TY - CONF AB - Hybrid systems have both continuous and discrete dynamics and are useful for modeling a variety of control systems, from air traffic control protocols to robotic maneuvers and beyond. Recently, numerous powerful and scalable tools for analyzing hybrid systems have emerged. Several of these tools implement automated formal methods for mathematically proving a system meets a specification. This tutorial session will present three recent hybrid systems tools: C2E2, HyST, and TuLiP. C2E2 is a simulated-based verification tool for hybrid systems, and uses validated numerical solvers and bloating of simulation traces to verify systems meet specifications. HyST is a hybrid systems model transformation and translation tool, and uses a canonical intermediate representation to support most of the recent verification tools, as well as automated sound abstractions that simplify verification of a given hybrid system. TuLiP is a controller synthesis tool for hybrid systems, where given a temporal logic specification to be satisfied for a system (plant) model, TuLiP will find a controller that meets a given specification. © 2016 IEEE. AU - Duggirala, Parasara AU - Fan, Chuchu AU - Potok, Matthew AU - Qi, Bolun AU - Mitra, Sayan AU - Viswanathan, Mahesh AU - Bak, Stanley AU - Bogomolov, Sergiy AU - Johnson, Taylor AU - Nguyen, Luan AU - Schilling, Christian AU - Sogokon, Andrew AU - Tran, Hoang AU - Xiang, Weiming ID - 1134 T2 - 2016 IEEE Conference on Control Applications TI - Tutorial: Software tools for hybrid systems verification transformation and synthesis C2E2 HyST and TuLiP ER - TY - CONF AB - We propose an interactive sculpting system for seamlessly editing pre-computed animations of liquid, without the need for any resimulation. The input is a sequence of meshes without correspondences representing the liquid surface over time. Our method enables the efficient selection of consistent space-time parts of this animation, such as moving waves or droplets, which we call space-time features. Once selected, a feature can be copied, edited, or duplicated and then pasted back anywhere in space and time in the same or in another liquid animation sequence. Our method circumvents tedious user interactions by automatically computing the spatial and temporal ranges of the selected feature. We also provide space-time shape editing tools for non-uniform scaling, rotation, trajectory changes, and temporal editing to locally speed up or slow down motion. Using our tools, the user can edit and progressively refine any input simulation result, possibly using a library of precomputed space-time features extracted from other animations. In contrast to the trial-and-error loop usually required to edit animation results through the tuning of indirect simulation parameters, our method gives the user full control over the edited space-time behaviors. © 2016 Copyright held by the owner/author(s). AU - Manteaux, Pierre AU - Vimont, Ulysse AU - Wojtan, Christopher J AU - Rohmer, Damien AU - Cani, Marie ID - 1136 T2 - Proceedings of the 9th International Conference on Motion in Games TI - Space-time sculpting of liquid animation ER - TY - JOUR AB - RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. RASGRP1 deficiency was associated in T cells and B cells with decreased phosphorylation of the extracellular-signal-regulated serine kinase ERK, which was restored following expression of wild-type RASGRP1. RASGRP1 deficiency also resulted in defective proliferation, activation and motility of T cells and B cells. RASGRP1-deficient natural killer (NK) cells exhibited impaired cytotoxicity with defective granule convergence and actin accumulation. Interaction proteomics identified the dynein light chain DYNLL1 as interacting with RASGRP1, which links RASGRP1 to cytoskeletal dynamics. RASGRP1-deficient cells showed decreased activation of the GTPase RhoA. Treatment with lenalidomide increased RhoA activity and reversed the migration and activation defects of RASGRP1-deficient lymphocytes. AU - Salzer, Elisabeth AU - Çaǧdaş, Deniz AU - Hons, Miroslav AU - Mace, Emily AU - Garncarz, Wojciech AU - Petronczki, Oezlem AU - Platzer, René AU - Pfajfer, Laurène AU - Bilic, Ivan AU - Ban, Sol AU - Willmann, Katharina AU - Mukherjee, Malini AU - Supper, Verena AU - Hsu, Hsiangting AU - Banerjee, Pinaki AU - Sinha, Papiya AU - Mcclanahan, Fabienne AU - Zlabinger, Gerhard AU - Pickl, Winfried AU - Gribben, John AU - Stockinger, Hannes AU - Bennett, Keiryn AU - Huppa, Johannes AU - Dupré, Loï̈C AU - Sanal, Özden AU - Jäger, Ulrich AU - Sixt, Michael K AU - Tezcan, Ilhan AU - Orange, Jordan AU - Boztug, Kaan ID - 1137 IS - 12 JF - Nature Immunology TI - RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics VL - 17 ER - TY - CONF AB - Automata with monitor counters, where the transitions do not depend on counter values, and nested weighted automata are two expressive automata-theoretic frameworks for quantitative properties. For a well-studied and wide class of quantitative functions, we establish that automata with monitor counters and nested weighted automata are equivalent. We study for the first time such quantitative automata under probabilistic semantics. We show that several problems that are undecidable for the classical questions of emptiness and universality become decidable under the probabilistic semantics. We present a complete picture of decidability for such automata, and even an almost-complete picture of computational complexity, for the probabilistic questions we consider. © 2016 ACM. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Otop, Jan ID - 1138 T2 - Proceedings of the 31st Annual ACM/IEEE Symposium TI - Quantitative automata under probabilistic semantics ER - TY - CONF AB - Given a model of a system and an objective, the model-checking question asks whether the model satisfies the objective. We study polynomial-time problems in two classical models, graphs and Markov Decision Processes (MDPs), with respect to several fundamental -regular objectives, e.g., Rabin and Streett objectives. For many of these problems the best-known upper bounds are quadratic or cubic, yet no super-linear lower bounds are known. In this work our contributions are two-fold: First, we present several improved algorithms, and second, we present the first conditional super-linear lower bounds based on widely believed assumptions about the complexity of CNF-SAT and combinatorial Boolean matrix multiplication. A separation result for two models with respect to an objective means a conditional lower bound for one model that is strictly higher than the existing upper bound for the other model, and similarly for two objectives with respect to a model. Our results establish the following separation results: (1) A separation of models (graphs and MDPs) for disjunctive queries of reachability and Büchi objectives. (2) Two kinds of separations of objectives, both for graphs and MDPs, namely, (2a) the separation of dual objectives such as Streett/Rabin objectives, and (2b) the separation of conjunction and disjunction of multiple objectives of the same type such as safety, Büchi, and coBüchi. In summary, our results establish the first model and objective separation results for graphs and MDPs for various classical -regular objectives. Quite strikingly, we establish conditional lower bounds for the disjunction of objectives that are strictly higher than the existing upper bounds for the conjunction of the same objectives. © 2016 ACM. AU - Chatterjee, Krishnendu AU - Dvoák, Wolfgang AU - Henzinger, Monika H AU - Loitzenbauer, Veronika ID - 1140 T2 - Proceedings of the 31st Annual ACM/IEEE Symposium on Logic in Computer Science TI - Model and objective separation with conditional lower bounds: disjunction is harder than conjunction ER - TY - JOUR AB - Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach revealed that quinine effectively prevented heme effects on the cytoskeleton, restored phagocytosis and improved survival in sepsis. These mechanistic insights provide potential therapeutic targets for patients with sepsis or hemolytic disorders. AU - Martins, Rui AU - Maier, Julia AU - Gorki, Anna AU - Huber, Kilian AU - Sharif, Omar AU - Starkl, Philipp AU - Saluzzo, Simona AU - Quattrone, Federica AU - Gawish, Riem AU - Lakovits, Karin AU - Aichinger, Michael AU - Radic Sarikas, Branka AU - Lardeau, Charles AU - Hladik, Anastasiya AU - Korosec, Ana AU - Brown, Markus AU - Vaahtomeri, Kari AU - Duggan, Michelle AU - Kerjaschki, Dontscho AU - Esterbauer, Harald AU - Colinge, Jacques AU - Eisenbarth, Stephanie AU - Decker, Thomas AU - Bennett, Keiryn AU - Kubicek, Stefan AU - Sixt, Michael K AU - Superti Furga, Giulio AU - Knapp, Sylvia ID - 1142 IS - 12 JF - Nature Immunology TI - Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions VL - 17 ER - TY - JOUR AB - In this paper we introduce the Multiobjective Optimization Hierarchic Genetic Strategy with maturing (MO-mHGS), a meta-algorithm that performs evolutionary optimization in a hierarchy of populations. The maturing mechanism improves growth and reduces redundancy. The performance of MO-mHGS with selected state-of-the-art multiobjective evolutionary algorithms as internal algorithms is analysed on benchmark problems and their modifications for which single fitness evaluation time depends on the solution accuracy. We compare the proposed algorithm with the Island Model Genetic Algorithm as well as with single-deme methods, and discuss the impact of internal algorithms on the MO-mHGS meta-algorithm. © 2016 Elsevier B.V. AU - Łazarz, Radosław AU - Idzik, Michał AU - Gądek, Konrad AU - Gajda-Zagorska, Ewa P ID - 1141 IS - 1 JF - Journal of Computational Science TI - Hierarchic genetic strategy with maturing as a generic tool for multiobjective optimization VL - 17 ER - TY - JOUR AB - We study the ground