blue butterfly Maculinea arion
VL - 21
ER -
TY - JOUR
AB - Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.
AU - Diaz Jr, Luis
AU - Williams, Richard
AU - Wu, Jian
AU - Kinde, Isaac
AU - Hecht, Joel
AU - Berlin, Jordan
AU - Allen, Benjamin
AU - Božić, Ivana
AU - Reiter, Johannes
AU - Nowak, Martin
AU - Kinzler, Kenneth
AU - Oliner, Kelly
AU - Vogelstein, Bert
ID - 3157
IS - 7404
JF - Nature
TI - The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers
VL - 486
ER -
TY - JOUR
AB - We describe here the development and characterization of a conditionally inducible mouse model expressing Lifeact-GFP, a peptide that reports the dynamics of filamentous actin. We have used this model to study platelets, megakaryocytes and melanoblasts and we provide evidence that Lifeact-GFP is a useful reporter in these cell types ex vivo. In the case of platelets and megakaryocytes, these cells are not transfectable by traditional methods, so conditional activation of Lifeact allows the study of actin dynamics in these cells live. We studied melanoblasts in native skin explants from embryos, allowing the visualization of live actin dynamics during cytokinesis and migration. Our study revealed that melanoblasts lacking the small GTPase Rac1 show a delay in the formation of new pseudopodia following cytokinesis that accounts for the previously reported cytokinesis delay in these cells. Thus, through use of this mouse model, we were able to gain insights into the actin dynamics of cells that could only previously be studied using fixed specimens or following isolation from their native tissue environment.
AU - Schachtner, Hannah
AU - Li, Ang
AU - Stevenson, David
AU - Calaminus, Simon
AU - Thomas, Steven
AU - Watson, Steve
AU - Sixt, Michael K
AU - Wedlich Söldner, Roland
AU - Strathdee, Douglas
AU - Machesky, Laura
ID - 3158
IS - 11-12
JF - European Journal of Cell Biology
TI - Tissue inducible Lifeact expression allows visualization of actin dynamics in vivo and ex vivo
VL - 91
ER -
TY - JOUR
AB - The structure of hierarchical networks in biological and physical systems has long been characterized using the Horton-Strahler ordering scheme. The scheme assigns an integer order to each edge in the network based on the topology of branching such that the order increases from distal parts of the network (e.g., mountain streams or capillaries) to the "root" of the network (e.g., the river outlet or the aorta). However, Horton-Strahler ordering cannot be applied to networks with loops because they they create a contradiction in the edge ordering in terms of which edge precedes another in the hierarchy. Here, we present a generalization of the Horton-Strahler order to weighted planar reticular networks, where weights are assumed to correlate with the importance of network edges, e.g., weights estimated from edge widths may correlate to flow capacity. Our method assigns hierarchical levels not only to edges of the network, but also to its loops, and classifies the edges into reticular edges, which are responsible for loop formation, and tree edges. In addition, we perform a detailed and rigorous theoretical analysis of the sensitivity of the hierarchical levels to weight perturbations. In doing so, we show that the ordering of the reticular edges is more robust to noise in weight estimation than is the ordering of the tree edges. We discuss applications of this generalized Horton-Strahler ordering to the study of leaf venation and other biological networks.
AU - Mileyko, Yuriy
AU - Edelsbrunner, Herbert
AU - Price, Charles
AU - Weitz, Joshua
ID - 3159
IS - 6
JF - PLoS One
TI - Hierarchical ordering of reticular networks
VL - 7
ER -
TY - JOUR
AB - There is a long-running controversy about how early cell fate decisions are made in the developing mammalian embryo. 1,2 In particular, it is controversial when the first events that can predict the establishment of the pluripotent and extra-embryonic lineages in the blastocyst of the pre-implantation embryo occur. It has long been proposed that the position and polarity of cells at the 16- to 32-cell stage embryo influence their decision to either give rise to the pluripotent cell lineage that eventually contributes to the inner cell mass (ICM), comprising the primitive endoderm (PE) and the epiblast (EPI), or the extra-embryonic trophectoderm (TE) surrounding the blastocoel. The positioning of cells in the embryo at this developmental stage could largely be the result of random events, making this a stochastic model of cell lineage allocation. Contrary to such a stochastic model, some studies have detected putative differences in the lineage potential of individual blastomeres before compaction, indicating that the first cell fate decisions may occur as early as at the 4-cell stage. Using a non-invasive, quantitative in vivo imaging assay to study the kinetic behavior of Oct4 (also known as POU5F1), a key transcription factor (TF) controlling pre-implantation development in the mouse embryo, 3-5 a recent study identifies Oct4 kinetics as a predictive measure of cell lineage patterning in the early mouse embryo. 6 Here, we discuss the implications of such molecular heterogeneities in early development and offer potential avenues toward a mechanistic understanding of these observations, contributing to the resolution of the controversy of developmental cell lineage allocation.
AU - Pantazis, Periklis
AU - Bollenbach, Tobias
ID - 3160
IS - 11
JF - Cell Cycle
TI - Transcription factor kinetics and the emerging asymmetry in the early mammalian embryo
VL - 11
ER -