@inproceedings{1393, abstract = {Probabilistic programs are usual functional or imperative programs with two added constructs: (1) the ability to draw values at random from distributions, and (2) the ability to condition values of variables in a program via observations. Models from diverse application areas such as computer vision, coding theory, cryptographic protocols, biology and reliability analysis can be written as probabilistic programs. Probabilistic inference is the problem of computing an explicit representation of the probability distribution implicitly specified by a probabilistic program. Depending on the application, the desired output from inference may vary-we may want to estimate the expected value of some function f with respect to the distribution, or the mode of the distribution, or simply a set of samples drawn from the distribution. In this paper, we describe connections this research area called \Probabilistic Programming" has with programming languages and software engineering, and this includes language design, and the static and dynamic analysis of programs. We survey current state of the art and speculate on promising directions for future research.}, author = {Gordon, Andrew and Henzinger, Thomas A and Nori, Aditya and Rajamani, Sriram}, booktitle = {Proceedings of the on Future of Software Engineering}, location = {Hyderabad, India}, pages = {167 -- 181}, publisher = {ACM}, title = {{Probabilistic programming}}, doi = {10.1145/2593882.2593900}, year = {2014}, } @phdthesis{1404, abstract = {The co-evolution of hosts and pathogens is characterized by continuous adaptations of both parties. Pathogens of social insects need to adapt towards disease defences at two levels: 1) individual immunity of each colony member consisting of behavioural defence strategies as well as humoral and cellular immune responses and 2) social immunity that is collectively performed by all group members comprising behavioural, physiological and organisational defence strategies. To disentangle the selection pressure on pathogens by the collective versus individual level of disease defence in social insects, we performed an evolution experiment using the Argentine Ant, Linepithema humile, as a host and a mixture of the general insect pathogenic fungus Metarhizium spp. (6 strains) as a pathogen. We allowed pathogen evolution over 10 serial host passages to two different evolution host treatments: (1) only individual host immunity in a single host treatment, and (2) simultaneously acting individual and social immunity in a social host treatment, in which an exposed ant was accompanied by two untreated nestmates. Before starting the pathogen evolution experiment, the 6 Metarhizium spp. strains were characterised concerning conidiospore size killing rates in singly and socially reared ants, their competitiveness under coinfecting conditions and their influence on ant behaviour. We analysed how the ancestral atrain mixture changed in conidiospere size, killing rate and strain composition dependent on host treatment (single or social hosts) during 10 passages and found that killing rate and conidiospere size of the pathogen increased under both evolution regimes, but different depending on host treatment. Testing the evolved strain mixtures that evolved under either the single or social host treatment under both single and social current rearing conditions in a full factorial design experiment revealed that the additional collective defences in insect societies add new selection pressure for their coevolving pathogens that compromise their ability to adapt to its host at the group level. To our knowledge, this is the first study directly measuring the influence of social immunity on pathogen evolution.}, author = {Stock, Miriam}, pages = {101}, publisher = {IST Austria}, title = {{Evolution of a fungal pathogen towards individual versus social immunity in ants}}, year = {2014}, } @inproceedings{1516, abstract = {We present a rigorous derivation of the BCS gap equation for superfluid fermionic gases with point interactions. Our starting point is the BCS energy functional, whose minimizer we investigate in the limit when the range of the interaction potential goes to zero. }, author = {Bräunlich, Gerhard and Hainzl, Christian and Seiringer, Robert}, booktitle = {Proceedings of the QMath12 Conference}, location = {Berlin, Germany}, pages = {127 -- 137}, publisher = {World Scientific Publishing}, title = {{On the BCS gap equation for superfluid fermionic gases}}, doi = {10.1142/9789814618144_0007}, year = {2014}, } @article{1629, abstract = {We propose a method for propagating edit operations in 2D vector graphics, based on geometric relationship functions. These functions quantify the geometric relationship of a point to a polygon, such as the distance to the boundary or the direction to the closest corner vertex. The level sets of the relationship functions describe points with the same relationship to a polygon. For a given query point, we first determine a set of relationships to local features, construct all level sets for these relationships, and accumulate them. The maxima of the resulting distribution are points with similar geometric relationships. We show extensions to handle mirror symmetries, and discuss the use of relationship functions as local coordinate systems. Our method can be applied, for example, to interactive floorplan editing, and it is especially useful for large layouts, where individual edits would be cumbersome. We demonstrate populating 2D layouts with tens to hundreds of objects by propagating relatively few edit operations.}, author = {Guerrero, Paul and Jeschke, Stefan and Wimmer, Michael and Wonka, Peter}, journal = {ACM Transactions on Graphics}, number = {2}, publisher = {ACM}, title = {{Edit propagation using geometric relationship functions}}, doi = {10.1145/2591010}, volume = {33}, year = {2014}, } @inproceedings{10793, abstract = {The Hanani–Tutte theorem is a classical result proved for the first time in the 1930s that characterizes planar graphs as graphs that admit a drawing in the plane in which every pair of edges not sharing a vertex cross an even number of times. We generalize this classical result to clustered graphs with two disjoint clusters, and show that a straightforward extension of our result to flat clustered graphs with three or more disjoint clusters is not possible. We also give a new and short proof for a related result by Di Battista and Frati based on the matroid intersection algorithm.}, author = {Fulek, Radoslav and Kynčl, Jan and Malinović, Igor and Pálvölgyi, Dömötör}, booktitle = {International Symposium on Graph Drawing}, issn = {0302-9743}, pages = {428--436}, publisher = {Springer Nature}, title = {{Clustered planarity testing revisited}}, doi = {10.1007/978-3-662-45803-7_36}, volume = {8871}, year = {2014}, } @inproceedings{1643, abstract = {We extend the notion of verifiable random functions (VRF) to constrained VRFs, which generalize the concept of constrained pseudorandom functions, put forward by Boneh and Waters (Asiacrypt’13), and independently by Kiayias et al. (CCS’13) and Boyle et al. (PKC’14), who call them delegatable PRFs and functional PRFs, respectively. In a standard VRF the secret key sk allows one to evaluate a pseudorandom function at any point of its domain; in addition, it enables computation of a non-interactive proof that the function value was computed correctly. In a constrained VRF from the key sk one can derive constrained keys skS for subsets S of the domain, which allow computation of function values and proofs only at points in S. After formally defining constrained VRFs, we derive instantiations from the multilinear-maps-based constrained PRFs by Boneh and Waters, yielding a VRF with constrained keys for any set that can be decided by a polynomial-size circuit. Our VRFs have the same function values as the Boneh-Waters PRFs and are proved secure under the same hardness assumption, showing that verifiability comes at no cost. Constrained (functional) VRFs were stated as an open problem by Boyle et al.}, author = {Fuchsbauer, Georg}, booktitle = {SCN 2014}, editor = {Abdalla, Michel and De Prisco, Roberto}, location = {Amalfi, Italy}, pages = {95 -- 114}, publisher = {Springer}, title = {{Constrained Verifiable Random Functions }}, doi = {10.1007/978-3-319-10879-7_7}, volume = {8642}, year = {2014}, } @inproceedings{1702, abstract = {In this paper we present INTERHORN, a solver for recursion-free Horn clauses. The main application domain of INTERHORN lies in solving interpolation problems arising in software verification. We show how a range of interpolation problems, including path, transition, nested, state/transition and well-founded interpolation can be handled directly by INTERHORN. By detailing these interpolation problems and their Horn clause representations, we hope to encourage the emergence of a common back-end interpolation interface useful for diverse verification tools.