state of a dilute Bose gas in a scaling limit where the Gross-Pitaevskii functional emerges. This is a repulsive nonlinear Schrödinger functional whose quartic term is proportional to the scattering length of the interparticle interaction potential. We propose a new derivation of this limit problem, with a method that bypasses some of the technical difficulties that previous derivations had to face. The new method is based on a combination of Dyson\'s lemma, the quantum de Finetti theorem and a second moment estimate for ground states of the effective Dyson Hamiltonian. It applies equally well to the case where magnetic fields or rotation are present. AU - Nam, Phan AU - Rougerie, Nicolas AU - Seiringer, Robert ID - 1143 IS - 2 JF - Analysis and PDE TI - Ground states of large bosonic systems: The gross Pitaevskii limit revisited VL - 9 ER - TY - JOUR AB - Auxin directs plant ontogenesis via differential accumulation within tissues depending largely on the activity of PIN proteins that mediate auxin efflux from cells and its directional cell-to-cell transport. Regardless of the developmental importance of PINs, the structure of these transporters is poorly characterized. Here, we present experimental data concerning protein topology of plasma membrane-localized PINs. Utilizing approaches based on pH-dependent quenching of fluorescent reporters combined with immunolocalization techniques, we mapped the membrane topology of PINs and further cross-validated our results using available topology modeling software. We delineated the topology of PIN1 with two transmembrane (TM) bundles of five α-helices linked by a large intracellular loop and a C-terminus positioned outside the cytoplasm. Using constraints derived from our experimental data, we also provide an updated position of helical regions generating a verisimilitude model of PIN1. Since the canonical long PINs show a high degree of conservation in TM domains and auxin transport capacity has been demonstrated for Arabidopsis representatives of this group, this empirically enhanced topological model of PIN1 will be an important starting point for further studies on PIN structure–function relationships. In addition, we have established protocols that can be used to probe the topology of other plasma membrane proteins in plants. © 2016 The Authors AU - Nodzyński, Tomasz AU - Vanneste, Steffen AU - Zwiewka, Marta AU - Pernisová, Markéta AU - Hejátko, Jan AU - Friml, Jirí ID - 1145 IS - 11 JF - Molecular Plant TI - Enquiry into the topology of plasma membrane localized PIN auxin transport components VL - 9 ER - TY - JOUR AB - Apical dominance is one of the fundamental developmental phenomena in plant biology, which determines the overall architecture of aerial plant parts. Here we show apex decapitation activated competition for dominance in adjacent upper and lower axillary buds. A two-nodal-bud pea (Pisum sativum L.) was used as a model system to monitor and assess auxin flow, auxin transport channels, and dormancy and initiation status of axillary buds. Auxin flow was manipulated by lateral stem wounds or chemically by auxin efflux inhibitors 2,3,5-triiodobenzoic acid (TIBA), 1-N-naphtylphtalamic acid (NPA), or protein synthesis inhibitor cycloheximide (CHX) treatments, which served to interfere with axillary bud competition. Redirecting auxin flow to different points influenced which bud formed the outgrowing and dominant shoot. The obtained results proved that competition between upper and lower axillary buds as secondary auxin sources is based on the same auxin canalization principle that operates between the shoot apex and axillary bud. © The Author(s) 2016. AU - Balla, Jozef AU - Medved'Ová, Zuzana AU - Kalousek, Petr AU - Matiješčuková, Natálie AU - Friml, Jirí AU - Reinöhl, Vilém AU - Procházka, Stanislav ID - 1147 JF - Scientific Reports TI - Auxin flow mediated competition between axillary buds to restore apical dominance VL - 6 ER - TY - JOUR AB - We study the usefulness of two most prominent publicly available rigorous ODE integrators: one provided by the CAPD group (capd.ii.uj.edu.pl), the other based on the COSY Infinity project (cosyinfinity.org). Both integrators are capable of handling entire sets of initial conditions and provide tight rigorous outer enclosures of the images under a time-T map. We conduct extensive benchmark computations using the well-known Lorenz system, and compare the computation time against the final accuracy achieved. We also discuss the effect of a few technical parameters, such as the order of the numerical integration method, the value of T, and the phase space resolution. We conclude that COSY may provide more precise results due to its ability of avoiding the variable dependency problem. However, the overall cost of computations conducted using CAPD is typically lower, especially when intervals of parameters are involved. Moreover, access to COSY is limited (registration required) and the rigorous ODE integrators are not publicly available, while CAPD is an open source free software project. Therefore, we recommend the latter integrator for this kind of computations. Nevertheless, proper choice of the various integration parameters turns out to be of even greater importance than the choice of the integrator itself. © 2016 IMACS. Published by Elsevier B.V. All rights reserved. AU - Miyaji, Tomoyuki AU - Pilarczyk, Pawel AU - Gameiro, Marcio AU - Kokubu, Hiroshi AU - Mischaikow, Konstantin ID - 1149 JF - Applied Numerical Mathematics TI - A study of rigorous ODE integrators for multi scale set oriented computations VL - 107 ER - TY - JOUR AB - When neutrophils infiltrate a site of inflammation, they have to stop at the right place to exert their effector function. In this issue of Developmental Cell, Wang et al. (2016) show that neutrophils sense reactive oxygen species via the TRPM2 channel to arrest migration at their target site. © 2016 Elsevier Inc. AU - Renkawitz, Jörg AU - Sixt, Michael K ID - 1150 IS - 5 JF - Developmental Cell TI - A Radical Break Restraining Neutrophil Migration VL - 38 ER - TY - JOUR AB - Tissue patterning in multicellular organisms is the output of precise spatio–temporal regulation of gene expression coupled with changes in hormone dynamics. In plants, the hormone auxin regulates growth and development at every stage of a plant’s life cycle. Auxin signaling occurs through binding of the auxin molecule to a TIR1/AFB F-box ubiquitin ligase, allowing interaction with Aux/IAA transcriptional repressor proteins. These are subsequently ubiquitinated and degraded via the 26S proteasome, leading to derepression of auxin response factors (ARFs). How auxin is able to elicit such a diverse range of developmental responses through a single signaling module has not yet been resolved. Here we present an alternative auxin-sensing mechanism in which the ARF ARF3/ETTIN controls gene expression through interactions with process-specific transcription factors. This noncanonical hormonesensing mechanism exhibits strong preference for the naturally occurring auxin indole 3-acetic acid (IAA) and is important for coordinating growth and patterning in diverse developmental contexts such as gynoecium morphogenesis, lateral root emergence, ovule development, and primary branch formation. Disrupting this IAA-sensing ability induces morphological aberrations with consequences for plant fitness. Therefore, our findings introduce a novel transcription factor-based mechanism of hormone perception in plants. © 2016 Simonini et al. AU - Simonini, Sara AU - Deb, Joyita AU - Moubayidin, Laila AU - Stephenson, Pauline AU - Valluru, Manoj AU - Freire Rios, Alejandra AU - Sorefan, Karim AU - Weijers, Dolf AU - Friml, Jirí AU - Östergaard, Lars ID - 1151 IS - 20 JF - Genes and Development TI - A noncanonical auxin sensing mechanism is required for organ morphogenesis in arabidopsis VL - 30 ER - TY - JOUR AB - Differential cell growth enables flexible organ bending in the presence of environmental signals such as light or gravity. A prominent example of the developmental processes based on differential cell growth is the formation of the apical hook that protects the fragile shoot apical meristem when it breaks through the soil during germination. Here, we combined in silico and in vivo approaches to identify a minimal mechanism producing auxin gradient-guided differential growth during the establishment of the apical hook in the model plant Arabidopsis thaliana. Computer simulation models based on experimental data demonstrate that asymmetric expression of the PIN-FORMED auxin efflux carrier at the concave (inner) versus convex (outer) side of the hook suffices to establish an auxin maximum in the epidermis at the concave side of the apical hook. Furthermore, we propose a mechanism that translates this maximum into differential growth, and thus curvature, of the apical hook. Through a combination of experimental and in silico computational approaches, we have identified the individual contributions of differential cell elongation and proliferation to defining the apical hook and reveal the role of auxin-ethylene crosstalk in balancing these two processes. © 2016 American Society of Plant Biologists. All rights reserved. AU - Žádníková, Petra AU - Wabnik, Krzysztof T AU - Abuzeineh, Anas AU - Gallemí, Marçal AU - Van Der Straeten, Dominique AU - Smith, Richard AU - Inze, Dirk AU - Friml, Jirí AU - Prusinkiewicz, Przemysław AU - Benková, Eva ID - 1153 IS - 10 JF - Plant Cell TI - A model of differential growth guided apical hook formation in plants VL - 28 ER - TY - JOUR AB - Cellular locomotion is a central hallmark of eukaryotic life. It is governed by cell-extrinsic molecular factors, which can either emerge in the soluble phase or as immobilized, often adhesive ligands. To encode for direction, every cue must be present as a spatial or