TY - GEN
AB - This book constitutes the proceedings of the 11th International Conference on Computational Methods in Systems Biology, CMSB 2013, held in Klosterneuburg, Austria, in September 2013. The 15 regular papers included in this volume were carefully reviewed and selected from 27 submissions. They deal with computational models for all levels, from molecular and cellular, to organs and entire organisms.
ED - Gupta, Ashutosh
ED - Henzinger, Thomas A
ID - 2288
SN - 978-3-642-40707-9
TI - Computational Methods in Systems Biology
VL - 8130
ER -
TY - JOUR
AB - Formal verification aims to improve the quality of software by detecting errors before they do harm. At the basis of formal verification is the logical notion of correctness, which purports to capture whether or not a program behaves as desired. We suggest that the boolean partition of software into correct and incorrect programs falls short of the practical need to assess the behavior of software in a more nuanced fashion against multiple criteria. We therefore propose to introduce quantitative fitness measures for programs, specifically for measuring the function, performance, and robustness of reactive programs such as concurrent processes. This article describes the goals of the ERC Advanced Investigator Project QUAREM. The project aims to build and evaluate a theory of quantitative fitness measures for reactive models. Such a theory must strive to obtain quantitative generalizations of the paradigms that have been success stories in qualitative reactive modeling, such as compositionality, property-preserving abstraction and abstraction refinement, model checking, and synthesis. The theory will be evaluated not only in the context of software and hardware engineering, but also in the context of systems biology. In particular, we will use the quantitative reactive models and fitness measures developed in this project for testing hypotheses about the mechanisms behind data from biological experiments.
AU - Henzinger, Thomas A
ID - 2289
IS - 4
JF - Computer Science Research and Development
TI - Quantitative reactive modeling and verification
VL - 28
ER -
TY - JOUR
AB - The plant hormone indole-acetic acid (auxin) is essential for many aspects of plant development. Auxin-mediated growth regulation typically involves the establishment of an auxin concentration gradient mediated by polarly localized auxin transporters. The localization of auxin carriers and their amount at the plasma membrane are controlled by membrane trafficking processes such as secretion, endocytosis, and recycling. In contrast to endocytosis or recycling, how the secretory pathway mediates the localization of auxin carriers is not well understood. In this study we have used the differential cell elongation process during apical hook development to elucidate the mechanisms underlying the post-Golgi trafficking of auxin carriers in Arabidopsis. We show that differential cell elongation during apical hook development is defective in Arabidopsis mutant echidna (ech). ECH protein is required for the trans-Golgi network (TGN)-mediated trafficking of the auxin influx carrier AUX1 to the plasma membrane. In contrast, ech mutation only marginally perturbs the trafficking of the highly related auxin influx carrier LIKE-AUX1-3 or the auxin efflux carrier PIN-FORMED-3, both also involved in hook development. Electron tomography reveals that the trafficking defects in ech mutant are associated with the perturbation of secretory vesicle genesis from the TGN. Our results identify differential mechanisms for the post-Golgi trafficking of de novo-synthesized auxin carriers to plasma membrane from the TGN and reveal how trafficking of auxin influx carriers mediates the control of differential cell elongation in apical hook development.
AU - Boutté, Yohann
AU - Jonsson, Kristoffer
AU - Mcfarlane, Heather
AU - Johnson, Errin
AU - Gendre, Delphine
AU - Swarup, Ranjan
AU - Friml, Jirí
AU - Samuels, Lacey
AU - Robert, Stéphanie
AU - Bhalerao, Rishikesh
ID - 2290
IS - 40
JF - PNAS
TI - ECHIDNA mediated post Golgi trafficking of auxin carriers for differential cell elongation
VL - 110
ER -
TY - CONF
AB - Cryptographic access control promises to offer easily distributed trust and broader applicability, while reducing reliance on low-level online monitors. Traditional implementations of cryptographic access control rely on simple cryptographic primitives whereas recent endeavors employ primitives with richer functionality and security guarantees. Worryingly, few of the existing cryptographic access-control schemes come with precise guarantees, the gap between the policy specification and the implementation being analyzed only informally, if at all. In this paper we begin addressing this shortcoming. Unlike prior work that targeted ad-hoc policy specification, we look at the well-established Role-Based Access Control (RBAC) model, as used in a typical file system. In short, we provide a precise syntax for a computational version of RBAC, offer rigorous definitions for cryptographic policy enforcement of a large class of RBAC security policies, and demonstrate that an implementation based on attribute-based encryption meets our security notions. We view our main contribution as being at the conceptual level. Although we work with RBAC for concreteness, our general methodology could guide future research for uses of cryptography in other access-control models.
AU - Ferrara, Anna
AU - Fuchsbauer, Georg
AU - Warinschi, Bogdan
ID - 2291
TI - Cryptographically enforced RBAC
ER -
TY - GEN
AB - This book constitutes the thoroughly refereed conference proceedings of the 38th International Symposium on Mathematical Foundations of Computer Science, MFCS 2013, held in Klosterneuburg, Austria, in August 2013. The 67 revised full papers presented together with six invited talks were carefully selected from 191 submissions. Topics covered include algorithmic game theory, algorithmic learning theory, algorithms and data structures, automata, formal languages, bioinformatics, complexity, computational geometry, computer-assisted reasoning, concurrency theory, databases and knowledge-based systems, foundations of computing, logic in computer science, models of computation, semantics and verification of programs, and theoretical issues in artificial intelligence.
ED - Chatterjee, Krishnendu
ED - Sgall, Jiri
ID - 2292
SN - 978-3-642-40312-5
TI - Mathematical Foundations of Computer Science 2013
VL - 8087
ER -
TY - CONF
AB - Many computer vision problems have an asymmetric distribution of information between training and test time. In this work, we study the case where we are given additional information about the training data, which however will not be available at test time. This situation is called learning using privileged information (LUPI). We introduce two maximum-margin techniques that are able to make use of this additional source of information, and we show that the framework is applicable to several scenarios that have been studied in computer vision before. Experiments with attributes, bounding boxes, image tags and rationales as additional information in object classification show promising results.
AU - Sharmanska, Viktoriia
AU - Quadrianto, Novi
AU - Lampert, Christoph
ID - 2293
TI - Learning to rank using privileged information
ER -
TY - CONF
AB - In this work we propose a system for automatic classification of Drosophila embryos into developmental stages.
While the system is designed to solve an actual problem in biological research, we believe that the principle underly-
ing it is interesting not only for biologists, but also for researchers in computer vision. The main idea is to combine two orthogonal sources of information: one is a classifier trained on strongly invariant features, which makes it applicable to images of very different conditions, but also leads to rather noisy predictions. The other is a label propagation step based on a more powerful similarity measure that however is only consistent within specific subsets of the data at a time.
In our biological setup, the information sources are the shape and the staining patterns of embryo images. We show
experimentally that while neither of the methods can be used by itself to achieve satisfactory results, their combina-
tion achieves prediction quality comparable to human performance.
