TY - CHAP AU - Vicente, Sara AU - Vladimir Kolmogorov AU - Rother, Carsten ED - Blake, Andrew ED - Kohli, Pushmeet ED - Rother, Carsten ID - 2922 T2 - Markov Random Fields for Vision and Image Processing TI - Graph-cut Based Image Segmentation with Connectivity Priors ER - TY - CHAP AU - Kumar, M Pawan AU - Vladimir Kolmogorov AU - Torr, Philip H ED - Blake, Andrew ED - Kohli, Pushmeet ED - Rother, Carsten ID - 2923 T2 - Markov Random Fields for Vision and Image Processing TI - Analyzing Convex Relaxations for MAP Estimation ER - TY - CHAP AU - Criminisi, Antonio AU - Cross, Geoffrey AU - Blake, Andrew AU - Vladimir Kolmogorov ED - Blake, Andrew ED - Kohli, Pushmeet ED - Rother, Carsten ID - 2924 T2 - Markov Random Fields for Vision and Image Processing TI - Bilayer Segmentation of Video ER - TY - CHAP AU - Rother, Carsten AU - Vladimir Kolmogorov AU - Boykov, Yuri AU - Blake, Andrew ED - Blake, Andrew ED - Kohli, Pushmeet ED - Rother, Carsten ID - 2925 T2 - Markov Random Fields for Vision and Image Processing TI - Interactive Foreground Extraction using graph cut ER - TY - CHAP AU - Boykov, Yuri AU - Vladimir Kolmogorov ED - Blake, Andrew ED - Kohli, Pushmeet ED - Rother, Carsten ID - 2935 T2 - Markov Random Fields for Vision and Image Processing TI - Basic graph cut algorithms ER - TY - JOUR AB - Rapid research progress in genotyping techniques have allowed large genome-wide association studies. Existing methods often focus on determining associations between single loci and a specic phenotype. However, a particular phenotype is usually the result of complex relationships between multiple loci and the environment. In this paper, we describe a two-stage method for detecting epistasis by combining the traditionally used single-locus search with a search for multiway interactions. Our method is based on an extended version of Fisher's exact test. To perform this test, a Markov chain is constructed on the space of multidimensional contingency tables using the elements of a Markov basis as moves. We test our method on simulated data and compare it to a two-stage logistic regression method and to a fully Bayesian method, showing that we are able to detect the interacting loci when other methods fail to do so. Finally, we apply our method to a genome-wide data set consisting of 685 dogs and identify epistasis associated with canine hair length for four pairs of single nucleotide polymorphisms (SNPs). AU - Malaspinas, Anna-Sapfo AU - Caroline Uhler ID - 2961 IS - 1 JF - Journal of Algebraic Statistics TI - Detecting epistasis via Markov bases VL - 2 ER - TY - CONF AB - Traditional statistical methods for the confidentiality protection for statistical databases do not scale well to deal with GWAS (genome-wide association studies) databases and external information on them. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach which provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information. Building on such notions, we propose new methods to release aggregate GWAS data without compromising an individual's privacy. We present methods for releasing differentially private minor allele frequencies, chi-square statistics and p-values. We compare these approaches on simulated data and on a GWAS study of canine hair length involving 685 dogs. We also propose a privacy-preserving method for finding genome-wide associations based on a differentially private approach to penalized logistic regression. AU - Fienberg, Stephen E AU - Slavkovic, Aleksandra AU - Caroline Uhler ID - 2960 TI - Privacy Preserving GWAS Data Sharing ER - TY - CONF AB - Zero-knowledge proofs of knowledge (ZK-PoK) for discrete logarithms and related problems are indispensable for practical cryptographic protocols. Recently, Camenisch, Kiayias, and Yung provided a specification language (the CKY-language) for such protocols which allows for a modular design and protocol analysis: for every zero-knowledge proof specified in this language, protocol designers are ensured that there exists an efficient protocol which indeed proves the specified statement. However, the protocols resulting from their compilation techniques only satisfy the classical notion of ZK-PoK, which is not retained are when they used as building blocks for higher-level applications or composed with other protocols. This problem can be tackled by moving to the Universal Composability (UC) framework, which guarantees retention of security when composing protocols in arbitrary ways. While there exist generic transformations from $\Sigma$-protocols to UC-secure protocols, these transformation are often too inefficient for practice. In this paper we introduce a specification language akin to the CKY-language and a compiler such that the resulting protocols are UC-secure and efficient. To this end, we propose an extension of the UC-framework addressing the issue that UC-secure zero-knowledge proofs are by definition proofs of knowledge, and state a special composition theorem which allows one to use the weaker -- but more efficient and often sufficient -- notion of proofs of membership in the UC-framework. We believe that our contributions enable the design of practically efficient protocols that are UC-secure and thus themselves can be used as building blocks. AU - Camenisch, Jan AU - Stephan Krenn AU - Shoup, Victor ED - Lee, Dong Hoon ED - Wang, Xiaoyun ID - 2975 TI - A Framework for Practical Universally Composable Zero-Knowledge Protocols VL - 7073 ER - TY - CONF AB - Cryptographic two-party protocols are used ubiquitously in everyday life. While some of these protocols are easy to understand and implement (e.g., key exchange or transmission of encrypted data), many of them are much more complex (e.g., e-banking and e-voting applications, or anonymous authentication and credential systems). For a software engineer without appropriate cryptographic skills the implementation of such protocols is often difficult, time consuming and error-prone. For this reason, a number of compilers supporting programmers have been published in recent years. However, they are either designed for very specific cryptographic primitives (e.g., zero-knowledge proofs of knowledge), or they only offer a very low level of abstraction and thus again demand substantial mathematical and cryptographic skills from the programmer. Finally, some of the existing compilers do not produce executable code, but only metacode which has to be instantiated with mathematical libraries, encryption routines, etc. before it can actually be used. In this paper we present a cryptographically aware compiler which is equally useful to cryptographers who want to benchmark protocols designed on paper, and to programmers who want to implement complex security sensitive protocols without having to understand all subtleties. Our tool offers a high level of abstraction and outputs well-structured and documented Java code. We believe that our compiler can contribute to shortening the development cycles of cryptographic applications and to reducing their error-proneness. AU - Bangerter, Endre AU - Stephan Krenn AU - Seifriz, Martial AU - Ultes-Nitsche, Ulrich ED - Venter, Hein S. ED - Coetzee, Marijke ED - Loock, Marianne ID - 2977 TI - cPLC - A Cryptographic Programming Language and Compiler ER - TY - CONF AB - Side channel attacks on cryptographic systems exploit information gained from physical implementations rather than theoretical weaknesses of a scheme. In recent years, major achievements were made for the class of so called access-driven cache attacks. Such attacks exploit the leakage of the memory locations accessed by a victim process. In this paper we consider the AES block cipher and present an attack which is capable of recovering the full secret key in almost realtime for AES-128, requiring only a very limited number of observed encryptions. Unlike previous attacks, we do not require any information about the plaintext (such as its distribution, etc.). Moreover, for the first time, we also show how the plaintext can be recovered without having access to the ciphertext at all. It is the first working attack on AES implementations using compressed tables. There, no efficient techniques to identify the beginning of AES rounds is known, which is the fundamental assumption underlying previous attacks. We have a fully working implementation of our attack which is able to recover AES keys after observing as little as 100 encryptions. It works against the OpenSSL 0.9.8n implementation of AES on Linux systems. Our spy process does not require any special privileges beyond those of a standard Linux user. A contribution of probably independent interest is a denial of service attack on the task scheduler of current Linux systems (CFS), which allows one to observe (on average) every single memory access of a victim process. AU - Gullasch, David AU - Bangerter, Endre AU - Stephan Krenn ID - 2976 TI - Cache Games - Bringing Access-Based Cache Attacks on AES to Practice ER - TY - JOUR AB - The phytohormone auxin is vital to plant growth and development. A unique property of auxin among all other plant hormones is its cell-to-cell polar transport that requires activity of polarly localized PIN-FORMED (PIN) auxin efflux transporters. Despite the substantial molecular insight into the cellular PIN polarization, the mechanistic understanding for developmentally and environmentally regulated PIN polarization is scarce. The long-standing belief that auxin modulates its own transport by means of a positive feedback mechanism has inspired both experimentalists and theoreticians for more than two decades. Recently, theoretical models for auxin-dependent patterning in plants include the feedback between auxin transport and the PIN protein localization. These computer models aid to assess the complexity of plant development by testing and predicting plausible scenarios for various developmental processes that occur in planta. Although the majority of these models rely on purely heuristic principles, the most recent mechanistic models tentatively integrate biologically testable components into known cellular processes that underlie the PIN polarity regulation. The existing and emerging computational approaches to describe PIN polarization are presented and discussed in the light of recent experimental data on the PIN polar targeting. AU - Wabnik, Krzysztof T AU - Govaerts, Willy AU - Friml, Jirí AU - Kleine Vehn, Jürgen ID - 3092 IS - 8 JF - Molecular BioSystems TI - Feedback models for polarized auxin transport: An emerging trend VL - 7 ER - TY - JOUR AB - The phytohormone auxin is an important determinant of plant development. Directional auxin flow within tissues depends on polar localization of PIN auxin transporters. To explore regulation of PIN-mediated auxin transport, we screened for suppressors of PIN1 overexpression (supo) and identified an inositol polyphosphate 1-phosphatase mutant (supo1), with elevated inositol trisphosphate (InsP 3) and cytosolic Ca 2+ levels. Pharmacological and genetic increases in InsP 3 or Ca 2+ levels also suppressed the PIN1 gain-of-function phenotypes and caused defects in basal PIN localization, auxin transport and auxin-mediated development. In contrast, the reductions in InsP 3 levels and Ca 2+ signaling antagonized the effects of the supo1 mutation and disrupted preferentially apical PIN localization. InsP 3 and Ca 2+ are evolutionarily conserved second messengers involved in various cellular functions, particularly stress responses. Our findings implicate them as modifiers of cell polarity and polar auxin transport, and highlight a potential integration point through which Ca 2+ signaling-related stimuli could influence auxin-mediated development. AU - Zhang, Jing AU - Vanneste, Steffen AU - Brewer, Philip B AU - Michniewicz, Marta AU - Peter Grones AU - Kleine-Vehn, Jürgen AU - Löfke, Christian AU - Teichmann, Thomas AU - Bielach, Agnieszka AU - Cannoot, Bernard AU - Hoyerová, Klára AU - Xu Chen AU - Xue, Hong-Wei AU - Eva Benková AU - Zažímalová, Eva AU - Jirí Friml ID - 3089 IS - 6 JF - Developmental Cell TI - Inositol trisphosphate-induced ca^2+ signaling modulates auxin transport and pin polarity VL - 20 ER - TY - JOUR AB - The polarized transport of the phytohormone auxin [1], which is crucial for the regulation of different stages of plant development [2, 3], depends on the asymmetric plasma membrane distribution of the PIN-FORMED (PIN) auxin efflux carriers [4, 5]. The PIN polar localization results from clathrin-mediated endocytosis (CME) from the plasma membrane and subsequent polar recycling [6]. The Arabidopsis genome encodes two groups of dynamin-related proteins (DRPs) that show homology to mammalian dynamin - a protein required for fission of endocytic vesicles during CME [7, 8]. Here we show by coimmunoprecipitation (coIP), bimolecular fluorescence complementation (BiFC), and Förster resonance energy transfer (FRET) that members of the DRP1 group closely associate with PIN proteins at the cell plate. Localization and phenotypic analysis of novel drp1 mutants revealed a requirement for DRP1 function in correct PIN distribution and in auxin-mediated development. We propose that rapid and specific internalization of PIN proteins mediated by the DRP1 proteins and the associated CME machinery from the cell plate membranes during cytokinesis is an important mechanism for proper polar PIN positioning in interphase cells. AU - Mravec, Jozef AU - Petrášek, Jan AU - Li, Na AU - Boeren, Sjef AU - Karlova, Rumyana AU - Kitakura, Saeko AU - Pařezová, Markéta AU - Naramoto, Satoshi AU - Nodzyński, Thomasz AU - Dhonukshe, Pankaj AU - Bednarek, Sebastian Y AU - Zažímalová, Eva AU - De Vries, Sacco AU - Jirí Friml ID - 3090 IS - 12 JF - Current Biology TI - Cell plate restricted association of DRP1A and PIN proteins is required for cell polarity establishment in arabidopsis VL - 21 ER - TY - JOUR AB - Background: Whereas the majority of animals develop toward a predetermined body plan, plants show iterative growth and continually produce new organs and structures from actively dividing meristems. This raises an intriguing question: How are these newly developed organs patterned? In Arabidopsis embryos, radial symmetry is broken by the bisymmetric specification of the cotyledons in the apical domain. Subsequently, this bisymmetry is propagated to the root promeristem. Results: Here we present a mutually inhibitory feedback loop between auxin and cytokinin that sets distinct boundaries of hormonal output. Cytokinins promote the bisymmetric distribution of the PIN-FORMED (PIN) auxin efflux proteins, which channel auxin toward a central domain. High auxin promotes transcription of the cytokinin signaling inhibitor AHP6, which closes the interaction loop. This bisymmetric auxin response domain specifies the differentiation of protoxylem in a bisymmetric pattern. In embryonic roots, cytokinin is required to translate a bisymmetric auxin response in the cotyledons to a bisymmetric vascular pattern in the root promeristem. Conclusions: Our results present an interactive feedback loop between hormonal signaling and transport by which small biases in hormonal input are propagated into distinct signaling domains to specify the vascular pattern in the root meristem. It is an intriguing possibility that such a mechanism could transform radial patterns and allow continuous vascular connections between other newly emerging organs. AU - Bishopp, Anthony AU - Help, Hanna AU - El-Showk, Sedeer AU - Weijers, Dolf AU - Scheres, Ben AU - Jirí Friml AU - Eva Benková AU - Mähönen, Ari Pekka AU - Helariutta, Ykä ID - 3088 IS - 11 JF - Current Biology TI - A mutually inhibitory interaction between auxin and