temporal gradient. Here, we developed a microfluidic chamber that allows measurement of cell migration in combined response to surface immobilized and soluble molecular gradients. As a proof of principle we study the response of dendritic cells to their major guidance cues, chemokines. The majority of data on chemokine gradient sensing is based on in vitro studies employing soluble gradients. Despite evidence suggesting that in vivo chemokines are often immobilized to sugar residues, limited information is available how cells respond to immobilized chemokines. We tracked migration of dendritic cells towards immobilized gradients of the chemokine CCL21 and varying superimposed soluble gradients of CCL19. Differential migratory patterns illustrate the potential of our setup to quantitatively study the competitive response to both types of gradients. Beyond chemokines our approach is broadly applicable to alternative systems of chemo- and haptotaxis such as cells migrating along gradients of adhesion receptor ligands vs. any soluble cue. AU - Schwarz, Jan AU - Bierbaum, Veronika AU - Merrin, Jack AU - Frank, Tino AU - Hauschild, Robert AU - Bollenbach, Mark Tobias AU - Tay, Savaş AU - Sixt, Michael K AU - Mehling, Matthias ID - 1154 JF - Scientific Reports TI - A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients VL - 6 ER - TY - JOUR AB - We consider sample covariance matrices of the form Q = ( σ1/2X)(σ1/2X)∗, where the sample X is an M ×N random matrix whose entries are real independent random variables with variance 1/N and whereσ is an M × M positive-definite deterministic matrix. We analyze the asymptotic fluctuations of the largest rescaled eigenvalue of Q when both M and N tend to infinity with N/M →d ϵ (0,∞). For a large class of populations σ in the sub-critical regime, we show that the distribution of the largest rescaled eigenvalue of Q is given by the type-1 Tracy-Widom distribution under the additional assumptions that (1) either the entries of X are i.i.d. Gaussians or (2) that σ is diagonal and that the entries of X have a sub-exponential decay. AU - Lee, Ji AU - Schnelli, Kevin ID - 1157 IS - 6 JF - Annals of Applied Probability TI - Tracy-widom distribution for the largest eigenvalue of real sample covariance matrices with general population VL - 26 ER - TY - JOUR AB - The increasing complexity of dynamic models in systems and synthetic biology poses computational challenges especially for the identification of model parameters. While modularization of the corresponding optimization problems could help reduce the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit a simple decomposition of most biomolecular networks into subnetworks, or modules. Drawing on ideas from network modularization and multiple-shooting optimization, we present here a modular parameter identification approach that explicitly allows for such interdependencies. Interfaces between our modules are given by the experimentally measured molecular species. This definition allows deriving good (initial) estimates for the inter-module communication directly from the experimental data. Given these estimates, the states and parameter sensitivities of different modules can be integrated independently. To achieve consistency between modules, we iteratively adjust the estimates for inter-module communication while optimizing the parameters. After convergence to an optimal parameter set---but not during earlier iterations---the intermodule communication as well as the individual modules\' state dynamics agree with the dynamics of the nonmodularized network. Our modular parameter identification approach allows for easy parallelization; it can reduce the computational complexity for larger networks and decrease the probability to converge to suboptimal local minima. We demonstrate the algorithm\'s performance in parameter estimation for two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling pathway. AU - Lang, Moritz AU - Stelling, Jörg ID - 1170 IS - 6 JF - SIAM Journal on Scientific Computing TI - Modular parameter identification of biomolecular networks VL - 38 ER - TY - JOUR AU - Tkacik, Gasper ID - 1171 JF - Physics of Life Reviews TI - Understanding regulatory networks requires more than computing a multitude of graph statistics: Comment on "Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function" by O. C. Martin et al. VL - 17 ER - TY - JOUR AB - A central issue in cell biology is the physico-chemical basis of organelle biogenesis in intracellular trafficking pathways, its most impressive manifestation being the biogenesis of Golgi cisternae. At a basic level, such morphologically and chemically distinct compartments should arise from an interplay between the molecular transport and chemical maturation. Here, we formulate analytically tractable, minimalist models, that incorporate this interplay between transport and chemical progression in physical space, and explore the conditions for de novo biogenesis of distinct cisternae. We propose new quantitative measures that can discriminate between the various models of transport in a qualitative manner-this includes measures of the dynamics in steady state and the dynamical response to perturbations of the kind amenable to live-cell imaging. AU - Sachdeva, Himani AU - Barma, Mustansir AU - Rao, Madan ID - 1172 JF - Scientific Reports TI - Nonequilibrium description of de novo biogenesis and transport through Golgi-like cisternae VL - 6 ER - TY - JOUR AB - Boldyreva, Palacio and Warinschi introduced a multiple forking game as an extension of general forking. The notion of (multiple) forking is a useful abstraction from the actual simulation of cryptographic scheme to the adversary in a security reduction, and is achieved through the intermediary of a so-called wrapper algorithm. Multiple forking has turned out to be a useful tool in the security argument of several cryptographic protocols. However, a reduction employing multiple forking incurs a significant degradation of (Formula presented.) , where (Formula presented.) denotes the upper bound on the underlying random oracle calls and (Formula presented.) , the number of forkings. In this work we take a closer look at the reasons for the degradation with a tighter security bound in mind. We nail down the exact set of conditions for success in the multiple forking game. A careful analysis of the cryptographic schemes and corresponding security reduction employing multiple forking leads to the formulation of ‘dependence’ and ‘independence’ conditions pertaining to the output of the wrapper in different rounds. Based on the (in)dependence conditions we propose a general framework of multiple forking and a General Multiple Forking Lemma. Leveraging (in)dependence to the full allows us to improve the degradation factor in the multiple forking game by a factor of (Formula presented.). By implication, the cost of a single forking involving two random oracles (augmented forking) matches that involving a single random oracle (elementary forking). Finally, we study the effect of these observations on the concrete security of existing schemes employing multiple forking. We conclude that by careful design of the protocol (and the wrapper in the security reduction) it is possible to harness our observations to the full extent. AU - Kamath Hosdurg, Chethan AU - Chatterjee, Sanjit ID - 1177 IS - 4 JF - Algorithmica TI - A closer look at multiple-forking: Leveraging (in)dependence for a tighter bound VL - 74 ER - TY - CONF AB - Computational notions of entropy have recently found many applications, including leakage-resilient cryptography, deterministic encryption or memory delegation. The two main types of results which make computational notions so useful are (1) Chain rules, which quantify by how much the computational entropy of a variable decreases if conditioned on some other variable (2) Transformations, which quantify to which extend one type of entropy implies another. Such chain rules and transformations typically lose a significant amount in quality of the entropy, and are the reason why applying these results one gets rather weak quantitative security bounds. In this paper we for the first time prove lower bounds in this context, showing that existing results for transformations are, unfortunately, basically optimal for non-adaptive black-box reductions (and it’s hard to imagine how non black-box reductions or adaptivity could be useful here.) A variable X has k bits of HILL entropy of quality (ϵ,s) if there exists a variable Y with k bits min-entropy which cannot be distinguished from X with advantage ϵ by distinguishing circuits of size s. A weaker notion is Metric entropy, where we switch quantifiers, and only require that for every distinguisher of size s, such a Y exists. We first describe our result concerning transformations. By definition, HILL implies Metric without any loss in quality. Metric entropy often comes up in applications, but must be transformed to HILL for meaningful security guarantees. The best known result states that if a variable X has k bits of Metric entropy of quality (ϵ,s) , then it has k bits of HILL with quality (2ϵ,s⋅ϵ2). We show that this loss of a factor Ω(ϵ−2) in circuit size is necessary. In fact, we show the stronger result that this loss is already necessary when transforming so called deterministic real valued Metric entropy to randomised boolean Metric (both these variants of Metric entropy are implied by HILL without loss in quality). The chain rule for HILL entropy states that if X has k bits of HILL entropy of quality (ϵ,s) , then for any variable Z of length m, X conditioned on Z has k−m bits of HILL entropy with quality (ϵ,s⋅ϵ2/2m). We show that a loss of Ω(2m/ϵ) in circuit size necessary here. Note that this still leaves a gap of ϵ between the known bound and our lower bound. AU - Pietrzak, Krzysztof Z AU - Maciej, Skorski ID - 1179 TI - Pseudoentropy: Lower-bounds for chain rules and transformations VL - 9985 ER - TY - JOUR AB - This review accompanies a 2016 SFN mini-symposium presenting examples of current studies that address a central question: How do neural stem cells (NSCs) divide in different ways to produce heterogeneous daughter types at the right time and in proper numbers to build a cerebral cortex with the appropriate size and structure? We will focus on four aspects of corticogenesis: cytokinesis events that follow apical mitoses of NSCs; coordinating abscission with delamination from the apical membrane; timing of neurogenesis and its indirect regulation through emergence of intermediate progenitors; and capacity of single NSCs to generate the correct number and laminar fate of cortical neurons. Defects in these mechanisms can cause microcephaly and other brain malformations, and understanding them is critical to designing diagnostic tools and preventive and corrective therapies. AU - Dwyer, Noelle AU - Chen, Bin AU - Chou, Shen AU - Hippenmeyer, Simon AU - Nguyen, Laurent AU - Ghashghaei, Troy ID - 1181 IS - 45 JF - Journal of Neuroscience TI - Neural stem cells to cerebral cortex: Emerging mechanisms regulating progenitor behavior and productivity VL - 36 ER - TY - CONF AB - Balanced knockout tournaments are ubiquitous in sports competitions and are also used in decisionmaking and elections. The traditional computational question, that asks to compute a draw (optimal draw) that maximizes the winning probability for a distinguished player, has received a lot of attention. Previous works consider the problem where the pairwise winning probabilities are known precisely, while we study how robust is the winning probability with respect to small errors in the pairwise winning probabilities. First, we present several illuminating examples to establish: (a) there exist deterministic tournaments (where the pairwise winning probabilities are 0 or 1) where one optimal draw is much more robust than the other; and (b) in general, there exist tournaments with slightly suboptimal draws that are more robust than all the optimal draws. The above examples motivate the study of the computational problem of robust draws that guarantee a specified winning probability. Second, we present a polynomial-time algorithm for approximating the robustness of a draw for sufficiently small errors in pairwise winning probabilities, and obtain that the stated computational problem is NP-complete. We also show that two natural cases of deterministic tournaments where the optimal draw could be computed in polynomial time also admit polynomial-time algorithms to compute robust optimal draws. AU - Chatterjee, Krishnendu AU - Ibsen-Jensen, Rasmus AU - Tkadlec, Josef ID - 1182 TI - Robust draws in balanced knockout tournaments VL - 2016-January ER - TY - JOUR AB - Across multicellular organisms, the costs of reproduction and self-maintenance result in a life history trade-off between fecundity and longevity. Queens of perennial social Hymenoptera are both highly fertile and long-lived, and thus, this fundamental trade-off is lacking. Whether social insect males similarly evade the fecundity/longevity trade-off remains largely unstudied. Wingless males of the ant genus Cardiocondyla stay in their natal colonies throughout their relatively long lives and mate with multiple female sexuals. Here, we show that Cardiocondyla obscurior males that were allowed to mate with large numbers of female sexuals had a shortened life span compared to males that mated at a low frequency or virgin males. Although frequent mating negatively affects longevity, males clearly benefit from a “live fast, die young strategy” by inseminating as many female sexuals as possible at a cost to their own survival. AU - Metzler, Sina AU - Heinze, Jürgen AU - Schrempf, Alexandra ID - 1184 IS - 24 JF - Ecology and Evolution TI - Mating and longevity in ant males VL - 6 ER - TY - JOUR AB - The developmental programme of the pistil is under the control of both auxin and cytokinin. Crosstalk between these factors converges on regulation of the auxin carrier PIN-FORMED 1 (PIN1). Here, we show that in the triple transcription factor mutant cytokinin response factor 2 (crf2) crf3 crf6 both pistil length and ovule number were reduced. PIN1 expression was also lower in the triple mutant and the phenotypes could not be rescued by exogenous cytokinin application. pin1 complementation studies using genomic PIN1 constructs showed that the pistil phenotypes were only rescued when the PCRE1 domain, to which CRFs bind, was present. Without this domain, pin mutants resemble the crf2 crf3 crf6 triple mutant, indicating the pivotal role of CRFs in auxin-cytokinin crosstalk. AU - Cucinotta, Mara AU - Manrique, Silvia AU - Guazzotti, Andrea AU - Quadrelli, Nadia AU - Mendes, Marta AU - Benková, Eva AU - Colombo, Lucia ID - 1185 IS - 23 JF - Development TI - Cytokinin response factors integrate auxin and cytokinin pathways for female reproductive organ development VL - 143 ER - TY - JOUR AB - The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca 2+ -binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp-Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus. AU - Gutierrez-Fernandez, Javier AU - Saleh, Malek AU - Alcorlo, Martín AU - Gómez Mejóa, Alejandro AU - Pantoja Uceda, David AU - Treviño, Miguel AU - Vob, Franziska AU - Abdullah, Mohammed AU - Galán Bartual, Sergio AU - Seinen, Jolien AU - Sánchez Murcia, Pedro AU - Gago, Federico AU - Bruix, Marta AU - Hammerschmidt, Sven AU - Hermoso, Juan ID - 1186 JF - Scientific Reports TI - Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis VL - 6 ER - TY - JOUR AB - We consider a population dynamics model coupling cell growth to a diffusion in the space of metabolic phenotypes as it can be obtained from realistic constraints-based modelling. In the asymptotic regime of slow diffusion, that coincides with the relevant experimental range, the resulting non-linear Fokker–Planck equation is solved for the steady state in the WKB approximation that maps it into the ground state of a quantum particle in an Airy potential plus a centrifugal term. We retrieve scaling laws for growth rate fluctuations and time response with respect to the distance from the maximum growth rate suggesting that suboptimal populations can have a faster response to perturbations. AU - De Martino, Daniele AU - Masoero, Davide ID - 1188 IS - 12 JF - Journal of Statistical Mechanics: Theory and Experiment TI - Asymptotic analysis of noisy fitness maximization, applied to metabolism & growth VL - 2016 ER - TY - JOUR AB - The genetic analysis of experimentally evolving populations typically relies on short reads from pooled individuals (Pool-Seq). While this method provides reliable allele frequency estimates, the underlying haplotype structure remains poorly characterized. With small population sizes and adaptive variants that start from low frequencies, the interpretation of selection signatures in most Evolve and Resequencing studies remains challenging. To facilitate the characterization of selection targets, we propose a new approach that reconstructs selected haplotypes from replicated time series, using Pool-Seq data. We identify selected haplotypes through the correlated frequencies of alleles carried by them. Computer simulations indicate that selected haplotype-blocks of several Mb can be reconstructed with high confidence and low error rates, even when allele frequencies change only by 20% across three replicates. Applying this method to real data from D. melanogaster populations adapting to a hot environment, we identify a selected haplotype-block of 6.93 Mb. We confirm the presence of this haplotype-block in evolved populations by experimental haplotyping, demonstrating the power and accuracy of our haplotype reconstruction from Pool-Seq data. We propose that the combination of allele frequency estimates with haplotype information will provide the key to understanding the dynamics of adaptive alleles. AU - Franssen, Susan AU - Barton, Nicholas H AU - Schlötterer, Christian ID - 1195 IS - 1 JF - Molecular Biology and Evolution TI - Reconstruction of haplotype-blocks selected during experimental evolution. VL - 34 ER - TY - JOUR AU - Hilbe, Christian AU - Traulsen, Arne ID - 1200 JF - Physics of Life Reviews TI - Only the combination of mathematics and agent based simulations can leverage the full potential of evolutionary modeling: Comment on “Evolutionary game theory using agent-based methods” by C. Adami, J. Schossau and A. Hintze VL - 19 ER - TY - JOUR AB - In this issue of Cell, Skau et al. show that the formin FMN2 organizes a perinuclear actin cytoskeleton that protects the nucleus and its genomic content of migrating cells squeezing through small spaces. AU - Renkawitz, Jörg AU - Sixt, Michael K ID - 1201 IS - 6 JF - Cell TI - Formin’ a nuclear protection VL - 167 ER - TY - JOUR AU - Milutinovic, Barbara AU - Peuß, Robert AU - Ferro, Kevin AU - Kurtz, Joachim ID - 1202 IS - 4 JF - Zoology TI - Immune priming in arthropods: an update focusing on the red flour beetle VL - 119 ER - TY - JOUR AB - Haemophilus haemolyticus has been recently discovered to have the potential to cause invasive disease. It is closely related to nontypeable Haemophilus influenzae (NT H. influenzae). NT H. influenzae and H. haemolyticus are often misidentified because none of the existing tests targeting the known phenotypes of H. haemolyticus are able to specifically identify H. haemolyticus. Through comparative genomic analysis of H. haemolyticus and NT H. influenzae, we identified genes unique to H. haemolyticus that can be used as targets for the identification of H. haemolyticus. A real-time PCR targeting purT (encoding phosphoribosylglycinamide