AU - Kazmar, Tomas
AU - Kvon, Evgeny
AU - Stark, Alexander
AU - Lampert, Christoph
ID - 2294
TI - Drosophila Embryo Stage Annotation using Label Propagation
ER -
TY - CONF
AB - We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, we establish decidability (with optimal EXPTIME-complete complexity) of the qualitative analysis problems for POMDPs with all parity objectives under finite-memory strategies. We also establish asymptotically optimal (exponential) memory bounds.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Tracol, Mathieu
ID - 2295
TI - What is decidable about partially observable Markov decision processes with omega-regular objectives
VL - 23
ER -
TY - JOUR
AB - We present an overview of mathematical results on the low temperature properties of dilute quantum gases, which have been obtained in the past few years. The presentation includes a discussion of Bose-Einstein condensation, the excitation spectrum for trapped gases and its relation to superfluidity, as well as the appearance of quantized vortices in rotating systems. All these properties are intensely being studied in current experiments on cold atomic gases. We will give a description of the mathematics involved in understanding these phenomena, starting from the underlying many-body Schrödinger equation.
AU - Seiringer, Robert
ID - 2297
IS - 2
JF - Japanese Journal of Mathematics
TI - Hot topics in cold gases: A mathematical physics perspective
VL - 8
ER -
TY - CONF
AB - We present a shape analysis for programs that manipulate overlaid data structures which share sets of objects. The abstract domain contains Separation Logic formulas that (1) combine a per-object separating conjunction with a per-field separating conjunction and (2) constrain a set of variables interpreted as sets of objects. The definition of the abstract domain operators is based on a notion of homomorphism between formulas, viewed as graphs, used recently to define optimal decision procedures for fragments of the Separation Logic. Based on a Frame Rule that supports the two versions of the separating conjunction, the analysis is able to reason in a modular manner about non-overlaid data structures and then, compose information only at a few program points, e.g., procedure returns. We have implemented this analysis in a prototype tool and applied it on several interesting case studies that manipulate overlaid and nested linked lists.
AU - Dragoi, Cezara
AU - Enea, Constantin
AU - Sighireanu, Mihaela
ID - 2298
TI - Local shape analysis for overlaid data structures
VL - 7935
ER -
TY - JOUR
AB - The standard hardware design flow involves: (a) design of an integrated circuit using a hardware description language, (b) extensive functional and formal verification, and (c) logical synthesis. However, the above-mentioned processes consume significant effort and time. An alternative approach is to use a formal specification language as a high-level hardware description language and synthesize hardware from formal specifications. Our work is a case study of the synthesis of the widely and industrially used AMBA AHB protocol from formal specifications. Bloem et al. presented the first formal specifications for the AMBA AHB Arbiter and synthesized the AHB Arbiter circuit. However, in the first formal specification some important assumptions were missing. Our contributions are as follows: (a) We present detailed formal specifications for the AHB Arbiter incorporating the missing details, and obtain significant improvements in the synthesis results (both with respect to the number of gates in the synthesized circuit and with respect to the time taken to synthesize the circuit), and (b) we present formal specifications to generate compact circuits for the remaining two main components of AMBA AHB, namely, AHB Master and AHB Slave. Thus with systematic description we are able to automatically and completely synthesize an important and widely used industrial protocol.
AU - Godhal, Yashdeep
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
ID - 2299
IS - 5-6
JF - International Journal on Software Tools for Technology Transfer
TI - Synthesis of AMBA AHB from formal specification: A case study
VL - 15
ER -
TY - JOUR
AB - We consider Ising models in two and three dimensions with nearest neighbor ferromagnetic interactions and long-range, power law decaying, antiferromagnetic interactions. If the strength of the ferromagnetic coupling J is larger than a critical value Jc, then the ground state is homogeneous and ferromagnetic. As the critical value is approached from smaller values of J, it is believed that the ground state consists of a periodic array of stripes (d=2) or slabs (d=3), all of the same size and alternating magnetization. Here we prove rigorously that the ground state energy per site converges to that of the optimal periodic striped or slabbed state, in the limit that J tends to the ferromagnetic transition point. While this theorem does not prove rigorously that the ground state is precisely striped or slabbed, it does prove that in any suitably large box the ground state is striped or slabbed with high probability.
AU - Giuliani, Alessandro
AU - Lieb, Élliott
AU - Seiringer, Robert
ID - 2300
IS - 6
JF - Physical Review B
TI - Realization of stripes and slabs in two and three dimensions
VL - 88
ER -
TY - CONF
AB - We describe the design and implementation of P, a domain-specific language to write asynchronous event driven code. P allows the programmer to specify the system as a collection of interacting state machines, which communicate with each other using events. P unifies modeling and programming into one activity for the programmer. Not only can a P program be compiled into executable code, but it can also be tested using model checking techniques. P allows the programmer to specify the environment, used to "close" the system during testing, as nondeterministic ghost machines. Ghost machines are erased during compilation to executable code; a type system ensures that the erasure is semantics preserving. The P language is designed so that a P program can be checked for responsiveness-the ability to handle every event in a timely manner. By default, a machine needs to handle every event that arrives in every state. But handling every event in every state is impractical. The language provides a notion of deferred events where the programmer can annotate when she wants to delay processing an event. The default safety checker looks for presence of unhan-dled events. The language also provides default liveness checks that an event cannot be potentially deferred forever. P was used to implement and verify the core of the USB device driver stack that ships with Microsoft Windows 8. The resulting driver is more reliable and performs better than its prior incarnation (which did not use P); we have more confidence in the robustness of its design due to the language abstractions and verification provided by P.
AU - Desai, Ankush
AU - Gupta, Vivek
AU - Jackson, Ethan
AU - Qadeer, Shaz
AU - Rajamani, Sriram
AU - Zufferey, Damien
ID - 2301
T2 - Proceedings of the 34th ACM SIGPLAN Conference on Programming Language Design and Implementation
TI - P: Safe asynchronous event-driven programming
ER -
TY - JOUR
AB - MADM (Mosaic Analysis with Double Markers) technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cre recombinase/loxP-dependent interchromosomal mitotic recombination to reconstitute two split marker genes—green GFP and red tdTomato—and can label sparse clones of homozygous mutant cells in one color and wild-type cells in the other color in an otherwise unlabeled background. At present, major MADM applications include lineage tracing, single cell labeling, conditional knockouts in small populations of cells and induction of uniparental chromosome disomy to assess effects of genomic imprinting. MADM can be applied universally in the mouse with the sole limitation being the specificity of the promoter controlling Cre recombinase expression. Here I review recent developments and extensions of the MADM technique and give an overview of the major discoveries and progresses enabled by the implementation of the novel genetic MADM tools.
AU - Hippenmeyer, Simon
ID - 2303
IS - 6
JF - Frontiers in Biology
TI - Dissection of gene function at clonal level using mosaic analysis with double markers
VL - 8
ER -
TY - JOUR
AB - This extended abstract is concerned with the irregularities of distribution of one-dimensional permuted van der Corput sequences that are generated from linear permutations. We show how to obtain upper bounds for the discrepancy and diaphony of these sequences, by relating them to Kronecker sequences and applying earlier results of Faure and Niederreiter.