cytokinin specifies vascular pattern in roots VL - 21 ER - TY - JOUR AB - Plants take up iron from the soil using the IRON-REGULATED TRANSPORTER 1 (IRT1) high-affinity iron transporter at the root surface. Sophisticated regulatory mechanisms allow plants to tightly control the levels of IRT1, ensuring optimal absorption of essential but toxic iron. Here, we demonstrate that overexpression of Arabidopsis thaliana IRT1 leads to constitutive IRT1 protein accumulation, metal overload, and oxidative stress. IRT1 is unexpectedly found in trans-Golgi network/early endosomes of root hair cells, and its levels and localization are unaffected by iron nutrition. Using pharmacological approaches, we show that IRT1 cycles to the plasma membrane to perform iron and metal uptake at the cell surface and is sent to the vacuole for proper turnover. We also prove that IRT1 is monoubiquitinated on several cytosol-exposed residues in vivo and that mutation of two putative monoubiquitination target residues in IRT1 triggers stabilization at the plasma membrane and leads to extreme lethality. Together, these data suggest a model in which monoubiquitin-dependent internalization/sorting and turnover keep the plasma membrane pool of IRT1 low to ensure proper iron uptake and to prevent metal toxicity. More generally, our work demonstrates the existence of monoubiquitin-dependent trafficking to lytic vacuoles in plants and points to proteasome-independent turnover of plasma membrane proteins. AU - Barberon, Marie AU - Zelazny, Enric AU - Robert, Stéphanie AU - Conéjéro, Geneviève AU - Curie, Cathy AU - Jirí Friml AU - Vert, Grégory ID - 3093 IS - 32 JF - PNAS TI - Monoubiquitin dependent endocytosis of the Iron Regulated Transporter 1 IRT1 transporter controls iron uptake in plants VL - 108 ER - TY - JOUR AB - Summary Gravitropism aligns plant growth with gravity. It involves gravity perception and the asymmetric distribution of the phytohormone auxin. Here we provide insights into the mechanism for hypocotyl gravitropic growth. We show that the Arabidopsis thaliana PIN3 auxin transporter is required for the asymmetric auxin distribution for the gravitropic response. Gravistimulation polarizes PIN3 to the bottom side of hypocotyl endodermal cells, which correlates with an increased auxin response at the lower hypocotyl side. Both PIN3 polarization and hypocotyl bending require the activity of the trafficking regulator GNOM and the protein kinase PINOID. Our data suggest that gravity-induced PIN3 polarization diverts the auxin flow to mediate the asymmetric distribution of auxin for gravitropic shoot bending. AU - Rakusová, Hana AU - Gallego-Bartolomé, Javier AU - Vanstraelen, Marleen AU - Robert, Hélène S AU - Alabadí, David AU - Blázquez, Miguel A AU - Eva Benková AU - Jirí Friml ID - 3094 IS - 5 JF - Plant Journal TI - Polarization of PIN3 dependent auxin transport for hypocotyl gravitropic response in Arabidopsis thaliana VL - 67 ER - TY - JOUR AU - Sauer, Michael AU - Friml, Jirí ID - 3091 JF - Molecular Systems Biology TI - Fleeting hormone cues get stabilized for plant organogenesis VL - 7 ER - TY - JOUR AB - Multicellular organisms depend on cell production, cell fate specification, and correct patterning to shape their adult body. In plants, auxin plays a prominent role in the timely coordination of these different cellular processes. A well-studied example is lateral root initiation, in which auxin triggers founder cell specification and cell cycle activation of xylem pole–positioned pericycle cells. Here, we report that the E2Fa transcription factor of Arabidopsis thaliana is an essential component that regulates the asymmetric cell division marking lateral root initiation. Moreover, we demonstrate that E2Fa expression is regulated by the LATERAL ORGAN BOUNDARY DOMAIN18/LATERAL ORGAN BOUNDARY DOMAIN33 (LBD18/LBD33) dimer that is, in turn, regulated by the auxin signaling pathway. LBD18/LBD33 mediates lateral root organogenesis through E2Fa transcriptional activation, whereas E2Fa expression under control of the LBD18 promoter eliminates the need for LBD18. Besides lateral root initiation, vascular patterning is disrupted in E2Fa knockout plants, similarly as it is affected in auxin signaling and lbd mutants, indicating that the transcriptional induction of E2Fa through LBDs represents a general mechanism for auxin-dependent cell cycle activation. Our data illustrate how a conserved mechanism driving cell cycle entry has been adapted evolutionarily to connect auxin signaling with control of processes determining plant architecture. AU - Berckmans, Barbara AU - Vassileva, Valya AU - Schmid, Stephan P AU - Maes, Sara AU - Parizot, Boris AU - Naramoto, Satoshi AU - Magyar, Zoltan AU - Lessa Alvim Kamei, Claire AU - Koncz, Csaba AU - Bögre, Laszlo AU - Persiau, Geert AU - De Jaeger, Geert AU - Jirí Friml AU - Simon, Rüdiger AU - Beeckman, Tom AU - de Veyldera, Lieven ID - 3102 IS - 10 JF - Plant Cell TI - Auxin Dependent cell cycle reactivation through transcriptional regulation of arabidopsis E2Fa by lateral organ boundary proteins VL - 23 ER - TY - JOUR AB - Endocytosis in plants has an essential role not only for basic cellular functions but also for growth and development, hormonal signaling and communication with the environment including nutrient delivery, toxin avoidance, and pathogen defense. The major endocytic mechanism in plants depends on the coat protein clathrin. It starts by clathrin-coated vesicle formation at the plasma membrane, where specific cargoes are recognized and packaged for internalization. Recently, genetic, biochemical and advanced microscopy studies provided initial insights into mechanisms and roles of clathrin-mediated endocytosis in plants. Here we summarize the present state of knowledge and compare mechanisms of clathrin-mediated endocytosis in plants with animal and yeast paradigms as well as review plant-specific regulations and roles of this process. AU - Chen, Xu AU - Irani, Niloufer AU - Friml, Jirí ID - 3103 IS - 6 JF - Current Opinion in Plant Biology TI - Clathrin-mediated endocytosis: The gateway into plant cells VL - 14 ER - TY - JOUR AB - Cancer cell of origin is difficult to identify by analyzing cells within terminal stage tumors, whose identity could be concealed by the acquired plasticity. Thus, an ideal approach to identify the cell of origin is to analyze proliferative abnormalities in distinct lineages prior to malignancy. Here, we use mosaic analysis with double markers (MADM) in mice to model gliomagenesis by initiating concurrent p53/Nf1 mutations sporadically in neural stem cells (NSCs). Surprisingly, MADM-based lineage tracing revealed significant aberrant growth prior to malignancy only in oligodendrocyte precursor cells (OPCs), but not in any other NSC-derived lineages or NSCs themselves. Upon tumor formation, phenotypic and transcriptome analyses of tumor cells revealed salient OPC features. Finally, introducing the same p53/Nf1 mutations directly into OPCs consistently led to gliomagenesis. Our findings suggest OPCs as the cell of origin in this model, even when initial mutations occur in NSCs, and highlight the importance of analyzing premalignant stages to identify the cancer cell of origin. AU - Liu, Chong AU - Sage, Jonathan C AU - Miller, Michael R AU - Verhaak, Roel G AU - Simon Hippenmeyer AU - Vogel, Hannes AU - Foreman, Oded AU - Bronson, Roderick T AU - Nishiyama, Akiko AU - Luo, Liqun AU - Zong, Hui ID - 3147 IS - 2 JF - Cell TI - Mosaic analysis with double markers reveals tumor cell of origin in glioma VL - 146 ER - TY - CONF AB - We introduce a new class of functions that can be minimized in polynomial time in the value oracle model. These are functions f satisfying f(x) + f(y) ≥ f(x ∏ y) + f(x ∐ y) where the domain of each variable x i corresponds to nodes of a rooted binary tree, and operations ∏,∐ are defined with respect to this tree. Special cases include previously studied L-convex and bisubmodular functions, which can be obtained with particular choices of trees. We present a polynomial-time algorithm for minimizing functions in the new class. It combines Murota's steepest descent algorithm for L-convex functions with bisubmodular minimization algorithms. AU - Vladimir Kolmogorov ID - 3204 TI - Submodularity on a tree: Unifying Submodularity on a tree: Unifying L-convex and bisubmodular functions convex and bisubmodular functions VL - 6907 ER - TY - CONF AB - In this paper we address the problem of finding the most probable state of discrete Markov random field (MRF) with associative pairwise terms. Although of practical importance, this problem is known to be NP-hard in general. We propose a new type of MRF decomposition, submod-ular decomposition (SMD). Unlike existing decomposition approaches SMD decomposes the initial problem into sub-problems corresponding to a specific class label while preserving the graph structure of each subproblem. Such decomposition enables us to take into account several types of global constraints in an efficient manner. We study theoretical properties of the proposed approach and demonstrate its applicability on a number of problems. AU - Osokin, Anton AU - Vetrov, Dmitry AU - Vladimir Kolmogorov ID - 3206 TI - Submodular decomposition framework for inference in associative Markov networks with global constraints ER - TY - CONF AB - This paper proposes a novel Linear Programming (LP) based algorithm, called Dynamic Tree-Block Coordinate Ascent (DT-BCA), for performing maximum a posteriori (MAP) inference in probabilistic graphical models. Unlike traditional message passing algorithms, which operate uniformly on the whole factor graph, our method dynamically chooses regions of the factor graph on which to focus message-passing efforts. We propose two criteria for selecting regions, including an efficiently computable upper-bound on the increase in the objective possible by passing messages in any particular region. This bound is derived from the theory of primal-dual methods from combinatorial optimization, and the forest that maximizes the bounds can be chosen efficiently using a maximum-spanning-tree-like algorithm. Experimental results show that our dynamic schedules significantly speed up state-of-the-art LP-based message-passing algorithms on a wide variety of real-world problems. AU - Tarlow, Daniel AU - Batra, Druv AU - Kohli, Pushmeet AU - Vladimir Kolmogorov ID - 3205 TI - Dynamic tree block coordinate ascent ER - TY - CONF AB - Cosegmentation is typically defined as the task of jointly segmenting something similar in a given set of images. Existing methods are too generic and so far have not demonstrated competitive results for any specific task. In this paper we overcome this limitation by adding two new aspects to cosegmentation: (1) the "something" has to be an object, and (2) the "similarity" measure is learned. In this way, we are able to achieve excellent results on the recently introduced iCoseg dataset, which contains small sets of images of either the same object instance or similar objects of the same class. The challenge of this dataset lies in the extreme changes in viewpoint, lighting, and object deformations within each set. We are able to considerably outperform several competitors. To achieve this performance, we borrow recent ideas from object recognition: the use of powerful features extracted from a pool of candidate object-like segmentations. We believe that our work will be beneficial to several application areas, such as image retrieval. AU - Vicente, Sara AU - Rother, Carsten AU - Vladimir Kolmogorov ID - 3207 TI - Object cosegmentation ER - TY - CONF AB - The famous Leftover Hash Lemma (LHL) states that (almost) universal hash functions are good randomness extractors. Despite its numerous applications, LHL-based extractors suffer from the following two limitations: - Large Entropy Loss: to extract v bits from distribution X of min-entropy m which are ε-close to uniform, one must set v ≤ m - 2log(1/ε), meaning that the entropy loss L = def m - v ≥ 2 log(1/ε). For many applications, such entropy loss is too large. - Large Seed Length: the seed length n of (almost) universal hash function required by the LHL must be at least n ≥ min (u - v, v + 2log(1/ε)) - O(1), where u is the length of the source, and must grow with the number of extracted bits. Quite surprisingly, we show that both limitations of the LHL - large entropy loss and large seed - can be overcome (or, at least, mitigated) in various important scenarios. First, we show that entropy loss could be reduced to L = log(1/ε) for the setting of deriving secret keys for a wide range of cryptographic applications. Specifically, the security of these schemes with an LHL-derived key gracefully degrades from ε to at most ε + √ε2-L. (Notice that, unlike standard LHL, this bound is meaningful even when one extracts more bits than the min-entropy we have!) Based on these results we build a general computational extractor that enjoys low entropy loss and can be used to instantiate a generic key derivation function for any cryptographic application. Second, we study the soundness of the natural expand-then-extract approach, where one uses a pseudorandom generator (PRG) to expand a short "input seed" S into a longer "output seed" S′, and then use the resulting S′ as the seed required by the LHL (or, more generally, by any randomness extractor). We show that, in general, the expand-then-extract approach is not sound if the Decisional Diffie-Hellman assumption is true. Despite that, we show that it is sound either: (1) when extracting a "small" (logarithmic in the security of the PRG) number of bits; or (2) in minicrypt. Implication (2) suggests that the expand-then-extract approach is likely secure when used with "practical" PRGs, despite lacking a reductionist proof of security! © 2011 International Association for Cryptologic Research. AU - Barak, Boaz AU - Dodis, Yevgeniy AU - Krawczyk, Hugo AU - Pereira, Olivier AU - Krzysztof Pietrzak AU - Standaert, François-Xavier AU - Yu, Yu ID - 3240 TI - Leftover hash lemma revisited VL - 6841 ER - TY - CONF AB - Verification of programs with procedures, multi-threaded programs, and higher-order functional programs can be effectively au- tomated using abstraction and refinement schemes that rely on spurious counterexamples for abstraction discovery. The analysis of counterexam- ples can be automated by a series of interpolation queries, or, alterna- tively, as a constraint solving query expressed by a set of recursion free Horn clauses. (A set of interpolation queries can be formulated as a single constraint over Horn clauses with linear dependency structure between the unknown relations.) In this paper we present an algorithm for solving recursion free Horn clauses over a combined theory of linear real/rational arithmetic and uninterpreted functions. Our algorithm performs resolu- tion to deal with the clausal structure and relies on partial solutions to deal with (non-local) instances of functionality axioms. AU - Gupta, Ashutosh AU - Popeea, Corneliu AU - Rybalchenko, Andrey ED - Yang, Hongseok ID - 3264 TI - Solving recursion-free Horn clauses over LI+UIF VL - 7078 ER - TY - CONF AB - We present a joint image segmentation and labeling model (JSL) which, given a bag of figure-ground segment hypotheses extracted at multiple image locations and scales, constructs a joint probability distribution over both the compatible image interpretations (tilings or image segmentations) composed from those segments, and over their labeling into categories. The process of drawing samples from the joint distribution can be interpreted as first sampling tilings, modeled as maximal cliques, from a