TY - JOUR
AB - Nestin-cre transgenic mice have been widely used to direct recombination to neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs). Here we report that a readily utilized, and the only commercially available, Nestin-cre line is insufficient for directing recombination in early embryonic NSCs and NPCs. Analysis of recombination efficiency in multiple cre-dependent reporters and a genetic mosaic line revealed consistent temporal and spatial patterns of recombination in NSCs and NPCs. For comparison we utilized a knock-in Emx1cre line and found robust recombination in NSCs and NPCs in ventricular and subventricular zones of the cerebral cortices as early as embryonic day 12.5. In addition we found that the rate of Nestin-cre driven recombination only reaches sufficiently high levels in NSCs and NPCs during late embryonic and early postnatal periods. These findings are important when commercially available cre lines are considered for directing recombination to embryonic NSCs and NPCs.
AU - Liang, Huixuan
AU - Hippenmeyer, Simon
AU - Ghashghaei, H.
ID - 2263
IS - 12
JF - Biology open
TI - A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors
VL - 1
ER -
TY - JOUR
AB - We introduce propagation models (PMs), a formalism able to express several kinds of equations that describe the behavior of biochemical reaction networks. Furthermore, we introduce the propagation abstract data type (PADT), which separates concerns regarding different numerical algorithms for the transient analysis of biochemical reaction networks from concerns regarding their implementation, thus allowing for portable and efficient solutions. The state of a propagation abstract data type is given by a vector that assigns mass values to a set of nodes, and its (next) operator propagates mass values through this set of nodes. We propose an approximate implementation of the (next) operator, based on threshold abstraction, which propagates only "significant" mass values and thus achieves a compromise between efficiency and accuracy. Finally, we give three use cases for propagation models: the chemical master equation (CME), the reaction rate equation (RRE), and a hybrid method that combines these two equations. These three applications use propagation models in order to propagate probabilities and/or expected values and variances of the model's variables.
AU - Henzinger, Thomas A
AU - Mateescu, Maria
ID - 2302
IS - 2
JF - IEEE ACM Transactions on Computational Biology and Bioinformatics
TI - The propagation approach for computing biochemical reaction networks
VL - 10
ER -
TY - JOUR
AB - We show that bosons interacting via pair potentials with negative scattering length form bound states for a suitable number of particles. In other words, the absence of many-particle bound states of any kind implies the non-negativity of the scattering length of the interaction potential.
AU - Seiringer, Robert
ID - 2318
IS - 3
JF - Journal of Spectral Theory
TI - Absence of bound states implies non-negativity of the scattering length
VL - 2
ER -
TY - JOUR
AB - The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data-a common practice in phylogenomic analyses-introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses.
AU - Ebersberger, Ingo
AU - De Matos Simoes, Ricardo
AU - Kupczok, Anne
AU - Gube, Matthias
AU - Kothe, Erika
AU - Voigt, Kerstin
AU - Von Haeseler, Arndt
ID - 2411
IS - 5
JF - Molecular Biology and Evolution
TI - A consistent phylogenetic backbone for the fungi
VL - 29
ER -
TY - CONF
AB - We consider Markov decision processes (MDPs) with specifications given as Büchi (liveness) objectives. We consider the problem of computing the set of almost-sure winning vertices from where the objective can be ensured with probability 1. We study for the first time the average case complexity of the classical algorithm for computing the set of almost-sure winning vertices for MDPs with Büchi objectives. Our contributions are as follows: First, we show that for MDPs with constant out-degree the expected number of iterations is at most logarithmic and the average case running time is linear (as compared to the worst case linear number of iterations and quadratic time complexity). Second, for the average case analysis over all MDPs we show that the expected number of iterations is constant and the average case running time is linear (again as compared to the worst case linear number of iterations and quadratic time complexity). Finally we also show that given that all MDPs are equally likely, the probability that the classical algorithm requires more than constant number of iterations is exponentially small.
AU - Chatterjee, Krishnendu
AU - Joglekar, Manas
AU - Shah, Nisarg
ID - 2715
TI - Average case analysis of the classical algorithm for Markov decision processes with Büchi objectives
VL - 18
ER -
TY - CONF
AB - We study the problem of maximum marginal prediction (MMP) in probabilistic graphical models, a task that occurs, for example, as the Bayes optimal decision rule under a Hamming loss. MMP is typically performed as a two-stage procedure: one estimates each variable's marginal probability and then forms a prediction from the states of maximal probability. In this work we propose a simple yet effective technique for accelerating MMP when inference is sampling-based: instead of the above two-stage procedure we directly estimate the posterior probability of each decision variable. This allows us to identify the point of time when we are sufficiently certain about any individual decision. Whenever this is the case, we dynamically prune the variables we are confident about from the underlying factor graph. Consequently, at any time only samples of variables whose decision is still uncertain need to be created. Experiments in two prototypical scenarios, multi-label classification and image inpainting, show that adaptive sampling can drastically accelerate MMP without sacrificing prediction accuracy.
AU - Lampert, Christoph
ID - 2825
TI - Dynamic pruning of factor graphs for maximum marginal prediction
VL - 1
ER -
TY - JOUR
AB - We study evolutionary game theory in a setting where individuals learn from each other. We extend the traditional approach by assuming that a population contains individuals with different learning abilities. In particular, we explore the situation where individuals have different search spaces, when attempting to learn the strategies of others. The search space of an individual specifies the set of strategies learnable by that individual. The search space is genetically given and does not change under social evolutionary dynamics. We introduce a general framework and study a specific example in the context of direct reciprocity. For this example, we obtain the counter intuitive result that cooperation can only evolve for intermediate benefit-to-cost ratios, while small and large benefit-to-cost ratios favor defection. Our paper is a step toward making a connection between computational learning theory and evolutionary game dynamics.
AU - Chatterjee, Krishnendu
AU - Zufferey, Damien
AU - Nowak, Martin
ID - 2848
JF - Journal of Theoretical Biology
TI - Evolutionary game dynamics in populations with different learners
VL - 301
ER -
TY - JOUR
AU - Edelsbrunner, Herbert
AU - Strelkova, Nataliya
ID - 2849
IS - 6
JF - Russian Mathematical Surveys
TI - On the configuration space of Steiner minimal trees
VL - 67
ER -
TY - CONF
AB - Formal verification aims to improve the quality of hardware and software by detecting errors before they do harm. At the basis of formal verification lies the logical notion of correctness, which purports to capture whether or not a circuit or program behaves as desired. We suggest that the boolean partition into correct and incorrect systems falls short of the practical need to assess the behavior of hardware and software in a more nuanced fashion against multiple criteria.
AU - Henzinger, Thomas A
ID - 2888
T2 - Conference proceedings MODELS 2012
TI - Quantitative reactive models
VL - 7590
ER -
TY - CONF
AB - Systems are often specified using multiple requirements on their behavior. In practice, these requirements can be contradictory. The classical approach to specification, verification, and synthesis demands more detailed specifications that resolve any contradictions in the requirements. These detailed specifications are usually large, cumbersome, and hard to maintain or modify. In contrast, quantitative frameworks allow the formalization of the intuitive idea that what is desired is an implementation that comes "closest" to satisfying the mutually incompatible requirements, according to a measure of fit that can be defined by the requirements engineer. One flexible framework for quantifying how "well" an implementation satisfies a specification is offered by simulation distances that are parameterized by an error model. We introduce this framework, study its properties, and provide an algorithmic solution for the following quantitative synthesis question: given two (or more) behavioral requirements specified by possibly incompatible finite-state machines, and an error model, find the finite-state implementation that minimizes the maximal simulation distance to the given requirements. Furthermore, we generalize the framework to handle infinite alphabets (for example, realvalued domains). We also demonstrate how quantitative specifications based on simulation distances might lead to smaller and easier to modify specifications. Finally, we illustrate our approach using case studies on error correcting codes and scheduler synthesis.
AU - Cerny, Pavol
AU - Gopi, Sivakanth
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Totla, Nishant
ID - 2890
T2 - Proceedings of the tenth ACM international conference on Embedded software
TI - Synthesis from incompatible specifications
ER -
TY - CONF
AB - Quantitative automata are nondeterministic finite automata with edge weights. They value a
run by some function from the sequence of visited weights to the reals, and value a word by its
minimal/maximal run. They generalize boolean automata, and have gained much attention in
recent years. Unfortunately, important automaton classes, such as sum, discounted-sum, and
limit-average automata, cannot be determinized. Yet, the quantitative setting provides the potential
of approximate determinization. We define approximate determinization with respect to
a distance function, and investigate this potential.
We show that sum automata cannot be determinized approximately with respect to any
distance function. However, restricting to nonnegative weights allows for approximate determinization
with respect to some distance functions.
Discounted-sum automata allow for approximate determinization, as the influence of a word’s
suffix is decaying. However, the naive approach, of unfolding the automaton computations up
to a sufficient level, is shown to be doubly exponential in the discount factor. We provide an
alternative construction that is singly exponential in the discount factor, in the precision, and
in the number of states. We prove matching lower bounds, showing exponential dependency on
each of these three parameters.
Average and limit-average automata are shown to prohibit approximate determinization with
respect to any distance function, and this is the case even for two weights, 0 and 1.
AU - Boker, Udi
AU - Henzinger, Thomas A
ID - 2891
T2 - Leibniz International Proceedings in Informatics
TI - Approximate determinization of quantitative automata
VL - 18
ER -
TY - JOUR
AB - We present an algorithm for simplifying linear cartographic objects and results obtained with a computer program implementing this algorithm.