AU - Pausinger, Florian
ID - 2304
JF - Electronic Notes in Discrete Mathematics
TI - Van der Corput sequences and linear permutations
VL - 43
ER -
TY - CONF
AB - We study the complexity of central controller synthesis problems for finite-state Markov decision processes, where the objective is to optimize both the expected mean-payoff performance of the system and its stability. e argue that the basic theoretical notion of expressing the stability in terms of the variance of the mean-payoff (called global variance in our paper) is not always sufficient, since it ignores possible instabilities on respective runs. For this reason we propose alernative definitions of stability, which we call local and hybrid variance, and which express how rewards on each run deviate from the run's own mean-payoff and from the expected mean-payoff, respectively. We show that a strategy ensuring both the expected mean-payoff and the variance below given bounds requires randomization and memory, under all the above semantics of variance. We then look at the problem of determining whether there is a such a strategy. For the global variance, we show that the problem is in PSPACE, and that the answer can be approximated in pseudo-polynomial time. For the hybrid variance, the analogous decision problem is in NP, and a polynomial-time approximating algorithm also exists. For local variance, we show that the decision problem is in NP. Since the overall performance can be traded for stability (and vice versa), we also present algorithms for approximating the associated Pareto curve in all the three cases. Finally, we study a special case of the decision problems, where we require a given expected mean-payoff together with zero variance. Here we show that the problems can be all solved in polynomial time.
AU - Brázdil, Tomáš
AU - Chatterjee, Krishnendu
AU - Forejt, Vojtěch
AU - Kučera, Antonín
ID - 2305
T2 - 28th Annual ACM/IEEE Symposium
TI - Trading performance for stability in Markov decision processes
ER -
TY - BOOK
AB - Das Buch ist sowohl eine Einführung in die Themen Linked Data, Open Data und Open Linked Data als es auch den konkreten Bezug auf Bibliotheken behandelt. Hierzu werden konkrete Anwendungsprojekte beschrieben. Der Band wendet sich dabei sowohl an Personen aus der Bibliothekspraxis als auch an Personen aus dem Bibliotheksmanagement, die noch nicht mit dem Thema vertraut sind.
AU - Danowski, Patrick
AU - Pohl, Adrian
ID - 2306
TI - (Open) Linked Data in Bibliotheken
VL - 50
ER -
TY - CONF
AB - We define the model-measuring problem: given a model M and specification φ, what is the maximal distance ρ such that all models M′ within distance ρ from M satisfy (or violate) φ. The model measuring problem presupposes a distance function on models. We concentrate on automatic distance functions, which are defined by weighted automata. The model-measuring problem subsumes several generalizations of the classical model-checking problem, in particular, quantitative model-checking problems that measure the degree of satisfaction of a specification, and robustness problems that measure how much a model can be perturbed without violating the specification. We show that for automatic distance functions, and ω-regular linear-time and branching-time specifications, the model-measuring problem can be solved. We use automata-theoretic model-checking methods for model measuring, replacing the emptiness question for standard word and tree automata by the optimal-weight question for the weighted versions of these automata. We consider weighted automata that accumulate weights by maximizing, summing, discounting, and limit averaging. We give several examples of using the model-measuring problem to compute various notions of robustness and quantitative satisfaction for temporal specifications.
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 2327
TI - From model checking to model measuring
VL - 8052
ER -
TY - CONF
AB - Linearizability of concurrent data structures is usually proved by monolithic simulation arguments relying on identifying the so-called linearization points. Regrettably, such proofs, whether manual or automatic, are often complicated and scale poorly to advanced non-blocking concurrency patterns, such as helping and optimistic updates.
In response, we propose a more modular way of checking linearizability of concurrent queue algorithms that does not involve identifying linearization points. We reduce the task of proving linearizability with respect to the queue specification to establishing four basic properties, each of which can be proved independently by simpler arguments. As a demonstration of our approach, we verify the Herlihy and Wing queue, an algorithm that is challenging to verify by a simulation proof.
AU - Henzinger, Thomas A
AU - Sezgin, Ali
AU - Vafeiadis, Viktor
ID - 2328
TI - Aspect-oriented linearizability proofs
VL - 8052
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 both finite-state game graphs, and recursive game graphs (or pushdown game graphs) that model the control flow of sequential programs with recursion. The objectives we study are multidimensional mean-payoff objectives, where the goal of player 1 is to ensure that the mean-payoff is non-negative in all dimensions. 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. Our main contributions are as follows: (1) We show that finite-state multidimensional mean-payoff games can be solved in polynomial time if the number of dimensions and the maximal absolute value of the weights are fixed; whereas if the number of dimensions is arbitrary, then the problem is known to be coNP-complete. (2) We show that pushdown graphs with multidimensional mean-payoff objectives can be solved in polynomial time. For both (1) and (2) our algorithms are based on hyperplane separation technique. (3) For pushdown games under global strategies both one and multidimensional mean-payoff objectives problems are known to be undecidable, and we show that under modular strategies the multidimensional problem is also undecidable; under modular strategies the one-dimensional problem is NP-complete. We show that if the number of modules, the number of exits, and the maximal absolute value of the weights are fixed, then pushdown games under modular strategies with one-dimensional mean-payoff objectives can be solved in polynomial time, and if either the number of exits or the number of modules is unbounded, then the problem is NP-hard. (4) Finally we show that a fixed parameter tractable algorithm for finite-state multidimensional mean-payoff games or pushdown games under modular strategies with one-dimensional mean-payoff objectives would imply the fixed parameter tractability of parity games.
AU - Chatterjee, Krishnendu
AU - Velner, Yaron
ID - 2329
TI - Hyperplane separation technique for multidimensional mean-payoff games
VL - 8052
ER -
TY - JOUR
AB - Here, we describe a novel virulent bacteriophage that infects Bacillus weihenstephanensis, isolated from soil in Austria. It is the first phage to be discovered that infects this species. Here, we present the complete genome sequence of this podovirus.
AU - Fernandes Redondo, Rodrigo A
AU - Kupczok, Anne
AU - Stift, Gertraud
AU - Bollback, Jonathan P
ID - 2410
IS - 3
JF - Genome Announcements
TI - Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis
VL - 1
ER -
TY - JOUR
AB - Background: The CRISPR/Cas system is known to act as an adaptive and heritable immune system in Eubacteria and Archaea. Immunity is encoded in an array of spacer sequences. Each spacer can provide specific immunity to invasive elements that carry the same or a similar sequence. Even in closely related strains, spacer content is very dynamic and evolves quickly. Standard models of nucleotide evolutioncannot be applied to quantify its rate of change since processes other than single nucleotide changes determine its evolution.Methods We present probabilistic models that are specific for spacer content evolution. They account for the different processes of insertion and deletion. Insertions can be constrained to occur on one end only or are allowed to occur throughout the array. One deletion event can affect one spacer or a whole fragment of adjacent spacers. Parameters of the underlying models are estimated for a pair of arrays by maximum likelihood using explicit ancestor enumeration.Results Simulations show that parameters are well estimated on average under the models presented here. There is a bias in the rate estimation when including fragment deletions. The models also estimate times between pairs of strains. But with increasing time, spacer overlap goes to zero, and thus there is an upper bound on the distance that can be estimated. Spacer content similarities are displayed in a distance based phylogeny using the estimated times.We use the presented models to analyze different Yersinia pestis data sets and find that the results among them are largely congruent. The models also capture the variation in diversity of spacers among the data sets. A comparison of spacer-based phylogenies and Cas gene phylogenies shows that they resolve very different time scales for this data set.Conclusions The simulations and data analyses show that the presented models are useful for quantifying spacer content evolution and for displaying spacer content similarities of closely related strains in a phylogeny. This allows for comparisons of different CRISPR arrays or for comparisons between CRISPR arrays and nucleotide substitution rates.