graph connecting spatially non-overlapping segments in the bag [1], followed by sampling labels for those segments, conditioned on the choice of a particular tiling. We learn the segmentation and labeling parameters jointly, based on Maximum Likelihood with a novel Incremental Saddle Point estimation procedure. The partition function over tilings and labelings is increasingly more accurately approximated by including incorrect configurations that a not-yet-competent model rates probable during learning. We show that the proposed methodologymatches the current state of the art in the Stanford dataset [2], as well as in VOC2010, where 41.7% accuracy on the test set is achieved. AU - Ion, Adrian AU - Carreira, Joao AU - Sminchisescu, Cristian ID - 3266 T2 - NIPS Proceedings TI - Probabilistic joint image segmentation and labeling VL - 24 ER - TY - JOUR AB - The unintentional scattering of light between neighboring surfaces in complex projection environments increases the brightness and decreases the contrast, disrupting the appearance of the desired imagery. To achieve satisfactory projection results, the inverse problem of global illumination must be solved to cancel this secondary scattering. In this paper, we propose a global illumination cancellation method that minimizes the perceptual difference between the desired imagery and the actual total illumination in the resulting physical environment. Using Gauss-Newton and active set methods, we design a fast solver for the bound constrained nonlinear least squares problem raised by the perceptual error metrics. Our solver is further accelerated with a CUDA implementation and multi-resolution method to achieve 1–2 fps for problems with approximately 3000 variables. We demonstrate the global illumination cancellation algorithm with our multi-projector system. Results show that our method preserves the color fidelity of the desired imagery significantly better than previous methods. AU - Sheng, Yu AU - Cutler, Barbara AU - Chen, Chao AU - Nasman, Joshua ID - 3269 IS - 4 JF - Computer Graphics Forum TI - Perceptual global illumination cancellation in complex projection environments VL - 30 ER - TY - JOUR AB - We address the problem of localizing homology classes, namely, finding the cycle representing a given class with the most concise geometric measure. We study the problem with different measures: volume, diameter and radius. For volume, that is, the 1-norm of a cycle, two main results are presented. First, we prove that the problem is NP-hard to approximate within any constant factor. Second, we prove that for homology of dimension two or higher, the problem is NP-hard to approximate even when the Betti number is O(1). The latter result leads to the inapproximability of the problem of computing the nonbounding cycle with the smallest volume and computing cycles representing a homology basis with the minimal total volume. As for the other two measures defined by pairwise geodesic distance, diameter and radius, we show that the localization problem is NP-hard for diameter but is polynomial for radius. Our work is restricted to homology over the ℤ2 field. AU - Chen, Chao AU - Freedman, Daniel ID - 3267 IS - 3 JF - Discrete & Computational Geometry TI - Hardness results for homology localization VL - 45 ER - TY - CHAP AB - Algebraic topology is generally considered one of the purest subfield of mathematics. However, over the last decade two interesting new lines of research have emerged, one focusing on algorithms for algebraic topology, and the other on applications of algebraic topology in engineering and science. Amongst the new areas in which the techniques have been applied are computer vision and image processing. In this paper, we survey the results of these endeavours. Because algebraic topology is an area of mathematics with which most computer vision practitioners have no experience, we review the machinery behind the theories of homology and persistent homology; our review emphasizes intuitive explanations. In terms of applications to computer vision, we focus on four illustrative problems: shape signatures, natural image statistics, image denoising, and segmentation. Our hope is that this review will stimulate interest on the part of computer vision researchers to both use and extend the tools of this new field. AU - Freedman, Daniel AU - Chen, Chao ID - 3268 T2 - Computer Vision TI - Algebraic topology for computer vision ER - TY - JOUR AB - The zonula adherens (ZA) of epithelial cells is a site of cell-cell adhesion where cellular forces are exerted and resisted. Increasing evidence indicates that E-cadherin adhesion molecules at the ZA serve to sense force applied on the junctions and coordinate cytoskeletal responses to those forces. Efforts to understand the role that cadherins play in mechanotransduction have been limited by the lack of assays to measure the impact of forces on the ZA. In this study we used 4D imaging of GFP-tagged E-cadherin to analyse the movement of the ZA. Junctions in confluent epithelial monolayers displayed prominent movements oriented orthogonal (perpendicular) to the ZA itself. Two components were identified in these movements: a relatively slow unidirectional (translational) component that could be readily fitted by least-squares regression analysis, upon which were superimposed more rapid oscillatory movements. Myosin IIB was a dominant factor responsible for driving the unilateral translational movements. In contrast, frequency spectrum analysis revealed that depletion of Myosin IIA increased the power of the oscillatory movements. This implies that Myosin IIA may serve to dampen oscillatory movements of the ZA. This extends our recent analysis of Myosin II at the ZA to demonstrate that Myosin IIA and Myosin IIB make distinct contributions to junctional movement at the ZA. AU - Smutny, Michael AU - Wu, Selwin AU - Gomez, Guillermo AU - Mangold, Sabine AU - Yap, Alpha AU - Hamilton, Nicholas ID - 3288 IS - 7 JF - PLoS One TI - Multicomponent analysis of junctional movements regulated by Myosin II isoforms at the epithelial zonula adherens VL - 6 ER - TY - JOUR AB - Cationic antimicrobial peptides (CAMPs) selectively target bacterial membranes by electrostatic interactions with negatively charged lipids. It turned out that for inhibition of microbial growth a high CAMP membrane concentration is required, which can be realized by the incorporation of hydrophobic groups within the peptide. Increasing hydrophobicity, however, reduces the CAMP selectivity for bacterial over eukaryotic host membranes, thereby causing the risk of detrimental side-effects. In this study we addressed how cationic amphipathic peptides—in particular a CAMP with Lysine–Leucine–Lysine repeats (termed KLK)—affect the localization and dynamics of molecules in eukaryotic membranes. We found KLK to selectively inhibit the endocytosis of a subgroup of membrane proteins and lipids by electrostatically interacting with negatively charged sialic acid moieties. Ultrastructural characterization revealed the formation of membrane invaginations representing fission or fusion intermediates, in which the sialylated proteins and lipids were immobilized. Experiments on structurally different cationic amphipathic peptides (KLK, 6-MO-LF11-322 and NK14-2) indicated a cooperation of electrostatic and hydrophobic forces that selectively arrest sialylated membrane constituents. AU - Weghuber, Julian AU - Aichinger, Michael C. AU - Brameshuber, Mario AU - Stefan Wieser AU - Verena Ruprecht AU - Plochberger, Birgit AU - Madl, Josef AU - Horner, Andreas AU - Reipert, Siegfried AU - Lohner, Karl AU - Henics, Tamas AU - Schuetz, Gerhard J ID - 3286 IS - 10 JF - Biochimica et Biophysica Acta (BBA) - Biomembranes TI - Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells VL - 1808 ER - TY - JOUR AB - Diffusing membrane constituents are constantly exposed to a variety of forces that influence their stochastic path. Single molecule experiments allow for resolving trajectories at extremely high spatial and temporal accuracy, thereby offering insights into en route interactions of the tracer. In this review we discuss approaches to derive information about the underlying processes, based on single molecule tracking experiments. In particular, we focus on a new versatile way to analyze single molecule diffusion in the absence of a full analytical treatment. The method is based on comprehensive comparison of an experimental data set against the hypothetical outcome of multiple experiments performed on the computer. Since Monte Carlo simulations can be easily and rapidly performed even on state-of-the-art PCs, our method provides a simple way for testing various - even complicated - diffusion models. We describe the new method in detail, and show the applicability on two specific examples: firstly, kinetic rate constants can be derived for the transient interaction of mobile membrane proteins; secondly, residence time and corral size can be extracted for confined diffusion. AU - Ruprecht, Verena AU - Axmann, Markus AU - Wieser, Stefan AU - Schuetz, Gerhard ID - 3287 IS - 8 JF - Current Protein & Peptide Science TI - What can we learn from single molecule trajectories? VL - 12 ER - TY - JOUR AB - Resolving the dynamical interplay of proteins and lipids in the live-cell plasma membrane represents a central goal in current cell biology. Superresolution concepts have introduced a means of capturing spatial heterogeneity at a nanoscopic length scale. Similar concepts for detecting dynamical transitions (superresolution chronoscopy) are still lacking. Here, we show that recently introduced spot-variation fluorescence correlation spectroscopy allows for sensing transient confinement times of membrane constituents at dramatically improved resolution. Using standard diffraction-limited optics, spot-variation fluorescence correlation spectroscopy captures signatures of single retardation events far below the transit time of the tracer through the focal spot. We provide an analytical description of special cases of transient binding of a tracer to pointlike traps, or association of a tracer with nanodomains. The influence of trap mobility and the underlying binding kinetics are quantified. Experimental approaches are suggested that allow for gaining quantitative mechanistic insights into the interaction processes of membrane constituents. AU - Ruprecht, Verena AU - Wieser, Stefan AU - Marguet, Didier AU - Schuetz, Gerhard ID - 3285 IS - 11 JF - Biophysical Journal TI - Spot variation fluorescence correlation spectroscopy allows for superresolution chronoscopy of confinement times in membranes VL - 100 ER - TY - CONF AB - Cloud computing aims to give users virtually unlimited pay-per-use computing resources without the burden of managing the underlying infrastructure. We present a new job execution environment Flextic that exploits scal- able static scheduling techniques to provide the user with a flexible pricing model, such as a tradeoff between dif- ferent degrees of execution speed and execution price, and at the same time, reduce scheduling overhead for the cloud provider. We have evaluated a prototype of Flextic on Amazon EC2 and compared it against Hadoop. For various data parallel jobs from machine learning, im- age processing, and gene sequencing that we considered, Flextic has low scheduling overhead and reduces job du- ration by up to 15% compared to Hadoop, a dynamic cloud scheduler. AU - Henzinger, Thomas A AU - Singh, Anmol AU - Singh, Vasu AU - Wies, Thomas AU - Zufferey, Damien ID - 3302 TI - Static scheduling in clouds ER - TY - CONF AB - The chemical master equation is a differential equation describing the time evolution of the probability distribution over the possible “states” of a biochemical system. The solution of this equation is of interest within the systems biology field ever since the importance of the molec- ular noise has been acknowledged. Unfortunately, most of the systems do not have analytical solutions, and numerical solutions suffer from the course of dimensionality and therefore need to be approximated. Here, we introduce the concept of tail approximation, which retrieves an approximation of the probabilities in the tail of a distribution from the total probability of the tail and its conditional expectation. This approximation method can then be used to numerically compute the solution of the chemical master equation on a subset of the state space, thus fighting the explosion of the state space, for which this problem is renowned. AU - Henzinger, Thomas A AU - Mateescu, Maria ID - 3301 TI - Tail approximation for the chemical master equation ER - TY - CONF AB - We introduce propagation models, a formalism designed to support general and efficient data structures for the transient analysis of biochemical reaction networks. We give two use cases for propagation abstract data types: the uniformization method and numerical integration. We also sketch an implementation of a propagation abstract data type, which uses abstraction to approximate states. AU - Henzinger, Thomas A AU - Mateescu, Maria ID - 3299 TI - Propagation models for computing biochemical reaction networks ER - TY - CONF AB - In addition to being correct, a system should be robust, that is, it should behave reasonably even after receiving unexpected inputs. In this paper, we summarize two formal notions of robustness that we have introduced previously for reactive systems. One of the notions is based on assigning costs for failures on a user-provided notion of incorrect transitions in a specification. Here, we define a system to be robust if a finite number of incorrect inputs does not lead to an infinite number of incorrect outputs. We also give a more refined notion of robustness that aims to minimize the ratio of output failures to input failures. The second notion is aimed at liveness. In contrast to the previous notion, it has no concept of recovery from an error. Instead, it compares the ratio of the number of liveness constraints that the system violates to the number of liveness constraints that the environment violates. AU - Bloem, Roderick AU - Chatterjee, Krishnendu AU - Greimel, Karin AU - Henzinger, Thomas A AU - Jobstmann, Barbara ID - 3316 T2 - 6th IEEE International Symposium on Industrial and Embedded Systems TI - Specification-centered robustness ER - TY - JOUR AB - Parvalbumin is thought to act in a manner similar to EGTA, but how a slow Ca2+ buffer affects nanodomain-coupling regimes at GABAergic synapses is unclear. Direct measurements of parvalbumin concentration and paired recordings in rodent hippocampus and cerebellum revealed that parvalbumin affects synaptic dynamics only when expressed at high levels. Modeling suggests that, in high concentrations, parvalbumin may exert BAPTA-like effects, modulating nanodomain coupling via competition with local saturation of endogenous fixed buffers. AU - Eggermann, Emmanuel AU - Jonas, Peter M ID - 3318 JF - Nature Neuroscience TI - How the “slow” Ca(2+) buffer parvalbumin affects transmitter release in nanodomain coupling regimes at GABAergic synapses VL - 15 ER - TY - CHAP AB - We study the topology of the Megaparsec Cosmic Web in terms of the scale-dependent Betti numbers, which formalize the topological information content of the cosmic mass distribution. While the Betti numbers do not fully quantify topology, they extend the information beyond conventional cosmological studies of topology in terms of genus and Euler characteristic. The richer information content of Betti numbers goes along the availability of fast algorithms to compute them. For continuous density fields, we determine the scale-dependence