formyltransferase 2 in the purine synthesis pathway) was developed and evaluated. The lower limit of detection was 40 genomes/PCR; the sensitivity and specificity in detecting H. haemolyticus were 98.9% and 97%, respectively. To improve the discrimination of H. haemolyticus and NT H. influenzae, a testing scheme combining two targets (H. haemolyticus purT and H. influenzae hpd, encoding protein D lipoprotein) was also evaluated and showed 96.7% sensitivity and 98.2% specificity for the identification of H. haemolyticus and 92.8% sensitivity and 100% specificity for the identification of H. influenzae, respectively. The dual-target testing scheme can be used for the diagnosis and surveillance of infection and disease caused by H. haemolyticus and NT H. influenzae. AU - Hu, Fang AU - Rishishwar, Lavanya AU - Sivadas, Ambily AU - Mitchell, Gabriel AU - King, Jordan AU - Murphy, Timothy AU - Gilsdorf, Janet AU - Mayer, Leonard AU - Wang, Xin ID - 1203 IS - 12 JF - Journal of Clinical Microbiology TI - Comparative genomic analysis of Haemophilus haemolyticus and nontypeable Haemophilus influenzae and a new testing scheme for their discrimination VL - 54 ER - TY - JOUR AB - In science, as in life, "surprises" can be adequately appreciated only in the presence of a null model, what we expect a priori. In physics, theories sometimes express the values of dimensionless physical constants as combinations of mathematical constants like π or e. The inverse problem also arises, whereby the measured value of a physical constant admits a "surprisingly" simple approximation in terms of well-known mathematical constants. Can we estimate the probability for this to be a mere coincidence, rather than an inkling of some theory? We answer the question in the most naive form. AU - Amir, Ariel AU - Lemeshko, Mikhail AU - Tokieda, Tadashi ID - 1204 IS - 6 JF - American Mathematical Monthly TI - Surprises in numerical expressions of physical constants VL - 123 ER - TY - JOUR AB - We study a polar molecule immersed in a superfluid environment, such as a helium nanodroplet or a Bose–Einstein condensate, in the presence of a strong electrostatic field. We show that coupling of the molecular pendular motion, induced by the field, to the fluctuating bath leads to formation of pendulons—spherical harmonic librators dressed by a field of many-particle excitations. We study the behavior of the pendulon in a broad range of molecule–bath and molecule–field interaction strengths, and reveal that its spectrum features a series of instabilities which are absent in the field-free case of the angulon quasiparticle. Furthermore, we show that an external field allows to fine-tune the positions of these instabilities in the molecular rotational spectrum. This opens the door to detailed experimental studies of redistribution of orbital angular momentum in many-particle systems. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim AU - Redchenko, Elena AU - Lemeshko, Mikhail ID - 1206 IS - 22 JF - ChemPhysChem TI - Libration of strongly oriented polar molecules inside a superfluid VL - 17 ER - TY - JOUR AB - NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies. AU - Letts, James A AU - Degliesposti, Gianluca AU - Fiedorczuk, Karol AU - Skehel, Mark AU - Sazanov, Leonid A ID - 1209 IS - 47 JF - Journal of Biological Chemistry TI - Purification of ovine respiratory complex i results in a highly active and stable preparation VL - 291 ER - TY - CHAP AB - Mechanisms for cell protection are essential for survival of multicellular organisms. In plants, the apical hook, which is transiently formed in darkness when the germinating seedling penetrates towards the soil surface, plays such protective role and shields the vitally important shoot apical meristem and cotyledons from damage. The apical hook is formed by bending of the upper hypocotyl soon after germination, and it is maintained in a closed stage while the hypocotyl continues to penetrate through the soil and rapidly opens when exposed to light in proximity of the soil surface. To uncover the complex molecular network orchestrating this spatiotemporally tightly coordinated process, monitoring of the apical hook development in real time is indispensable. Here we describe an imaging platform that enables high-resolution kinetic analysis of this dynamic developmental process. © Springer Science+Business Media New York 2017. AU - Zhu, Qiang AU - Žádníková, Petra AU - Smet, Dajo AU - Van Der Straeten, Dominique AU - Benková, Eva ID - 1210 T2 - Plant Hormones TI - Real time analysis of the apical hook development VL - 1497 ER - TY - JOUR AB - Plants adjust their growth according to gravity. Gravitropism involves gravity perception, signal transduction, and asymmetric growth response, with organ bending as a consequence [1]. Asymmetric growth results from the asymmetric distribution of the plant-specific signaling molecule auxin [2] that is generated by lateral transport, mediated in the hypocotyl predominantly by the auxin transporter PIN-FORMED3 (PIN3) [3–5]. Gravity stimulation polarizes PIN3 to the bottom sides of endodermal cells, correlating with increased auxin accumulation in adjacent tissues at the lower side of the stimulated organ, where auxin induces cell elongation and, hence, organ bending. A curvature response allows the hypocotyl to resume straight growth at a defined angle [6], implying that at some point auxin symmetry is restored to prevent overbending. Here, we present initial insights into cellular and molecular mechanisms that lead to the termination of the tropic response. We identified an auxin feedback on PIN3 polarization as underlying mechanism that restores symmetry of the PIN3-dependent auxin flow. Thus, two mechanistically distinct PIN3 polarization events redirect auxin fluxes at different time points of the gravity response: first, gravity-mediated redirection of PIN3-mediated auxin flow toward the lower hypocotyl side, where auxin gradually accumulates and promotes growth, and later PIN3 polarization to the opposite cell side, depleting this auxin maximum to end the bending. Accordingly, genetic or pharmacological interference with the late PIN3 polarization prevents termination of the response and leads to hypocotyl overbending. This observation reveals a role of auxin feedback on PIN polarity in the termination of the tropic response. © 2016 Elsevier Ltd AU - Rakusová, Hana AU - Abbas, Mohamad AU - Han, Huibin AU - Song, Siyuan AU - Robert, Hélène AU - Friml, Jirí ID - 1212 IS - 22 JF - Current Biology TI - Termination of shoot gravitropic responses by auxin feedback on PIN3 polarity VL - 26 ER - TY - CONF AB - With the accelerated development of robot technologies, optimal control becomes one of the central themes of research. In traditional approaches, the controller, by its internal functionality, finds appropriate actions on the basis of the history of sensor values, guided by the goals, intentions, objectives, learning schemes, and so forth. While very successful with classical robots, these methods run into severe difficulties when applied to soft robots, a new field of robotics with large interest for human-robot interaction. We claim that a novel controller paradigm opens new perspective for this field. This paper applies a recently developed neuro controller with differential extrinsic synaptic plasticity to a muscle-tendon driven arm-shoulder system from the Myorobotics toolkit. In the experiments, we observe a vast variety of self-organized behavior patterns: when left alone, the arm realizes pseudo-random sequences of different poses. By applying physical forces, the system can be entrained into definite motion patterns like wiping a table. Most interestingly, after attaching an object, the controller gets in a functional resonance with the object's internal dynamics, starting to shake spontaneously bottles half-filled with water or sensitively driving an attached pendulum into a circular mode. When attached to the crank of a wheel the neural system independently develops to rotate it. In this way, the robot discovers affordances of objects its body is interacting with. AU - Martius, Georg S AU - Hostettler, Raphael AU - Knoll, Alois AU - Der, Ralf ID - 1214 TI - Compliant control for soft robots: Emergent behavior of a tendon driven anthropomorphic arm VL - 2016-November ER - TY - JOUR AB - A framework fo r extracting features in 2D transient flows, based on the acceleration field to ensure Galilean invariance is proposed in this paper. The minima of the acceleration magnitude (a superset of acceleration zeros) are extracted and discriminated into vortices and saddle points, based on the spectral properties of the velocity Jacobian. The extraction of topological features is performed with purely combinatorial algorithms from discrete computational topology. The feature points are prioritized with persistence, as a physically meaningful importance measure. These feature points are tracked in time with a robust algorithm for tracking features. Thus, a space-time hierarchy of the minima is built and vortex merging events are detected. We apply the acceleration feature extraction strategy to three two-dimensional shear flows: (1) an incompressible periodic cylinder wake, (2) an incompressible planar mixing layer and (3) a weakly compressible planar jet. The vortex-like acceleration feature points are shown to be well aligned with acceleration zeros, maxima of the vorticity magnitude, minima of the pressure field and minima of λ2. AU - Kasten, Jens AU - Reininghaus, Jan AU - Hotz, Ingrid AU - Hege, Hans AU - Noack, Bernd AU - Daviller, Guillaume AU - Morzyński, Marek ID - 1216 IS - 1 JF - Archives of Mechanics TI - Acceleration feature points of unsteady shear flows VL - 68 ER - TY - JOUR AB - Understanding the regulation of T-cell responses during inflammation