AU - Kupczok, Anne
AU - Bollback, Jonathan P
ID - 2412
IS - 1
JF - BMC Evolutionary Biology
TI - Probabilistic models for CRISPR spacer content evolution
VL - 13
ER -
TY - CHAP
AB - Progress in understanding the global brain dynamics has remained slow to date in large part because of the highly multiscale nature of brain activity. Indeed, normal brain dynamics is characterized by complex interactions between multiple levels: from the microscopic scale of single neurons to the mesoscopic level of local groups of neurons, and finally to the macroscopic level of the whole brain. Among the most difficult tasks are those of identifying which scales are significant for a given particular function and describing how the scales affect each other. It is important to realize that the scales of time and space are linked together, or even intertwined, and that causal inference is far more ambiguous between than within levels. We approach this problem from the perspective of our recent work on simultaneous recording from micro- and macroelectrodes in the human brain. We propose a physiological description of these multilevel interactions, based on phase–amplitude coupling of neuronal oscillations that operate at multiple frequencies and on different spatial scales. Specifically, the amplitude of the oscillations on a particular spatial scale is modulated by phasic variations in neuronal excitability induced by lower frequency oscillations that emerge on a larger spatial scale. Following this general principle, it is possible to scale up or scale down the multiscale brain dynamics. It is expected that large-scale network oscillations in the low-frequency range, mediating downward effects, may play an important role in attention and consciousness.
AU - Valderrama, Mario
AU - Botella Soler, Vicente
AU - Le Van Quyen, Michel
ED - Meyer, Misha
ED - Pesenson, Z.
ID - 2413
SN - 9783527411986
T2 - Multiscale Analysis and Nonlinear Dynamics: From Genes to the Brain
TI - Neuronal oscillations scale up and scale down the brain dynamics
ER -
TY - JOUR
AB - The mode of action of auxin is based on its non-uniform distribution within tissues and organs. Despite the wide use of several auxin analogues in research and agriculture, little is known about the specificity of different auxin-related transport and signalling processes towards these compounds. Using seedlings of Arabidopsis thaliana and suspension-cultured cells of Nicotiana tabacum (BY-2), the physiological activity of several auxin analogues was investigated, together with their capacity to induce auxin-dependent gene expression, to inhibit endocytosis and to be transported across the plasma membrane. This study shows that the specificity criteria for different auxin-related processes vary widely. Notably, the special behaviour of some synthetic auxin analogues suggests that they might be useful tools in investigations of the molecular mechanism of auxin action. Thus, due to their differential stimulatory effects on DR5 expression, indole-3-propionic (IPA) and 2,4,5-trichlorophenoxy acetic (2,4,5-T) acids can serve in studies of TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALLING F-BOX (TIR1/AFB)-mediated auxin signalling, and 5-fluoroindole-3-acetic acid (5-F-IAA) can help to discriminate between transcriptional and non-transcriptional pathways of auxin signalling. The results demonstrate that the major determinants for the auxin-like physiological potential of a particular compound are very complex and involve its chemical and metabolic stability, its ability to distribute in tissues in a polar manner and its activity towards auxin signalling machinery.
AU - Simon, Sibu
AU - Kubeš, Martin
AU - Baster, Pawel
AU - Robert, Stéphanie
AU - Dobrev, Petre
AU - Friml, Jirí
AU - Petrášek, Jan
AU - Zažímalová, Eva
ID - 2443
IS - 4
JF - New Phytologist
TI - Defining the selectivity of processes along the auxin response chain: A study using auxin analogues
VL - 200
ER -
TY - CONF
AB - We consider two core algorithmic problems for probabilistic verification: the maximal end-component decomposition and the almost-sure reachability set computation for Markov decision processes (MDPs). For MDPs with treewidth k, we present two improved static algorithms for both the problems that run in time O(n·k 2.38·2k ) and O(m·logn· k), respectively, where n is the number of states and m is the number of edges, significantly improving the previous known O(n·k·√n· k) bound for low treewidth. We also present decremental algorithms for both problems for MDPs with constant treewidth that run in amortized logarithmic time, which is a huge improvement over the previously known algorithms that require amortized linear time.
AU - Chatterjee, Krishnendu
AU - Ła̧Cki, Jakub
ID - 2444
TI - Faster algorithms for Markov decision processes with low treewidth
VL - 8044
ER -
TY - CONF
AB - The model-checking problem for probabilistic systems crucially relies on the translation of LTL to deterministic Rabin automata (DRW). Our recent Safraless translation [KE12, GKE12] for the LTL(F,G) fragment produces smaller automata as compared to the traditional approach. In this work, instead of DRW we consider deterministic automata with acceptance condition given as disjunction of generalized Rabin pairs (DGRW). The Safraless translation of LTL(F,G) formulas to DGRW results in smaller automata as compared to DRW. We present algorithms for probabilistic model-checking as well as game solving for DGRW conditions. Our new algorithms lead to improvement both in terms of theoretical bounds as well as practical evaluation. We compare PRISM with and without our new translation, and show that the new translation leads to significant improvements.
AU - Chatterjee, Krishnendu
AU - Gaiser, Andreas
AU - Kretinsky, Jan
ID - 2446
TI - Automata with generalized Rabin pairs for probabilistic model checking and LTL synthesis
VL - 8044
ER -
TY - CONF
AB - Separation logic (SL) has gained widespread popularity because of its ability to succinctly express complex invariants of a program’s heap configurations. Several specialized provers have been developed for decidable SL fragments. However, these provers cannot be easily extended or combined with solvers for other theories that are important in program verification, e.g., linear arithmetic. In this paper, we present a reduction of decidable SL fragments to a decidable first-order theory that fits well into the satisfiability modulo theories (SMT) framework. We show how to use this reduction to automate satisfiability, entailment, frame inference, and abduction problems for separation logic using SMT solvers. Our approach provides a simple method of integrating separation logic into existing verification tools that provide SMT backends, and an elegant way of combining SL fragments with other decidable first-order theories. We implemented this approach in a verification tool and applied it to heap-manipulating programs whose verification involves reasoning in theory combinations.
AU - Piskac, Ruzica
AU - Wies, Thomas
AU - Zufferey, Damien
ID - 2447
TI - Automating separation logic using SMT
VL - 8044
ER -
TY - JOUR
AB - Cell-to-cell directional flow of the phytohormone auxin is primarily established by polar localization of the PIN auxin transporters, a process tightly regulated at multiple levels by auxin itself. We recently reported that, in the context of strong auxin flows, activity of the vacuolar ZIFL1.1 transporter is required for fine-tuning of polar auxin transport rates in the Arabidopsis root. In particular, ZIFL1.1 function protects plasma-membrane stability of the PIN2 carrier in epidermal root tip cells under conditions normally triggering PIN2 degradation. Here, we show that ZIFL1.1 activity at the root tip also promotes PIN1 plasma-membrane abundance in central cylinder cells, thus supporting the notion that ZIFL1.1 acts as a general positive modulator of polar auxin transport in roots.