}, author = {Gupta, Ashutosh and Popeea, Corneliu and Rybalchenko, Andrey}, booktitle = {Electronic Proceedings in Theoretical Computer Science, EPTCS}, location = {Vienna, Austria}, pages = {31 -- 38}, publisher = {Open Publishing}, title = {{Generalised interpolation by solving recursion free-horn clauses}}, doi = {10.4204/EPTCS.169.5}, volume = {169}, year = {2014}, } @inproceedings{1708, abstract = {It has been long argued that, because of inherent ambiguity and noise, the brain needs to represent uncertainty in the form of probability distributions. The neural encoding of such distributions remains however highly controversial. Here we present a novel circuit model for representing multidimensional real-valued distributions using a spike based spatio-temporal code. Our model combines the computational advantages of the currently competing models for probabilistic codes and exhibits realistic neural responses along a variety of classic measures. Furthermore, the model highlights the challenges associated with interpreting neural activity in relation to behavioral uncertainty and points to alternative population-level approaches for the experimental validation of distributed representations.}, author = {Savin, Cristina and Denève, Sophie}, location = {Montreal, Canada}, number = {January}, pages = {2024 -- 2032}, publisher = {Neural Information Processing Systems}, title = {{Spatio-temporal representations of uncertainty in spiking neural networks}}, volume = {3}, year = {2014}, } @article{1761, abstract = {Metal silicides formed by means of thermal annealing processes are employed as contact materials in microelectronics. Control of the structure of silicide/silicon interfaces becomes a critical issue when the characteristic size of the device is reduced below a few tens of nanometers. Here, we report on silicide clustering occurring within the channel of PtSi/Si/PtSi Schottky-barrier transistors. This phenomenon is investigated through atomistic simulations and low-temperature resonant-tunneling spectroscopy. Our results provide evidence for the segregation of a PtSi cluster with a diameter of a few nanometers from the silicide contact. The cluster acts as a metallic quantum dot giving rise to distinct signatures of quantum transport through its discrete energy states.}, author = {Mongillo, Massimo and Spathis, Panayotis N and Georgios Katsaros and De Franceschi, Silvano and Gentile, Pascal and Rurali, Riccardo and Cartoixà, Xavier}, journal = {Physical Review X}, number = {4}, publisher = {American Physical Society}, title = {{PtSi clustering in silicon probed by transport spectroscopy}}, doi = {10.1103/PhysRevX.3.041025}, volume = {3}, year = {2014}, } @article{1791, abstract = {Acute gene inactivation using short hairpin RNA (shRNA, knockdown) in developing brain is a powerful technique to study genetic function; however, discrepancies between knockdown and knockout murine phenotypes have left unanswered questions. For example, doublecortin (Dcx) knockdown but not knockout shows a neocortical neuronal migration phenotype. Here we report that in utero electroporation of shRNA, but not siRNA or miRNA, to Dcx demonstrates a migration phenotype in Dcx knockouts akin to the effect in wild-type mice, suggestingshRNA-mediated off-target toxicity. This effect wasnot limited to Dcx, as it was observed in Dclk1 knockouts, as well as with a fraction of scrambled shRNAs, suggesting a sequence-dependent but not sequence-specific effect. Profiling RNAs from electroporated cells showed a defect in endogenous let7 miRNA levels, and disruption of let7 or Dicer recapitulated the migration defect. The results suggest that shRNA-mediated knockdown can produce untoward migration effects by altering endogenous miRNA pathways.}, author = {Baek, SeungTae and Kerjan, Géraldine and Bielas, Stephanie L and Lee, Jieun and Fenstermaker, Ali G and Gaia Novarino and Gleeson, Joseph G}, journal = {Neuron}, number = {6}, pages = {1255 -- 1262}, publisher = {Elsevier}, title = {{Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous MicroRNA dysregulation}}, doi = {10.1016/j.neuron.2014.04.036}, volume = {82}, year = {2014}, } @inbook{1806, abstract = {The generation of asymmetry, at both cellular and tissue level, is one of the most essential capabilities of all eukaryotic organisms. It mediates basically all multicellular development ranging from embryogenesis and de novo organ formation till responses to various environmental stimuli. In plants, the awe-inspiring number of such processes is regulated by phytohormone auxin and its directional, cell-to-cell transport. The mediators of this transport, PIN auxin transporters, are asymmetrically localized at the plasma membrane, and this polar localization determines the directionality of intercellular auxin flow. Thus, auxin transport contributes crucially to the generation of local auxin gradients or maxima, which instruct given cell to change its developmental program. Here, we introduce and discuss the molecular components and cellular mechanisms regulating the generation and maintenance of cellular PIN polarity, as the general hallmarks of cell polarity in plants.}, author = {Baster, Pawel and Friml, Jiří}, booktitle = {Auxin and Its Role in Plant Development}, editor = {Zažímalová, Eva and Petrášek, Jan and Benková, Eva}, pages = {143 -- 170}, publisher = {Springer}, title = {{Auxin on the road navigated by cellular PIN polarity}}, doi = {10.1007/978-3-7091-1526-8_8}, year = {2014}, } @article{1816, abstract = {Watermarking techniques for vector graphics dislocate vertices in order to embed imperceptible, yet detectable, statistical features into the input data. The embedding process may result in a change of the topology of the input data, e.g., by introducing self-intersections, which is undesirable or even disastrous for many applications. In this paper we present a watermarking framework for two-dimensional vector graphics that employs conventional watermarking techniques but still provides the guarantee that the topology of the input data is preserved. The geometric part of this framework computes so-called maximum perturbation regions (MPR) of vertices. We propose two efficient algorithms to compute MPRs based on Voronoi diagrams and constrained triangulations. Furthermore, we present two algorithms to conditionally correct the watermarked data in order to increase the watermark embedding capacity and still guarantee topological correctness. While we focus on the watermarking of input formed by straight-line segments, one of our approaches can also be extended to circular arcs. We conclude the paper by demonstrating and analyzing the applicability of our framework in conjunction with two well-known watermarking techniques.}, author = {Huber, Stefan and Held, Martin and Meerwald, Peter and Kwitt, Roland}, journal = {International Journal of Computational Geometry and Applications}, number = {1}, pages = {61 -- 86}, publisher = {World Scientific Publishing}, title = {{Topology-preserving watermarking of vector graphics}}, doi = {10.1142/S0218195914500034}, volume = {24}, year = {2014}, } @article{1821, abstract = {We review recent progress towards a rigorous understanding of the Bogoliubov approximation for bosonic quantum many-body systems. We focus, in particular, on the excitation spectrum of a Bose gas in the mean-field (Hartree) limit. A list of open problems will be discussed at the end.}, author = {Seiringer, Robert}, journal = {Journal of Mathematical Physics}, number = {7}, publisher = {American Institute of Physics}, title = {{Bose gases, Bose-Einstein condensation, and the Bogoliubov approximation}}, doi = {10.1063/1.4881536}, volume = {55}, year = {2014}, } @article{1822, author = {Jakšić, Vojkan and Pillet, Claude and Seiringer, Robert}, journal = {Journal of Mathematical Physics}, number = {7}, publisher = {American Institute of Physics}, title = {{Introduction}}, doi = {10.1063/1.4884877}, volume = {55}, year = {2014}, } @inbook{1829, abstract = {Hitting and batting tasks, such as tennis forehands, ping-pong strokes, or baseball batting, depend on predictions where the ball can be intercepted and how it can properly be returned to the opponent. These predictions get more accurate over time, hence the behaviors need to be continuously modified. As a result, movement templates with a learned global shape need to be adapted during the execution so that the racket reaches a target position and velocity that will return the ball over to the other side of the net or court. It requires altering learned movements to hit a varying target with the necessary velocity at a specific instant in time. Such a task cannot be incorporated straightforwardly in most movement representations suitable for learning. For example, the standard formulation of the dynamical system based motor primitives (introduced by Ijspeert et al (2002b)) does not satisfy this property despite their flexibility which has allowed learning tasks ranging from locomotion to kendama. In order to fulfill this requirement, we reformulate the Ijspeert framework to incorporate the possibility of specifying a desired hitting point and a desired hitting velocity while maintaining all advantages of the original formulation.We show that the proposed movement template formulation works well in two scenarios, i.e., for hitting a ball on a string with a table tennis racket at a specified velocity and for returning balls launched by a ball gun successfully over the net using forehand movements.