AU - Edelsbrunner, Herbert
AU - Musin, Oleg
AU - Ukhalov, Alexey
AU - Yakimova, Olga
AU - Alexeev, Vladislav
AU - Bogaevskaya, Victoriya
AU - Gorohov, Andrey
AU - Preobrazhenskaya, Margarita
ID - 2902
IS - 6
JF - Modeling and Analysis of Information Systems
TI - Fractal and computational geometry for generalizing cartographic objects
VL - 19
ER -
TY - CONF
AB - In order to enjoy a digital version of the Jordan Curve Theorem, it is common to use the closed topology for the foreground and the open topology for the background of a 2-dimensional binary image. In this paper, we introduce a single topology that enjoys this theorem for all thresholds decomposing a real-valued image into foreground and background. This topology is easy to construct and it generalizes to n-dimensional images.
AU - Edelsbrunner, Herbert
AU - Symonova, Olga
ID - 2903
TI - The adaptive topology of a digital image
ER -
TY - JOUR
AB - Generalized van der Corput sequences are onedimensional, infinite sequences in the unit interval. They are generated from permutations in integer base b and are the building blocks of the multi-dimensional Halton sequences. Motivated by recent progress of Atanassov on the uniform distribution behavior of Halton sequences, we study, among others, permutations of the form P(i) = ai (mod b) for coprime integers a and b. We show that multipliers a that either divide b - 1 or b + 1 generate van der Corput sequences with weak distribution properties. We give explicit lower bounds for the asymptotic distribution behavior of these sequences and relate them to sequences generated from the identity permutation in smaller bases, which are, due to Faure, the weakest distributed generalized van der Corput sequences.
AU - Pausinger, Florian
ID - 2904
IS - 3
JF - Journal de Theorie des Nombres des Bordeaux
SN - 2118-8572
TI - Weak multipliers for generalized van der Corput sequences
VL - 24
ER -
TY - JOUR
AU - Edelsbrunner, Herbert
AU - Strelkova, Nataliya
ID - 2912
IS - 6
JF - Uspekhi Mat. Nauk
TI - Configuration space for shortest networks
VL - 67
ER -
TY - CONF
AU - Kroemer, Oliver
AU - Lampert, Christoph
AU - Peters, Jan
ID - 2915
TI - Multi-modal learning for dynamic tactile sensing
ER -
TY - CONF
AB - The classical (boolean) notion of refinement for behavioral interfaces of system components is the alternating refinement preorder. In this paper, we define a quantitative measure for interfaces, called interface simulation distance. It makes the alternating refinement preorder quantitative by, intu- itively, tolerating errors (while counting them) in the alternating simulation game. We show that the interface simulation distance satisfies the triangle inequality, that the distance between two interfaces does not increase under parallel composition with a third interface, and that the distance between two interfaces can be bounded from above and below by distances between abstractions of the two interfaces. We illustrate the framework, and the properties of the distances under composition of interfaces, with two case studies.
AU - Cerny, Pavol
AU - Chmelik, Martin
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 2916
T2 - Electronic Proceedings in Theoretical Computer Science
TI - Interface Simulation Distances
VL - 96
ER -
TY - JOUR
AB - The search for extra-terrestrial intelligence (SETI) has been performed principally as a one-way survey, listening of radio frequencies across the Milky Way and other galaxies. However, scientists have engaged in an active messaging only rarely. This suggests the simple rationale that if other civilizations exist and take a similar approach to ours, namely listening but not broadcasting, the result is a silent universe. A simple game theoretical model, the prisoner's dilemma, explains this situation: each player (civilization) can passively search (defect), or actively search and broadcast (cooperate). In order to maximize the payoff (or, equivalently, minimize the risks) the best strategy is not to broadcast. In fact, the active search has been opposed on the basis that it might be dangerous to expose ourselves. However, most of these ideas have not been based on objective arguments, and ignore accounting of the possible gains and losses. Thus, the question stands: should we perform an active search? I develop a game-theoretical framework where civilizations can be of different types, and explicitly apply it to a situation where societies are either interested in establishing a two-way communication or belligerent and in urge to exploit ours. The framework gives a quantitative solution (a mixed-strategy), which is how frequent we should perform the active SETI. This frequency is roughly proportional to the inverse of the risk, and can be extremely small. However, given the immense amount of stars being scanned, it supports active SETI. The model is compared with simulations, and the possible actions are evaluated through the San Marino scale, measuring the risks of messaging.
AU - Vladar, Harold
ID - 2917
IS - 1
JF - International Journal of Astrobiology
TI - The game of active search for extra terrestrial intelligence Breaking the Great Silence
VL - 12
ER -
TY - GEN
AB - This paper addresses the problem of approximate MAP-MRF inference in general graphical models. Following [36], we consider a family of linear programming relaxations of the problem where each relaxation is specified by a set of nested pairs of factors for which the marginalization constraint needs to be enforced. We develop a generalization of the TRW-S algorithm [9] for this problem, where we use a decomposition into junction chains, monotonic w.r.t. some ordering on the nodes. This generalizes the monotonic chains in [9] in a natural way. We also show how to deal with nested factors in an efficient way. Experiments show an improvement over min-sum diffusion, MPLP and subgradient ascent algorithms on a number of computer vision and natural language processing problems.
AU - Kolmogorov, Vladimir
AU - Schoenemann, Thomas
ID - 2928
T2 - arXiv
TI - Generalized sequential tree-reweighted message passing
ER -
TY - CONF
AB - In this paper we investigate k-submodular functions. This natural family of discrete functions includes submodular and bisubmodular functions as the special cases k = 1 and k = 2 respectively.
In particular we generalize the known Min-Max-Theorem for submodular and bisubmodular functions. This theorem asserts that the minimum of the (bi)submodular function can be found by solving a maximization problem over a (bi)submodular polyhedron. We define a k-submodular polyhedron, prove a Min-Max-Theorem for k-submodular functions, and give a greedy algorithm to construct the vertices of the polyhedron.
AU - Huber, Anna
AU - Kolmogorov, Vladimir
ID - 2930
TI - Towards minimizing k-submodular functions
VL - 7422
ER -
TY - JOUR
AB - In this paper, we present a new approach for establishing correspondences between sparse image features related by an unknown nonrigid mapping and corrupted by clutter and occlusion, such as points extracted from images of different instances of the same object category. We formulate this matching task as an energy minimization problem by defining an elaborate objective function of the appearance and the spatial arrangement of the features. Optimization of this energy is an instance of graph matching, which is in general an NP-hard problem. We describe a novel graph matching optimization technique, which we refer to as dual decomposition (DD), and demonstrate on a variety of examples that this method outperforms existing graph matching algorithms. In the majority of our examples, DD is able to find the global minimum within a minute. The ability to globally optimize the objective allows us to accurately learn the parameters of our matching model from training examples. We show on several matching tasks that our learned model yields results superior to those of state-of-the-art methods.
AU - Torresani, Lorenzo
AU - Kolmogorov, Vladimir
AU - Rother, Carsten
ID - 2931
IS - 2
JF - IEEE Transactions on Pattern Analysis and Machine Intelligence
TI - A dual decomposition approach to feature correspondence
VL - 35
ER -
TY - CONF
AB - The notion of delays arises naturally in many computational models, such as, in the design of circuits, control systems, and dataflow languages. In this work, we introduce automata with delay blocks (ADBs), extending finite state automata with variable time delay blocks, for deferring individual transition output symbols, in a discrete-time setting. We show that the ADB languages strictly subsume the regular languages, and are incomparable in expressive power to the context-free languages. We show that ADBs are closed under union, concatenation and Kleene star, and under intersection with regular languages, but not closed under complementation and intersection with other ADB languages. We show that the emptiness and the membership problems are decidable in polynomial time for ADBs, whereas the universality problem is undecidable. Finally we consider the linear-time model checking problem, i.e., whether the language of an ADB is contained in a regular language, and show that the model checking problem is PSPACE-complete. Copyright 2012 ACM.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Prabhu, Vinayak
ID - 2936
T2 - roceedings of the tenth ACM international conference on Embedded software
TI - Finite automata with time delay blocks
ER -
TY - CONF
AB - Developers building cryptography into security-sensitive applications face a daunting task. Not only must they understand the security guarantees delivered by the constructions they choose, they must also implement and combine them correctly and efficiently. Cryptographic compilers free developers from this task by turning high-level specifications of security goals into efficient implementations. Yet, trusting such tools is hard as they rely on complex mathematical machinery and claim security properties that are subtle and difficult to verify. In this paper we present ZKCrypt, an optimizing cryptographic compiler achieving an unprecedented level of assurance without sacrificing practicality for a comprehensive class of cryptographic protocols, known as Zero-Knowledge Proofs of Knowledge. The pipeline of ZKCrypt integrates purpose-built verified compilers and verifying compilers producing formal proofs in the CertiCrypt framework. By combining the guarantees delivered by each stage, ZKCrypt provides assurance that the output implementation securely realizes the abstract proof goal given as input. We report on the main characteristics of ZKCrypt, highlight new definitions and concepts at its foundations, and illustrate its applicability through a representative example of an anonymous credential system.