AU - Remy, Estelle
AU - Baster, Pawel
AU - Friml, Jirí
AU - Duque, Paula
ID - 2448
IS - 10
JF - Plant Signaling & Behavior
TI - ZIFL1.1 transporter modulates polar auxin transport by stabilizing membrane abundance of multiple PINs in Arabidopsis root tip
VL - 8
ER -
TY - JOUR
AB - Intracellular protein routing is mediated by vesicular transport which is tightly regulated in eukaryotes. The protein and lipid homeostasis depends on coordinated delivery of de novo synthesized or recycled cargoes to the plasma membrane by exocytosis and their subsequent removal by rerouting them for recycling or degradation. Here, we report the characterization of protein affected trafficking 3 (pat3) mutant that we identified by an epifluorescence-based forward genetic screen for mutants defective in subcellular distribution of Arabidopsis auxin transporter PIN1–GFP. While pat3 displays largely normal plant morphology and development in nutrient-rich conditions, it shows strong ectopic intracellular accumulations of different plasma membrane cargoes in structures that resemble prevacuolar compartments (PVC) with an aberrant morphology. Genetic mapping revealed that pat3 is defective in vacuolar protein sorting 35A (VPS35A), a putative subunit of the retromer complex that mediates retrograde trafficking between the PVC and trans-Golgi network. Similarly, a mutant defective in another retromer subunit, vps29, shows comparable subcellular defects in PVC morphology and protein accumulation. Thus, our data provide evidence that the retromer components VPS35A and VPS29 are essential for normal PVC morphology and normal trafficking of plasma membrane proteins in plants. In addition, we show that, out of the three VPS35 retromer subunits present in Arabidopsis thaliana genome, the VPS35 homolog A plays a prevailing role in trafficking to the lytic vacuole, presenting another level of complexity in the retromer-dependent vacuolar sorting.
AU - Nodzyński, Tomasz
AU - Feraru, Murguel
AU - Hirsch, Sibylle
AU - De Rycke, Riet
AU - Nicuales, Claudiu
AU - Van Leene, Jelle
AU - De Jaeger, Geert
AU - Vanneste, Steffen
AU - Friml, Jirí
ID - 2449
IS - 6
JF - Molecular Plant
TI - Retromer subunits VPS35A and VPS29 mediate prevacuolar compartment (PVC) function in Arabidopsis
VL - 6
ER -
TY - JOUR
AB - We introduce a new method for efficiently simulating liquid with extreme amounts of spatial adaptivity. Our method combines several key components to drastically speed up the simulation of large-scale fluid phenomena: We leverage an alternative Eulerian tetrahedral mesh discretization to significantly reduce the complexity of the pressure solve while increasing the robustness with respect to element quality and removing the possibility of locking. Next, we enable subtle free-surface phenomena by deriving novel second-order boundary conditions consistent with our discretization. We couple this discretization with a spatially adaptive Fluid-Implicit Particle (FLIP) method, enabling efficient, robust, minimally-dissipative simulations that can undergo sharp changes in spatial resolution while minimizing artifacts. Along the way, we provide a new method for generating a smooth and detailed surface from a set of particles with variable sizes. Finally, we explore several new sizing functions for determining spatially adaptive simulation resolutions, and we show how to couple them to our simulator. We combine each of these elements to produce a simulation algorithm that is capable of creating animations at high maximum resolutions while avoiding common pitfalls like inaccurate boundary conditions and inefficient computation.
AU - Ando, Ryoichi
AU - Thuerey, Nils
AU - Wojtan, Christopher J
ID - 2466
IS - 4
JF - ACM Transactions on Graphics
TI - Highly adaptive liquid simulations on tetrahedral meshes
VL - 32
ER -
TY - JOUR
AB - This paper presents a method for computing topology changes for triangle meshes in an interactive geometric modeling environment. Most triangle meshes in practice do not exhibit desirable geometric properties, so we develop a solution that is independent of standard assumptions and robust to geometric errors. Specifically, we provide the first method for topology change applicable to arbitrary non-solid, non-manifold, non-closed, self-intersecting surfaces. We prove that this new method for topology change produces the expected conventional results when applied to solid (closed, manifold, non-self-intersecting) surfaces---that is, we prove a backwards-compatibility property relative to prior work. Beyond solid surfaces, we present empirical evidence that our method remains tolerant to a variety of surface aberrations through the incorporation of a novel error correction scheme. Finally, we demonstrate how topology change applied to non-solid objects enables wholly new and useful behaviors.
AU - Bernstein, Gilbert
AU - Wojtan, Christopher J
ID - 2467
IS - 4
JF - ACM Transactions on Graphics
TI - Putting holes in holey geometry: Topology change for arbitrary surfaces
VL - 32
ER -
TY - JOUR
AB - Our work concerns the combination of an Eulerian liquid simulation with a high-resolution surface tracker (e.g. the level set method or a Lagrangian triangle mesh). The naive application of a high-resolution surface tracker to a low-resolution velocity field can produce many visually disturbing physical and topological artifacts that limit their use in practice. We address these problems by defining an error function which compares the current state of the surface tracker to the set of physically valid surface states. By reducing this error with a gradient descent technique, we introduce a novel physics-based surface fairing method. Similarly, by treating this error function as a potential energy, we derive a new surface correction force that mimics the vortex sheet equations. We demonstrate our results with both level set and mesh-based surface trackers.
AU - Bojsen-Hansen, Morten
AU - Wojtan, Christopher J
ID - 2468
IS - 4
JF - ACM Transactions on Graphics
TI - Liquid surface tracking with error compensation
VL - 32
ER -
TY - JOUR
AB - Cadherins are transmembrane proteins that mediate cell–cell adhesion in animals. By regulating contact formation and stability, cadherins play a crucial role in tissue morphogenesis and homeostasis. Here, we review the three major unctions of cadherins in cell–cell contact formation and stability. Two of those functions lead to a decrease in interfacial ension at the forming cell–cell contact, thereby promoting contact expansion — first, by providing adhesion tension that lowers interfacial tension at the cell–cell contact, and second, by signaling to the actomyosin cytoskeleton in order to reduce cortex tension and thus interfacial tension at the contact. The third function of cadherins in cell–cell contact formation is to stabilize the contact by resisting mechanical forces that pull on the contact.
AU - Maître, Jean-Léon
AU - Heisenberg, Carl-Philipp J
ID - 2469
IS - 14
JF - Current Biology
TI - Three functions of cadherins in cell adhesion
VL - 23
ER -
TY - JOUR
AB - Background:Auxin binding protein 1 (ABP1) is a putative auxin receptor and its function is indispensable for plant growth and development. ABP1 has been shown to be involved in auxin-dependent regulation of cell division and expansion, in plasma-membrane-related processes such as changes in transmembrane potential, and in the regulation of clathrin-dependent endocytosis. However, the ABP1-regulated downstream pathway remains elusive.Methodology/Principal Findings:Using auxin transport assays and quantitative analysis of cellular morphology we show that ABP1 regulates auxin efflux from tobacco BY-2 cells. The overexpression of ABP1can counterbalance increased auxin efflux and auxin starvation phenotypes caused by the overexpression of PIN auxin efflux carrier. Relevant mechanism involves the ABP1-controlled vesicle trafficking processes, including positive regulation of endocytosis of PIN auxin efflux carriers, as indicated by fluorescence recovery after photobleaching (FRAP) and pharmacological manipulations.Conclusions/Significance:The findings indicate the involvement of ABP1 in control of rate of auxin transport across plasma membrane emphasizing the role of ABP1 in regulation of PIN activity at the plasma membrane, and highlighting the relevance of ABP1 for the formation of developmentally important, PIN-dependent auxin gradients.