}, author = {Muelling, Katharina and Kroemer, Oliver and Lampert, Christoph and Schölkopf, Bernhard}, booktitle = {Learning Motor Skills}, editor = {Kober, Jens and Peters, Jan}, pages = {69 -- 82}, publisher = {Springer}, title = {{Movement templates for learning of hitting and batting}}, doi = {10.1007/978-3-319-03194-1_3}, volume = {97}, year = {2014}, } @article{1844, abstract = {Local protein interactions ("molecular context" effects) dictate amino acid replacements and can be described in terms of site-specific, energetic preferences for any different amino acid. It has been recently debated whether these preferences remain approximately constant during evolution or whether, due to coevolution of sites, they change strongly. Such research highlights an unresolved and fundamental issue with far-reaching implications for phylogenetic analysis and molecular evolution modeling. Here, we take advantage of the recent availability of phenotypically supported laboratory resurrections of Precambrian thioredoxins and β-lactamases to experimentally address the change of site-specific amino acid preferences over long geological timescales. Extensive mutational analyses support the notion that evolutionary adjustment to a new amino acid may occur, but to a large extent this is insufficient to erase the primitive preference for amino acid replacements. Generally, site-specific amino acid preferences appear to remain conserved throughout evolutionary history despite local sequence divergence. We show such preference conservation to be readily understandable in molecular terms and we provide crystallographic evidence for an intriguing structural-switch mechanism: Energetic preference for an ancestral amino acid in a modern protein can be linked to reorganization upon mutation to the ancestral local structure around the mutated site. Finally, we point out that site-specific preference conservation naturally leads to one plausible evolutionary explanation for the existence of intragenic global suppressor mutations.}, author = {Risso, Valeria and Manssour Triedo, Fadia and Delgado Delgado, Asuncion and Arco, Rocio and Barroso Deljesús, Alicia and Inglés Prieto, Álvaro and Godoy Ruiz, Raquel and Gavira, Josè and Gaucher, Eric and Ibarra Molero, Beatriz and Sánchez Ruiz, Jose}, journal = {Molecular Biology and Evolution}, number = {2}, pages = {440 -- 455}, publisher = {Oxford University Press}, title = {{Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history}}, doi = {10.1093/molbev/msu312}, volume = {32}, year = {2014}, } @article{1842, abstract = {We prove polynomial upper bounds of geometric Ramsey numbers of pathwidth-2 outerplanar triangulations in both convex and general cases. We also prove that the geometric Ramsey numbers of the ladder graph on 2n vertices are bounded by O(n3) and O(n10), in the convex and general case, respectively. We then apply similar methods to prove an (Formula presented.) upper bound on the Ramsey number of a path with n ordered vertices.}, author = {Cibulka, Josef and Gao, Pu and Krcál, Marek and Valla, Tomáš and Valtr, Pavel}, journal = {Discrete & Computational Geometry}, number = {1}, pages = {64 -- 79}, publisher = {Springer}, title = {{On the geometric ramsey number of outerplanar graphs}}, doi = {10.1007/s00454-014-9646-x}, volume = {53}, year = {2014}, } @article{1854, abstract = {In this paper, we present a method for non-rigid, partial shape matching in vector graphics. Given a user-specified query region in a 2D shape, similar regions are found, even if they are non-linearly distorted. Furthermore, a non-linear mapping is established between the query regions and these matches, which allows the automatic transfer of editing operations such as texturing. This is achieved by a two-step approach. First, pointwise correspondences between the query region and the whole shape are established. The transformation parameters of these correspondences are registered in an appropriate transformation space. For transformations between similar regions, these parameters form surfaces in transformation space, which are extracted in the second step of our method. The extracted regions may be related to the query region by a non-rigid transform, enabling non-rigid shape matching. In this paper, we present a method for non-rigid, partial shape matching in vector graphics. Given a user-specified query region in a 2D shape, similar regions are found, even if they are non-linearly distorted. Furthermore, a non-linear mapping is established between the query regions and these matches, which allows the automatic transfer of editing operations such as texturing. This is achieved by a two-step approach. First, pointwise correspondences between the query region and the whole shape are established. The transformation parameters of these correspondences are registered in an appropriate transformation space. For transformations between similar regions, these parameters form surfaces in transformation space, which are extracted in the second step of our method. The extracted regions may be related to the query region by a non-rigid transform, enabling non-rigid shape matching.}, author = {Guerrero, Paul and Auzinger, Thomas and Wimmer, Michael and Jeschke, Stefan}, journal = {Computer Graphics Forum}, number = {1}, pages = {239 -- 252}, publisher = {Wiley}, title = {{Partial shape matching using transformation parameter similarity}}, doi = {10.1111/cgf.12509}, volume = {34}, year = {2014}, } @article{1852, abstract = {To control morphogenesis, molecular regulatory networks have to interfere with the mechanical properties of the individual cells of developing organs and tissues, but how this is achieved is not well known. We study this issue here in the shoot meristem of higher plants, a group of undifferentiated cells where complex changes in growth rates and directions lead to the continuous formation of new organs [1, 2]. Here, we show that the plant hormone auxin plays an important role in this process via a dual, local effect on the extracellular matrix, the cell wall, which determines cell shape. Our study reveals that auxin not only causes a limited reduction in wall stiffness but also directly interferes with wall anisotropy via the regulation of cortical microtubule dynamics. We further show that to induce growth isotropy and organ outgrowth, auxin somehow interferes with the cortical microtubule-ordering activity of a network of proteins, including AUXIN BINDING PROTEIN 1 and KATANIN 1. Numerical simulations further indicate that the induced isotropy is sufficient to amplify the effects of the relatively minor changes in wall stiffness to promote organogenesis and the establishment of new growth axes in a robust manner.}, author = {Sassi, Massimiliano and Ali, Olivier and Boudon, Frédéric and Cloarec, Gladys and Abad, Ursula and Cellier, Coralie and Chen, Xu and Gilles, Benjamin and Milani, Pascale and Friml, Jirí and Vernoux, Teva and Godin, Christophe and Hamant, Olivier and Traas, Jan}, journal = {Current Biology}, number = {19}, pages = {2335 -- 2342}, publisher = {Cell Press}, title = {{An auxin-mediated shift toward growth isotropy promotes organ formation at the shoot meristem in Arabidopsis}}, doi = {10.1016/j.cub.2014.08.036}, volume = {24}, year = {2014}, } @inproceedings{1853, abstract = {Wireless sensor networks (WSNs) composed of low-power, low-cost sensor nodes are expected to form the backbone of future intelligent networks for a broad range of civil, industrial and military applications. These sensor nodes are often deployed through random spreading, and function in dynamic environments. Many applications of WSNs such as pollution tracking, forest fire detection, and military surveillance require knowledge of the location of constituent nodes. But the use of technologies such as GPS on all nodes is prohibitive due to power and cost constraints. So, the sensor nodes need to autonomously determine their locations. Most localization techniques use anchor nodes with known locations to determine the position of remaining nodes. Localization techniques have two conflicting requirements. On one hand, an ideal localization technique should be computationally simple and on the other hand, it must be resistant to attacks that compromise anchor nodes. In this paper, we propose a computationally light-weight game theoretic secure localization technique and demonstrate its effectiveness in comparison to existing techniques.