of Betti numbers by invoking the cosmologically familiar filtration of sublevel or superlevel sets defined by density thresholds. For the discrete galaxy distribution, however, the analysis is based on the alpha shapes of the particles. These simplicial complexes constitute an ordered sequence of nested subsets of the Delaunay tessellation, a filtration defined by the scale parameter, α. As they are homotopy equivalent to the sublevel sets of the distance field, they are an excellent tool for assessing the topological structure of a discrete point distribution. In order to develop an intuitive understanding for the behavior of Betti numbers as a function of α, and their relation to the morphological patterns in the Cosmic Web, we first study them within the context of simple heuristic Voronoi clustering models. These can be tuned to consist of specific morphological elements of the Cosmic Web, i.e. clusters, filaments, or sheets. To elucidate the relative prominence of the various Betti numbers in different stages of morphological evolution, we introduce the concept of alpha tracks. Subsequently, we address the topology of structures emerging in the standard LCDM scenario and in cosmological scenarios with alternative dark energy content. The evolution of the Betti numbers is shown to reflect the hierarchical evolution of the Cosmic Web. We also demonstrate that the scale-dependence of the Betti numbers yields a promising measure of cosmological parameters, with a potential to help in determining the nature of dark energy and to probe primordial non-Gaussianities. We also discuss the expected Betti numbers as a function of the density threshold for superlevel sets of a Gaussian random field. Finally, we introduce the concept of persistent homology. It measures scale levels of the mass distribution and allows us to separate small from large scale features. Within the context of the hierarchical cosmic structure formation, persistence provides a natural formalism for a multiscale topology study of the Cosmic Web. AU - Van De Weygaert, Rien AU - Vegter, Gert AU - Edelsbrunner, Herbert AU - Jones, Bernard AU - Pranav, Pratyush AU - Park, Changbom AU - Hellwing, Wojciech AU - Eldering, Bob AU - Kruithof, Nico AU - Bos, Patrick AU - Hidding, Johan AU - Feldbrugge, Job AU - Ten Have, Eline AU - Van Engelen, Matti AU - Caroli, Manuel AU - Teillaud, Monique ED - Gavrilova, Marina ED - Tan, Kenneth ED - Mostafavi, Mir ID - 3335 T2 - Transactions on Computational Science XIV TI - Alpha, Betti and the Megaparsec Universe: On the topology of the Cosmic Web VL - 6970 ER - TY - CONF AB - We consider the offset-deconstruction problem: Given a polygonal shape Q with n vertices, can it be expressed, up to a tolerance µ in Hausdorff distance, as the Minkowski sum of another polygonal shape P with a disk of fixed radius? If it does, we also seek a preferably simple-looking solution shape P; then, P's offset constitutes an accurate, vertex-reduced, and smoothened approximation of Q. We give an O(n log n)-time exact decision algorithm that handles any polygonal shape, assuming the real-RAM model of computation. An alternative algorithm, based purely on rational arithmetic, answers the same deconstruction problem, up to an uncertainty parameter, and its running time depends on the parameter δ (in addition to the other input parameters: n, δ and the radius of the disk). If the input shape is found to be approximable, the rational-arithmetic algorithm also computes an approximate solution shape for the problem. For convex shapes, the complexity of the exact decision algorithm drops to O(n), which is also the time required to compute a solution shape P with at most one more vertex than a vertex-minimal one. Our study is motivated by applications from two different domains. However, since the offset operation has numerous uses, we anticipate that the reverse question that we study here will be still more broadly applicable. We present results obtained with our implementation of the rational-arithmetic algorithm. AU - Berberich, Eric AU - Halperin, Dan AU - Kerber, Michael AU - Pogalnikova, Roza ID - 3329 T2 - Proceedings of the twenty-seventh annual symposium on Computational geometry TI - Deconstructing approximate offsets ER - TY - JOUR AB - Given an algebraic hypersurface O in ℝd, how many simplices are necessary for a simplicial complex isotopic to O? We address this problem and the variant where all vertices of the complex must lie on O. We give asymptotically tight worst-case bounds for algebraic plane curves. Our results gradually improve known bounds in higher dimensions; however, the question for tight bounds remains unsolved for d ≥ 3. AU - Kerber, Michael AU - Sagraloff, Michael ID - 3332 IS - 3 JF - Graphs and Combinatorics TI - A note on the complexity of real algebraic hypersurfaces VL - 27 ER - TY - CONF AB - We consider the problem of approximating all real roots of a square-free polynomial f. Given isolating intervals, our algorithm refines each of them to a width at most 2-L, that is, each of the roots is approximated to L bits after the binary point. Our method provides a certified answer for arbitrary real polynomials, only requiring finite approximations of the polynomial coefficient and choosing a suitable working precision adaptively. In this way, we get a correct algorithm that is simple to implement and practically efficient. Our algorithm uses the quadratic interval refinement method; we adapt that method to be able to cope with inaccuracies when evaluating f, without sacrificing its quadratic convergence behavior. We prove a bound on the bit complexity of our algorithm in terms of degree, coefficient size and discriminant. Our bound improves previous work on integer polynomials by a factor of deg f and essentially matches best known theoretical bounds on root approximation which are obtained by very sophisticated algorithms. AU - Kerber, Michael AU - Sagraloff, Michael ID - 3330 TI - Root refinement for real polynomials ER - TY - CONF AB - We report on a generic uni- and bivariate algebraic kernel that is publicly available with CGAL 3.7. It comprises complete, correct, though efficient state-of-the-art implementations on polynomials, roots of polynomial systems, and the support to analyze algebraic curves defined by bivariate polynomials. The kernel design is generic, that is, various number types and substeps can be exchanged. It is accompanied with a ready-to-use interface to enable arrangements induced by algebraic curves, that have already been used as basis for various geometric applications, as arrangements on Dupin cyclides or the triangulation of algebraic surfaces. We present two novel applications: arrangements of rotated algebraic curves and Boolean set operations on polygons bounded by segments of algebraic curves. We also provide experiments showing that our general implementation is competitive and even often clearly outperforms existing implementations that are explicitly tailored for specific types of non-linear curves that are available in CGAL. AU - Berberich, Eric AU - Hemmer, Michael AU - Kerber, Michael ID - 3328 TI - A generic algebraic kernel for non linear geometric applications ER - TY - JOUR AU - Edelsbrunner, Herbert AU - Pach, János AU - Ziegler, Günter ID - 3334 IS - 1 JF - Discrete & Computational Geometry TI - Letter from the new editors-in-chief VL - 45 ER - TY - JOUR AB - Compositional theories are crucial when designing large and complex systems from smaller components. In this work we propose such a theory for synchronous concurrent systems. Our approach follows so-called interface theories, which use game-theoretic interpretations of composition and refinement. These are appropriate for systems with distinct inputs and outputs, and explicit conditions on inputs that must be enforced during composition. Our interfaces model systems that execute in an infinite sequence of synchronous rounds. At each round, a contract must be satisfied. The contract is simply a relation specifying the set of valid input/output pairs. Interfaces can be composed by parallel, serial or feedback composition. A refinement relation between interfaces is defined, and shown to have two main properties: (1) it is preserved by composition, and (2) it is equivalent to substitutability, namely, the ability to replace an interface by another one in any context. Shared refinement and abstraction operators, corresponding to greatest lower and least upper bounds with respect to refinement, are also defined. Input-complete interfaces, that impose no restrictions on inputs, and deterministic interfaces, that produce a unique output for any legal input, are discussed as special cases, and an interesting duality between the two classes is exposed. A number of illustrative examples are provided, as well as algorithms to compute compositions, check refinement, and so on, for finite-state interfaces. AU - Tripakis, Stavros AU - Lickly, Ben AU - Henzinger, Thomas A AU - Lee, Edward ID - 3353 IS - 4 JF - ACM Transactions on Programming Languages and Systems (TOPLAS) TI - A theory of synchronous relational interfaces VL - 33 ER - TY - CONF AB - Byzantine Fault Tolerant (BFT) protocols aim to improve the reliability of distributed systems. They enable systems to tolerate arbitrary failures in a bounded number of nodes. BFT protocols are usually proven correct for certain safety and liveness properties. However, recent studies have shown that the performance of state-of-the-art BFT protocols decreases drastically in the presence of even a single malicious node. This motivates a formal quantitative analysis of BFT protocols to investigate their performance characteristics under different scenarios. We present HyPerf, a new hybrid methodology based on model checking and simulation techniques for evaluating the performance of BFT protocols. We build a transition system corresponding to a BFT protocol and systematically explore the set of behaviors allowed by the protocol. We associate certain timing information with different operations in the protocol, like cryptographic operations and message transmission. After an elaborate state exploration, we use the time information to evaluate the performance characteristics of the protocol using simulation techniques. We integrate our framework in Mace, a tool for building and verifying distributed systems. We evaluate the performance of PBFT using our framework. We describe two different use-cases of our methodology. For the benign operation of the protocol, we use the time information as random variables to compute the probability distribution of the execution times. In the presence of faults, we estimate the worst-case performance of the protocol for various attacks that can be employed by malicious nodes. Our results show the importance of hybrid techniques in systematically analyzing the performance of large-scale systems. AU - Halalai, Raluca AU - Henzinger, Thomas A AU - Singh, Vasu ID - 3355 TI - Quantitative evaluation of BFT protocols ER - TY - CONF AB - A controller for a discrete game with ω-regular objectives requires attention if, intuitively, it requires measuring the state and switching from the current control action. Minimum attention controllers are preferable in modern shared implementations of cyber-physical systems because they produce the least burden on system resources such as processor time or communication bandwidth. We give algorithms to compute minimum attention controllers for ω-regular objectives in imperfect information discrete two-player games. We show a polynomial-time reduction from minimum attention controller synthesis to synthesis of controllers for mean-payoff parity objectives in games of incomplete information. This gives an optimal EXPTIME-complete synthesis algorithm. We show that the minimum attention controller problem is decidable for infinite state systems with finite bisimulation quotients. In particular, the problem is decidable for timed and rectangular automata. AU - Chatterjee, Krishnendu AU - Majumdar, Ritankar ED - Fahrenberg, Uli ED - Tripakis, Stavros ID - 3350 TI - Minimum attention controller synthesis for omega regular objectives VL - 6919 ER - TY - CONF AB - In two-player games on graph, the players construct an infinite path through the game graph and get a reward computed by a payoff function over infinite paths. Over weighted graphs, the typical and most studied payoff functions compute the limit-average or the discounted sum of the rewards along the path. Besides their simple definition, these two payoff functions enjoy the property that memoryless optimal strategies always exist. In an attempt to construct other simple payoff functions, we define a class of payoff functions which compute an (infinite) weighted average of the rewards. This new class contains both the limit-average and the discounted sum functions, and we show that they are the only members of this class which induce memoryless optimal strategies, showing that there is essentially no other simple payoff functions. AU - Chatterjee, Krishnendu AU - Doyen, Laurent AU - Singh, Rohit ED - Owe, Olaf ED - Steffen, Martin ED - Telle, Jan Arne ID - 3351 TI - On memoryless quantitative objectives VL - 6914 ER - TY - JOUR AB - We consider two-player games played on a finite state space for an infinite number of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine the successor state. We consider ω-regular winning conditions specified as parity objectives. Both players are allowed to use randomization when choosing their moves. We study the computation of the limit-winning set of states, consisting of the states where the sup-inf value of the game for player 1 is 1: in other words, a state is limit-winning if player 1 can ensure a probability of winning arbitrarily close to 1. We show that the limit-winning set can be computed in O(n2d+2) time, where n is the size of the game structure and 2d is the number of priorities (or colors). The membership problem of whether a state belongs to the limit-winning set can be decided in NP ∩ coNP. While this complexity is the same as for the simpler class of turn-based parity games, where in each state only one of the two players has a choice of moves, our algorithms are considerably more involved than those for turn-based games. This is because concurrent games do not satisfy two of the most fundamental properties of turn-based parity games. First, in concurrent games limit-winning strategies require randomization; and second, they require infinite memory. AU - Chatterjee, Krishnendu AU - De Alfaro, Luca AU - Henzinger, Thomas A ID - 3354 IS - 4 JF - ACM Transactions on Computational Logic (TOCL) TI - Qualitative concurrent parity games VL - 12 ER - TY - CONF AB - Games on graphs provide a natural model for reactive non-terminating systems. In such games, the interaction of two players on an arena results in an infinite path that describes a run of the system. Different settings are used to model various open systems in computer science, as for instance turn-based or concurrent moves, and deterministic or stochastic transitions. In this paper, we are interested in turn-based games, and specifically in deterministic parity games and stochastic reachability games (also known as simple stochastic games). We present a simple, direct and efficient reduction from deterministic parity games to simple stochastic games: it yields an arena whose size is linear up to a logarithmic factor in size of the original arena. AU - Chatterjee, Krishnendu AU - Fijalkow, Nathanaël ID - 3349 TI - A reduction from parity games to simple stochastic games VL - 54 ER - TY - JOUR AB - Recently reported synthetic routes for