AU - Čovanová, Milada
AU - Sauer, Michael
AU - Rychtář, Jan
AU - Friml, Jirí
AU - Petrášek, Jan
AU - Zažímalová, Eva
ID - 2470
IS - 7
JF - PLoS One
TI - Overexpression of the auxin binding PROTEIN1 modulates PIN-dependent auxin transport in tobacco cells
VL - 8
ER -
TY - JOUR
AB - The impact of disulfide bonds on protein stability goes beyond simple equilibrium thermodynamics effects associated with the conformational entropy of the unfolded state. Indeed, disulfide crosslinks may play a role in the prevention of dysfunctional association and strongly affect the rates of irreversible enzyme inactivation, highly relevant in biotechnological applications. While these kinetic-stability effects remain poorly understood, by analogy with proposed mechanisms for processes of protein aggregation and fibrillogenesis, we propose that they may be determined by the properties of sparsely-populated, partially-unfolded intermediates. Here we report the successful design, on the basis of high temperature molecular-dynamics simulations, of six thermodynamically and kinetically stabilized variants of phytase from Citrobacter braakii (a biotechnologically important enzyme) with one, two or three engineered disulfides. Activity measurements and 3D crystal structure determination demonstrate that the engineered crosslinks do not cause dramatic alterations in the native structure. The inactivation kinetics for all the variants displays a strongly non-Arrhenius temperature dependence, with the time-scale for the irreversible denaturation process reaching a minimum at a given temperature within the range of the denaturation transition. We show this striking feature to be a signature of a key role played by a partially unfolded, intermediate state/ensemble. Energetic and mutational analyses confirm that the intermediate is highly unfolded (akin to a proposed critical intermediate in the misfolding of the prion protein), a result that explains the observed kinetic stabilization. Our results provide a rationale for the kinetic-stability consequences of disulfide-crosslink engineering and an experimental methodology to arrive at energetic/structural descriptions of the sparsely populated and elusive intermediates that play key roles in irreversible protein denaturation.
AU - Sanchez Romero, Inmaculada
AU - Ariza, Antonio
AU - Wilson, Keith
AU - Skjøt, Michael
AU - Vind, Jesper
AU - De Maria, Leonardo
AU - Skov, Lars
AU - Sánchez Ruiz, Jose
ID - 2471
IS - 7
JF - PLoS One
TI - Mechanism of protein kinetic stabilization by engineered disulfide crosslinks
VL - 8
ER -
TY - JOUR
AB - Plant-specific PIN-formed (PIN) efflux transporters for the plant hormone auxin are required for tissue-specific directional auxin transport and cellular auxin homeostasis. The Arabidopsis PIN protein family has been shown to play important roles in developmental processes such as embryogenesis, organogenesis, vascular tissue differentiation, root meristem patterning and tropic growth. Here we analyzed roles of the less characterised Arabidopsis PIN6 auxin transporter. PIN6 is auxin-inducible and is expressed during multiple auxin-regulated developmental processes. Loss of pin6 function interfered with primary root growth and lateral root development. Misexpression of PIN6 affected auxin transport and interfered with auxin homeostasis in other growth processes such as shoot apical dominance, lateral root primordia development, adventitious root formation, root hair outgrowth and root waving. These changes in auxin-regulated growth correlated with a reduction in total auxin transport as well as with an altered activity of DR5-GUS auxin response reporter. Overall, the data indicate that PIN6 regulates auxin homeostasis during plant development.
AU - Cazzonelli, Christopher
AU - Vanstraelen, Marleen
AU - Simon, Sibu
AU - Yin, Kuide
AU - Carron Arthur, Ashley
AU - Nisar, Nazia
AU - Tarle, Gauri
AU - Cuttriss, Abby
AU - Searle, Iain
AU - Benková, Eva
AU - Mathesius, Ulrike
AU - Masle, Josette
AU - Friml, Jirí
AU - Pogson, Barry
ID - 2472
IS - 7
JF - PLoS One
TI - Role of the Arabidopsis PIN6 auxin transporter in auxin homeostasis and auxin-mediated development
VL - 8
ER -
TY - JOUR
AB - When a mutation with selective advantage s spreads through a panmictic population, it may cause two lineages at a linked locus to coalesce; the probability of coalescence is exp(−2rT), where T∼log(2Ns)/s is the time to fixation, N is the number of haploid individuals, and r is the recombination rate. Population structure delays fixation, and so weakens the effect of a selective sweep. However, favourable alleles spread through a spatially continuous population behind a narrow wavefront; ancestral lineages are confined at the tip of this front, and so coalesce rapidly. In extremely dense populations, coalescence is dominated by rare fluctuations ahead of the front. However, we show that for moderate densities, a simple quasi-deterministic approximation applies: the rate of coalescence within the front is λ∼2g(η)/(ρℓ), where ρ is the population density and is the characteristic scale of the wavefront; g(η) depends only on the strength of random drift, . The net effect of a sweep on coalescence also depends crucially on whether two lineages are ever both within the wavefront at the same time: even in the extreme case when coalescence within the front is instantaneous, the net rate of coalescence may be lower than in a single panmictic population. Sweeps can also have a substantial impact on the rate of gene flow. A single lineage will jump to a new location when it is hit by a sweep, with mean square displacement ; this can be substantial if the species’ range, L, is large, even if the species-wide rate of sweeps per map length, Λ/R, is small. This effect is half as strong in two dimensions. In contrast, the rate of coalescence between lineages, at random locations in space and on the genetic map, is proportional to (c/L)(Λ/R), where c is the wavespeed: thus, on average, one-dimensional structure is likely to reduce coalescence due to sweeps, relative to panmixis. In two dimensions, genes must move along the front before they can coalesce; this process is rapid, being dominated by rare fluctuations. This leads to a dramatically higher rate of coalescence within the wavefront than if lineages simply diffused along the front. Nevertheless, the net rate of coalescence due to a sweep through a two-dimensional population is likely to be lower than it would be with panmixis.
AU - Barton, Nicholas H
AU - Etheridge, Alison
AU - Kelleher, Jerome
AU - Véber, Amandine
ID - 2473
IS - 8
JF - Theoretical Population Biology
TI - Genetic hitch-hiking in spatially extended populations
VL - 87
ER -
TY - JOUR
AB - We study the problem of object recognition for categories for which we have no training examples, a task also called zero-data or zero-shot learning. This situation has hardly been studied in computer vision research, even though it occurs frequently: the world contains tens of thousands of different object classes and for only few of them image collections have been formed and suitably annotated. To tackle the problem we introduce attribute-based classification: objects are identified based on a high-level description that is phrased in terms of semantic attributes, such as the object's color or shape. Because the identification of each such property transcends the specific learning task at hand, the attribute classifiers can be pre-learned independently, e.g. from existing image datasets unrelated to the current task. Afterwards, new classes can be detected based on their attribute representation, without the need for a new training phase. In this paper we also introduce a new dataset, Animals with Attributes, of over 30,000 images of 50 animal classes, annotated with 85 semantic attributes. Extensive experiments on this and two more datasets show that attribute-based classification indeed is able to categorize images without access to any training images of the target classes.