AU - Almeida, José
AU - Barbosa, Manuel
AU - Bangerter, Endre
AU - Barthe, Gilles
AU - Krenn, Stephan
AU - Béguelin, Santiago
ID - 2937
T2 - Proceedings of the 2012 ACM conference on Computer and communications security
TI - Full proof cryptography: Verifiable compilation of efficient zero-knowledge protocols
ER -
TY - JOUR
AB - Social insects have a very high potential to become invasive pest species. Here, we explore how their social lifestyle and their interaction with parasites may contribute to this invasive success. Similar to solitary species, parasite release followed by the evolution of increased competitive ability can promote establishment of introduced social insect hosts in their introduced range. Genetic bottlenecks during introduction of low numbers of founder individuals decrease the genetic diversity at three levels: the population, the colony and the individual, with the colony level being specific to social insects. Reduced genetic diversity can affect both the individual immune system and the collective colony-level disease defences (social immunity). Still, the dual immune system is likely to make social insects more robust to parasite attack. Changes in social structure from small, family-based, territorially aggressive societies in native populations towards huge networks of cooperating nests (unicoloniality) occur in some invasive social insects, for example, most invasive ants and some termites. Unicoloniality is likely to affect disease dynamics in multiple ways. The free exchange of individuals within the population leads to an increased genetic heterogeneity among individuals of a single nest, thereby decreasing disease transmission. However, the multitude of reproductively active queens per colony buffers the effect of individual diseased queens and their offspring, which may result in a higher level of vertical disease transmission in unicolonial societies. Lastly, unicoloniality provides a competitive advantage over native species, allowing them to quickly become the dominant species in the habitat, which in turn selects for parasite adaptation to this common host genotype and thus eventually a high parasite pressure. Overall, invasions by insect societies are characterized by general features applying to all introduced species, as well as idiosyncrasies that emerge from their social lifestyle. It is important to study these effects in concert to be able to develop efficient management and biocontrol strategies. © 2012 British Ecological Society.
AU - Ugelvig, Line V
AU - Cremer, Sylvia
ID - 2938
IS - 6
JF - Functional Ecology
TI - Effects of social immunity and unicoloniality on host parasite interactions in invasive insect societies
VL - 26
ER -
TY - JOUR
AU - Dolbilin, Nikolai
AU - Edelsbrunner, Herbert
AU - Musin, Oleg
ID - 2941
IS - 4
JF - Russian Mathematical Surveys
TI - On the optimality of functionals over triangulations of Delaunay sets
VL - 67
ER -
TY - CONF
AB - Interface theories provide a formal framework for component-based development of software and hardware which supports the incremental design of systems and the independent implementability of components. These capabilities are ensured through mathematical properties of the parallel composition operator and the refinement relation for components. More recently, a conjunction operation was added to interface theories in order to provide support for handling multiple viewpoints, requirements engineering, and component reuse. Unfortunately, the conjunction operator does not allow independent implementability in general. In this paper, we study conditions that need to be imposed on interface models in order to enforce independent implementability with respect to conjunction. We focus on multiple viewpoint specifications and propose a new compatibility criterion between two interfaces, which we call orthogonality. We show that orthogonal interfaces can be refined separately, while preserving both orthogonality and composability with other interfaces. We illustrate the independent implementability of different viewpoints with a FIFO buffer example.
AU - Henzinger, Thomas A
AU - Nickovic, Dejan
ID - 2942
T2 - Conference proceedings Monterey Workshop 2012
TI - Independent implementability of viewpoints
VL - 7539
ER -
TY - JOUR
AB - We examine whether the Escherichia coli chromosome is folded into a self-adherent nucleoprotein complex, or alternately is a confined but otherwise unconstrained self-avoiding polymer. We address this through in vivo visualization, using an inducible GFP fusion to the nucleoid-associated protein Fis to non-specifically decorate the entire chromosome. For a range of different growth conditions, the chromosome is a compact structure that does not fill the volume of the cell, and which moves from the new pole to the cell centre. During rapid growth, chromosome segregation occurs well before cell division, with daughter chromosomes coupled by a thin inter-daughter filament before complete segregation, whereas during slow growth chromosomes stay adjacent until cell division occurs. Image correlation analysis indicates that sub-nucleoid structure is stable on a 1min timescale, comparable to the timescale for redistribution time measured for GFP-Fis after photobleaching. Optical deconvolution and writhe calculation analysis indicate that the nucleoid has a large-scale coiled organization rather than being an amorphous mass. Our observations are consistent with the chromosome having a self-adherent filament organization.
AU - Hadizadeh Yazdi, Nastaran
AU - Guet, Calin C
AU - Johnson, Reid
AU - Marko, John
ID - 2943
IS - 6
JF - Molecular Microbiology
TI - Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions
VL - 86
ER -
TY - JOUR
AB - In search of foreign antigens, lymphocytes recirculate from the blood, through lymph nodes, into lymphatics and back to the blood. Dendritic cells also migrate to lymph nodes for optimal interaction with lymphocytes. This continuous trafficking of immune cells into and out of lymph nodes is essential for immune surveillance of foreign invaders. In this article, we review our current understanding of the functions of high endothelial venules (HEVs), stroma and lymphatics in the entry, positioning and exit of immune cells in lymph nodes during homeostasis, and we highlight the unexpected role of dendritic cells in the control of lymphocyte homing through HEVs.
AU - Girard, Jean
AU - Moussion, Christine
AU - Förster, Reinhold
ID - 2945
IS - 11
JF - Nature Reviews Immunology
TI - HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes
VL - 12
ER -
TY - JOUR
AB - MicroRNAs (miRNAs) are small noncoding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3′-untranslated region (3′-UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected.
AU - Dueck, Anne
AU - Ziegler, Christian
AU - Eichner, Alexander
AU - Berezikov, Eugène
AU - Meister, Gunter
ID - 2946
IS - 19
JF - Nucleic Acids Research
TI - MicroRNAs associated with the different human Argonaute proteins
VL - 40
ER -
TY - CONF
AB - We introduce games with probabilistic uncertainty, a model for controller synthesis in which the controller observes the state through imprecise sensors that provide correct information about the current state with a fixed probability. That is, in each step, the sensors return an observed state, and given the observed state, there is a probability distribution (due to the estimation error) over the actual current state. The controller must base its decision on the observed state (rather than the actual current state, which it does not know). On the other hand, we assume that the environment can perfectly observe the current state. We show that controller synthesis for qualitative ω-regular objectives in our model can be reduced in polynomial time to standard partial-observation stochastic games, and vice-versa. As a consequence we establish the precise decidability frontier for the new class of games, and establish optimal complexity results for all the decidable problems.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Majumdar, Ritankar
ID - 2947
TI - Equivalence of games with probabilistic uncertainty and partial observation games
VL - 7561
ER -
TY - JOUR
AU - Dupret, David
AU - Csicsvari, Jozsef L
ID - 2949
IS - 11
JF - Nature Neuroscience
TI - The medial entorhinal cortex keeps Up
VL - 15
ER -
TY - JOUR
AB - Contractile actomyosin rings drive various fundamental morphogenetic processes ranging from cytokinesis to wound healing. Actomyosin rings are generally thought to function by circumferential contraction. Here, we show that the spreading of the enveloping cell layer (EVL) over the yolk cell during zebrafish gastrulation is driven by a contractile actomyosin ring. In contrast to previous suggestions, we find that this ring functions not only by circumferential contraction but also by a flow-friction mechanism. This generates a pulling force through resistance against retrograde actomyosin flow. EVL spreading proceeds normally in situations where circumferential contraction is unproductive, indicating that the flow-friction mechanism is sufficient. Thus, actomyosin rings can function in epithelial morphogenesis through a combination of cable-constriction and flow-friction mechanisms.
AU - Behrndt, Martin
AU - Salbreux, Guillaume
AU - Campinho, Pedro
AU - Hauschild, Robert
AU - Oswald, Felix
AU - Roensch, Julia
AU - Grill, Stephan
AU - Heisenberg, Carl-Philipp J
ID - 2950
IS - 6104
JF - Science
TI - Forces driving epithelial spreading in zebrafish gastrulation
VL - 338
ER -
TY - JOUR
AB - Differential cell adhesion and cortex tension are thought to drive cell sorting by controlling cell-cell contact formation. Here, we show that cell adhesion and cortex tension have different mechanical functions in controlling progenitor cell-cell contact formation and sorting during zebrafish gastrulation. Cortex tension controls cell-cell contact expansion by modulating interfacial tension at the contact. By contrast, adhesion has little direct function in contact expansion, but instead is needed to mechanically couple the cortices of adhering cells at their contacts, allowing cortex tension to control contact expansion. The coupling function of adhesion is mediated by E-cadherin and limited by the mechanical anchoring of E-cadherin to the cortex. Thus, cell adhesion provides the mechanical scaffold for cell cortex tension to drive cell sorting during gastrulation.
AU - Maître, Jean-Léon
AU - Berthoumieux, Hélène
AU - Krens, Gabriel
AU - Salbreux, Guillaume
AU - Julicher, Frank
AU - Paluch, Ewa
AU - Heisenberg, Carl-Philipp J
ID - 2951
IS - 6104
JF - Science
TI - Adhesion functions in cell sorting by mechanically coupling the cortices of adhering cells
VL - 338
ER -
TY - JOUR
AB - Body axis elongation represents a common and fundamental morphogenetic process in development. A key mechanism triggering body axis elongation without additional growth is convergent extension (CE), whereby a tissue undergoes simultaneous narrowing and extension. Both collective cell migration and cell intercalation are thought to drive CE and are used to different degrees in various species as they elongate their body axis. Here, we provide an overview of CE as a general strategy for body axis elongation and discuss conserved and divergent mechanisms underlying CE among different species.