}, author = {Jha, Susmit and Tripakis, Stavros and Seshia, Sanjit and Chatterjee, Krishnendu}, location = {Cambridge, USA}, pages = {85 -- 90}, publisher = {IEEE}, title = {{Game theoretic secure localization in wireless sensor networks}}, doi = {10.1109/IOT.2014.7030120}, year = {2014}, } @article{1862, abstract = {The prominent and evolutionarily ancient role of the plant hormone auxin is the regulation of cell expansion. Cell expansion requires ordered arrangement of the cytoskeleton but molecular mechanisms underlying its regulation by signalling molecules including auxin are unknown. Here we show in the model plant Arabidopsis thaliana that in elongating cells exogenous application of auxin or redistribution of endogenous auxin induces very rapid microtubule re-orientation from transverse to longitudinal, coherent with the inhibition of cell expansion. This fast auxin effect requires auxin binding protein 1 (ABP1) and involves a contribution of downstream signalling components such as ROP6 GTPase, ROP-interactive protein RIC1 and the microtubule-severing protein katanin. These components are required for rapid auxin-and ABP1-mediated re-orientation of microtubules to regulate cell elongation in roots and dark-grown hypocotyls as well as asymmetric growth during gravitropic responses.}, author = {Chen, Xu and Grandont, Laurie and Li, Hongjiang and Hauschild, Robert and Paque, Sébastien and Abuzeineh, Anas and Rakusova, Hana and Benková, Eva and Perrot Rechenmann, Catherine and Friml, Jirí}, issn = {1476-4687}, journal = {Nature}, number = {729}, pages = {90 -- 93}, publisher = {Nature Publishing Group}, title = {{Inhibition of cell expansion by rapid ABP1-mediated auxin effect on microtubules}}, doi = {10.1038/nature13889}, volume = {516}, year = {2014}, } @inproceedings{1869, abstract = {Boolean controllers for systems with complex datapaths are often very difficult to implement correctly, in particular when concurrency is involved. Yet, in many instances it is easy to formally specify correctness. For example, the specification for the controller of a pipelined processor only has to state that the pipelined processor gives the same results as a non-pipelined reference design. This makes such controllers a good target for automated synthesis. However, an efficient abstraction for the complex datapath elements is needed, as a bit-precise description is often infeasible. We present Suraq, the first controller synthesis tool which uses uninterpreted functions for the abstraction. Quantified firstorder formulas (with specific quantifier structure) serve as the specification language from which Suraq synthesizes Boolean controllers. Suraq transforms the specification into an unsatisfiable SMT formula, and uses Craig interpolation to compute its results. Using Suraq, we were able to synthesize a controller (consisting of two Boolean signals) for a five-stage pipelined DLX processor in roughly one hour and 15 minutes.}, author = {Hofferek, Georg and Gupta, Ashutosh}, booktitle = {HVC 2014}, editor = {Yahav, Eran}, location = {Haifa, Israel}, pages = {68 -- 74}, publisher = {Springer}, title = {{Suraq - a controller synthesis tool using uninterpreted functions}}, doi = {10.1007/978-3-319-13338-6_6}, volume = {8855}, year = {2014}, } @inproceedings{1872, abstract = {Extensionality axioms are common when reasoning about data collections, such as arrays and functions in program analysis, or sets in mathematics. An extensionality axiom asserts that two collections are equal if they consist of the same elements at the same indices. Using extensionality is often required to show that two collections are equal. A typical example is the set theory theorem (∀x)(∀y)x∪y = y ∪x. Interestingly, while humans have no problem with proving such set identities using extensionality, they are very hard for superposition theorem provers because of the calculi they use. In this paper we show how addition of a new inference rule, called extensionality resolution, allows first-order theorem provers to easily solve problems no modern first-order theorem prover can solve. We illustrate this by running the VAMPIRE theorem prover with extensionality resolution on a number of set theory and array problems. Extensionality resolution helps VAMPIRE to solve problems from the TPTP library of first-order problems that were never solved before by any prover.}, author = {Gupta, Ashutosh and Kovács, Laura and Kragl, Bernhard and Voronkov, Andrei}, booktitle = {ATVA 2014}, editor = {Cassez, Franck and Raskin, Jean-François}, location = {Sydney, Australia}, pages = {185 -- 200}, publisher = {Springer}, title = {{Extensional crisis and proving identity}}, doi = {10.1007/978-3-319-11936-6_14}, volume = {8837}, year = {2014}, } @inproceedings{1870, abstract = {We investigate the problem of checking if a finite-state transducer is robust to uncertainty in its input. Our notion of robustness is based on the analytic notion of Lipschitz continuity - a transducer is K-(Lipschitz) robust if the perturbation in its output is at most K times the perturbation in its input. We quantify input and output perturbation using similarity functions. We show that K-robustness is undecidable even for deterministic transducers. We identify a class of functional transducers, which admits a polynomial time automata-theoretic decision procedure for K-robustness. This class includes Mealy machines and functional letter-to-letter transducers. We also study K-robustness of nondeterministic transducers. Since a nondeterministic transducer generates a set of output words for each input word, we quantify output perturbation using setsimilarity functions. We show that K-robustness of nondeterministic transducers is undecidable, even for letter-to-letter transducers. We identify a class of set-similarity functions which admit decidable K-robustness of letter-to-letter transducers.}, author = {Henzinger, Thomas A and Otop, Jan and Samanta, Roopsha}, booktitle = {Leibniz International Proceedings in Informatics, LIPIcs}, location = {Delhi, India}, pages = {431 -- 443}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Lipschitz robustness of finite-state transducers}}, doi = {10.4230/LIPIcs.FSTTCS.2014.431}, volume = {29}, year = {2014}, } @inproceedings{1875, abstract = {We present a formal framework for repairing infinite-state, imperative, sequential programs, with (possibly recursive) procedures and multiple assertions; the framework can generate repaired programs by modifying the original erroneous program in multiple program locations, and can ensure the readability of the repaired program using user-defined expression templates; the framework also generates a set of inductive assertions that serve as a proof of correctness of the repaired program. As a step toward integrating programmer intent and intuition in automated program repair, we present a cost-aware formulation - given a cost function associated with permissible statement modifications, the goal is to ensure that the total program modification cost does not exceed a given repair budget. As part of our predicate abstractionbased solution framework, we present a sound and complete algorithm for repair of Boolean programs. We have developed a prototype tool based on SMT solving and used it successfully to repair diverse errors in benchmark C programs.}, author = {Samanta, Roopsha and Olivo, Oswaldo and Allen, Emerson}, editor = {Müller-Olm, Markus and Seidl, Helmut}, location = {Munich, Germany}, pages = {268 -- 284}, publisher = {Springer}, title = {{Cost-aware automatic program repair}}, doi = {10.1007/978-3-319-10936-7_17}, volume = {8723}, year = {2014}, } @article{1876, abstract = {We study densities of functionals over uniformly bounded triangulations of a Delaunay set of vertices, and prove that the minimum is attained for the Delaunay triangulation if this is the case for finite sets.}, author = {Dolbilin, Nikolai and Edelsbrunner, Herbert and Glazyrin, Alexey and Musin, Oleg}, issn = {16093321}, journal = {Moscow Mathematical Journal}, number = {3}, pages = {491 -- 504}, publisher = {Independent University of Moscow}, title = {{Functionals on triangulations of delaunay sets}}, doi = {10.17323/1609-4514-2014-14-3-491-504}, volume = {14}, year = {2014}, } @article{1877, abstract = {During inflammation, lymph nodes swell with an influx of immune cells. New findings identify a signalling pathway that induces relaxation in the contractile cells that give structure to these organs.