AU - Lampert, Christoph
AU - Nickisch, Hannes
AU - Harmeling, Stefan
ID - 2516
IS - 3
JF - IEEE Transactions on Pattern Analysis and Machine Intelligence
TI - Attribute-based classification for zero-shot learning of object categories
VL - 36
ER -
TY - CONF
AB - Traditional formal methods are based on a Boolean satisfaction notion: a reactive system satisfies, or not, a given specification. We generalize formal methods to also address the quality of systems. As an adequate specification formalism we introduce the linear temporal logic LTL[F]. The satisfaction value of an LTL[F] formula is a number between 0 and 1, describing the quality of the satisfaction. The logic generalizes traditional LTL by augmenting it with a (parameterized) set F of arbitrary functions over the interval [0,1]. For example, F may contain the maximum or minimum between the satisfaction values of subformulas, their product, and their average. The classical decision problems in formal methods, such as satisfiability, model checking, and synthesis, are generalized to search and optimization problems in the quantitative setting. For example, model checking asks for the quality in which a specification is satisfied, and synthesis returns a system satisfying the specification with the highest quality. Reasoning about quality gives rise to other natural questions, like the distance between specifications. We formalize these basic questions and study them for LTL[F]. By extending the automata-theoretic approach for LTL to a setting that takes quality into an account, we are able to solve the above problems and show that reasoning about LTL[F] has roughly the same complexity as reasoning about traditional LTL.
AU - Almagor, Shaull
AU - Boker, Udi
AU - Kupferman, Orna
ID - 2517
IS - Part 2
TI - Formalizing and reasoning about quality
VL - 7966
ER -
TY - CONF
AB - A class of valued constraint satisfaction problems (VCSPs) is characterised by a valued constraint language, a fixed set of cost functions on a finite domain. An instance of the problem is specified by a sum of cost functions from the language with the goal to minimise the sum. We study which classes of finite-valued languages can be solved exactly by the basic linear programming relaxation (BLP). Thapper and Živný showed [20] that if BLP solves the language then the language admits a binary commutative fractional polymorphism. We prove that the converse is also true. This leads to a necessary and a sufficient condition which can be checked in polynomial time for a given language. In contrast, the previous necessary and sufficient condition due to [20] involved infinitely many inequalities. More recently, Thapper and Živný [21] showed (using, in particular, a technique introduced in this paper) that core languages that do not satisfy our condition are NP-hard. Taken together, these results imply that a finite-valued language can either be solved using Linear Programming or is NP-hard.
AU - Kolmogorov, Vladimir
ID - 2518
IS - 1
TI - The power of linear programming for finite-valued CSPs: A constructive characterization
VL - 7965
ER -
TY - CONF
AB - We propose a probabilistic model to infer supervised latent variables in
the Hamming space from observed data. Our model allows simultaneous
inference of the number of binary latent variables, and their values. The
latent variables preserve neighbourhood structure of the data in a sense
that objects in the same semantic concept have similar latent values, and
objects in different concepts have dissimilar latent values. We formulate
the supervised infinite latent variable problem based on an intuitive
principle of pulling objects together if they are of the same type, and
pushing them apart if they are not. We then combine this principle with a
flexible Indian Buffet Process prior on the latent variables. We show that
the inferred supervised latent variables can be directly used to perform a
nearest neighbour search for the purpose of retrieval. We introduce a new
application of dynamically extending hash codes, and show how to
effectively couple the structure of the hash codes with continuously
growing structure of the neighbourhood preserving infinite latent feature
space.
AU - Quadrianto, Novi
AU - Sharmanska, Viktoriia
AU - Knowles, David
AU - Ghahramani, Zoubin
ID - 2520
SN - 9780974903996
T2 - Proceedings of the 29th conference uncertainty in Artificial Intelligence
TI - The supervised IBP: Neighbourhood preserving infinite latent feature models
ER -
TY - JOUR
AB - We consider non-interacting particles subject to a fixed external potential V and a self-generated magnetic field B. The total energy includes the field energy β∫B2 and we minimize over all particle states and magnetic fields. In the case of spin-1/2 particles this minimization leads to the coupled Maxwell-Pauli system. The parameter β tunes the coupling strength between the field and the particles and it effectively determines the strength of the field. We investigate the stability and the semiclassical asymptotics, h→0, of the total ground state energy E(β,h,V). The relevant parameter measuring the field strength in the semiclassical limit is κ=βh. We are not able to give the exact leading order semiclassical asymptotics uniformly in κ or even for fixed κ. We do however give upper and lower bounds on E with almost matching dependence on κ. In the simultaneous limit h→0 and κ→∞ we show that the standard non-magnetic Weyl asymptotics holds. The same result also holds for the spinless case, i.e. where the Pauli operator is replaced by the Schrödinger operator.
AU - Erdös, László
AU - Fournais, Søren
AU - Solovej, Jan
ID - 2698
IS - 6
JF - Journal of the European Mathematical Society
TI - Stability and semiclassics in self-generated fields
VL - 15
ER -
TY - CONF
AB - Even though both population and quantitative genetics, and evolutionary computation, deal with the same questions, they have developed largely independently of each other. I review key results from each field, emphasising those that apply independently of the (usually unknown) relation between genotype and phenotype. The infinitesimal model provides a simple framework for predicting the response of complex traits to selection, which in biology has proved remarkably successful. This allows one to choose the schedule of population sizes and selection intensities that will maximise the response to selection, given that the total number of individuals realised, C = ∑t Nt, is constrained. This argument shows that for an additive trait (i.e., determined by the sum of effects of the genes), the optimum population size and the maximum possible response (i.e., the total change in trait mean) are both proportional to √C.
AU - Barton, Nicholas H
AU - Paixao, Tiago
ID - 2718
T2 - Proceedings of the 15th annual conference on Genetic and evolutionary computation
TI - Can quantitative and population genetics help us understand evolutionary computation?
ER -
TY - CONF
AB - Prediction of the evolutionary process is a long standing problem both in the theory of evolutionary biology and evolutionary computation (EC). It has long been realized that heritable variation is crucial to both the response to selection and the success of genetic algorithms. However, not all variation contributes in the same way to the response. Quantitative genetics has developed a large body of work trying to estimate and understand how different components of the variance in fitness in the population contribute to the response to selection. We illustrate how to apply some concepts of quantitative genetics to the analysis of genetic algorithms. In particular, we derive estimates for the short term prediction of the response to selection and we use variance decomposition to gain insight on local aspects of the landscape. Finally, we propose a new population based genetic algorithm that uses these methods to improve its operation.
AU - Paixao, Tiago
AU - Barton, Nicholas H
ID - 2719
T2 - Proceedings of the 15th annual conference on Genetic and evolutionary computation
TI - A variance decomposition approach to the analysis of genetic algorithms
ER -
TY - JOUR
AB - Knowledge of the rate and fitness effects of mutations is essential for understanding the process of evolution. Mutations are inherently difficult to study because they are rare and are frequently eliminated by natural selection. In the ciliate Tetrahymena thermophila, mutations can accumulate in the germline genome without being exposed to selection. We have conducted a mutation accumulation (MA) experiment in this species. Assuming that all mutations are deleterious and have the same effect, we estimate that the deleterious mutation rate per haploid germline genome per generation is U = 0.0047 (95% credible interval: 0.0015, 0.0125), and that germline mutations decrease fitness by s = 11% when expressed in a homozygous state (95% CI: 4.4%, 27%). We also estimate that deleterious mutations are partially recessive on average (h = 0.26; 95% CI: –0.022, 0.62) and that the rate of lethal mutations is <10% of the deleterious mutation rate. Comparisons between the observed evolutionary responses in the germline and somatic genomes and the results from individual-based simulations of MA suggest that the two genomes have similar mutational parameters. These are the first estimates of the deleterious mutation rate and fitness effects from the eukaryotic supergroup Chromalveolata and are within the range of those of other eukaryotes.