AU - Tada, Masazumi
AU - Heisenberg, Carl-Philipp J
ID - 2952
IS - 21
JF - Development
TI - Convergent extension Using collective cell migration and cell intercalation to shape embryos
VL - 139
ER -
TY - JOUR
AU - Heisenberg, Carl-Philipp J
AU - Fässler, Reinhard
ID - 2953
IS - 5
JF - Current Opinion in Cell Biology
TI - Cell-cell adhesion and extracellular matrix diversity counts
VL - 24
ER -
TY - JOUR
AB - Spontaneous postsynaptic currents (PSCs) provide key information about the mechanisms of synaptic transmission and the activity modes of neuronal networks. However, detecting spontaneous PSCs in vitro and in vivo has been challenging, because of the small amplitude, the variable kinetics, and the undefined time of generation of these events. Here, we describe a, to our knowledge, new method for detecting spontaneous synaptic events by deconvolution, using a template that approximates the average time course of spontaneous PSCs. A recorded PSC trace is deconvolved from the template, resulting in a series of delta-like functions. The maxima of these delta-like events are reliably detected, revealing the precise onset times of the spontaneous PSCs. Among all detection methods, the deconvolution-based method has a unique temporal resolution, allowing the detection of individual events in high-frequency bursts. Furthermore, the deconvolution-based method has a high amplitude resolution, because deconvolution can substantially increase the signal/noise ratio. When tested against previously published methods using experimental data, the deconvolution-based method was superior for spontaneous PSCs recorded in vivo. Using the high-resolution deconvolution-based detection algorithm, we show that the frequency of spontaneous excitatory postsynaptic currents in dentate gyrus granule cells is 4.5 times higher in vivo than in vitro.
AU - Pernia-Andrade, Alejandro
AU - Goswami, Sarit
AU - Stickler, Yvonne
AU - Fröbe, Ulrich
AU - Schlögl, Alois
AU - Jonas, Peter M
ID - 2954
IS - 7
JF - Biophysical Journal
TI - A deconvolution based method with high sensitivity and temporal resolution for detection of spontaneous synaptic currents in vitro and in vivo
VL - 103
ER -
TY - CONF
AB - We consider two-player stochastic games played on finite graphs with reachability objectives where the first player tries to ensure a target state to be visited almost-surely (i.e., with probability 1), or positively (i.e., with positive probability), no matter the strategy of the second player. We classify such games according to the information and 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, the players (a) may not be allowed to use randomization (pure strategies), or (b) may choose a probability distribution over actions but the actual random choice is external and not visible to the player (actions invisible), or (c) may use full randomization. Our main results for pure strategies are as follows. (1) For one-sided games with player 1 having partial observation we show that (in contrast to full randomized strategies) belief-based (subset-construction based) strategies are not sufficient, and we present an exponential upper bound on memory both for almostsure 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. (2) For one-sided games with player 2 having partial observation we show that non-elementary memory is both necessary and sufficient for both almost-sure and positive 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 result exhibits serious flaws in previous results of 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 - 2955
T2 - Proceedings of the 2012 27th Annual ACM/IEEE Symposium on Logic in Computer Science
TI - Partial-observation stochastic games: How to win when belief fails
ER -
TY - CONF
AB - Two-player games on graphs are central in many problems in formal verification and program analysis such as synthesis and verification of open systems. In this work we consider solving recursive game graphs (or pushdown game graphs) that can model the control flow of sequential programs with recursion. While pushdown games have been studied before with qualitative objectives, such as reachability and parity objectives, in this work we study for the first time such games with the most well-studied quantitative objective, namely, mean payoff objectives. In pushdown games two types of strategies are relevant: (1) global strategies, that depend on the entire global history; and (2) modular strategies, that have only local memory and thus do not depend on the context of invocation, but only on the history of the current invocation of the module. Our main results are as follows: (1) One-player pushdown games with mean-payoff objectives under global strategies are decidable in polynomial time. (2) Two-player pushdown games with mean-payoff objectives under global strategies are undecidable. (3) One-player pushdown games with mean-payoff objectives under modular strategies are NP-hard. (4) Two-player pushdown games with mean-payoff objectives under modular strategies can be solved in NP (i.e., both one-player and two-player pushdown games with mean-payoff objectives under modular strategies are NP-complete). We also establish the optimal strategy complexity showing that global strategies for mean-payoff objectives require infinite memory even in one-player pushdown games; and memoryless modular strategies are sufficient in two-player pushdown games. Finally we also show that all the problems have the same computational complexity if the stack boundedness condition is added, where along with the mean-payoff objective the player must also ensure that the stack height is bounded.
AU - Chatterjee, Krishnendu
AU - Velner, Yaron
ID - 2956
T2 - Proceedings of the 2012 27th Annual ACM/IEEE Symposium on Logic in Computer Science
TI - Mean payoff pushdown games
ER -
TY - CONF
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 words are accepted with probability arbitrarily close to 1. 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 (regular) words, then the positive and almost problems are decidable for all probabilistic automata with parity conditions. For most decidable problems we show an optimal PSPACE-complete complexity bound.
AU - Chatterjee, Krishnendu
AU - Tracol, Mathieu
ID - 2957
T2 - Proceedings of the 2012 27th Annual ACM/IEEE Symposium on Logic in Computer Science
TI - Decidable problems for probabilistic automata on infinite words
ER -
TY - JOUR
AB - The activity of hippocampal pyramidal cells reflects both the current position of the animal and information related to its current behavior. Here we investigated whether single hippocampal neurons can encode several independent features defining trials during a memory task. We also tested whether task-related information is represented by partial remapping of the place cell population or, instead, via firing rate modulation of spatially stable place cells. To address these two questions, the activity of hippocampal neurons was recorded in rats performing a conditional discrimination task on a modified T-maze in which the identity of a food reward guided behavior. When the rat was on the central arm of the maze, the firing rate of pyramidal cells changed depending on two independent factors: (1) the identity of the food reward given to the animal and (2) the previous location of the animal on the maze. Importantly, some pyramidal cells encoded information relative to both factors. This trial-type specific and retrospective coding did not interfere with the spatial representation of the maze: hippocampal cells had stable place fields and their theta-phase precession profiles were unaltered during the task, indicating that trial-related information was encoded via rate remapping. During error trials, encoding of both trial-related information and spatial location was impaired. Finally, we found that pyramidal cells also encode trial-related information via rate remapping during the continuous version of the rewarded alternation task without delays. These results suggest that hippocampal neurons can encode several task-related cognitive aspects via rate remapping.
AU - Allen, Kevin
AU - Rawlins, J Nick
AU - Bannerman, David
AU - Csicsvari, Jozsef L
ID - 2958
IS - 42
JF - Journal of Neuroscience
TI - Hippocampal place cells can encode multiple trial-dependent features through rate remapping
VL - 32
ER -
TY - JOUR
AB - We study maximum likelihood estimation in Gaussian graphical models from a geometric point of view. An algebraic elimination criterion allows us to find exact lower bounds on the number of observations needed to ensure that the maximum likelihood estimator (MLE) exists with probability one. This is applied to bipartite graphs, grids and colored graphs. We also study the ML degree, and we present the first instance of a graph for which the MLE exists with probability one, even when the number of observations equals the treewidth.
AU - Uhler, Caroline
ID - 2959
IS - 1
JF - Annals of Statistics
TI - Geometry of maximum likelihood estimation in Gaussian graphical models
VL - 40
ER -
TY - JOUR
AB - The choice of summary statistics is a crucial step in approximate Bayesian computation (ABC). Since statistics are often not sufficient, this choice involves a trade-off between loss of information and reduction of dimensionality. The latter may increase the efficiency of ABC. Here, we propose an approach for choosing summary statistics based on boosting, a technique from the machine learning literature. We consider different types of boosting and compare them to partial least squares regression as an alternative. To mitigate the lack of sufficiency, we also propose an approach for choosing summary statistics locally, in the putative neighborhood of the true parameter value. We study a demographic model motivated by the re-introduction of Alpine ibex (Capra ibex) into the Swiss Alps. The parameters of interest are the mean and standard deviation across microsatellites of the scaled ancestral mutation rate (θanc = 4 Ne u), and the proportion of males obtaining access to matings per breeding season (ω). By simulation, we assess the properties of the posterior distribution obtained with the various methods. According to our criteria, ABC with summary statistics chosen locally via boosting with the L2-loss performs best. Applying that method to the ibex data, we estimate θanc ≈ 1.288, and find that most of the variation across loci of the ancestral mutation rate u is between 7.7×10−4 and 3.5×10−3 per locus per generation. The proportion of males with access to matings is estimated to ω ≈ 0.21, which is in good agreement with recent independent estimates.
AU - Aeschbacher, Simon
AU - Beaumont, Mark
AU - Futschik, Andreas
ID - 2962
IS - 3
JF - Genetics
TI - A novel approach for choosing summary statistics in approximate Bayesian computation
VL - 192
ER -
TY - JOUR
AB - Zebra finches are an ubiquitous model system for the study of vocal learning in animal communication. Their song has been well described, but its possible function(s) in social communication are only partly understood. The so-called ‘directed song’ is a high-intensity, high-performance song given during courtship in close proximity to the female, which is known to mediate mate choice and mating. However, this singing mode constitutes only a fraction of zebra finch males’ prolific song output. Potential communicative functions of their second, ‘undirected’ singing mode remain unresolved in the face of contradicting reports of both facilitating and inhibiting effects of social company on singing. We addressed this issue by experimentally manipulating social contexts in a within-subject design, comparing a solo versus male or female only company condition, each lasting for 24 hours. Males’ total song output was significantly higher when a conspecific was in audible and visible distance than when they were alone. Male and female company had an equally facilitating effect on song output. Our findings thus indicate that singing motivation is facilitated rather than inhibited by social company, suggesting that singing in zebra finches might function both in inter- and intrasexual communication.