and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. In this regard, prostaglandin E 2 (PGE 2) is mostly considered a myeloid-derived immunosuppressive molecule. We describe for the first time that T cells secrete PGE 2 during T-cell receptor stimulation. In addition, we show that autocrine PGE 2 signaling through EP receptors is essential for optimal CD4 + T-cell activation in vitro and in vivo, and for T helper 1 (Th1) and regulatory T cell differentiation. PGE 2 was found to provide additive co-stimulatory signaling through AKT activation. Intravital multiphoton microscopy showed that triggering EP receptors in T cells is also essential for the stability of T cell-dendritic cell (DC) interactions and Th-cell accumulation in draining lymph nodes (LNs) during inflammation. We further demonstrated that blocking EP receptors in T cells during the initial phase of collagen-induced arthritis in mice resulted in a reduction of clinical arthritis. This could be attributable to defective T-cell activation, accompanied by a decline in activated and interferon-γ-producing CD4 + Th1 cells in draining LNs. In conclusion, we prove that T lymphocytes secret picomolar concentrations of PGE 2, which in turn provide additive co-stimulatory signaling, enabling T cells to attain a favorable activation threshold. PGE 2 signaling in T cells is also required for maintaining long and stable interactions with DCs within LNs. Blockade of EP receptors in vivo impairs T-cell activation and development of T cell-mediated inflammatory responses. This may have implications in various pathophysiological settings. AU - Sreeramkumar, Vinatha AU - Hons, Miroslav AU - Punzón, Carmen AU - Stein, Jens AU - Sancho, David AU - Fresno Forcelledo, Manuel AU - Cuesta, Natalia ID - 1217 IS - 1 JF - Immunology and Cell Biology TI - Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors VL - 94 ER - TY - JOUR AB - Investigating the physiology of cyanobacteria cultured under a diel light regime is relevant for a better understanding of the resulting growth characteristics and for specific biotechnological applications that are foreseen for these photosynthetic organisms. Here, we present the results of a multiomics study of the model cyanobacterium Synechocystis sp. strain PCC 6803, cultured in a lab-scale photobioreactor in physiological conditions relevant for large-scale culturing. The culture was sparged withN2 andCO2, leading to an anoxic environment during the dark period. Growth followed the availability of light. Metabolite analysis performed with 1Hnuclear magnetic resonance analysis showed that amino acids involved in nitrogen and sulfur assimilation showed elevated levels in the light. Most protein levels, analyzed through mass spectrometry, remained rather stable. However, several high-light-response proteins and stress-response proteins showed distinct changes at the onset of the light period. Microarray-based transcript analysis found common patterns of~56% of the transcriptome following the diel regime. These oscillating transcripts could be grouped coarsely into genes that were upregulated and downregulated in the dark period. The accumulated glycogen was degraded in the anaerobic environment in the dark. A small part was degraded gradually, reflecting basic maintenance requirements of the cells in darkness. Surprisingly, the largest part was degraded rapidly in a short time span at the end of the dark period. This degradation could allow rapid formation of metabolic intermediates at the end of the dark period, preparing the cells for the resumption of growth at the start of the light period. AU - Angermayr, Andreas AU - Van Alphen, Pascal AU - Hasdemir, Dicle AU - Kramer, Gertjan AU - Iqbal, Muzamal AU - Van Grondelle, Wilmar AU - Hoefsloot, Huub AU - Choi, Younghae AU - Hellingwerf, Klaas ID - 1218 IS - 14 JF - Applied and Environmental Microbiology TI - Culturing synechocystis sp. Strain pcc 6803 with N2 and CO2 in a diel regime reveals multiphase glycogen dynamics with low maintenance costs VL - 82 ER - TY - JOUR AB - We consider N×N random matrices of the form H = W + V where W is a real symmetric or complex Hermitian Wigner matrix and V is a random or deterministic, real, diagonal matrix whose entries are independent of W. We assume subexponential decay for the matrix entries of W, and we choose V so that the eigenvalues ofW and V are typically of the same order. For a large class of diagonal matrices V , we show that the local statistics in the bulk of the spectrum are universal in the limit of large N. AU - Lee, Jioon AU - Schnelli, Kevin AU - Stetler, Ben AU - Yau, Horngtzer ID - 1219 IS - 3 JF - Annals of Probability TI - Bulk universality for deformed wigner matrices VL - 44 ER - TY - CONF AB - Theoretical and numerical aspects of aerodynamic efficiency of propulsion systems coupled to the boundary layer of a fuselage are studied. We discuss the effects of local flow fields, which are affected both by conservative flow acceleration as well as total pressure losses, on the efficiency of boundary layer immersed propulsion devices. We introduce the concept of a boundary layer retardation turbine that helps reduce skin friction over the fuselage. We numerically investigate efficiency gains offered by boundary layer and wake interacting devices. We discuss the results in terms of a total energy consumption framework and show that efficiency gains of any device depend on all the other elements of the propulsion system. AU - Mikić, Gregor AU - Stoll, Alex AU - Bevirt, Joe AU - Grah, Rok AU - Moore, Mark ID - 1220 TI - Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency ER - TY - JOUR AB - The Auxin Binding Protein 1 (ABP1) is one of the most studied proteins in plants. Since decades ago, it has been the prime receptor candidate for the plant hormone auxin with a plethora of described functions in auxin signaling and development. The developmental importance of ABP1 has recently been questioned by identification of Arabidopsis thaliana abp1 knock-out alleles that show no obvious phenotypes under normal growth conditions. In this study, we examined the contradiction between the normal growth and development of the abp1 knock-outs and the strong morphological defects observed in three different ethanol-inducible abp1 knock-down mutants ( abp1-AS, SS12K, SS12S). By analyzing segregating populations of abp1 knock-out vs. abp1 knock-down crosses we show that the strong morphological defects that were believed to be the result of conditional down-regulation of ABP1 can be reproduced also in the absence of the functional ABP1 protein. This data suggests that the phenotypes in abp1 knock-down lines are due to the off-target effects and asks for further reflections on the biological function of ABP1 or alternative explanations for the missing phenotypic defects in the abp1 loss-of-function alleles. AU - Michalko, Jaroslav AU - Glanc, Matous AU - Perrot Rechenmann, Catherine AU - Friml, Jirí ID - 1221 JF - F1000 Research TI - Strong morphological defects in conditional Arabidopsis abp1 knock-down mutants generated in absence of functional ABP1 protein VL - 5 ER - TY - JOUR AB - We consider packings of congruent circles on a square flat torus, i.e., periodic (w.r.t. a square lattice) planar circle packings, with the maximal circle radius. This problem is interesting due to a practical reason—the problem of “super resolution of images.” We have found optimal arrangements for N=6, 7 and 8 circles. Surprisingly, for the case N=7 there are three different optimal arrangements. Our proof is based on a computer enumeration of toroidal irreducible contact graphs. AU - Musin, Oleg AU - Nikitenko, Anton ID - 1222 IS - 1 JF - Discrete & Computational Geometry TI - Optimal packings of congruent circles on a square flat torus VL - 55 ER - TY - JOUR AB - We consider a random Schrödinger operator on the binary tree with a random potential which is the sum of a random radially symmetric potential, Qr, and a random transversally periodic potential, κQt, with coupling constant κ. Using a new one-dimensional dynamical systems approach combined with Jensen's inequality in hyperbolic space (our key estimate) we obtain a fractional moment estimate proving localization for small and large κ. Together with a previous result we therefore obtain a model with two Anderson transitions, from localization to delocalization and back to localization, when increasing κ. As a by-product we also have a partially new proof of one-dimensional Anderson localization at any disorder. AU - Froese, Richard AU - Lee, Darrick AU - Sadel, Christian AU - Spitzer, Wolfgang AU - Stolz, Günter ID - 1223 IS - 3 JF - Journal of Spectral Theory TI - Localization for transversally periodic random potentials on binary trees VL - 6 ER - TY - JOUR AB - Sexual dimorphism in resource allocation is expected to change during the life cycle of dioecious plants because of temporal differences between the sexes in reproductive investment. Given the potential for sex-specific differences in reproductive costs, resource availability may contribute to variation in reproductive allocation in females and males. Here, we used Rumex hastatulus, a dioecious, wind-pollinated annual plant, to investigate whether sexual dimorphism varies with life-history stage and nutrient availability, and determine whether allocation patterns differ depending on reproductive commitment. To examine if the costs of reproduction varied between the sexes, reproduction was either allowed or prevented through bud removal, and biomass allocation was measured at maturity. In a second experiment to assess variation in sexual dimorphism across the life cycle, and whether this varied with resource availability, plants were grown in high and low nutrients and allocation to roots, aboveground vegetative growth and reproduction were measured at three