}, author = {Sixt, Michael K and Vaahtomeri, Kari}, journal = {Nature}, number = {7523}, pages = {441 -- 442}, publisher = {Springer Nature}, title = {{Physiology: Relax and come in}}, doi = {10.1038/514441a}, volume = {514}, year = {2014}, } @article{1886, abstract = {Information processing in the sensory periphery is shaped by natural stimulus statistics. In the periphery, a transmission bottleneck constrains performance; thus efficient coding implies that natural signal components with a predictably wider range should be compressed. In a different regime—when sampling limitations constrain performance—efficient coding implies that more resources should be allocated to informative features that are more variable. We propose that this regime is relevant for sensory cortex when it extracts complex features from limited numbers of sensory samples. To test this prediction, we use central visual processing as a model: we show that visual sensitivity for local multi-point spatial correlations, described by dozens of independently-measured parameters, can be quantitatively predicted from the structure of natural images. This suggests that efficient coding applies centrally, where it extends to higher-order sensory features and operates in a regime in which sensitivity increases with feature variability.}, author = {Hermundstad, Ann and Briguglio, John and Conte, Mary and Victor, Jonathan and Balasubramanian, Vijay and Tkacik, Gasper}, journal = {eLife}, number = {November}, publisher = {eLife Sciences Publications}, title = {{Variance predicts salience in central sensory processing}}, doi = {10.7554/eLife.03722}, year = {2014}, } @article{1890, abstract = {To search for a target in a complex environment is an everyday behavior that ends with finding the target. When we search for two identical targets, however, we must continue the search after finding the first target and memorize its location. We used fixation-related potentials to investigate the neural correlates of different stages of the search, that is, before and after finding the first target. Having found the first target influenced subsequent distractor processing. Compared to distractor fixations before the first target fixation, a negative shift was observed for three subsequent distractor fixations. These results suggest that processing a target in continued search modulates the brain's response, either transiently by reflecting temporary working memory processes or permanently by reflecting working memory retention.}, author = {Körner, Christof and Braunstein, Verena and Stangl, Matthias and Schlögl, Alois and Neuper, Christa and Ischebeck, Anja}, journal = {Psychophysiology}, number = {4}, pages = {385 -- 395}, publisher = {Wiley-Blackwell}, title = {{Sequential effects in continued visual search: Using fixation-related potentials to compare distractor processing before and after target detection}}, doi = {10.1111/psyp.12062}, volume = {51}, year = {2014}, } @article{1892, abstract = {Behavioural variation among conspecifics is typically contingent on individual state or environmental conditions. Sex-specific genetic polymorphisms are enigmatic because they lack conditionality, and genes causing adaptive trait variation in one sex may reduce Darwinian fitness in the other. One way to avoid such genetic antagonism is to control sex-specific traits by inheritance via sex chromosomes. Here, controlled laboratory crossings suggest that in snail-brooding cichlid fish a single locus, two-allele polymorphism located on a sex-linked chromosome of heterogametic males generates an extreme reproductive dimorphism. Both natural and sexual selection are responsible for exceptionally large body size of bourgeois males, creating a niche for a miniature male phenotype to evolve. This extreme intrasexual dimorphism results from selection on opposite size thresholds caused by a single ecological factor, empty snail shells used as breeding substrate. Paternity analyses reveal that in the field parasitic dwarf males sire the majority of offspring in direct sperm competition with large nest owners exceeding their size more than 40 times. Apparently, use of empty snail shells as breeding substrate and single locus sex-linked inheritance of growth are the major ecological and genetic mechanisms responsible for the extreme intrasexual diversity observed in Lamprologus callipterus.}, author = {Ocana, Sabine and Meidl, Patrick and Bonfils, Danielle and Taborsky, Michael}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1794}, publisher = {The Royal Society}, title = {{Y-linked Mendelian inheritance of giant and dwarf male morphs in shell-brooding cichlids}}, doi = {10.1098/rspb.2014.0253}, volume = {281}, year = {2014}, } @article{1891, abstract = {We provide theoretical tests of a novel experimental technique to determine mechanostability of proteins based on stretching a mechanically protected protein by single-molecule force spectroscopy. This technique involves stretching a homogeneous or heterogeneous chain of reference proteins (single-molecule markers) in which one of them acts as host to the guest protein under study. The guest protein is grafted into the host through genetic engineering. It is expected that unraveling of the host precedes the unraveling of the guest removing ambiguities in the reading of the force-extension patterns of the guest protein. We study examples of such systems within a coarse-grained structure-based model. We consider systems with various ratios of mechanostability for the host and guest molecules and compare them to experimental results involving cohesin I as the guest molecule. For a comparison, we also study the force-displacement patterns in proteins that are linked in a serial fashion. We find that the mechanostability of the guest is similar to that of the isolated or serially linked protein. We also demonstrate that the ideal configuration of this strategy would be one in which the host is much more mechanostable than the single-molecule markers. We finally show that it is troublesome to use the highly stable cystine knot proteins as a host to graft a guest in stretching studies because this would involve a cleaving procedure.}, author = {Chwastyk, Mateusz and Galera Prat, Albert and Sikora, Mateusz K and Gómez Sicilia, Àngel and Carrión Vázquez, Mariano and Cieplak, Marek}, journal = {Proteins: Structure, Function and Bioinformatics}, number = {5}, pages = {717 -- 726}, publisher = {Wiley-Blackwell}, title = {{Theoretical tests of the mechanical protection strategy in protein nanomechanics}}, doi = {10.1002/prot.24436}, volume = {82}, year = {2014}, } @article{1884, abstract = {Unbiased high-throughput massively parallel sequencing methods have transformed the process of discovery of novel putative driver gene mutations in cancer. In chronic lymphocytic leukemia (CLL), these methods have yielded several unexpected findings, including the driver genes SF3B1, NOTCH1 and POT1. Recent analysis, utilizing down-sampling of existing datasets, has shown that the discovery process of putative drivers is far from complete across cancer. In CLL, while driver gene mutations affecting >10% of patients were efficiently discovered with previously published CLL cohorts of up to 160 samples subjected to whole exome sequencing (WES), this sample size has only 0.78 power to detect drivers affecting 5% of patients, and only 0.12 power for drivers affecting 2% of patients. These calculations emphasize the need to apply unbiased WES to larger patient cohorts.}, author = {Landau, Dan and Stewart, Chip and Reiter, Johannes and Lawrence, Michael and Sougnez, Carrie and Brown, Jennifer and Lopez Guillermo, Armando and Gabriel, Stacey and Lander, Eric and Neuberg, Donna and López Otín, Carlos and Campo, Elias and Getz, Gad and Wu, Catherine}, journal = {Blood}, number = {21}, pages = {1952 -- 1952}, publisher = {American Society of Hematology}, title = {{Novel putative driver gene mutations in chronic lymphocytic leukemia (CLL): results from a combined analysis of whole exome sequencing of 262 primary CLL aamples}}, volume = {124}, year = {2014}, } @article{1889, abstract = {We study translation-invariant quasi-free states for a system of fermions with two-particle interactions. The associated energy functional is similar to the BCS functional but also includes direct and exchange energies. We show that for suitable short-range interactions, these latter terms only lead to a renormalization of the chemical potential, with the usual properties of the BCS functional left unchanged. Our analysis thus represents a rigorous justification of part of the BCS approximation. We give bounds on the critical temperature below which the system displays superfluidity.}, author = {Bräunlich, Gerhard and Hainzl, Christian and Seiringer, Robert}, journal = {Reviews in Mathematical Physics}, number = {7}, publisher = {World Scientific Publishing}, title = {{Translation-invariant quasi-free states for fermionic systems and the BCS approximation}}, doi = {10.1142/S0129055X14500123}, volume = {26}, year = {2014}, } @article{1894, abstract = {Background: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. Methods and Results: Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. Conclusions: Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute the considerable insight to the Epsilonproteobacterial Dsb systems, which have been poorly understood so far.