AU - Jesse, Fabienne
AU - Riebel, Katharina
ID - 2963
IS - 3
JF - Behavioural Processes
TI - Social facilitation of male song by male and female conspecifics in the zebra finch, Taeniopygia guttata
VL - 91
ER -
TY - THES
AB - CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. These neurons receive multiple excitatory inputs from numerous sources. Therefore, the rules of spatiotemporal integration of multiple synaptic inputs and propagation of action potentials are important to understand how CA3 neurons contribute to higher brain functions at cellular level. By using confocally targeted patch-clamp recording techniques, we investigated the biophysical properties of rat CA3 pyramidal neuron dendrites. We found two distinct dendritic domains critical for action potential initiation and propagation: In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+-channel mediated dendritic spikes are efficiently evoked by local dendritic depolarization or waveforms mimicking synaptic events. These findings can be explained by a high Na+-to-K+ conductance density ratio of CA3 pyramidal neuron dendrites. The results challenge the prevailing view that proximal mossy fiber inputs activate CA3 pyramidal neurons more efficiently than distal perforant inputs by showing that the distal synapses trigger a different form of activity represented by dendritic spikes. The high probability of dendritic spike initiation in the distal area may enhance the computational power of CA3 pyramidal neurons in the hippocampal network.
AU - Kim, Sooyun
ID - 2964
TI - Active properties of hippocampal CA3 pyramidal neuron dendrites
ER -
TY - JOUR
AB - Dieser Artikel soll die sechs verschiedenen Creative Commons Lizenzen erläutern und ihre Bedeutung im Rahmen des wissenschaftlichen Publizierens und des Open Access erklären (CC-BY, CC-BY-SA, CC-BY-NC, CC-BY-ND, CC-BYNC-SA, CC-BY-NC-ND).
AU - Danowski, Patrick
ID - 2965
IS - 2
JF - Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen & Bibliothekare
TI - Kontext Open Access: Creative Commons
VL - 65
ER -
TY - JOUR
AB - Background: The outcome of male-male competition can be predicted from the relative fighting qualities of the opponents, which often depend on their age. In insects, freshly emerged and still sexually inactive males are morphologically indistinct from older, sexually active males. These young inactive males may thus be easy targets for older males if they cannot conceal themselves from their attacks. The ant Cardiocondyla obscurior is characterised by lethal fighting between wingless (" ergatoid" ) males. Here, we analyse for how long young males are defenceless after eclosion, and how early adult males can detect the presence of rival males.Results: We found that old ergatoid males consistently won fights against ergatoid males younger than two days. Old males did not differentiate between different types of unpigmented pupae several days before emergence, but had more frequent contact to ready-to-eclose pupae of female sexuals and winged males than of workers and ergatoid males. In rare cases, old ergatoid males displayed alleviated biting of pigmented ergatoid male pupae shortly before adult eclosion, as well as copulation attempts to dark pupae of female sexuals and winged males. Ergatoid male behaviour may be promoted by a closer similarity of the chemical profile of ready-to-eclose pupae to the profile of adults than that of young pupae several days prior to emergence.Conclusion: Young ergatoid males of C. obscurior would benefit greatly by hiding their identity from older, resident males, as they are highly vulnerable during the first two days of their adult lives. In contrast to the winged males of the same species, which are able to prevent ergatoid male attacks by chemical female mimicry, young ergatoids do not seem to be able to produce a protective chemical profile. Conflicts in male-male competition between ergatoid males of different age thus seem to be resolved in favour of the older males. This might represent selection at the colony level rather than the individual level. © 2012 Cremer et al.; licensee BioMed Central Ltd.
AU - Cremer, Sylvia
AU - Suefuji, Masaki
AU - Schrempf, Alexandra
AU - Heinze, Jürgen
ID - 2966
JF - BMC Ecology
TI - The dynamics of male-male competition in Cardiocondyla obscurior ants
VL - 12
ER -
TY - JOUR
AB - For programs whose data variables range over Boolean or finite domains, program verification is decidable, and this forms the basis of recent tools for software model checking. In this article, we consider algorithmic verification of programs that use Boolean variables, and in addition, access a single read-only array whose length is potentially unbounded, and whose elements range over an unbounded data domain. We show that the reachability problem, while undecidable in general, is (1) PSPACE-complete for programs in which the array-accessing for-loops are not nested, (2) decidable for a restricted class of programs with doubly nested loops. The second result establishes connections to automata and logics defining languages over data words.
AU - Alur, Rajeev
AU - Cerny, Pavol
AU - Weinstein, Scott
ID - 2967
IS - 3
JF - ACM Transactions on Computational Logic (TOCL)
TI - Algorithmic analysis of array-accessing programs
VL - 13
ER -
TY - JOUR
AB - Little is known about the stability of trophic relationships in complex natural communities over evolutionary timescales. Here, we use sequence data from 18 nuclear loci to reconstruct and compare the intraspecific histories of major Pleistocene refugial populations in the Middle East, the Balkans and Iberia in a guild of four Chalcid parasitoids (Cecidostiba fungosa, Cecidostiba semifascia, Hobbya stenonota and Mesopolobus amaenus) all attacking Cynipid oak galls. We develop a likelihood method to numerically estimate models of divergence between three populations from multilocus data. We investigate the power of this framework on simulated data, and-using triplet alignments of intronic loci-quantify the support for all possible divergence relationships between refugial populations in the four parasitoids. Although an East to West order of population divergence has highest support in all but one species, we cannot rule out alternative population tree topologies. Comparing the estimated times of population splits between species, we find that one species, M. amaenus, has a significantly older history than the rest of the guild and must have arrived in central Europe at least one glacial cycle prior to other guild members. This suggests that although all four species may share a common origin in the East, they expanded westwards into Europe at different times. © 2012 Blackwell Publishing Ltd.
AU - Lohse, Konrad
AU - Barton, Nicholas H
AU - Melika, George
AU - Stone, Graham
ID - 2968
IS - 18
JF - Molecular Ecology
TI - A likelihood based comparison of population histories in a parasitoid guild
VL - 21
ER -
TY - JOUR
AB - The coupling between presynaptic Ca^(2+) channels and Ca^(2+) sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca^(2+) channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic
opening of presynaptic Ca^(2+) channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal
granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca^(2+) concentration and the unselective Ca^(2+) channel blocker Cd^(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ~50%, suggesting that the opening of presynaptic Ca^(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca^(2+) channel blocker
ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced
mIPSC frequency. Furthermore, both the fast Ca^(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency,
suggesting that Ca^(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB_(1) receptor
agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca^(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca^(2+) channels may be important for hippocampal information processing.
AU - Goswami, Sarit
AU - Bucurenciu, Iancu
AU - Jonas, Peter M
ID - 2969
IS - 41
JF - Journal of Neuroscience
TI - Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca^(2+) channels via microdomain coupling
VL - 32
ER -
TY - JOUR
AB - Morphogen gradients regulate the patterning and growth of many tissues, hence a key question is how they are established and maintained during development. Theoretical descriptions have helped to explain how gradient shape is controlled by the rates of morphogen production, spreading and degradation. These effective rates have been measured using fluorescence recovery after photobleaching (FRAP) and photoactivation. To unravel which molecular events determine the effective rates, such tissue-level assays have been combined with genetic analysis, high-resolution assays, and models that take into account interactions with receptors, extracellular components and trafficking. Nevertheless, because of the natural and experimental data variability, and the underlying assumptions of transport models, it remains challenging to conclusively distinguish between cellular mechanisms.
AU - Kicheva, Anna
AU - Bollenbach, Mark Tobias
AU - Wartlick, Ortrud
AU - Julicher, Frank
AU - Gonzalez Gaitan, Marcos
ID - 2970
IS - 6
JF - Current Opinion in Genetics & Development
TI - Investigating the principles of morphogen gradient formation: from tissues to cells
VL - 22
ER -
TY - CONF
AB - We study the task of interactive semantic labeling of a segmentation hierarchy. To this end we propose a framework interleaving two components: an automatic labeling step, based on a Conditional Random Field whose dependencies are defined by the inclusion tree of the segmentation hierarchy, and an interaction step that integrates incremental input from a human user. Evaluated on two distinct datasets, the proposed interactive approach efficiently integrates human interventions and illustrates the advantages of structured prediction in an interactive framework.
AU - Zankl, Georg
AU - Haxhimusa, Yll
AU - Ion, Adrian
ID - 2971
TI - Interactive labeling of image segmentation hierarchies
VL - 7476
ER -
TY - JOUR
AB - Energy parity games are infinite two-player turn-based games played on weighted graphs. The objective of the game combines a (qualitative) parity condition with the (quantitative) requirement that the sum of the weights (i.e., the level of energy in the game) must remain positive. Beside their own interest in the design and synthesis of resource-constrained omega-regular specifications, energy parity games provide one of the simplest model of games with combined qualitative and quantitative objectives. Our main results are as follows: (a) exponential memory is sufficient and may be necessary for winning strategies in energy parity games; (b) the problem of deciding the winner in energy parity games can be solved in NP ∩ coNP; and (c) we give an algorithm to solve energy parity by reduction to energy games. We also show that the problem of deciding the winner in energy parity games is logspace-equivalent to the problem of deciding the winner in mean-payoff parity games, which can thus be solved in NP ∩ coNP. As a consequence we also obtain a conceptually simple algorithm to solve mean-payoff parity games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 2972
JF - Theoretical Computer Science
TI - Energy parity games
VL - 458
ER -
TY - CONF
AB - We construct a perfectly binding string commitment scheme whose security is based on the learning parity with noise (LPN) assumption, or equivalently, the hardness of decoding random linear codes. Our scheme not only allows for a simple and efficient zero-knowledge proof of knowledge for committed values (essentially a Σ-protocol), but also for such proofs showing any kind of relation amongst committed values, i.e. proving that messages m_0,...,m_u, are such that m_0=C(m_1,...,m_u) for any circuit C.