the production of hollow nanoparticles have stimulated significant interest for the possibilities this novel geometry offers. While advantageous properties have been found and innovative applications have been proposed, the development of the full potential of these new nanostructures is still strongly tied to the extent of control that can be accomplished over their characteristics (e.g., composition, size, shell thickness, and nanocrystalline structure). In the present work, we investigate the means and limits of control over these parameters that can be obtained by the Kirkendall effect synthetic route on cadmium chalcogenide nanocrystalline shells. We demonstrate that the selection of the reactants and oxidation conditions allows some extent of control of the nanocrystalline structure and thickness of the shell. However, the tuning range is limited by the intrinsic restrictions of the synthetic procedure and by the dependence of the particle geometry on the same reaction conditions. Thus, we further explore the range of control over the shell parameters that can be accomplished through post-synthesis processes, such as chemical etching and thermal annealing. AU - Ibáñez, Maria AU - Fan, Jiandong AU - Li, Wenhua AU - Cadavid, Doris AU - Nafria, Raquel AU - Carrete, Alex AU - Cabot, Andreu ID - 335 IS - 12 JF - Chemistry of Materials TI - Means and limits of control of the shell parameters in hollow nanoparticles obtained by the Kirkendall effect VL - 23 ER - TY - JOUR AB - Exploring the connection of biology with reactive systems to better understand living systems. AU - Fisher, Jasmin AU - Harel, David AU - Henzinger, Thomas A ID - 3352 IS - 10 JF - Communications of the ACM TI - Biology as reactivity VL - 54 ER - TY - CONF AB - State-transition systems communicating by shared variables have been the underlying model of choice for applications of model checking. Such formalisms, however, have difficulty with modeling process creation or death and communication reconfigurability. Here, we introduce “dynamic reactive modules” (DRM), a state-transition modeling formalism that supports dynamic reconfiguration and creation/death of processes. The resulting formalism supports two types of variables, data variables and reference variables. Reference variables enable changing the connectivity between processes and referring to instances of processes. We show how this new formalism supports parallel composition and refinement through trace containment. DRM provide a natural language for modeling (and ultimately reasoning about) biological systems and multiple threads communicating through shared variables. AU - Fisher, Jasmin AU - Henzinger, Thomas A AU - Nickovic, Dejan AU - Piterman, Nir AU - Singh, Anmol AU - Vardi, Moshe ID - 3362 TI - Dynamic reactive modules VL - 6901 ER - TY - CONF AB - We present the tool Quasy, a quantitative synthesis tool. Quasy takes qualitative and quantitative specifications and automatically constructs a system that satisfies the qualitative specification and optimizes the quantitative specification, if such a system exists. The user can choose between a system that satisfies and optimizes the specifications (a) under all possible environment behaviors or (b) under the most-likely environment behaviors given as a probability distribution on the possible input sequences. Quasy solves these two quantitative synthesis problems by reduction to instances of 2-player games and Markov Decision Processes (MDPs) with quantitative winning objectives. Quasy can also be seen as a game solver for quantitative games. Most notable, it can solve lexicographic mean-payoff games with 2 players, MDPs with mean-payoff objectives, and ergodic MDPs with mean-payoff parity objectives. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Jobstmann, Barbara AU - Singh, Rohit ID - 3365 TI - QUASY: quantitative synthesis tool VL - 6605 ER - TY - CONF AB - In this paper, we present the first output-sensitive algorithm to compute the persistence diagram of a filtered simplicial complex. For any Γ>0, it returns only those homology classes with persistence at least Γ. Instead of the classical reduction via column operations, our algorithm performs rank computations on submatrices of the boundary matrix. For an arbitrary constant δ ∈ (0,1), the running time is O(C(1-δ)ΓR(n)log n), where C(1-δ)Γ is the number of homology classes with persistence at least (1-δ)Γ, n is the total number of simplices, and R(n) is the complexity of computing the rank of an n x n matrix with O(n) nonzero entries. Depending on the choice of the rank algorithm, this yields a deterministic O(C(1-δ)Γn2.376) algorithm, a O(C(1-δ)Γn2.28) Las-Vegas algorithm, or a O(C(1-δ)Γn2+ε) Monte-Carlo algorithm for an arbitrary ε>0. AU - Chen, Chao AU - Kerber, Michael ID - 3367 TI - An output sensitive algorithm for persistent homology ER - TY - GEN AB - We consider probabilistic automata on infinite words with acceptance defined by safety, reachability, Büchi, coBüchi, and limit-average conditions. We consider quantitative and qualitative decision problems. We present extensions and adaptations of proofs for probabilistic finite automata and present a complete characterization of the decidability and undecidability frontier of the quantitative and qualitative decision problems for probabilistic automata on infinite words. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Tracol, Mathieu ID - 3363 TI - The decidability frontier for probabilistic automata on infinite words ER - TY - JOUR AB - Nowak et al.1 argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues. AU - Abbot, Patrick AU - Abe, Jun AU - Alcock, John AU - Alizon, Samuel AU - Alpedrinha, Joao AU - Andersson, Malte AU - Andre, Jean AU - Van Baalen, Minus AU - Balloux, Francois AU - Balshine, Sigal AU - Barton, Nicholas H AU - Beukeboom, Leo AU - Biernaskie, Jay AU - Bilde, Trine AU - Borgia, Gerald AU - Breed, Michael AU - Brown, Sam AU - Bshary, Redouan AU - Buckling, Angus AU - Burley, Nancy AU - Burton Chellew, Max AU - Cant, Michael AU - Chapuisat, Michel AU - Charnov, Eric AU - Clutton Brock, Tim AU - Cockburn, Andrew AU - Cole, Blaine AU - Colegrave, Nick AU - Cosmides, Leda AU - Couzin, Iain AU - Coyne, Jerry AU - Creel, Scott AU - Crespi, Bernard AU - Curry, Robert AU - Dall, Sasha AU - Day, Troy AU - Dickinson, Janis AU - Dugatkin, Lee AU - El Mouden, Claire AU - Emlen, Stephen AU - Evans, Jay AU - Ferriere, Regis AU - Field, Jeremy AU - Foitzik, Susanne AU - Foster, Kevin AU - Foster, William AU - Fox, Charles AU - Gadau, Juergen AU - Gandon, Sylvain AU - Gardner, Andy AU - Gardner, Michael AU - Getty, Thomas AU - Goodisman, Michael AU - Grafen, Alan AU - Grosberg, Rick AU - Grozinger, Christina AU - Gouyon, Pierre AU - Gwynne, Darryl AU - Harvey, Paul AU - Hatchwell, Ben AU - Heinze, Jürgen AU - Helantera, Heikki AU - Helms, Ken AU - Hill, Kim AU - Jiricny, Natalie AU - Johnstone, Rufus AU - Kacelnik, Alex AU - Kiers, E Toby AU - Kokko, Hanna AU - Komdeur, Jan AU - Korb, Judith AU - Kronauer, Daniel AU - Kümmerli, Rolf AU - Lehmann, Laurent AU - Linksvayer, Timothy AU - Lion, Sébastien AU - Lyon, Bruce AU - Marshall, James AU - Mcelreath, Richard AU - Michalakis, Yannis AU - Michod, Richard AU - Mock, Douglas AU - Monnin, Thibaud AU - Montgomerie, Robert AU - Moore, Allen AU - Mueller, Ulrich AU - Noë, Ronald AU - Okasha, Samir AU - Pamilo, Pekka AU - Parker, Geoff AU - Pedersen, Jes AU - Pen, Ido AU - Pfennig, David AU - Queller, David AU - Rankin, Daniel AU - Reece, Sarah AU - Reeve, Hudson AU - Reuter, Max AU - Roberts, Gilbert AU - Robson, Simon AU - Roze, Denis AU - Rousset, Francois AU - Rueppell, Olav AU - Sachs, Joel AU - Santorelli, Lorenzo AU - Schmid Hempel, Paul AU - Schwarz, Michael AU - Scott Phillips, Tom AU - Shellmann Sherman, Janet AU - Sherman, Paul AU - Shuker, David AU - Smith, Jeff AU - Spagna, Joseph AU - Strassmann, Beverly AU - Suarez, Andrew AU - Sundström, Liselotte AU - Taborsky, Michael AU - Taylor, Peter AU - Thompson, Graham AU - Tooby, John AU - Tsutsui, Neil AU - Tsuji, Kazuki AU - Turillazzi, Stefano AU - Úbeda, Francisco AU - Vargo, Edward AU - Voelkl, Bernard AU - Wenseleers, Tom AU - West, Stuart AU - West Eberhard, Mary AU - Westneat, David AU - Wiernasz, Diane AU - Wild, Geoff AU - Wrangham, Richard AU - Young, Andrew AU - Zeh, David AU - Zeh, Jeanne AU - Zink, Andrew ID - 3372 IS - 7339 JF - Nature TI - Inclusive fitness theory and eusociality VL - 471 ER - TY - JOUR AB - The Minisymposium “Cell Migration and Motility” was attended by approximately 500 visitors and covered a broad range of questions in the field using diverse model systems. Topics comprised actin dynamics, cell polarity, force transduction, signal transduction, bar- rier transmigration, and chemotactic guidance. AU - Sixt, Michael K AU - Parent, Carole ID - 3371 IS - 6 JF - Molecular Biology and Evolution TI - Cells on the move in Philadelphia VL - 22 ER - TY - JOUR AB - Genetic regulatory networks enable cells to respond to changes in internal and external conditions by dynamically coordinating their gene expression profiles. Our ability to make quantitative measurements in these biochemical circuits has deepened our understanding of what kinds of computations genetic regulatory networks can perform, and with what reliability. These advances have motivated researchers to look for connections between the architecture and function of genetic regulatory networks. Transmitting information between a network's inputs and outputs has been proposed as one such possible measure of function, relevant in certain biological contexts. Here we summarize recent developments in the application of information theory to gene regulatory networks. We first review basic concepts in information theory necessary for understanding recent work. We then discuss the functional complexity of gene regulation, which arises from the molecular nature of the regulatory interactions. We end by reviewing some experiments that support the view that genetic networks responsible for early development of multicellular organisms might be maximizing transmitted 'positional information'. AU - Tkacik, Gasper AU - Walczak, Aleksandra ID - 3374 IS - 15 JF - Journal of Physics: Condensed Matter TI - Information transmission in genetic regulatory networks a review VL - 23 ER - TY - JOUR AB - Tissue surface tension (TST) is an important mechanical property influencing cell sorting and tissue envelopment. The study by Manning et al. (1) reported on a mathematical model describing TST on the basis of the balance between adhesive and tensile properties of the constituent cells. The model predicts that, in high-adhesion cell aggregates, surface cells will be stretched to maintain the same area of cell–cell contact as interior bulk cells, resulting in an elongated and flattened cell shape. The authors (1) observed flat and elongated cells at the surface of high-adhesion zebrafish germ-layer explants, which they argue are undifferentiated stretched germ-layer progenitor cells, and they use this observation as a validation of their model. AU - Krens, Gabriel AU - Möllmert, Stephanie AU - Heisenberg, Carl-Philipp J ID - 3368 IS - 3 JF - PNAS TI - Enveloping cell layer differentiation at the surface of zebrafish germ layer tissue explants VL - 108 ER - TY - JOUR AB - Supertree methods are widely applied and give rise to new conclusions about phylogenies (e.g., Bininda-Emonds et al. 2007). Although several desiderata for supertree methods exist (Wilkinson, Thorley, et al. 2004), only few of them have been studied in greater detail, examples include shape bias (Wilkinson et al. 2005) or pareto properties (Wilkinson et al. 2007). Here I look more closely at two matrix representation methods, matrix representation with compatibility (MRC) and matrix representation with parsimony (MRP). Different null models of random data are studied and the resulting tree shapes are investigated. Thereby I consider unrooted trees and a bias in tree shape is determined by a tree balance measure. The measure for unrooted trees is a modification of a tree balance measure for rooted trees. I observe that depending on the underlying null model of random data, the methods may resolve conflict in favor of more balanced tree shapes. The analyses refer only to trees with the same taxon set, also known as the consensus setting (e.g., Wilkinson et al. 2007), but I will be able to draw conclusions on how to deal with missing data. AU - Kupczok, Anne ID - 3370 IS - 2 JF - Systematic Biology TI - Consequences of different null models on the tree shape bias of supertree methods VL - 60 ER - TY - JOUR AB - Rab3 interacting molecules (RIMs) are highly enriched in the active zones of presynaptic terminals. It is generally thought that they operate as effectors of the small G protein Rab3. Three recent papers, by Han et al. (this issue of Neuron), Deng et al. (this issue of Neuron), and Kaeser et al. (a recent issue of Cell), shed new light on the functional role of RIM in presynaptic terminals. First, RIM tethers Ca2+ channels to active zones. Second, RIM contributes to priming of synaptic vesicles by interacting with another presynaptic protein, Munc13. AU - Pernia-Andrade, Alejandro AU - Jonas, Peter M ID - 3369 IS - 2 JF - Neuron TI - The multiple faces of RIM VL - 69 ER - TY - JOUR AB - Facial branchiomotor neurons (FBMNs) in zebrafish and mouse embryonic hindbrain undergo a characteristic tangential migration from rhombomere (r) 4, where they are born, to r6/7. Cohesion among neuroepithelial cells (NCs) has been suggested to function in FBMN migration by inhibiting FBMNs positioned in the basal neuroepithelium such that they move apically between NCs towards the midline of the neuroepithelium instead of tangentially along the basal side of the neuroepithelium towards r6/7. However, direct experimental evaluation of this hypothesis is still lacking. Here, we have used a combination of biophysical cell adhesion measurements and high-resolution time-lapse microscopy to determine the role of NC cohesion in FBMN migration. We show that reducing NC cohesion by interfering with Cadherin 2 (Cdh2) activity results in FBMNs positioned at the basal side of the neuroepithelium moving apically towards the neural tube midline instead of tangentially towards r6/7. In embryos with strongly reduced NC cohesion, ectopic apical FBMN movement frequently results in fusion of the bilateral FBMN clusters over the apical midline of the neural tube. By contrast, reducing cohesion among FBMNs by interfering with Contactin 2 (Cntn2) expression in these cells has little effect on apical FBMN movement, but reduces the fusion of the bilateral FBMN clusters in embryos with strongly diminished NC cohesion. These data provide direct experimental evidence that NC cohesion functions in tangential FBMN migration by restricting their apical movement. AU - Stockinger, Petra AU - Heisenberg, Carl-Philipp J AU - Maître, Jean-Léon ID - 3396 IS - 21 JF - Development TI - Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron migration in the zebrafish neural tube VL - 138 ER - TY - JOUR AB - Random genetic drift shifts clines in space, alters their width, and distorts their shape. Such random fluctuations complicate inferences from cline width and position. Notably, the effect of genetic drift on the expected shape of the cline is opposite to the naive (but quite common) misinterpretation of classic results on the expected cline. While random drift on average broadens the overall cline in expected allele frequency, it narrows the width of any particular cline. The opposing effects arise because locally, drift drives alleles to fixation—but fluctuations in position widen the expected