developmental stages. Males prevented from reproducing compensated with increased above- and belowground allocation to a much larger degree than females, suggesting that male reproductive costs reduce vegetative growth. The proportional allocation to roots, reproductive structures and aboveground vegetative growth varied between the sexes and among life-cycle stages, but not with nutrient treatment. Females allocated proportionally more resources to roots than males at peak flowering, but this pattern was reversed at reproductive maturity under low-nutrient conditions. Our study illustrates the importance of temporal dynamics in sex-specific resource allocation and provides support for high male reproductive costs in wind-pollinated plants. AU - Teitel, Zachary AU - Pickup, Melinda AU - Field, David AU - Barrett, Spencer ID - 1224 IS - 1 JF - Plant Biology TI - The dynamics of resource allocation and costs of reproduction in a sexually dimorphic, wind-pollinated dioecious plant VL - 18 ER - TY - JOUR AB - Mitochondrial complex I (also known as NADH:ubiquinone oxidoreductase) contributes to cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane. It is the largest protein assembly of the respiratory chain with a total mass of 970 kilodaltons. Here we present a nearly complete atomic structure of ovine (Ovis aries) mitochondrial complex I at 3.9 Å resolution, solved by cryo-electron microscopy with cross-linking and mass-spectrometry mapping experiments. All 14 conserved core subunits and 31 mitochondria-specific supernumerary subunits are resolved within the L-shaped molecule. The hydrophilic matrix arm comprises flavin mononucleotide and 8 iron-sulfur clusters involved in electron transfer, and the membrane arm contains 78 transmembrane helices, mostly contributed by antiporter-like subunits involved in proton translocation. Supernumerary subunits form an interlinked, stabilizing shell around the conserved core. Tightly bound lipids (including cardiolipins) further stabilize interactions between the hydrophobic subunits. Subunits with possible regulatory roles contain additional cofactors, NADPH and two phosphopantetheine molecules, which are shown to be involved in inter-subunit interactions. We observe two different conformations of the complex, which may be related to the conformationally driven coupling mechanism and to the active-deactive transition of the enzyme. Our structure provides insight into the mechanism, assembly, maturation and dysfunction of mitochondrial complex I, and allows detailed molecular analysis of disease-causing mutations. AU - Fiedorczuk, Karol AU - Letts, James A AU - Degliesposti, Gianluca AU - Kaszuba, Karol AU - Skehel, Mark AU - Sazanov, Leonid A ID - 1226 IS - 7625 JF - Nature TI - Atomic structure of the entire mammalian mitochondrial complex i VL - 538 ER - TY - CONF AB - Many biological systems can be modeled as multiaffine hybrid systems. Due to the nonlinearity of multiaffine systems, it is difficult to verify their properties of interest directly. A common strategy to tackle this problem is to construct and analyze a discrete overapproximation of the original system. However, the conservativeness of a discrete abstraction significantly determines the level of confidence we can have in the properties of the original system. In this paper, in order to reduce the conservativeness of a discrete abstraction, we propose a new method based on a sufficient and necessary decision condition for computing discrete transitions between states in the abstract system. We assume the state space partition of a multiaffine system to be based on a set of multivariate polynomials. Hence, a rectangular partition defined in terms of polynomials of the form (xi − c) is just a simple case of multivariate polynomial partition, and the new decision condition applies naturally. We analyze and demonstrate the improvement of our method over the existing methods using some examples. AU - Kong, Hui AU - Bartocci, Ezio AU - Bogomolov, Sergiy AU - Grosu, Radu AU - Henzinger, Thomas A AU - Jiang, Yu AU - Schilling, Christian ID - 1227 TI - Discrete abstraction of multiaffine systems VL - 9957 ER - TY - CONF AB - We study the time-and memory-complexities of the problem of computing labels of (multiple) randomly selected challenge-nodes in a directed acyclic graph. The w-bit label of a node is the hash of the labels of its parents, and the hash function is modeled as a random oracle. Specific instances of this problem underlie both proofs of space [Dziembowski et al. CRYPTO’15] as well as popular memory-hard functions like scrypt. As our main tool, we introduce the new notion of a probabilistic parallel entangled pebbling game, a new type of combinatorial pebbling game on a graph, which is closely related to the labeling game on the same graph. As a first application of our framework, we prove that for scrypt, when the underlying hash function is invoked n times, the cumulative memory complexity (CMC) (a notion recently introduced by Alwen and Serbinenko (STOC’15) to capture amortized memory-hardness for parallel adversaries) is at least Ω(w · (n/ log(n))2). This bound holds for adversaries that can store many natural functions of the labels (e.g., linear combinations), but still not arbitrary functions thereof. We then introduce and study a combinatorial quantity, and show how a sufficiently small upper bound on it (which we conjecture) extends our CMC bound for scrypt to hold against arbitrary adversaries. We also show that such an upper bound solves the main open problem for proofs-of-space protocols: namely, establishing that the time complexity of computing the label of a random node in a graph on n nodes (given an initial kw-bit state) reduces tightly to the time complexity for black pebbling on the same graph (given an initial k-node pebbling). AU - Alwen, Joel F AU - Chen, Binyi AU - Kamath Hosdurg, Chethan AU - Kolmogorov, Vladimir AU - Pietrzak, Krzysztof Z AU - Tessaro, Stefano ID - 1231 TI - On the complexity of scrypt and proofs of space in the parallel random oracle model VL - 9666 ER - TY - JOUR AB - Mitochondrial electron transport chain complexes are organized into supercomplexes responsible for carrying out cellular respiration. Here we present three architectures of mammalian (ovine) supercomplexes determined by cryo-electron microscopy. We identify two distinct arrangements of supercomplex CICIII 2 CIV (the respirasome) - a major 'tight' form and a minor 'loose' form (resolved at the resolution of 5.8 Å and 6.7 Å, respectively), which may represent different stages in supercomplex assembly or disassembly. We have also determined an architecture of supercomplex CICIII 2 at 7.8 Å resolution. All observed density can be attributed to the known 80 subunits of the individual complexes, including 132 transmembrane helices. The individual complexes form tight interactions that vary between the architectures, with complex IV subunit COX7a switching contact from complex III to complex I. The arrangement of active sites within the supercomplex may help control reactive oxygen species production. To our knowledge, these are the first complete architectures of the dominant, physiologically relevant state of the electron transport chain. AU - Letts, James A AU - Fiedorczuk, Karol AU - Sazanov, Leonid A ID - 1232 IS - 7622 JF - Nature TI - The architecture of respiratory supercomplexes VL - 537 ER - TY - CONF AB - About three decades ago it was realized that implementing private channels between parties which can be adaptively corrupted requires an encryption scheme that is secure against selective opening attacks. Whether standard (IND-CPA) security implies security against selective opening attacks has been a major open question since. The only known reduction from selective opening to IND-CPA security loses an exponential factor. A polynomial reduction is only known for the very special case where the distribution considered in the selective opening security experiment is a product distribution, i.e., the messages are sampled independently from each other. In this paper we give a reduction whose loss is quantified via the dependence graph (where message dependencies correspond to edges) of the underlying message distribution. In particular, for some concrete distributions including Markov distributions, our reduction is polynomial. AU - Fuchsbauer, Georg AU - Heuer, Felix AU - Kiltz, Eike AU - Pietrzak, Krzysztof Z ID - 1233 TI - Standard security does imply security against selective opening for markov distributions VL - 9562 ER - TY - JOUR AB - The dynamic localization of endosomal compartments labeled with targeted fluorescent protein tags is routinely followed by time lapse fluorescence microscopy approaches and single particle tracking algorithms. In this way trajectories of individual endosomes can be mapped and linked to physiological processes as cell growth. However, other aspects of dynamic behavior including endosomal interactions are difficult to follow in this manner. Therefore, we characterized the localization and dynamic properties of early and late endosomes throughout the entire course of root hair formation by means of spinning disc time lapse imaging and post-acquisition automated multitracking and quantitative analysis. Our results show differential motile behavior of early and late endosomes and interactions of late endosomes that may be specified to particular root hair domains. Detailed data analysis revealed a particular transient interaction between late endosomes—termed herein as dancing-endosomes—which is not concluding to vesicular fusion. Endosomes preferentially located in the root hair tip interacted as dancing-endosomes and traveled short distances during this interaction. Finally, sizes of early and late endosomes were addressed by means of super-resolution structured