To get soundness which is exponentially small in a security parameter t, and when the zero-knowledge property relies on the LPN problem with secrets of length l, our 3 round protocol has communication complexity O(t|C|l log(l)) and computational complexity of O(t|C|l) bit operations. The hidden constants are small, and the computation consists mostly of computing inner products of bit-vectors.
AU - Jain, Abhishek
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Tentes, Aris
ED - Wang, Xiaoyun
ED - Sako, Kazue
ID - 2974
TI - Commitments and efficient zero knowledge proofs from learning parity with noise
VL - 7658
ER -
TY - CONF
AB - Leakage resilient cryptography attempts to incorporate side-channel leakage into the black-box security model and designs cryptographic schemes that are provably secure within it. Informally, a scheme is leakage-resilient if it remains secure even if an adversary learns a bounded amount of arbitrary information about the schemes internal state. Unfortunately, most leakage resilient schemes are unnecessarily complicated in order to achieve strong provable security guarantees. As advocated by Yu et al. [CCS’10], this mostly is an artefact of the security proof and in practice much simpler construction may already suffice to protect against realistic side-channel attacks. In this paper, we show that indeed for simpler constructions leakage-resilience can be obtained when we aim for relaxed security notions where the leakage-functions and/or the inputs to the primitive are chosen non-adaptively. For example, we show that a three round Feistel network instantiated with a leakage resilient PRF yields a leakage resilient PRP if the inputs are chosen non-adaptively (This complements the result of Dodis and Pietrzak [CRYPTO’10] who show that if a adaptive queries are allowed, a superlogarithmic number of rounds is necessary.) We also show that a minor variation of the classical GGM construction gives a leakage resilient PRF if both, the leakage-function and the inputs, are chosen non-adaptively.
AU - Faust, Sebastian
AU - Pietrzak, Krzysztof Z
AU - Schipper, Joachim
ID - 2048
T2 - Conference proceedings CHES 2012
TI - Practical leakage-resilient symmetric cryptography
VL - 7428
ER -
TY - CONF
AB - We propose a new authentication protocol that is provably secure based on a ring variant of the learning parity with noise (LPN) problem. The protocol follows the design principle of the LPN-based protocol from Eurocrypt’11 (Kiltz et al.), and like it, is a two round protocol secure against active attacks. Moreover, our protocol has small communication complexity and a very small footprint which makes it applicable in scenarios that involve low-cost, resource-constrained devices.
Performance-wise, our protocol is more efficient than previous LPN-based schemes, such as the many variants of the Hopper-Blum (HB) protocol and the aforementioned protocol from Eurocrypt’11. Our implementation results show that it is even comparable to the standard challenge-and-response protocols based on the AES block-cipher. Our basic protocol is roughly 20 times slower than AES, but with the advantage of having 10 times smaller code size. Furthermore, if a few hundred bytes of non-volatile memory are available to allow the storage of some off-line pre-computations, then the online phase of our protocols is only twice as slow as AES.
AU - Heyse, Stefan
AU - Kiltz, Eike
AU - Lyubashevsky, Vadim
AU - Paar, Christof
AU - Pietrzak, Krzysztof Z
ID - 2049
T2 - Conference proceedings FSE 2012
TI - Lapin: An efficient authentication protocol based on ring-LPN
VL - 7549
ER -
TY - JOUR
AB - Background: Characterizing root system architecture (RSA) is essential to understanding the development and function of vascular plants. Identifying RSA-associated genes also represents an underexplored opportunity for crop improvement. Software tools are needed to accelerate the pace at which quantitative traits of RSA are estimated from images of root networks.Results: We have developed GiA Roots (General Image Analysis of Roots), a semi-automated software tool designed specifically for the high-throughput analysis of root system images. GiA Roots includes user-assisted algorithms to distinguish root from background and a fully automated pipeline that extracts dozens of root system phenotypes. Quantitative information on each phenotype, along with intermediate steps for full reproducibility, is returned to the end-user for downstream analysis. GiA Roots has a GUI front end and a command-line interface for interweaving the software into large-scale workflows. GiA Roots can also be extended to estimate novel phenotypes specified by the end-user.Conclusions: We demonstrate the use of GiA Roots on a set of 2393 images of rice roots representing 12 genotypes from the species Oryza sativa. We validate trait measurements against prior analyses of this image set that demonstrated that RSA traits are likely heritable and associated with genotypic differences. Moreover, we demonstrate that GiA Roots is extensible and an end-user can add functionality so that GiA Roots can estimate novel RSA traits. In summary, we show that the software can function as an efficient tool as part of a workflow to move from large numbers of root images to downstream analysis.
AU - Galkovskyi, Taras
AU - Mileyko, Yuriy
AU - Bucksch, Alexander
AU - Moore, Brad
AU - Symonova, Olga
AU - Price, Charles
AU - Topp, Chrostopher
AU - Iyer Pascuzzi, Anjali
AU - Zurek, Paul
AU - Fang, Suqin
AU - Harer, John
AU - Benfey, Philip
AU - Weitz, Joshua
ID - 492
JF - BMC Plant Biology
TI - GiA Roots: Software for the high throughput analysis of plant root system architecture
VL - 12
ER -
TY - JOUR
AB - The BCI competition IV stands in the tradition of prior BCI competitions that aim to provide high quality neuroscientific data for open access to the scientific community. As experienced already in prior competitions not only scientists from the narrow field of BCI compete, but scholars with a broad variety of backgrounds and nationalities. They include high specialists as well as students.The goals of all BCI competitions have always been to challenge with respect to novel paradigms and complex data. We report on the following challenges: (1) asynchronous data, (2) synthetic, (3) multi-class continuous data, (4) sessionto-session transfer, (5) directionally modulated MEG, (6) finger movements recorded by ECoG. As after past competitions, our hope is that winning entries may enhance the analysis methods of future BCIs.
AU - Tangermann, Michael
AU - Müller, Klaus
AU - Aertsen, Ad
AU - Birbaumer, Niels
AU - Braun, Christoph
AU - Brunner, Clemens
AU - Leeb, Robert
AU - Mehring, Carsten
AU - Miller, Kai
AU - Müller Putz, Gernot
AU - Nolte, Guido
AU - Pfurtscheller, Gert
AU - Preissl, Hubert
AU - Schalk, Gerwin
AU - Schlögl, Alois
AU - Vidaurre, Carmen
AU - Waldert, Stephan
AU - Blankertz, Benjamin
ID - 493
JF - Frontiers in Neuroscience
TI - Review of the BCI competition IV
VL - 6
ER -
TY - JOUR
AB - We solve the longstanding open problems of the blow-up involved in the translations, when possible, of a nondeterministic Büchi word automaton (NBW) to a nondeterministic co-Büchi word automaton (NCW) and to a deterministic co-Büchi word automaton (DCW). For the NBW to NCW translation, the currently known upper bound is 2o(nlog n) and the lower bound is 1.5n. We improve the upper bound to n2n and describe a matching lower bound of 2ω(n). For the NBW to DCW translation, the currently known upper bound is 2o(nlog n). We improve it to 2 o(n), which is asymptotically tight. Both of our upper-bound constructions are based on a simple subset construction, do not involve intermediate automata with richer acceptance conditions, and can be implemented symbolically. We continue and solve the open problems of translating nondeterministic Streett, Rabin, Muller, and parity word automata to NCW and to DCW. Going via an intermediate NBW is not optimal and we describe direct, simple, and asymptotically tight constructions, involving a 2o(n) blow-up. The constructions are variants of the subset construction, providing a unified approach for translating all common classes of automata to NCW and DCW. Beyond the theoretical importance of the results, we point to numerous applications of the new constructions. In particular, they imply a simple subset-construction based translation, when possible, of LTL to deterministic Büchi word automata.
AU - Boker, Udi
AU - Kupferman, Orna
ID - 494
IS - 4
JF - ACM Transactions on Computational Logic (TOCL)
TI - Translating to Co-Büchi made tight, unified, and useful
VL - 13
ER -
TY - CONF
AB - An automaton with advice is a finite state automaton which has access to an additional fixed infinite string called an advice tape. We refine the Myhill-Nerode theorem to characterize the languages of finite strings that are accepted by automata with advice. We do the same for tree automata with advice.
AU - Kruckman, Alex
AU - Rubin, Sasha
AU - Sheridan, John
AU - Zax, Ben
ID - 495
T2 - Proceedings GandALF 2012
TI - A Myhill Nerode theorem for automata with advice
VL - 96
ER -
TY - CONF
AB - We study the expressive power of logical interpretations on the class of scattered trees, namely those with countably many infinite branches. Scattered trees can be thought of as the tree analogue of scattered linear orders. Every scattered tree has an ordinal rank that reflects the structure of its infinite branches. We prove, roughly, that trees and orders of large rank cannot be interpreted in scattered trees of small rank. We consider a quite general notion of interpretation: each element of the interpreted structure is represented by a set of tuples of subsets of the interpreting tree. Our trees are countable, not necessarily finitely branching, and may have finitely many unary predicates as labellings. We also show how to replace injective set-interpretations in (not necessarily scattered) trees by 'finitary' set-interpretations.