cline. The effect of genetic drift can be predicted from standardized variance in allele frequencies, averaged across the habitat: 〈F〉. A cline maintained by spatially varying selection (step change) is expected to be narrower by a factor of relative to the cline in the absence of drift. The expected cline is broader by the inverse of this factor. In a tension zone maintained by underdominance, the expected cline width is narrower by about 1 – 〈F〉relative to the width in the absence of drift. Individual clines can differ substantially from the expectation, and we give quantitative predictions for the variance in cline position and width. The predictions apply to clines in almost one-dimensional circumstances such as hybrid zones in rivers, deep valleys, or along a coast line and give a guide to what patterns to expect in two dimensions. AU - Polechova, Jitka AU - Barton, Nicholas H ID - 3394 IS - 1 JF - Genetics TI - Genetic drift widens the expected cline but narrows the expected cline width VL - 189 ER - TY - JOUR AB - What determines the genetic contribution that an individual makes to future generations? With biparental reproduction, each individual leaves a 'pedigree' of descendants, determined by the biparental relationships in the population. The pedigree of an individual constrains the lines of descent of each of its genes. An individual's reproductive value is the expected number of copies of each of its genes that is passed on to distant generations conditional on its pedigree. For the simplest model of biparental reproduction analogous to the Wright-Fisher model, an individual's reproductive value is determined within ~10 generations, independent of population size. Partial selfing and subdivision do not greatly slow this convergence. Our central result is that the probability that a gene will survive is proportional to the reproductive value of the individual that carries it, and that conditional on survival, after a few tens of generations, the distribution of the number of surviving copies is the same for all individuals, whatever their reproductive value. These results can be generalized to the joint distribution of surviving blocks of ancestral genome. Selection on unlinked loci in the genetic background may greatly increase the variance in reproductive value, but the above results nevertheless still hold. The almost linear relationship between survival probability and reproductive value also holds for weakly favored alleles. Thus, the influence of the complex pedigree of descendants on an individual's genetic contribution to the population can be summarized through a single number: its reproductive value. AU - Barton, Nicholas H AU - Etheridge, Alison ID - 3390 IS - 4 JF - Genetics TI - The relation between reproductive value and genetic contribution VL - 188 ER - TY - JOUR AB - Evolutionary biology shares many concepts with statistical physics: both deal with populations, whether of molecules or organisms, and both seek to simplify evolution in very many dimensions. Often, methodologies have undergone parallel and independent development, as with stochastic methods in population genetics. Here, we discuss aspects of population genetics that have embraced methods from physics: non-equilibrium statistical mechanics, travelling waves and Monte-Carlo methods, among others, have been used to study polygenic evolution, rates of adaptation and range expansions. These applications indicate that evolutionary biology can further benefit from interactions with other areas of statistical physics; for example, by following the distribution of paths taken by a population through time AU - de Vladar, Harold AU - Barton, Nicholas H ID - 3391 IS - 8 JF - Trends in Ecology and Evolution TI - The contribution of statistical physics to evolutionary biology VL - 26 ER - TY - JOUR AB - Recent advances in microscopy techniques and biophysical measurements have provided novel insight into the molecular, cellular and biophysical basis of cell adhesion. However, comparably little is known about a core element of cell–cell adhesion—the energy of adhesion at the cell–cell contact. In this review, we discuss approaches to understand the nature and regulation of adhesion energy, and propose strategies to determine adhesion energy between cells in vitro and in vivo. AU - Maître, Jean-Léon AU - Heisenberg, Carl-Philipp J ID - 3397 IS - 5 JF - Current Opinion in Cell Biology TI - The role of adhesion energy in controlling cell-cell contacts VL - 23 ER - TY - JOUR AB - Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and gates non-selective cation channels. The origins of glutamate receptors are not well understood as they differ structurally and functionally from simple bacterial ligand-gated ion channels. Here we report the discovery of an ionotropic glutamate receptor that combines the typical eukaryotic domain architecture with the 'TXVGYG' signature sequence of the selectivity filter found in K+ channels. This receptor exhibits functional properties intermediate between bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors. AU - Janovjak, Harald L AU - Sandoz, Guillaume AU - Isacoff, Ehud ID - 3405 IS - 232 JF - Nature Communications TI - Modern ionotropic glutamate receptor with a K+ selectivity signature sequence VL - 2 ER - TY - JOUR AB - An oriented attachment and growth mechanism allows an accurate control of the size and morphology of Cu2-xS nanocrystals, from spheres and disks to tetradecahedrons and dodecahedrons. The synthesis conditions and the growth mechanism are detailed here. AU - Li, Wenhua AU - Shavel, Alexey AU - Guzman, Roger AU - Rubio Garcia, Javier AU - Flox, Cristina AU - Fan, Jiandong AU - Cadavid, Doris AU - Ibáñez, Maria AU - Arbiol, Jordi AU - Morante, Joan AU - Cabot, Andreu ID - 341 IS - 37 JF - Chemical Communications TI - Morphology evolution of Cu2−xS nanoparticles: from spheres to dodecahedrons VL - 47 ER - TY - JOUR AB - Transcription factors are central to sustaining pluripotency, yet little is known about transcription factor dynamics in defining pluripotency in the early mammalian embryo. Here, we establish a fluorescence decay after photoactivation (FDAP) assay to quantitatively study the kinetic behaviour of Oct4, a key transcription factor controlling pre-implantation development in the mouse embryo. FDAP measurements reveal that each cell in a developing embryo shows one of two distinct Oct4 kinetics, before there are any morphologically distinguishable differences or outward signs of lineage patterning. The differences revealed by FDAP are due to differences in the accessibility of Oct4 to its DNA binding sites in the nucleus. Lineage tracing of the cells in the two distinct sub-populations demonstrates that the Oct4 kinetics predict lineages of the early embryo. Cells with slower Oct4 kinetics are more likely to give rise to the pluripotent cell lineage that contributes to the inner cell mass. Those with faster Oct4 kinetics contribute mostly to the extra-embryonic lineage. Our findings identify Oct4 kinetics, rather than differences in total transcription factor expression levels, as a predictive measure of developmental cell lineage patterning in the early mouse embryo. AU - Plachta, Nicolas AU - Bollenbach, Mark Tobias AU - Pease, Shirley AU - Fraser, Scott AU - Pantazis, Periklis ID - 3429 IS - 2 JF - Nature Cell Biology TI - Oct4 kinetics predict cell lineage patterning in the early mammalian embryo VL - 13 ER - TY - JOUR AB - Cell migration on two-dimensional (2D) substrates follows entirely different rules than cell migration in three-dimensional (3D) environments. This is especially relevant for leukocytes that are able to migrate in the absence of adhesion receptors within the confined geometry of artificial 3D extracellular matrix scaffolds and within the interstitial space in vivo. Here, we describe in detail a simple and economical protocol to visualize dendritic cell migration in 3D collagen scaffolds along chemotactic gradients. This method can be adapted to other cell types and may serve as a physiologically relevant paradigm for the directed locomotion of most amoeboid cells. AU - Sixt, Michael K AU - Lämmermann, Tim ID - 3505 JF - Cell Migration TI - In vitro analysis of chemotactic leukocyte migration in 3D environments VL - 769 ER - TY - JOUR AB - Advanced stages of Scyllarus phyllosoma larvae were collected by demersal trawling during fishery research surveys in the western Mediterranean Sea in 2003–2005. Nucleotide sequence analysis of the mitochondrial 16S rDNA gene allowed the final-stage phyllosoma of Scyllarus arctus to be identified among these larvae. Its morphology is described and illustrated. This constitutes the second complete description of a Scyllaridae phyllosoma with its specific identity being validated by molecular techniques (the first was S. pygmaeus). These results also solved a long lasting taxonomic anomaly of several species assigned to the ancient genus Phyllosoma Leach, 1814. Detailed examination indicated that the final-stage phyllosoma of S. arctus shows closer affinities with the American scyllarid Scyllarus depressus or with the Australian Scyllarus sp. b (sensu Phillips et al., 1981) than to its sympatric species S. pygmaeus. AU - Palero, Ferran AU - Guerao, Guillermo AU - Clark, Paul AU - Abello, Pere ID - 3784 IS - 2 JF - Journal of the Marine Biological Association of the United Kingdom TI - Scyllarus arctus (Crustacea: Decapoda: Scyllaridae) final stage phyllosoma identified by DNA analysis, with morphological description VL - 91 ER - TY - JOUR AB - We bound the difference in length of two curves in terms of their total curvatures and the Fréchet distance. The bound is independent of the dimension of the ambient Euclidean space, it improves upon a bound by Cohen-Steiner and Edelsbrunner, and it generalizes a result by Fáry and Chakerian. AU - Fasy, Brittany Terese ID - 3781 IS - 1-2 JF - Acta Sci. Math. (Szeged) TI - The difference in length of curves in R^n VL - 77 ER - TY - CHAP AB - We address the problem of covering ℝ n with congruent balls, while minimizing the number of balls that contain an average point. Considering the 1-parameter family of lattices defined by stretching or compressing the integer grid in diagonal direction, we give a closed formula for the covering density that depends on the distortion parameter. We observe that our family contains the thinnest lattice coverings in dimensions 2 to 5. We also consider the problem of packing congruent balls in ℝ n , for which we give a closed formula for the packing density as well. Again we observe that our family contains optimal configurations, this time densest packings in dimensions 2 and 3. AU - Edelsbrunner, Herbert AU - Kerber, Michael ED - Calude, Cristian ED - Rozenberg, Grzegorz ED - Salomaa, Arto ID - 3796 T2 - Rainbow of Computer Science TI - Covering and packing with spheres by diagonal distortion in R^n VL - 6570 ER - TY - JOUR AB - In this survey, we compare several languages for specifying Markovian population models such as queuing networks and chemical reaction networks. All these languages — matrix descriptions, stochastic Petri nets, stoichiometric equations, stochastic process algebras, and guarded command models — describe continuous-time Markov chains, but they differ according to important properties, such as compositionality, expressiveness and succinctness, executability, and ease of use. Moreover, they provide different support for checking the well-formedness of a model and for analyzing a model. AU - Henzinger, Thomas A AU - Jobstmann, Barbara AU - Wolf, Verena ID - 3381 IS - 4 JF - IJFCS: International Journal of Foundations of Computer Science TI - Formalisms for specifying Markovian population models VL - 22 ER - TY - JOUR AB - We present a detailed study of the local density of states (LDOS) associated with the surface-state band near a step edge of the strong topological insulator Bi2Te3 and reveal a one-dimensional bound state that runs parallel to the step edge and is bound to it at some characteristic distance. This bound state is clearly observed in the bulk gap region, while it becomes entangled with the oscillations of the warped surface band at high energy, and with the valence-band states near the Dirac point. We obtain excellent fits to theoretical predictions [Alpichshev, 2011] that properly incorporate the three-dimensional nature of the problem to the surface state. Fitting the data at different energies, we can recalculate the LDOS originating from the Dirac band without the contribution of the bulk bands or incoherent tunneling effects. AU - Alpichshev, Zhanybek AU - Analytis, J G AU - Chu, J H AU - Fisher, I R AU - Kapitulnik, A ID - 386 IS - 4 JF - Physical Review B - Condensed Matter and Materials Physics TI - STM imaging of a bound state along a step on the surface of the topological insulator Bi2Te3 VL - 84 ER - TY - JOUR AB - We consider two-player games played in real time on game structures with clocks where the objectives of players are described using parity conditions. The games are concurrent in that at each turn, both players independently propose a time delay and an action, and the action with the shorter delay is chosen. To prevent a player from winning by blocking time, we restrict each player to play strategies that ensure that the player cannot be responsible for causing a zeno run. First, we present an efficient reduction of these games to turn-based (i.e., not concurrent) finite-state (i.e., untimed) parity games. Our reduction improves the best known complexity for solving timed parity games. Moreover, the rich class of algorithms for classical parity games can now be applied to timed parity games. The states of the resulting game are based on clock regions of the original game, and the state space of the finite game is linear in the size of the region graph. Second, we consider two restricted classes of strategies for the player that represents the controller in a real-time synthesis problem, namely, limit-robust and bounded-robust winning strategies. Using a limit-robust winning strategy, the controller cannot choose an exact real-valued time delay but must allow for some nonzero jitter in each of its actions. If there is a given lower bound on the jitter, then the strategy is bounded-robust winning. We show that exact strategies are more powerful than limit-robust strategies, which are more powerful than bounded-robust winning strategies for any bound. For both kinds of robust strategies, we present efficient reductions to standard timed automaton games. These reductions provide algorithms for the synthesis of robust real-time controllers. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Prabhu, Vinayak ID - 3315 IS - 4 JF - Logical Methods in Computer Science TI - Timed parity games: Complexity and robustness VL - 7 ER - TY - JOUR AB - The elevation function on a smoothly embedded 2-manifold in R-3 reflects the multiscale topography of cavities and protrusions as local maxima. The function has been useful in identifying coarse docking configurations for protein pairs. Transporting the concept from the smooth to the piecewise linear category, this paper describes an algorithm for finding all local maxima. While its worst-case running time is the same as of the algorithm used in prior work, its performance in practice is orders of magnitudes superior. We cast light on this improvement by relating the running time to the total absolute Gaussian curvature of the 2-manifold. AU - Wang, Bei AU - Edelsbrunner, Herbert AU - Morozov, Dmitriy ID - 3965 IS - 2.2 JF - Journal of Experimental Algorithmics TI - Computing elevation maxima by searching the Gauss sphere VL - 16 ER - TY - JOUR AB - PIN-FORMED (PIN)-dependent auxin transport is essential for plant development and its modulation in response to the environment or endogenous signals. A NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3)-like protein, MACCHI-BOU 4 (MAB4), has been shown to control PIN1 localization during organ formation, but its contribution is limited. The Arabidopsis genome contains four genes, MAB4/ENP/NPY1-LIKE1 (MEL1), MEL2, MEL3 and MEL4, highly homologous to MAB4. Genetic analysis disclosed functional redundancy between MAB4 and MEL genes in regulation of not only organ formation but also of root gravitropism, revealing that NPH3 family proteins have a wider range of functions than previously suspected. Multiple mutants showed severe reduction in PIN abundance and PIN polar localization, leading to defective expression of an auxin responsive marker DR5rev::GFP. Pharmacological analyses and fluorescence recovery after photo-bleaching experiments showed that mel mutations increase PIN2 internalization from the plasma membrane, but affect neither intracellular PIN2 trafficking nor PIN2 lateral diffusion at the plasma membrane. Notably, all MAB4 subfamily proteins show polar localization at the cell periphery in plants. The MAB4 polarity was almost identical to PIN polarity. Our results suggest that the MAB4 subfamily proteins specifically retain PIN proteins in a polarized manner at the plasma membrane, thus controlling directional auxin transport and plant development. AU - Furutani, Masahiko AU - Sakamoto, Norihito AU - Yoshida, Shuhei AU - Kajiwara, Takahito AU - Robert, Hélène S AU - Jirí Friml AU - Tasaka, Masao ID - 3086 IS - 10 JF - Development TI - Polar localized NPH3-like proteins regulate polarity and endocytosis of PIN-FORMED auxin efflux carriers VL - 138 ER - TY - JOUR AB - Endocytosis is a crucial mechanism by which eukaryotic cells internalize extracellular and plasma membrane material, and it is required for a multitude of cellular and developmental processes in unicellular and multicellular organisms. In animals and yeast, the best characterized pathway for endocytosis depends on the function of the vesicle coat protein clathrin. Clathrinmediated endocytosis has recently been demonstrated also in plant cells, but its physiological and developmental roles remain unclear. Here, we assessed the roles of the clathrin-mediated mechanism of endocytosis in plants by genetic means. We interfered with clathrin heavy chain (CHC) function through mutants and dominant-negative approaches in Arabidopsis thaliana and established tools to manipulate clathrin function in a cell type-specific manner. The chc2 single mutants and dominant-negative CHC1 (HUB) transgenic lines were defective in bulk endocytosis as well as in internalization of prominent plasma membrane proteins. Interference with clathrin-mediated endocytosis led to defects in constitutive endocytic recycling of PIN auxin transporters and their polar distribution in embryos and roots. Consistent with this, these lines had altered auxin distribution patterns and associated auxin transport-related phenotypes, such as aberrant embryo patterning, imperfect cotyledon specification, agravitropic growth, and impaired lateral root organogenesis. Together, these data demonstrate a fundamental role for clathrin function in cell polarity, growth, patterning, and organogenesis in plants. AU - Kitakura, Saeko AU - Vanneste, Steffen AU - Robert, Stéphanie AU - Löfke, Christian AU - Teichmann, Thomas AU - Tanaka, Hirokazu AU - Jirí Friml ID - 3087 IS - 5 JF - Plant Cell TI - Clathrin mediates endocytosis and polar distribution of PIN auxin transporters in Arabidopsis VL - 23 ER - TY - JOUR AB - Phototropism is an adaptation response, through which plants grow towards the light. It involves light perception and asymmetric distribution of the plant hormone auxin. Here we identify a crucial part of the mechanism for phototropism, revealing how light perception initiates auxin redistribution that leads to directional growth. We show that light polarizes the cellular localization of the auxin efflux carrier PIN3 in hypocotyl endodermis cells, resulting in changes in auxin distribution and differential growth. In the dark, high expression and activity of the PINOID (PID) kinase correlates with apolar targeting of PIN3 to all cell sides. Following illumination, light represses PINOID transcription and PIN3 is polarized specifically to the inner cell sides by GNOM ARF GTPase GEF (guanine nucleotide exchange factor)-dependent trafficking. Thus, differential trafficking at the shaded and illuminated hypocotyl side aligns PIN3 polarity with the light direction, and presumably redirects auxin flow towards the shaded side, where auxin promotes growth, causing hypocotyls to bend towards the light. Our results imply that PID phosphorylation-dependent recruitment of PIN proteins into distinct trafficking pathways is a mechanism to polarize auxin fluxes in response to different environmental and endogenous cues. AU - Ding, Zhaojun AU - Galván-Ampudia, Carlos S AU - Demarsy, Emilie AU - Łangowski, Łukasz AU - Kleine-Vehn, Jürgen AU - Fan, Yuanwei AU - Morita, Miyo T AU - Tasaka, Masao AU - Fankhauser, Christian AU - Offringa, Remko AU - Jirí Friml ID - 3085 IS - 4 JF - Nature Cell Biology TI - Light-mediated polarization of the PIN3 auxin transporter for the phototropic response in Arabidopsis VL - 13 ER - TY - JOUR AB - A central question in developmental biology concerns the mechanism of generation and maintenance of cell polarity, because these processes are essential for many cellular functions and multicellular development [1]. In plants, cell polarity has an additional role in mediating directional transport of the plant hormone auxin that is crucial for multiple developmental processes [2-4]. In addition, plant cells have a complex extracellular matrix, the cell wall [5, 6], whose role in regulating cellular processes, including cell polarity, is unexplored. We have found that polar distribution of PIN auxin transporters [7] in plant cells is maintained by connections between polar domains at the plasma membrane and the cell wall. Genetic and pharmacological interference with cellulose, the major component of the cell wall, or mechanical interference with the cell wall disrupts these connections and leads to increased lateral diffusion and loss of polar distribution of PIN transporters for the phytohormone auxin. Our results reveal a plant-specific mechanism for cell polarity maintenance and provide a conceptual framework for modulating cell polarity and plant development via endogenous and environmental manipulations of the cellulose-based extracellular matrix. AU - Feraru, Elena AU - Feraru, Mugurel I AU - Kleine-Vehn, Jürgen AU - Martinière, Alexandre AU - Mouille, Grégory AU - Vanneste, Steffen AU - Vernhettes, Samantha AU - Runions, John AU - Jirí Friml ID - 3084 IS - 4 JF - Current Biology TI - PIN polarity maintenance by the cell wall in Arabidopsis VL - 21 ER - TY - JOUR AB - Shoot branching is one of the major determinants of plant architecture. Polar auxin transport in stems is necessary for the control of bud outgrowth by a dominant apex. Here, we show that following decapitation in pea (Pisum sativum L.), the axillary buds establish directional auxin export by subcellular polarization of PIN auxin transporters. Apical auxin application on the decapitated stem prevents this PIN polarization and canalization of laterally applied auxin. These results support a model in which the apical and lateral auxin sources compete for primary channels of auxin transport in the stem to control the outgrowth of axillary buds. AU - Balla, Jozef AU - Kalousek, Petr AU - Reinöhl, Vilém AU - Jirí Friml AU - Procházka, Stanislav ID - 3082 IS - 4 JF - Plant Journal TI - Competitive canalization of PIN dependent auxin flow from axillary buds controls pea bud outgrowth VL - 65 ER - TY - JOUR AU - Robinson, David G AU - Scheuring, David AU - Naramoto, Satoshi AU - Jirí Friml ID - 3083 IS - 3 JF - Plant Cell TI - ARF1 localizes to the golgi and the trans Golgi network VL - 23 ER - TY - JOUR AB - Subcellular trafficking is required for a multitude of functions in eukaryotic cells. It involves regulation of cargo sorting, vesicle formation, trafficking and fusion processes at multiple levels. Adaptor protein (AP) complexes are key regulators of cargo sorting into vesicles in yeast and mammals but their existence and function in plants have not been demonstrated. Here we report the identification of the protein-affected trafficking 4 (pat4) mutant defective in the putative δ subunit of the AP-3 complex. pat4 and pat2, a mutant isolated from the same GFP imaging-based forward genetic screen that lacks a functional putative AP-3 β, as well as dominant negative AP-3 μ transgenic lines display undistinguishable phenotypes characterized by largely normal morphology and development, but strong intracellular accumulation of membrane proteins in aberrant vacuolar structures. All mutants are defective in morphology and function of lytic and protein storage vacuoles (PSVs) but show normal sorting of reserve proteins to PSVs. Immunoprecipitation experiments and genetic studies revealed tight functional and physical associations of putative AP-3 β and AP-3 δ subunits. Furthermore, both proteins are closely linked with putative AP-3 μ and σ subunits and several components of the clathrin and dynamin machineries. Taken together, these results demonstrate that AP complexes, similar to those in other eukaryotes, exist in plants, and that AP-3 plays a specific role in the regulation of biogenesis and function of vacuoles in plant cells. © 2011 IBCB, SIBS, CAS All rights reserved AU - Zwiewka, Marta AU - Feraru, Elena AU - Möller, Barbara AU - Hwang, Inhwan AU - Feraru, Mugurel I AU - Kleine-Vehn, Jürgen AU - Weijers, Dolf AU - Jirí Friml ID - 3101 IS - 12 JF - Cell Research TI - The AP 3 adaptor complex is required for vacuolar function in Arabidopsis VL - 21 ER - TY - JOUR AB - Cell polarity reflected by asymmetric distribution of proteins at the plasma membrane is a fundamental feature of unicellular and multicellular organisms. It remains conceptually unclear how cell polarity is kept in cell wall-encapsulated plant cells. We have used super-resolution and semi-quantitative live-cell imaging in combination with pharmacological, genetic, and computational approaches to reveal insights into the mechanism of cell polarity maintenance in Arabidopsis thaliana. We show that polar-competent PIN transporters for the phytohormone auxin are delivered to the center of polar domains by super-polar recycling. Within the plasma membrane, PINs are recruited into non-mobile membrane clusters and their lateral diffusion is dramatically reduced, which ensures longer polar retention. At the circumventing edges of the polar domain, spatially defined internalization of escaped cargos occurs by clathrin-dependent endocytosis. Computer simulations confirm that the combination of these processes provides a robust mechanism for polarity maintenance in plant cells. Moreover, our study suggests that the regulation of lateral diffusion and spatially defined endocytosis, but not super-polar exocytosis have primary importance for PIN polarity maintenance. AU - Kleine-Vehn, Jürgen AU - Krzysztof Wabnik AU - Martinière, Alexandre AU - Łangowski, Łukasz AU - Willig, Katrin AU - Naramoto, Satoshi AU - Leitner, Johannes AU - Tanaka, Hirokazu AU - Jakobs, Stefan AU - Robert, Stéphanie AU - Luschnig, Christian AU - Govaerts, Willy J AU - Hell, Stefan W AU - Runions, John AU - Jirí Friml ID - 3098 JF - Molecular Systems Biology TI - Recycling, clustering and endocytosis jointly maintain PIN auxin carrier polarity at the plasma membrane VL - 7 ER - TY - JOUR AB - In multicellular organisms, morphogenesis relies on a strict coordination in time and space of cell proliferation and differentiation. In contrast to animals, plant development displays continuous organ formation and adaptive growth responses during their lifespan relying on a tight coordination of cell proliferation. How developmental signals interact with the plant cell-cycle machinery is largely unknown. Here, we characterize plant A2-type cyclins, a small gene family of mitotic cyclins, and show how they contribute to the fine-tuning of local proliferation during plant development. Moreover, the timely repression of CYCA2;3 expression in newly formed guard cells is shown to require the stomatal transcription factors FOUR LIPS/MYB124 and MYB88, providing a direct link between developmental programming and cell-cycle exit in plants. Thus, transcriptional downregulation of CYCA2s represents a critical mechanism to coordinate proliferation during plant development. AU - Vanneste, Steffen AU - Coppens, Frederik AU - Lee, EunKyoung AU - Donner, Tyler J AU - Xie, Zidian AU - Van Isterdael, Gert AU - Dhondt, Stijn AU - De Winter, Freya AU - De Rybel, Bert AU - Vuylsteke, Marnik AU - De Veylder, Lieven AU - Jirí Friml AU - Inzé, Dirk AU - Grotewold, Erich AU - Scarpella, Enrico AU - Sack, Fred AU - Beemster, Gerrit T AU - Beeckman, Tom ID - 3100 IS - 16 JF - EMBO Journal TI - Developmental regulation of CYCA2s contributes to tissue-specific proliferation in Arabidopsis VL - 30 ER - TY - JOUR AB - Endomembrane trafficking relies on the coordination of a highly complex, dynamic network of intracellular vesicles. Understanding the network will require a dissection of cargo and vesicle dynamics at the cellular level in vivo. This is also a key to establishing a link between vesicular networks and their functional roles in development. We used a high-content intracellular screen to discover small molecules targeting endomembrane trafficking in vivo in a complex eukaryote, Arabidopsis thaliana. Tens of thousands of molecules were prescreened and a selected subset was interrogated against a panel of plasma membrane (PM) and other endomembrane compartment markers to identify molecules that altered vesicle trafficking. The extensive image dataset was transformed by a flexible algorithm into a marker-by-phenotype-by-treatment time matrix and revealed groups of molecules that induced similar subcellular fingerprints (clusters). This matrix provides a platform for a systems view of trafficking. Molecules from distinct clusters presented avenues and enabled an entry point to dissect recycling at the PM, vacuolar sorting, and cell-plate maturation. Bioactivity in human cells indicated the value of the approach to identifying small molecules that are active in diverse organisms for biology and drug discovery. AU - Drakakaki, Georgia AU - Robert, Stéphanie AU - Szatmári, Anna-Maria AU - Brown, Michelle Q AU - Nagawa, Shingo AU - Van Damme, Daniël AU - Leonard, Marylin AU - Yang, Zhenbiao AU - Girke, Thomas AU - Schmid, Sandra L AU - Russinova, Eugenia AU - Jirí Friml AU - Raikhel, Natasha V AU - Hicks, Glen R ID - 3099 IS - 43 JF - PNAS TI - Clusters of bioactive compounds target dynamic endomembrane networks in vivo VL - 108 ER - TY - JOUR AB - Root system architecture depends on lateral root (LR) initiation that takes place in a relatively narrow developmental window (DW). Here, we analyzed the role of auxin gradients established along the parent root in defining this DW for LR initiation. Correlations between auxin distribution and response, and spatiotemporal control of LR initiation were analyzed in Arabidopsis thaliana and tomato (Solanum lycopersicum). In both Arabidopsis and tomato roots, a well defined zone, where auxin content and response are minimal, demarcates the position of a DW for founder cell specification and LR initiation. We show that in the zone of auxin minimum pericycle cells have highest probability to become founder cells and that auxin perception via the TIR1/AFB pathway, and polar auxin transport, are essential for the establishment of this zone. Altogether, this study reveals that the same morphogen-like molecule, auxin, can act simultaneously as a morphogenetic trigger of LR founder cell identity and as a gradient-dependent signal defining positioning of the founder cell specification. This auxin minimum zone might represent an important control mechanism ensuring the LR initiation steadiness and the acropetal LR initiation pattern. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust. AU - Dubrovsky, Joseph G AU - Napsucialy-Mendivil, Selene AU - Duclercq, Jérôme AU - Cheng, Yan AU - Shishkova, Svetlana O AU - Ivanchenko, Maria G AU - Jirí Friml AU - Murphy, Angus S AU - Eva Benková ID - 3095 IS - 4 JF - New Phytologist TI - Auxin minimum defines a developmental window for lateral root initiation VL - 191 ER - TY - JOUR AB - Cytokinin is an important regulator of plant growth and development. In Arabidopsis thaliana, the two-component phosphorelay mediated through a family of histidine kinases and response regulators is recognized as the principal cytokinin signal transduction mechanism activating the complex transcriptional response to control various developmental processes. Here, we identified an alternative mode of cytokinin action that uses endocytic trafficking as a means to direct plant organogenesis. This activity occurs downstream of known cytokinin receptors but through a branch of the cytokinin signaling pathway that does not involve transcriptional regulation. We show that cytokinin regulates endocytic recycling of the auxin efflux carrier PINFORMED1 (PIN1) by redirecting it for lytic degradation in vacuoles. Stimulation of the lytic PIN1 degradation is not a default effect for general downregulation of proteins from plasma membranes, but a specific mechanism to rapidly modulate the auxin distribution in cytokinin-mediated developmental processes. AU - Peter Marhavy AU - Bielach, Agnieszka AU - Abas, Lindy AU - Abuzeineh, Anas AU - Duclercq, Jérôme AU - Tanaka, Hirokazu AU - Pařezová, Markéta AU - Petrášek, Jan AU - Jirí Friml AU - Kleine-Vehn, Jürgen AU - Eva Benková ID - 3097 IS - 4 JF - Developmental Cell TI - Cytokinin modulates endocytic trafficking of PIN1 auxin efflux carrier to control plant organogenesis VL - 21 ER - TY - JOUR AB - Carrier-dependent, intercellular auxin transport is central to the developmental patterning of higher plants (tracheophytes). The evolution of this polar auxin transport might be linked to the translocation of some PIN auxin efflux carriers from their presumably ancestral localization at the endoplasmic reticulum (ER) to the polar domains at the plasma membrane. Here we propose an eventually ancient mechanism of intercellular auxin distribution by ER-localized auxin transporters involving intracellular auxin retention and switch-like release from the ER. The proposed model integrates feedback circuits utilizing the conserved nuclear auxin signaling for the regulation of PIN transcription and a hypothetical ER-based signaling for the regulation of PIN-dependent transport activity at the ER. Computer simulations of the model revealed its plausibility for generating auxin channels and localized auxin maxima highlighting the possibility of this alternative mechanism for polar auxin transport. AU - Wabnik, Krzysztof T AU - Kleine Vehn, Jürgen AU - Govaerts, Willy AU - Friml, Jirí ID - 3096 IS - 9 JF - Trends in Plant Science TI - Prototype cell-to-cell auxin transport mechanism by intracellular auxin compartmentalization VL - 16 ER - TY - JOUR AB - Hippocampal sharp waves (SPWs) and associated fast ("ripple") oscillations (SPW-Rs) in the CA1 region are among the most synchronous physiological patterns in the mammalian brain. Using two-dimensional arrays of electrodes for recording local field potentials and unit discharges in freely moving rats, we studied the emergence of ripple oscillations (140-220 Hz) and compared their origin and cellular-synaptic mechanisms with fast gamma oscillations (90-140 Hz). We show that (1) hippocampal SPW-Rs and fast gamma oscillations are quantitatively distinct patterns but involve the same networks and share similar mechanisms; (2) both the frequency and magnitude of fast oscillations are positively correlated with the magnitude of SPWs; (3) during both ripples and fast gamma oscillations the frequency of network oscillation is higher in CA1 than in CA3; and (4) the emergence of CA3 population bursts, a prerequisite for SPW-Rs, is biased by activity patterns in the dentate gyrus and entorhinal cortex, with the highest probability of ripples associated with an "optimum" level of dentate gamma power. We hypothesize that each hippocampal subnetwork possesses distinct resonant properties, tuned by the magnitude of the excitatory drive. AU - Sullivan, David W AU - Jozsef Csicsvari AU - Mizuseki, Kenji AU - Montgomery, Sean M AU - Diba, Kamran AU - Buzsáki, György ID - 3138 IS - 23 JF - Journal of Neuroscience TI - Relationships between hippocampal sharp waves ripples and fast gamma oscillation Influence of dentate and entorhinal cortical activity VL - 31 ER - TY - JOUR AB - Microinjection of recombinant DNA into zygotic pronuclei has been widely used for producing transgenic mice. However, with this method, the insertion site, integrity, and copy number of the transgene cannot be controlled. Here, we present an integrase-based approach to produce transgenic mice via pronuclear injection, whereby an intact single-copy transgene can be inserted into predetermined chromosomal loci with high efficiency (up to 40%), and faithfully transmitted through generations. We show that neighboring transgenic elements and bacterial DNA within the transgene cause profound silencing and expression variability of the transgenic marker. Removal of these undesirable elements leads to global high-level marker expression from transgenes driven by a ubiquitous promoter. We also obtained faithful marker expression from a tissue-specific promoter. The technique presented here will greatly facilitate murine transgenesis and precise structure/function dissection of mammalian gene function and regulation in vivo. AU - Tasic, Bosiljka AU - Simon Hippenmeyer AU - Wang, Charlene AU - Gamboa, Matthew AU - Zong, Hui AU - Chen-Tsai, Yanru AU - Luo, Liqun ID - 3145 IS - 19 JF - PNAS TI - Site specific integrase mediated transgenesis in mice via pronuclear injection VL - 108 ER - TY - JOUR AB - Regulated adhesion between cells and their environment is critical for normal cell migration. We have identified mutations in a gene encoding the Drosophila hydrogen peroxide (H2O2)-degrading enzyme Jafrac1, which lead to germ cell adhesion defects. During gastrulation, primordial germ cells (PGCs) associate tightly with the invaginating midgut primordium as it enters the embryo; however, in embryos from jafrac1 mutant mothers this association is disrupted, leaving some PGCs trailing on the outside of the embryo. We observed similar phenotypes in embryos from DE-cadherin/shotgun (shg) mutant mothers and were able to rescue the jafrac1 phenotype by increasing DE-cadherin levels. This and our biochemical evidence strongly suggest that Jafrac1-mediated reduction of H2O2 is required to maintain DE-cadherin protein levels in the early embryo. Our results present in vivo evidence of a peroxiredoxin regulating DE-cadherin-mediated adhesion. AU - DeGennaro, Matthew AU - Hurd, Thomas R AU - Daria Siekhaus AU - Biteau, Benoit AU - Jasper, Heinrich AU - Lehmann, Ruth ID - 3154 IS - 2 JF - Developmental Cell TI - Peroxiredoxin stabilization of DE-cadherin promotes primordial germ cell adhesion VL - 20 ER - TY - CONF AB - Tampering attacks are cryptanalytic attacks on the implementation of cryptographic algorithms (e.g., smart cards), where an adversary introduces faults with the hope that the tampered device will reveal secret information. Inspired by the work of Ishai et al. [Eurocrypt'06], we propose a compiler that transforms any circuit into a new circuit with the same functionality, but which is resilient against a well-defined and powerful tampering adversary. More concretely, our transformed circuits remain secure even if the adversary can adaptively tamper with every wire in the circuit as long as the tampering fails with some probability δ>0. This additional requirement is motivated by practical tampering attacks, where it is often difficult to guarantee the success of a specific attack. Formally, we show that a q-query tampering attack against the transformed circuit can be "simulated" with only black-box access to the original circuit and log(q) bits of additional auxiliary information. Thus, if the implemented cryptographic scheme is secure against log(q) bits of leakage, then our implementation is tamper-proof in the above sense. Surprisingly, allowing for this small amount of information leakage allows for much more efficient compilers, which moreover do not require randomness during evaluation. Similar to earlier works our compiler requires small, stateless and computation-independent tamper-proof gadgets. Thus, our result can be interpreted as reducing the problem of shielding arbitrary complex computation to protecting simple components. © 2011 Springer-Verlag. AU - Faust, Sebastian AU - Krzysztof Pietrzak AU - Venturi, Daniele ID - 3239 IS - Part 1 TI - Tamper proof circuits How to trade leakage for tamper resilience VL - 6755 ER - TY - CONF AB - If a cryptographic primitive remains secure even if ℓ bits about the secret key are leaked to the adversary, one would expect that at least one of n independent instantiations of the scheme remains secure given n·ℓ bits of leakage. This intuition has been proven true for schemes satisfying some special information-theoretic properties by Alwen et al. [Eurocrypt'10]. On the negative side, Lewko and Waters [FOCS'10] construct a CPA secure public-key encryption scheme for which this intuition fails. The counterexample of Lewko and Waters leaves open the interesting possibility that for any scheme there exists a constant c>0, such that n fold repetition remains secure against c·n·ℓ bits of leakage. Furthermore, their counterexample requires the n copies of the encryption scheme to share a common reference parameter, leaving open the possibility that the intuition is true for all schemes without common setup. In this work we give a stronger counterexample ruling out these possibilities. We construct a signature scheme such that: 1. a single instantiation remains secure given ℓ = log(k) bits of leakage where k is a security parameter. 2. any polynomial number of independent instantiations can be broken (in the strongest sense of key-recovery) given ℓ′ = poly(k) bits of leakage. Note that ℓ does not depend on the number of instances. The computational assumption underlying our counterexample is that non-interactive computationally sound proofs exist. Moreover, under a stronger (non-standard) assumption about such proofs, our counterexample does not require a common reference parameter. The underlying idea of our counterexample is rather generic and can be applied to other primitives like encryption schemes. © 2011 International Association for Cryptologic Research. AU - Jain, Abhishek AU - Krzysztof Pietrzak ID - 3236 TI - Parallel repetition for leakage resilience amplification revisited VL - 6597 ER - TY - JOUR AB - We present an algorithm to identify individual neural spikes observed on high-density multi-electrode arrays (MEAs). Our method can distinguish large numbers of distinct neural units, even when spikes overlap, and accounts for intrinsic variability of spikes from each unit. As MEAs grow larger, it is important to find spike-identification methods that are scalable, that is, the computational cost of spike fitting should scale well with the number of units observed. Our algorithm accomplishes this goal, and is fast, because it exploits the spatial locality of each unit and the basic biophysics of extracellular signal propagation. Human interaction plays a key role in our method; but effort is minimized and streamlined via a graphical interface. We illustrate our method on data from guinea pig retinal ganglion cells and document its performance on simulated data consisting of spikes added to experimentally measured background noise. We present several tests demonstrating that the algorithm is highly accurate: it exhibits low error rates on fits to synthetic data, low refractory violation rates, good receptive field coverage, and consistency across users. AU - Prentice, Jason S AU - Homann, Jan AU - Simmons, Kristina D AU - Gasper Tkacik AU - Balasubramanian, Vijay AU - Nelson, Philip C ID - 3276 IS - 7 JF - PLoS One TI - Fast, scalable, Bayesian spike identification for multi-electrode arrays VL - 6 ER - TY - CHAP AB - In this paper we present an efficient framework for computation of persis- tent homology of cubical data in arbitrary dimensions. An existing algorithm using simplicial complexes is adapted to the setting of cubical complexes. The proposed approach enables efficient application of persistent homology in domains where the data is naturally given in a cubical form. By avoiding triangulation of the data, we significantly reduce the size of the complex. We also present a data-structure de- signed to compactly store and quickly manipulate cubical complexes. By means of numerical experiments, we show high speed and memory efficiency of our ap- proach. We compare our framework to other available implementations, showing its superiority. Finally, we report performance on selected 3D and 4D data-sets. AU - Wagner, Hubert AU - Chen, Chao AU - Vuçini, Erald ED - Peikert, Ronald ED - Hauser, Helwig ED - Carr, Hamish ED - Fuchs, Raphael ID - 3271 T2 - Topological Methods in Data Analysis and Visualization II TI - Efficient computation of persistent homology for cubical data ER - TY - JOUR AB - Despite much research on the socially parasitic large blue butterflies (genus Maculinea) in the past 40 years, their relationship to their closest relatives, Phengaris, is controversial and the relationships among the remaining genera in the Glaucopsyche section are largely unresolved. The evolutionary history of this butterfly section is particularly important to understand the evolution of life history diversity con- nected to food-plant and host-ant associations in the larval stage. In the present study, we use a combi- nation of four nuclear and two mitochondrial genes to reconstruct the phylogeny of the Glaucopsyche section, and in particular, to study the relationships among and within the Phengaris–Maculinea species. We find a clear pattern between the clades recovered in the Glaucopsyche section phylogeny and their food-plant associations, with only the Phengaris–Maculinea clade utilising more than one plant family. Maculinea is, for the first time, recovered with strong support as a monophyletic group nested within Phengaris, with the closest relative being the rare genus Caerulea. The genus Glaucopsyche is polyphyletic, including the genera Sinia and Iolana. Interestingly, we find evidence for additional potential cryptic spe- cies within the highly endangered Maculinea, which has long been suspected from morphological, ecolog- ical and molecular studies. AU - Vila, Roger AU - Pierce, Naomi E AU - Nash, David R AU - Line Ugelvig ID - 3278 IS - 1 JF - Molecular Phylogenetics and Evolution TI - A phylogenetic revision of the Glaucopsyche section (Lepidoptera: Lycaenidae), with special focus on the Phengaris-Maculinea clade VL - 61 ER -