}, author = {Grabowska, Anna and Wywiał, Ewa and Dunin Horkawicz, Stanislaw and Łasica, Anna and Wösten, Marc and Nagy-Staron, Anna A and Godlewska, Renata and Bocian Ostrzycka, Katarzyna and Pieńkowska, Katarzyna and Łaniewski, Paweł and Bujnicki, Janusz and Van Putten, Jos and Jagusztyn Krynicka, Elzbieta}, journal = {PLoS One}, number = {9}, publisher = {Public Library of Science}, title = {{Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA}}, doi = {10.1371/journal.pone.0106247}, volume = {9}, year = {2014}, } @article{1895, abstract = {Major histocompatibility complex class I (MHCI) molecules were recently identified as novel regulators of synaptic plasticity. These molecules are expressed in various brain areas, especially in regions undergoing activity-dependent synaptic plasticity, but their role in the nucleus accumbens (NAc) is unknown. In this study, we investigated the effects of genetic disruption of MHCI function, through deletion of β2-microblobulin, which causes lack of cell surface expression of MHCI. First, we confirmed that MHCI molecules are expressed in the NAc core in wild-type mice. Second, we performed electrophysiological recordings with NAc core slices from wild-type and β2-microglobulin knock-out mice lacking cell surface expression of MHCI. We found that low frequency stimulation induced long-term depression in wild-type but not knock-out mice, whereas high frequency stimulation induced long-term potentiation in both genotypes, with a larger magnitude in knock-out mice. Furthermore, we demonstrated that knock-out mice showed more persistent behavioral sensitization to cocaine, which is a NAc-related behavior. Using this model, we analyzed the density of total AMPA receptors and their subunits GluR1 and GluR2 in the NAc core, by SDS-digested freeze-fracture replica labeling. After repeated cocaine exposure, the density of GluR1 was increased, but there was no change in total AMPA receptors and GluR2 levels in wildtype mice. In contrast, following repeated cocaine exposure, increased densities of total AMPA receptors, GluR1 and GluR2 were observed in knock-out mice. These results indicate that functional deficiency of MHCI enhances synaptic potentiation, induced by electrical and pharmacological stimulation.}, author = {Edamura, Mitsuhiro and Murakami, Gen and Meng, Hongrui and Itakura, Makoto and Shigemoto, Ryuichi and Fukuda, Atsuo and Nakahara, Daiichiro}, journal = {PLoS One}, number = {9}, publisher = {Public Library of Science}, title = {{Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice}}, doi = {10.1371/journal.pone.0107099}, volume = {9}, year = {2014}, } @article{1893, abstract = {Phosphatidylinositol (PtdIns) is a structural phospholipid that can be phosphorylated into various lipid signaling molecules, designated polyphosphoinositides (PPIs). The reversible phosphorylation of PPIs on the 3, 4, or 5 position of inositol is performed by a set of organelle-specific kinases and phosphatases, and the characteristic head groups make these molecules ideal for regulating biological processes in time and space. In yeast and mammals, PtdIns3P and PtdIns(3,5)P2 play crucial roles in trafficking toward the lytic compartments, whereas the role in plants is not yet fully understood. Here we identified the role of a land plant-specific subgroup of PPI phosphatases, the suppressor of actin 2 (SAC2) to SAC5, during vacuolar trafficking and morphogenesis in Arabidopsis thaliana. SAC2-SAC5 localize to the tonoplast along with PtdIns3P, the presumable product of their activity. In SAC gain- and loss-of-function mutants, the levels of PtdIns monophosphates and bisphosphates were changed, with opposite effects on the morphology of storage and lytic vacuoles, and the trafficking toward the vacuoles was defective. Moreover, multiple sac knockout mutants had an increased number of smaller storage and lytic vacuoles, whereas extralarge vacuoles were observed in the overexpression lines, correlating with various growth and developmental defects. The fragmented vacuolar phenotype of sac mutants could be mimicked by treating wild-type seedlings with PtdIns(3,5)P2, corroborating that this PPI is important for vacuole morphology. Taken together, these results provide evidence that PPIs, together with their metabolic enzymes SAC2-SAC5, are crucial for vacuolar trafficking and for vacuolar morphology and function in plants.}, author = {Nováková, Petra and Hirsch, Sibylle and Feraru, Elena and Tejos, Ricardo and Van Wijk, Ringo and Viaene, Tom and Heilmann, Mareike and Lerche, Jennifer and De Rycke, Riet and Feraru, Mugurel and Grones, Peter and Van Montagu, Marc and Heilmann, Ingo and Munnik, Teun and Friml, Jirí}, journal = {PNAS}, number = {7}, pages = {2818 -- 2823}, publisher = {National Academy of Sciences}, title = {{SAC phosphoinositide phosphatases at the tonoplast mediate vacuolar function in Arabidopsis}}, doi = {10.1073/pnas.1324264111}, volume = {111}, year = {2014}, } @article{1896, abstract = {Biopolymer length regulation is a complex process that involves a large number of biological, chemical, and physical subprocesses acting simultaneously across multiple spatial and temporal scales. An illustrative example important for genomic stability is the length regulation of telomeres - nucleoprotein structures at the ends of linear chromosomes consisting of tandemly repeated DNA sequences and a specialized set of proteins. Maintenance of telomeres is often facilitated by the enzyme telomerase but, particularly in telomerase-free systems, the maintenance of chromosomal termini depends on alternative lengthening of telomeres (ALT) mechanisms mediated by recombination. Various linear and circular DNA structures were identified to participate in ALT, however, dynamics of the whole process is still poorly understood. We propose a chemical kinetics model of ALT with kinetic rates systematically derived from the biophysics of DNA diffusion and looping. The reaction system is reduced to a coagulation-fragmentation system by quasi-steady-state approximation. The detailed treatment of kinetic rates yields explicit formulas for expected size distributions of telomeres that demonstrate the key role played by the J factor, a quantitative measure of bending of polymers. The results are in agreement with experimental data and point out interesting phenomena: an appearance of very long telomeric circles if the total telomere density exceeds a critical value (excess mass) and a nonlinear response of the telomere size distributions to the amount of telomeric DNA in the system. The results can be of general importance for understanding dynamics of telomeres in telomerase-independent systems as this mode of telomere maintenance is similar to the situation in tumor cells lacking telomerase activity. Furthermore, due to its universality, the model may also serve as a prototype of an interaction between linear and circular DNA structures in various settings.}, author = {Kollár, Richard and Bod'ová, Katarína and Nosek, Jozef and Tomáška, Ľubomír}, journal = {Physical Review E Statistical Nonlinear and Soft Matter Physics}, number = {3}, publisher = {American Institute of Physics}, title = {{Mathematical model of alternative mechanism of telomere length maintenance}}, doi = {10.1103/PhysRevE.89.032701}, volume = {89}, year = {2014}, } @article{1897, abstract = {GNOM is one of the most characterized membrane trafficking regulators in plants, with crucial roles in development. GNOM encodes an ARF-guanine nucleotide exchange factor (ARF-GEF) that activates small GTPases of the ARF (ADP ribosylation factor) class to mediate vesicle budding at endomembranes. The crucial role of GNOM in recycling of PIN auxin transporters and other proteins to the plasma membrane was identified in studies using the ARF-GEF inhibitor brefeldin A (BFA). GNOM, the most prominent regulator of recycling in plants, has been proposed to act and localize at so far elusive recycling endosomes. Here, we report the GNOM localization in context of its cellular function in Arabidopsis thaliana. State-of-the-art imaging, pharmacological interference, and ultrastructure analysis show that GNOM predominantly localizes to Golgi apparatus. Super-resolution confocal live imaging microscopy identified GNOM and its closest homolog GNOM-like 1 at distinct subdomains on Golgi cisternae. Short-term BFA treatment stabilizes GNOM at the Golgi apparatus, whereas prolonged exposures results in GNOM translocation to trans-Golgi network (TGN)/early endosomes (EEs). Malformed TGN/EE in gnom mutants suggests a role for GNOM in maintaining TGN/EE function. Our results redefine the subcellular action of GNOM and reevaluate the identity and function of recycling endosomes in plants.