AU - Rabinovich, Alexander
AU - Rubin, Sasha
ID - 496
TI - Interpretations in trees with countably many branches
ER -
TY - CONF
AB - One central issue in the formal design and analysis of reactive systems is the notion of refinement that asks whether all behaviors of the implementation is allowed by the specification. The local interpretation of behavior leads to the notion of simulation. Alternating transition systems (ATSs) provide a general model for composite reactive systems, and the simulation relation for ATSs is known as alternating simulation. The simulation relation for fair transition systems is called fair simulation. In this work our main contributions are as follows: (1) We present an improved algorithm for fair simulation with Büchi fairness constraints; our algorithm requires O(n 3·m) time as compared to the previous known O(n 6)-time algorithm, where n is the number of states and m is the number of transitions. (2) We present a game based algorithm for alternating simulation that requires O(m2)-time as compared to the previous known O((n·m)2)-time algorithm, where n is the number of states and m is the size of transition relation. (3) We present an iterative algorithm for alternating simulation that matches the time complexity of the game based algorithm, but is more space efficient than the game based algorithm. © Krishnendu Chatterjee, Siddhesh Chaubal, and Pritish Kamath.
AU - Chatterjee, Krishnendu
AU - Chaubal, Siddhesh
AU - Kamath, Pritish
ID - 497
TI - Faster algorithms for alternating refinement relations
VL - 16
ER -
TY - JOUR
AB - Understanding patterns and correlates of local adaptation in heterogeneous landscapes can provide important information in the selection of appropriate seed sources for restoration. We assessed the extent of local adaptation of fitness components in 12 population pairs of the perennial herb Rutidosis leptorrhynchoides (Asteraceae) and examined whether spatial scale (0.7-600 km), environmental distance, quantitative (QST) and neutral (FST) genetic differentiation, and size of the local and foreign populations could predict patterns of adaptive differentiation. Local adaptation varied among populations and fitness components. Including all population pairs, local adaptation was observed for seedling survival, but not for biomass, while foreign genotype advantage was observed for reproduction (number of inflorescences). Among population pairs, local adaptation increased with QST and local population size for biomass. QST was associated with environmental distance, suggesting ecological selection for phenotypic divergence. However, low FST and variation in population structure in small populations demonstrates the interaction of gene flow and drift in constraining local adaptation in R. leptorrhynchoides. Our study indicates that for species in heterogeneous landscapes, collecting seed from large populations from similar environments to candidate sites is likely to provide the most appropriate seed sources for restoration.
AU - Pickup, Melinda
AU - Field, David
AU - Rowell, David
AU - Young, Andrew
ID - 498
IS - 8
JF - Evolutionary Applications
TI - Predicting local adaptation in fragmented plant populations: Implications for restoration genetics
VL - 5
ER -
TY - JOUR
AU - Sixt, Michael K
ID - 506
IS - 3
JF - Journal of Cell Biology
TI - Cell migration: Fibroblasts find a new way to get ahead
VL - 197
ER -
TY - GEN
AB - Two-player games on graphs are central in many problems in formal verification and program analysis such as synthesis and verification of open systems. In this work we consider solving recursive game graphs (or pushdown game graphs) that can model the control flow of sequential programs with recursion. While pushdown games have been studied before with qualitative objectives, such as reachability and ω-regular objectives, in this work we study for the first time such games with the most well-studied quantitative objective, namely, mean-payoff objectives. In pushdown games two types of strategies are relevant: (1) global strategies, that depend on the entire global history; and (2) modular strategies, that have only local memory and thus do not depend on the context of invocation, but only on the history of the current invocation of the module. Our main results are as follows: (1) One-player pushdown games with mean-payoff objectives under global strategies are decidable in polynomial time. (2) Two- player pushdown games with mean-payoff objectives under global strategies are undecidable. (3) One-player pushdown games with mean-payoff objectives under modular strategies are NP- hard. (4) Two-player pushdown games with mean-payoff objectives under modular strategies can be solved in NP (i.e., both one-player and two-player pushdown games with mean-payoff objectives under modular strategies are NP-complete). We also establish the optimal strategy complexity showing that global strategies for mean-payoff objectives require infinite memory even in one-player pushdown games; and memoryless modular strategies are sufficient in two- player pushdown games. Finally we also show that all the problems have the same complexity if the stack boundedness condition is added, where along with the mean-payoff objective the player must also ensure that the stack height is bounded.
AU - Chatterjee, Krishnendu
AU - Velner, Yaron
ID - 5377
SN - 2664-1690
TI - Mean-payoff pushdown games
ER -
TY - GEN
AB - One central issue in the formal design and analysis of reactive systems is the notion of refinement that asks whether all behaviors of the implementation is allowed by the specification. The local interpretation of behavior leads to the notion of simulation. Alternating transition systems (ATSs) provide a general model for composite reactive systems, and the simulation relation for ATSs is known as alternating simulation. The simulation relation for fair transition systems is called fair simulation. In this work our main contributions are as follows: (1) We present an improved algorithm for fair simulation with Büchi fairness constraints; our algorithm requires O(n3 · m) time as compared to the previous known O(n6)-time algorithm, where n is the number of states and m is the number of transitions. (2) We present a game based algorithm for alternating simulation that requires O(m2)-time as compared to the previous known O((n · m)2)-time algorithm, where n is the number of states and m is the size of transition relation. (3) We present an iterative algorithm for alternating simulation that matches the time complexity of the game based algorithm, but is more space efficient than the game based algorithm.
AU - Chatterjee, Krishnendu
AU - Chaubal, Siddhesh
AU - Kamath, Pritish
ID - 5378
SN - 2664-1690
TI - Faster algorithms for alternating refinement relations
ER -
TY - GEN
AB - We consider the problem of inference in agraphical 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 pair-wise terms over a discretized domain. This allows the use of techniques originally devel-oped 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 out-perform 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 - 5396
SN - 2664-1690
TI - Approximating marginals using discrete energy minimization
ER -
TY - GEN
AB - This document is created as a part of the project “Repository for Research Data on IST Austria”. It summarises the actual state of research data at IST Austria, based on survey results. It supports the choice of appropriate software, which would best fit the requirements of their users, the researchers.
AU - Porsche, Jana
ID - 5398
TI - Actual state of research data @ ISTAustria
ER -
TY - CHAP
AU - Gupta, Ashutosh
ID - 5745
SN - 0302-9743
T2 - Automated Technology for Verification and Analysis
TI - Improved Single Pass Algorithms for Resolution Proof Reduction
VL - 7561
ER -
TY - JOUR
AB - First we note that the best polynomial approximation to vertical bar x vertical bar on the set, which consists of an interval on the positive half-axis and a point on the negative half-axis, can be given by means of the classical Chebyshev polynomials. Then we explore the cases when a solution of the related problem on two intervals can be given in elementary functions.
AU - Pausinger, Florian
ID - 6588
IS - 1
JF - Journal of Mathematical Physics, Analysis, Geometry
SN - 1812-9471
TI - Elementary solutions of the Bernstein problem on two intervals
VL - 8
ER -
TY - CONF
AB - Software model checking, as an undecidable problem, has three possible outcomes: (1) the program satisfies the specification, (2) the program does not satisfy the specification, and (3) the model checker fails. The third outcome usually manifests itself in a space-out, time-out, or one component of the verification tool giving up; in all of these failing cases, significant computation is performed by the verification tool before the failure, but no result is reported. We propose to reformulate the model-checking problem as follows, in order to have the verification tool report a summary of the performed work even in case of failure: given a program and a specification, the model checker returns a condition Ψ - usually a state predicate - such that the program satisfies the specification under the condition Ψ - that is, as long as the program does not leave the states in which Ψ is satisfied. In our experiments, we investigated as one major application of conditional model checking the sequential combination of model checkers with information passing. We give the condition that one model checker produces, as input to a second conditional model checker, such that the verification problem for the second is restricted to the part of the state space that is not covered by the condition, i.e., the second model checker works on the problems that the first model checker could not solve. Our experiments demonstrate that repeated application of conditional model checkers, passing information from one model checker to the next, can significantly improve the verification results and performance, i.e., we can now verify programs that we could not verify before.
AU - Beyer, Dirk
AU - Henzinger, Thomas A
AU - Keremoglu, Mehmet
AU - Wendler, Philipp
ID - 1384
T2 - Proceedings of the ACM SIGSOFT 20th International Symposium on the Foundations of Software Engineering
TI - Conditional model checking: A technique to pass information between verifiers
ER -
TY - JOUR
AB - Hierarchical Timing Language (HTL) is a coordination language for distributed, hard real-time applications. HTL is a hierarchical extension of Giotto and, like its predecessor, based on the logical execution time (LET) paradigm of real-time programming. Giotto is compiled into code for a virtual machine, called the EmbeddedMachine (or E machine). If HTL is targeted to the E machine, then the hierarchicalprogram structure needs to be flattened; the flattening makes separatecompilation difficult, and may result in E machinecode of exponential size. In this paper, we propose a generalization of the E machine, which supports a hierarchicalprogram structure at runtime through real-time trigger mechanisms that are arranged in a tree. We present the generalized E machine, and a modular compiler for HTL that generates code of linear size. The compiler may generate code for any part of a given HTL program separately in any order.