AU - Long, Hongan
AU - Paixao, Tiago
AU - Azevedo, Ricardo
AU - Zufall, Rebecca
ID - 2720
IS - 2
JF - Genetics
TI - Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila
VL - 195
ER -
TY - JOUR
AB - We consider random n×n matrices of the form (XX*+YY*)^{-1/2}YY*(XX*+YY*)^{-1/2}, where X and Y have independent entries with zero mean and variance one. These matrices are the natural generalization of the Gaussian case, which are known as MANOVA matrices and which have joint eigenvalue density given by the third classical ensemble, the Jacobi ensemble. We show that, away from the spectral edge, the eigenvalue density converges to the limiting density of the Jacobi ensemble even on the shortest possible scales of order 1/n (up to log n factors). This result is the analogue of the local Wigner semicircle law and the local Marchenko-Pastur law for general MANOVA matrices.
AU - Erdös, László
AU - Farrell, Brendan
ID - 2782
IS - 6
JF - Journal of Statistical Physics
TI - Local eigenvalue density for general MANOVA matrices
VL - 152
ER -
TY - JOUR
AB - A novel Taylor-Couette system has been constructed for investigations of transitional as well as high Reynolds number turbulent flows in very large aspect ratios. The flexibility of the setup enables studies of a variety of problems regarding hydrodynamic instabilities and turbulence in rotating flows. The inner and outer cylinders and the top and bottom endplates can be rotated independently with rotation rates of up to 30 Hz, thereby covering five orders of magnitude in Reynolds numbers (Re = 101-106). The radius ratio can be easily changed, the highest realized one is η = 0.98 corresponding to an aspect ratio of 260 gap width in the vertical and 300 in the azimuthal direction. For η < 0.98 the aspect ratio can be dynamically changed during measurements and complete transparency in the radial direction over the full length of the cylinders is provided by the usage of a precision glass inner cylinder. The temperatures of both cylinders are controlled independently. Overall this apparatus combines an unmatched variety in geometry, rotation rates, and temperatures, which is provided by a sophisticated high-precision bearing system. Possible applications are accurate studies of the onset of turbulence and spatio-temporal intermittent flow patterns in very large domains, transport processes of turbulence at high Re, the stability of Keplerian flows for different boundary conditions, and studies of baroclinic instabilities.
AU - Avila, Kerstin
AU - Hof, Björn
ID - 2806
IS - 6
JF - Review of Scientific Instruments
TI - High-precision Taylor-Couette experiment to study subcritical transitions and the role of boundary conditions and size effects
VL - 84
ER -
TY - CONF
AB - We consider several basic problems of algebraic topology, with connections to combinatorial and geometric questions, from the point of view of computational complexity. The extension problem asks, given topological spaces X; Y , a subspace A ⊆ X, and a (continuous) map f : A → Y , whether f can be extended to a map X → Y . For computational purposes, we assume that X and Y are represented as finite simplicial complexes, A is a subcomplex of X, and f is given as a simplicial map. In this generality the problem is undecidable, as follows from Novikov's result from the 1950s on uncomputability of the fundamental group π1(Y ). We thus study the problem under the assumption that, for some k ≥ 2, Y is (k - 1)-connected; informally, this means that Y has \no holes up to dimension k-1" (a basic example of such a Y is the sphere Sk). We prove that, on the one hand, this problem is still undecidable for dimX = 2k. On the other hand, for every fixed k ≥ 2, we obtain an algorithm that solves the extension problem in polynomial time assuming Y (k - 1)-connected and dimX ≤ 2k - 1. For dimX ≤ 2k - 2, the algorithm also provides a classification of all extensions up to homotopy (continuous deformation). This relies on results of our SODA 2012 paper, and the main new ingredient is a machinery of objects with polynomial-time homology, which is a polynomial-time analog of objects with effective homology developed earlier by Sergeraert et al. We also consider the computation of the higher homotopy groups πk(Y ), k ≥ 2, for a 1-connected Y . Their computability was established by Brown in 1957; we show that πk(Y ) can be computed in polynomial time for every fixed k ≥ 2. On the other hand, Anick proved in 1989 that computing πk(Y ) is #P-hard if k is a part of input, where Y is a cell complex with certain rather compact encoding. We strengthen his result to #P-hardness for Y given as a simplicial complex.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Matoušek, Jiří
AU - Vokřínek, Lukáš
AU - Wagner, Uli
ID - 2807
T2 - 45th Annual ACM Symposium on theory of computing
TI - Extending continuous maps: Polynomiality and undecidability
ER -
TY - JOUR
AB - In order to establish a reference for analysis of the function of auxin and the auxin biosynthesis regulators SHORT INTERNODE/ STYLISH (SHI/STY) during Physcomitrella patens reproductive development, we have described male (antheridial) and female (archegonial) development in detail, including temporal and positional information of organ initiation. This has allowed us to define discrete stages of organ morphogenesis and to show that reproductive organ development in P. patens is highly organized and that organ phyllotaxis differs between vegetative and reproductive development. Using the PpSHI1 and PpSHI2 reporter and knockout lines, the auxin reporters GmGH3pro:GUS and PpPINApro:GFP-GUS, and the auxin-conjugating transgene PpSHI2pro:IAAL, we could show that the PpSHI genes, and by inference also auxin, play important roles for reproductive organ development in moss. The PpSHI genes are required for the apical opening of the reproductive organs, the final differentiation of the egg cell, and the progression of canal cells into a cell death program. The apical cells of the archegonium, the canal cells, and the egg cell are also sites of auxin responsiveness and are affected by reduced levels of active auxin, suggesting that auxin mediates PpSHI function in the reproductive organs.
AU - Landberg, Katarina
AU - Pederson, Eric
AU - Viaene, Tom
AU - Bozorg, Behruz
AU - Friml, Jirí
AU - Jönsson, Henrik
AU - Thelander, Mattias
AU - Sundberg, Eva
ID - 2808
IS - 3
JF - Plant Physiology
TI - The moss physcomitrella patens reproductive organ development is highly organized, affected by the two SHI/STY genes and by the level of active auxin in the SHI/STY expression domain
VL - 162
ER -
TY - JOUR
AB - The epistatic interactions that underlie evolutionary constraint have mainly been studied for constant external conditions. However, environmental changes may modulate epistasis and hence affect genetic constraints. Here we investigate genetic constraints in the adaptive evolution of a novel regulatory function in variable environments, using the lac repressor, LacI, as a model system. We have systematically reconstructed mutational trajectories from wild type LacI to three different variants that each exhibit an inverse response to the inducing ligand IPTG, and analyzed the higher-order interactions between genetic and environmental changes. We find epistasis to depend strongly on the environment. As a result, mutational steps essential to inversion but inaccessible by positive selection in one environment, become accessible in another. We present a graphical method to analyze the observed complex higher-order interactions between multiple mutations and environmental change, and show how the interactions can be explained by a combination of mutational effects on allostery and thermodynamic stability. This dependency of genetic constraint on the environment should fundamentally affect evolutionary dynamics and affects the interpretation of phylogenetic data.
AU - De Vos, Marjon
AU - Poelwijk, Frank
AU - Battich, Nico
AU - Ndika, Joseph
AU - Tans, Sander
ID - 2810
IS - 6
JF - PLoS Genetics
TI - Environmental dependence of genetic constraint
VL - 9
ER -