}, author = {Naramoto, Satoshi and Otegui, Marisa and Kutsuna, Natsumaro and De Rycke, Riet and Dainobu, Tomoko and Karampelias, Michael and Fujimoto, Masaru and Feraru, Elena and Miki, Daisuke and Fukuda, Hiroo and Nakano, Akihiko and Friml, Jirí}, journal = {Plant Cell}, number = {7}, pages = {3062 -- 3076}, publisher = {American Society of Plant Biologists}, title = {{Insights into the localization and function of the membrane trafficking regulator GNOM ARF-GEF at the Golgi apparatus in Arabidopsis}}, doi = {10.1105/tpc.114.125880}, volume = {26}, year = {2014}, } @article{1899, abstract = {Asymmetric cell divisions allow stem cells to balance proliferation and differentiation. During embryogenesis, murine epidermis expands rapidly from a single layer of unspecified basal layer progenitors to a stratified, differentiated epithelium. Morphogenesis involves perpendicular (asymmetric) divisions and the spindle orientation protein LGN, but little is known about how the apical localization of LGN is regulated. Here, we combine conventional genetics and lentiviral-mediated in vivo RNAi to explore the functions of the LGN-interacting proteins Par3, mInsc and Gα i3. Whereas loss of each gene alone leads to randomized division angles, combined loss of Gnai3 and mInsc causes a phenotype of mostly planar divisions, akin to loss of LGN. These findings lend experimental support for the hitherto untested model that Par3-mInsc and Gα i3 act cooperatively to polarize LGN and promote perpendicular divisions. Finally, we uncover a developmental switch between delamination-driven early stratification and spindle-orientation-dependent differentiation that occurs around E15, revealing a two-step mechanism underlying epidermal maturation.}, author = {Williams, Scott and Ratliff, Lyndsay and Postiglione, Maria P and Knoblich, Juergen and Fuchs, Elaine}, journal = {Nature Cell Biology}, number = {8}, pages = {758 -- 769}, publisher = {Nature Publishing Group}, title = {{Par3-mInsc and Gα i3 cooperate to promote oriented epidermal cell divisions through LGN}}, doi = {10.1038/ncb3001}, volume = {16}, year = {2014}, } @article{1898, abstract = {Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported invivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission upto ~1 kHz. Presynaptic APs are ultrafast, with ~100μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca2+ channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling.}, author = {Ritzau Jost, Andreas and Delvendahl, Igor and Rings, Annika and Byczkowicz, Niklas and Harada, Harumi and Shigemoto, Ryuichi and Hirrlinger, Johannes and Eilers, Jens and Hallermann, Stefan}, journal = {Neuron}, number = {1}, pages = {152 -- 163}, publisher = {Elsevier}, title = {{Ultrafast action potentials mediate kilohertz signaling at a central synapse}}, doi = {10.1016/j.neuron.2014.08.036}, volume = {84}, year = {2014}, } @article{1906, abstract = {In this paper, we introduce a novel scene representation for the visualization of large-scale point clouds accompanied by a set of high-resolution photographs. Many real-world applications deal with very densely sampled point-cloud data, which are augmented with photographs that often reveal lighting variations and inaccuracies in registration. Consequently, the high-quality representation of the captured data, i.e., both point clouds and photographs together, is a challenging and time-consuming task. We propose a two-phase approach, in which the first (preprocessing) phase generates multiple overlapping surface patches and handles the problem of seamless texture generation locally for each patch. The second phase stitches these patches at render-time to produce a high-quality visualization of the data. As a result of the proposed localization of the global texturing problem, our algorithm is more than an order of magnitude faster than equivalent mesh-based texturing techniques. Furthermore, since our preprocessing phase requires only a minor fraction of the whole data set at once, we provide maximum flexibility when dealing with growing data sets.}, author = {Arikan, Murat and Preiner, Reinhold and Scheiblauer, Claus and Jeschke, Stefan and Wimmer, Michael}, journal = {IEEE Transactions on Visualization and Computer Graphics}, number = {9}, pages = {1280 -- 1292}, publisher = {IEEE}, title = {{Large-scale point-cloud visualization through localized textured surface reconstruction}}, doi = {10.1109/TVCG.2014.2312011}, volume = {20}, year = {2014}, } @article{1905, abstract = {The unprecedented polymorphism in the major histocompatibility complex (MHC) genes is thought to be maintained by balancing selection from parasites. However, do parasites also drive divergence at MHC loci between host populations, or do the effects of balancing selection maintain similarities among populations? We examined MHC variation in populations of the livebearing fish Poecilia mexicana and characterized their parasite communities. Poecilia mexicana populations in the Cueva del Azufre system are locally adapted to darkness and the presence of toxic hydrogen sulphide, representing highly divergent ecotypes or incipient species. Parasite communities differed significantly across populations, and populations with higher parasite loads had higher levels of diversity at class II MHC genes. However, despite different parasite communities, marked divergence in adaptive traits and in neutral genetic markers, we found MHC alleles to be remarkably similar among host populations. Our findings indicate that balancing selection from parasites maintains immunogenetic diversity of hosts, but this process does not promote MHC divergence in this system. On the contrary, we suggest that balancing selection on immunogenetic loci may outweigh divergent selection causing divergence, thereby hindering host divergence and speciation. Our findings support the hypothesis that balancing selection maintains MHC similarities among lineages during and after speciation (trans-species evolution).}, author = {Tobler, Michael and Plath, Martin and Riesch, Rüdiger and Schlupp, Ingo and Grasse, Anna V and Munimanda, Gopi and Setzer, C and Penn, Dustin and Moodley, Yoshan}, issn = {1420-9101}, journal = {Journal of Evolutionary Biology}, number = {5}, pages = {960 -- 974}, publisher = {Wiley}, title = {{Selection from parasites favours immunogenetic diversity but not divergence among locally adapted host populations}}, doi = {10.1111/jeb.12370}, volume = {27}, year = {2014}, } @article{1902, abstract = {In the 1960s-1980s, determination of bacterial growth rates was an important tool in microbial genetics, biochemistry, molecular biology, and microbial physiology. The exciting technical developments of the 1990s and the 2000s eclipsed that tool; as a result, many investigators today lack experience with growth rate measurements. Recently, investigators in a number of areas have started to use measurements of bacterial growth rates for a variety of purposes. Those measurements have been greatly facilitated by the availability of microwell plate readers that permit the simultaneous measurements on up to 384 different cultures. Only the exponential (logarithmic) portions of the resulting growth curves are useful for determining growth rates, and manual determination of that portion and calculation of growth rates can be tedious for high-throughput purposes. Here, we introduce the program GrowthRates that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase. GrowthRates is freely available for Macintosh, Windows, and Linux.We discuss the effects of culture volume, the classical bacterial growth curve, and the differences between determinations in rich media and minimal (mineral salts) media. This protocol covers calibration of the plate reader, growth of culture inocula for both rich and minimal media, and experimental setup. As a guide to reliability, we report typical day-to-day variation in growth rates and variation within experiments with respect to position of wells within the plates.}, author = {Hall, Barry and Acar, Hande and Nandipati, Anna and Barlow, Miriam}, issn = {1537-1719}, journal = {Molecular Biology and Evolution}, number = {1}, pages = {232 -- 238}, publisher = {Oxford University Press}, title = {{Growth rates made easy}}, doi = {10.1093/molbev/mst187}, volume = {31}, year = {2014}, } @article{1901, abstract = {In plants, the patterning of stem cell-enriched meristems requires a graded auxin response maximum that emerges from the concerted action of polar auxin transport, auxin biosynthesis, auxin metabolism, and cellular auxin response machinery. However, mechanisms underlying this auxin response maximum-mediated root stem cell maintenance are not fully understood. Here, we present unexpected evidence that WUSCHEL-RELATED HOMEOBOX 5 (WOX5) transcription factor modulates expression of auxin biosynthetic genes in the quiescent center (QC) of the root and thus provides a robust mechanism for the maintenance of auxin response maximum in the root tip. This WOX5 action is balanced through the activity of indole-3-acetic acid 17 (IAA17) auxin response repressor. Our combined genetic, cell biology, and computational modeling studies revealed a previously uncharacterized feedback loop linking WOX5-mediated auxin production to IAA17-dependent repression of auxin responses. This WOX5-IAA17 feedback circuit further assures the maintenance of auxin response maximum in the root tip and thereby contributes to the maintenance of distal stem cell (DSC) populations. Our experimental studies and in silico computer simulations both demonstrate that the WOX5-IAA17 feedback circuit is essential for the maintenance of auxin gradient in the root tip and the auxin-mediated root DSC differentiation.