AU - Ghosal, Arkadeb
AU - Iercan, Daniel
AU - Kirsch, Christoph
AU - Henzinger, Thomas A
AU - Sangiovanni Vincentelli, Alberto
ID - 3836
IS - 2
JF - Science of Computer Programming
TI - Separate compilation of hierarchical real-time programs into linear-bounded embedded machine code
VL - 77
ER -
TY - JOUR
AB - We summarize classical and recent results about two-player games played on graphs with ω-regular objectives. These games have applications in the verification and synthesis of reactive systems. Important distinctions are whether a graph game is turn-based or concurrent; deterministic or stochastic; zero-sum or not. We cluster known results and open problems according to these classifications.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
ID - 3846
IS - 2
JF - Journal of Computer and System Sciences
TI - A survey of stochastic ω regular games
VL - 78
ER -
TY - JOUR
AB - We consider the offset-deconstruction problem: Given a polygonal shape Q with n vertices, can it be expressed, up to a tolerance ε in Hausdorff distance, as the Minkowski sum of another polygonal shape P with a disk of fixed radius? If it does, we also seek a preferably simple-looking solution P; then, P's offset constitutes an accurate, vertex-reduced, and smoothened approximation of Q. We give an O(nlogn)-time exact decision algorithm that handles any polygonal shape, assuming the real-RAM model of computation. A variant of the algorithm, which we have implemented using the cgal library, is based on rational arithmetic and answers the same deconstruction problem up to an uncertainty parameter δ its running time additionally depends on δ. If the input shape is found to be approximable, this algorithm also computes an approximate solution for the problem. It also allows us to solve parameter-optimization problems induced by the offset-deconstruction problem. For convex shapes, the complexity of the exact decision algorithm drops to O(n), which is also the time required to compute a solution P with at most one more vertex than a vertex-minimal one.
AU - Berberich, Eric
AU - Halperin, Dan
AU - Kerber, Michael
AU - Pogalnikova, Roza
ID - 3115
IS - 4
JF - Discrete & Computational Geometry
TI - Deconstructing approximate offsets
VL - 48
ER -
TY - JOUR
AB - We consider the problem of minimizing a function represented as a sum of submodular terms. We assume each term allows an efficient computation of exchange capacities. This holds, for example, for terms depending on a small number of variables, or for certain cardinality-dependent terms. A naive application of submodular minimization algorithms would not exploit the existence of specialized exchange capacity subroutines for individual terms. To overcome this, we cast the problem as a submodular flow (SF) problem in an auxiliary graph in such a way that applying most existing SF algorithms would rely only on these subroutines. We then explore in more detail Iwata's capacity scaling approach for submodular flows (Iwata 1997 [19]). In particular, we show how to improve its complexity in the case when the function contains cardinality-dependent terms.
AU - Kolmogorov, Vladimir
ID - 3117
IS - 15
JF - Discrete Applied Mathematics
TI - Minimizing a sum of submodular functions
VL - 160
ER -
TY - JOUR
AB - We present a method for recovering a temporally coherent, deforming triangle mesh with arbitrarily changing topology from an incoherent sequence of static closed surfaces. We solve this problem using the surface geometry alone, without any prior information like surface templates or velocity fields. Our system combines a proven strategy for triangle mesh improvement, a robust multi-resolution non-rigid registration routine, and a reliable technique for changing surface mesh topology. We also introduce a novel topological constraint enforcement algorithm to ensure that the output and input always have similar topology. We apply our technique to a series of diverse input data from video reconstructions, physics simulations, and artistic morphs. The structured output of our algorithm allows us to efficiently track information like colors and displacement maps, recover velocity information, and solve PDEs on the mesh as a post process.
AU - Bojsen-Hansen, Morten
AU - Li, Hao
AU - Wojtan, Christopher J
ID - 3118
IS - 4
JF - ACM Transactions on Graphics
TI - Tracking surfaces with evolving topology
VL - 31
ER -
TY - CONF
AB - We present an approach for artist-directed animation of liquids using multiple levels of control over the simulation, ranging from the overall tracking of desired shapes to highly detailed secondary effects such as dripping streams, separating sheets of fluid, surface waves and ripples. The first portion of our technique is a volume preserving morph that allows the animator to produce a plausible fluid-like motion from a sparse set of control meshes. By rasterizing the resulting control meshes onto the simulation grid, the mesh velocities act as boundary conditions during the projection step of the fluid simulation. We can then blend this motion together with uncontrolled fluid velocities to achieve a more relaxed control over the fluid that captures natural inertial effects. Our method can produce highly detailed liquid surfaces with control over sub-grid details by using a mesh-based surface tracker on top of a coarse grid-based fluid simulation. We can create ripples and waves on the fluid surface attracting the surface mesh to the control mesh with spring-like forces and also by running a wave simulation over the surface mesh. Our video results demonstrate how our control scheme can be used to create animated characters and shapes that are made of water.
AU - Raveendran, Karthik
AU - Thuerey, Nils
AU - Wojtan, Christopher J
AU - Turk, Greg
ID - 3119
T2 - Proceedings of the ACM SIGGRAPH/Eurographics Symposium on Computer Animation
TI - Controlling liquids using meshes
ER -
TY - JOUR
AB - We introduce a strategy based on Kustin-Miller unprojection that allows us to construct many hundreds of Gorenstein codimension 4 ideals with 9 × 16 resolutions (that is, nine equations and sixteen first syzygies). Our two basic games are called Tom and Jerry; the main application is the biregular construction of most of the anticanonically polarised Mori Fano 3-folds of Altinok's thesis. There are 115 cases whose numerical data (in effect, the Hilbert series) allow a Type I projection. In every case, at least one Tom and one Jerry construction works, providing at least two deformation families of quasismooth Fano 3-folds having the same numerics but different topology. © 2012 Copyright Foundation Compositio Mathematica.
AU - Brown, Gavin
AU - Kerber, Michael
AU - Reid, Miles
ID - 3120
IS - 4
JF - Compositio Mathematica
TI - Fano 3 folds in codimension 4 Tom and Jerry Part I
VL - 148
ER -
TY - JOUR
AB - Voltage-activated Ca(2+) channels (VACCs) mediate Ca(2+) influx to trigger action potential-evoked neurotransmitter release, but the mechanism by which Ca(2+) regulates spontaneous transmission is unclear. We found that VACCs are the major physiological triggers for spontaneous release at mouse neocortical inhibitory synapses. Moreover, despite the absence of a synchronizing action potential, we found that spontaneous fusion of a GABA-containing vesicle required the activation of multiple tightly coupled VACCs of variable type.
AU - Williams, Courtney
AU - Chen, Wenyan
AU - Lee, Chia
AU - Yaeger, Daniel
AU - Vyleta, Nicholas
AU - Smith, Stephen
ID - 3121
IS - 9
JF - Nature Neuroscience
TI - Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA
VL - 15
ER -
TY - JOUR
AB - Since Darwin's pioneering research on plant reproductive biology (e.g. Darwin 1877), understanding the mechanisms maintaining the diverse sexual strategies of plants has remained an important challenge for evolutionary biologists. In some species, populations are sexually polymorphic and contain two or more mating morphs (sex phenotypes). Differences in morphology or phenology among the morphs influence patterns of non-random mating. In these populations, negative frequency-dependent selection arising from disassortative (intermorph) mating is usually required for the evolutionary maintenance of sexual polymorphism, but few studies have demonstrated the required patterns of non-random mating. In the current issue of Molecular Ecology, Shang (2012) make an important contribution to our understanding of how disassortative mating influences sex phenotype ratios in Acer pictum subsp. mono (painted maple), a heterodichogamous, deciduous tree of eastern China. They monitored sex expression in 97 adults and used paternity analysis of open-pollinated seed to examine disassortative mating among three sex phenotypes. Using a deterministic 'pollen transfer' model, Shang et al. present convincing evidence that differences in the degree of disassortative mating in progeny arrays of the sex phenotypes can explain their uneven frequencies in the adult population. This study provides a useful example of how the deployment of genetic markers, demographic monitoring and modelling can be integrated to investigate the maintenance of sexual diversity in plants.
AU - Field, David
AU - Barrett, Spencer
ID - 3122
IS - 15
JF - Molecular Ecology
TI - Disassortative mating and the maintenance of sexual polymorphism in painted maple
VL - 21
ER -
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 -
TY - JOUR
AB - Some inflammatory stimuli trigger activation of the NLRP3 inflammasome by inducing efflux of cellular potassium. Loss of cellular potassium is known to potently suppress protein synthesis, leading us to test whether the inhibition of protein synthesis itself serves as an activating signal for the NLRP3 inflammasome. Murine bone marrow-derived macrophages, either primed by LPS or unprimed, were exposed to a panel of inhibitors of ribosomal function: ricin, cycloheximide, puromycin, pactamycin, and anisomycin. Macrophages were also exposed to nigericin, ATP, monosodium urate (MSU), and poly I:C. Synthesis of pro-IL-ß and release of IL-1ß from cells in response to these agents was detected by immunoblotting and ELISA. Release of intracellular potassium was measured by mass spectrometry. Inhibition of translation by each of the tested translation inhibitors led to processing of IL-1ß, which was released from cells. Processing and release of IL-1ß was reduced or absent from cells deficient in NLRP3, ASC, or caspase-1, demonstrating the role of the NLRP3 inflammasome. Despite the inability of these inhibitors to trigger efflux of intracellular potassium, the addition of high extracellular potassium suppressed activation of the NLRP3 inflammasome. MSU and double-stranded RNA, which are known to activate the NLRP3 inflammasome, also substantially inhibited protein translation, supporting a close association between inhibition of translation and inflammasome activation. These data demonstrate that translational inhibition itself constitutes a heretofore-unrecognized mechanism underlying IL-1ß dependent inflammatory signaling and that other physical, chemical, or pathogen-associated agents that impair translation may lead to IL-1ß-dependent inflammation through activation of the NLRP3 inflammasome. For agents that inhibit translation through decreased cellular potassium, the application of high extracellular potassium restores protein translation and suppresses activation of the NLRP inflammasome. For agents that inhibit translation through mechanisms that do not involve loss of potassium, high extracellular potassium suppresses IL-1ß processing through a mechanism that remains undefined.
AU - Vyleta, Meghan
AU - Wong, John
AU - Magun, Bruce
ID - 3161
IS - 5
JF - PLoS One
TI - Suppression of ribosomal function triggers innate immune signaling through activation of the NLRP3 inflammasome
VL - 7
ER -