}, author = {Tian, Huiyu and Wabnik, Krzysztof T and Niu, Tiantian and Li, Hongjiang and Yu, Qianqian and Pollmann, Stephan and Vanneste, Steffen and Govaerts, Willy and Rolčík, Jakub and Geisler, Markus and Friml, Jirí and Ding, Zhaojun}, journal = {Molecular Plant}, number = {2}, pages = {277 -- 289}, publisher = {Oxford University Press}, title = {{WOX5-IAA17 feedback circuit-mediated cellular auxin response is crucial for the patterning of root stem cell niches in arabidopsis}}, doi = {10.1093/mp/sst118}, volume = {7}, year = {2014}, } @article{1904, abstract = {We prove a Strichartz inequality for a system of orthonormal functions, with an optimal behavior of the constant in the limit of a large number of functions. The estimate generalizes the usual Strichartz inequality, in the same fashion as the Lieb-Thirring inequality generalizes the Sobolev inequality. As an application, we consider the Schrödinger equation with a time-dependent potential and we show the existence of the wave operator in Schatten spaces.}, author = {Frank, Rupert and Lewin, Mathieu and Lieb, Élliott and Seiringer, Robert}, journal = {Journal of the European Mathematical Society}, number = {7}, pages = {1507 -- 1526}, publisher = {European Mathematical Society}, title = {{Strichartz inequality for orthonormal functions}}, doi = {10.4171/JEMS/467}, volume = {16}, year = {2014}, } @article{1900, abstract = {Epithelial cell layers need to be tightly regulated to maintain their integrity and correct function. Cell integration into epithelial sheets is now shown to depend on the N-WASP-regulated stabilization of cortical F-actin, which generates distinct patterns of apical-lateral contractility at E-cadherin-based cell-cell junctions.}, author = {Behrndt, Martin and Heisenberg, Carl-Philipp J}, journal = {Nature Cell Biology}, number = {2}, pages = {127 -- 129}, publisher = {Nature Publishing Group}, title = {{Lateral junction dynamics lead the way out}}, doi = {10.1038/ncb2913}, volume = {16}, year = {2014}, } @article{1909, abstract = {Summary: Phenotypes are often environmentally dependent, which requires organisms to track environmental change. The challenge for organisms is to construct phenotypes using the most accurate environmental cue. Here, we use a quantitative genetic model of adaptation by additive genetic variance, within- and transgenerational plasticity via linear reaction norms and indirect genetic effects respectively. We show how the relative influence on the eventual phenotype of these components depends on the predictability of environmental change (fast or slow, sinusoidal or stochastic) and the developmental lag τ between when the environment is perceived and when selection acts. We then decompose expected mean fitness into three components (variance load, adaptation and fluctuation load) to study the fitness costs of within- and transgenerational plasticity. A strongly negative maternal effect coefficient m minimizes the variance load, but a strongly positive m minimises the fluctuation load. The adaptation term is maximized closer to zero, with positive or negative m preferred under different environmental scenarios. Phenotypic plasticity is higher when τ is shorter and when the environment changes frequently between seasonal extremes. Expected mean population fitness is highest away from highest observed levels of phenotypic plasticity. Within- and transgenerational plasticity act in concert to deliver well-adapted phenotypes, which emphasizes the need to study both simultaneously when investigating phenotypic evolution.}, author = {Ezard, Thomas and Prizak, Roshan and Hoyle, Rebecca}, journal = {Functional Ecology}, number = {3}, pages = {693 -- 701}, publisher = {Wiley-Blackwell}, title = {{The fitness costs of adaptation via phenotypic plasticity and maternal effects}}, doi = {10.1111/1365-2435.12207}, volume = {28}, year = {2014}, } @article{1910, abstract = {angerhans cells (LCs) are a unique subset of dendritic cells (DCs) that express epithelial adhesion molecules, allowing them to form contacts with epithelial cells and reside in epidermal/epithelial tissues. The dynamic regulation of epithelial adhesion plays a decisive role in the life cycle of LCs. It controls whether LCs remain immature and sessile within the epidermis or mature and egress to initiate immune responses. So far, the molecular machinery regulating epithelial adhesion molecules during LC maturation remains elusive. Here, we generated pure populations of immature human LCs in vitro to systematically probe for gene-expression changes during LC maturation. LCs down-regulate a set of epithelial genes including E-cadherin, while they upregulate the mesenchymal marker N-cadherin known to facilitate cell migration. In addition, N-cadherin is constitutively expressed by monocyte-derived DCs known to exhibit characteristics of both inflammatory-type and interstitial/dermal DCs. Moreover, the transcription factors ZEB1 and ZEB2 (ZEB is zinc-finger E-box-binding homeobox) are upregulated in migratory LCs. ZEB1 and ZEB2 have been shown to induce epithelial-to-mesenchymal transition (EMT) and invasive behavior in cancer cells undergoing metastasis. Our results provide the first hint that the molecular EMT machinery might facilitate LC mobilization. Moreover, our study suggests that N-cadherin plays a role during DC migration.}, author = {Konradi, Sabine and Yasmin, Nighat and Haslwanter, Denise and Weber, Michele and Gesslbauer, Bernd and Sixt, Michael K and Strobl, Herbert}, journal = {European Journal of Immunology}, number = {2}, pages = {553 -- 560}, publisher = {Wiley-Blackwell}, title = {{Langerhans cell maturation is accompanied by induction of N-cadherin and the transcriptional regulators of epithelial-mesenchymal transition ZEB1/2}}, doi = {10.1002/eji.201343681}, volume = {44}, year = {2014}, } @inproceedings{1907, abstract = {Most cryptographic security proofs require showing that two systems are indistinguishable. A central tool in such proofs is that of a game, where winning the game means provoking a certain condition, and it is shown that the two systems considered cannot be distinguished unless this condition is provoked. Upper bounding the probability of winning such a game, i.e., provoking this condition, for an arbitrary strategy is usually hard, except in the special case where the best strategy for winning such a game is known to be non-adaptive. A sufficient criterion for ensuring the optimality of non-adaptive strategies is that of conditional equivalence to a system, a notion introduced in [1]. In this paper, we show that this criterion is not necessary to ensure the optimality of non-adaptive strategies by giving two results of independent interest: 1) the optimality of non-adaptive strategies is not preserved under parallel composition; 2) in contrast, conditional equivalence is preserved under parallel composition.}, author = {Demay, Grégory and Gazi, Peter and Maurer, Ueli and Tackmann, Björn}, booktitle = {IEEE International Symposium on Information Theory}, location = {Honolulu, USA}, publisher = {IEEE}, title = {{Optimality of non-adaptive strategies: The case of parallel games}}, doi = {10.1109/ISIT.2014.6875125}, year = {2014}, } @article{1908, abstract = {In large populations, multiple beneficial mutations may be simultaneously spreading. In asexual populations, these mutations must either arise on the same background or compete against each other. In sexual populations, recombination can bring together beneficial alleles from different backgrounds, but tightly linked alleles may still greatly interfere with each other. We show for well-mixed populations that when this interference is strong, the genome can be seen as consisting of many effectively asexual stretches linked together. The rate at which beneficial alleles fix is thus roughly proportional to the rate of recombination and depends only logarithmically on the mutation supply and the strength of selection. Our scaling arguments also allow us to predict, with reasonable accuracy, the fitness distribution of fixed mutations when the mutational effect sizes are broad. We focus on the regime in which crossovers occur more frequently than beneficial mutations, as is likely to be the case for many natural populations.}, author = {Weissman, Daniel and Hallatschek, Oskar}, journal = {Genetics}, number = {4}, pages = {1167 -- 1183}, publisher = {Genetics Society of America}, title = {{The rate of adaptation in large sexual populations with linear chromosomes}}, doi = {10.1534/genetics.113.160705}, volume = {196}, year = {2014}, }