illumination microscopy (SIM) to corroborate measurements on the spinning disc. This is a first study providing quantitative microscopic data on dynamic spatio-temporal interactions of endosomes during root hair tip growth. AU - Von Wangenheim, Daniel AU - Rosero, Amparo AU - Komis, George AU - Šamajová, Olga AU - Ovečka, Miroslav AU - Voigt, Boris AU - Šamaj, Jozef ID - 1238 IS - JAN2016 JF - Frontiers in Plant Science TI - Endosomal interactions during root hair growth VL - 6 ER - TY - CONF AB - Bitmap images of arbitrary dimension may be formally perceived as unions of m-dimensional boxes aligned with respect to a rectangular grid in ℝm. Cohomology and homology groups are well known topological invariants of such sets. Cohomological operations, such as the cup product, provide higher-order algebraic topological invariants, especially important for digital images of dimension higher than 3. If such an operation is determined at the level of simplicial chains [see e.g. González-Díaz, Real, Homology, Homotopy Appl, 2003, 83-93], then it is effectively computable. However, decomposing a cubical complex into a simplicial one deleteriously affects the efficiency of such an approach. In order to avoid this overhead, a direct cubical approach was applied in [Pilarczyk, Real, Adv. Comput. Math., 2015, 253-275] for the cup product in cohomology, and implemented in the ChainCon software package [http://www.pawelpilarczyk.com/chaincon/]. We establish a formula for the Steenrod square operations [see Steenrod, Annals of Mathematics. Second Series, 1947, 290-320] directly at the level of cubical chains, and we prove the correctness of this formula. An implementation of this formula is programmed in C++ within the ChainCon software framework. We provide a few examples and discuss the effectiveness of this approach. One specific application follows from the fact that Steenrod squares yield tests for the topological extension problem: Can a given map A → Sd to a sphere Sd be extended to a given super-complex X of A? In particular, the ROB-SAT problem, which is to decide for a given function f: X → ℝm and a value r > 0 whether every g: X → ℝm with ∥g - f ∥∞ ≤ r has a root, reduces to the extension problem. AU - Krcál, Marek AU - Pilarczyk, Pawel ID - 1237 TI - Computation of cubical Steenrod squares VL - 9667 ER - TY - JOUR AB - Background: Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. Results: We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from 10 healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at 1- or more than 1-month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in two independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions: A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers. AU - Kornienko, Aleksandra AU - Dotter, Christoph AU - Guenzl, Philipp AU - Gisslinger, Heinz AU - Gisslinger, Bettina AU - Cleary, Ciara AU - Kralovics, Robert AU - Pauler, Florian AU - Barlow, Denise ID - 1240 IS - 1 JF - Genome Biology TI - Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans VL - 17 ER - TY - JOUR AB - Nonadherent polarized cells have been observed to have a pearlike, elongated shape. Using a minimal model that describes the cell cortex as a thin layer of contractile active gel, we show that the anisotropy of active stresses, controlled by cortical viscosity and filament ordering, can account for this morphology. The predicted shapes can be determined from the flow pattern only; they prove to be independent of the mechanism at the origin of the cortical flow, and are only weakly sensitive to the cytoplasmic rheology. In the case of actin flows resulting from a contractile instability, we propose a phase diagram of three-dimensional cell shapes that encompasses nonpolarized spherical, elongated, as well as oblate shapes, all of which have been observed in experiment. AU - Callan Jones, Andrew AU - Ruprecht, Verena AU - Wieser, Stefan AU - Heisenberg, Carl-Philipp J AU - Voituriez, Raphaël ID - 1239 IS - 2 JF - Physical Review Letters TI - Cortical flow-driven shapes of nonadherent cells VL - 116 ER - TY - JOUR AB - A crucial step in the regulation of gene expression is binding of transcription factor (TF) proteins to regulatory sites along the DNA. But transcription factors act at nanomolar concentrations, and noise due to random arrival of these molecules at their binding sites can severely limit the precision of regulation. Recent work on the optimization of information flow through regulatory networks indicates that the lower end of the dynamic range of concentrations is simply inaccessible, overwhelmed by the impact of this noise. Motivated by the behavior of homeodomain proteins, such as the maternal morphogen Bicoid in the fruit fly embryo, we suggest a scheme in which transcription factors also act as indirect translational regulators, binding to the mRNA of other regulatory proteins. Intuitively, each mRNA molecule acts as an independent sensor of the input concentration, and averaging over these multiple sensors reduces the noise. We analyze information flow through this scheme and identify conditions under which it outperforms direct transcriptional regulation. Our results suggest that the dual role of homeodomain proteins is not just a historical accident, but a solution to a crucial physics problem in the regulation of gene expression. AU - Sokolowski, Thomas R AU - Walczak, Aleksandra AU - Bialek, William AU - Tkacik, Gasper ID - 1242 IS - 2 JF - Physical Review E Statistical Nonlinear and Soft Matter Physics TI - Extending the dynamic range of transcription factor action by translational regulation VL - 93 ER - TY - JOUR AB - How likely is it that a population escapes extinction through adaptive evolution? The answer to this question is of great relevance in conservation biology, where we aim at species’ rescue and the maintenance of biodiversity, and in agriculture and medicine, where we seek to hamper the emergence of pesticide or drug resistance. By reshuffling the genome, recombination has two antagonistic effects on the probability of evolutionary rescue: It generates and it breaks up favorable gene combinations. Which of the two effects prevails depends on the fitness effects of mutations and on the impact of stochasticity on the allele frequencies. In this article, we analyze a mathematical model for rescue after a sudden environmental change when adaptation is contingent on mutations at two loci. The analysis reveals a complex nonlinear dependence of population survival on recombination. We moreover find that, counterintuitively, a fast eradication of the wild type can promote rescue in the presence of recombination. The model also shows that two-step rescue is not unlikely to happen and can even be more likely than single-step rescue (where adaptation relies on a single mutation), depending on the circumstances. AU - Uecker, Hildegard AU - Hermisson, Joachim ID - 1241 IS - 2 JF - Genetics TI - The role of recombination in evolutionary rescue VL - 202 ER - TY - JOUR AB - The shaping of organs in plants depends on the intercellular flow of the phytohormone auxin, of which the directional signaling is determined by the polar subcellular localization of PIN-FORMED (PIN) auxin transport proteins. Phosphorylation dynamics of PIN proteins are affected by the protein phosphatase 2A (PP2A) and the PINOID kinase, which act antagonistically to mediate their apical-basal polar delivery. Here, we identified the ROTUNDA3 (RON3) protein as a regulator of the PP2A phosphatase activity in Arabidopsis thaliana. The RON3 gene was map-based cloned starting from the ron3-1 leaf mutant and found to be a unique, plant-specific gene coding for a protein with high and dispersed proline content. The ron3-1 and ron3-2 mutant phenotypes [i.e., reduced apical dominance, primary root length, lateral root emergence, and growth; increased ectopic stages II, IV, and V lateral root primordia; decreased auxin maxima in indole-3-acetic acid (IAA)-treated root apical meristems; hypergravitropic root growth and response; increased IAA levels in shoot apices; and reduced auxin accumulation in root meristems] support a role for RON3 in auxin biology. The affinity-purified PP2A complex with RON3 as bait suggested that RON3 might act in PIN transporter trafficking. Indeed, pharmacological interference with vesicle trafficking processes revealed that single ron3-2 and double ron3-2 rcn1 mutants have altered PIN polarity and endocytosis in specific cells. Our data indicate that RON3 contributes to auxin-mediated development by playing a role in PIN recycling and polarity establishment through regulation of the PP2A complex activity. AU - Karampelias, Michael AU - Neyt, Pia AU - De Groeve, Steven AU - Aesaert, Stijn AU - Coussens, Griet AU - Rolčík, Jakub AU - Bruno, Leonardo AU - De Winne, Nancy AU - Van Minnebruggen, Annemie AU - Van Montagu, Marc AU - Ponce, Maria AU - Micol, José AU - Friml, Jirí AU - De Jaeger, Geert AU - Van Lijsebettens, Mieke ID - 1247 IS - 10 JF - PNAS TI - ROTUNDA3 function in plant development by phosphatase 2A-mediated regulation of auxin transporter recycling VL - 113 ER - TY - JOUR AB - Near-field imaging is a powerful tool to investigate the complex structure of light at the nanoscale. Recent advances in near-field imaging have indicated the possibility for the complete reconstruction of both electric and magnetic components of the evanescent field. Here we study the electro-magnetic field structure of surface plasmon polariton waves propagating along subwavelength gold nanowires by performing phase- and polarization-resolved near-field microscopy in collection mode. By applying the optical reciprocity theorem, we describe the signal collected by the probe as an overlap integral of the nanowire's evanescent field and the probe's response function. As a result, we find that the probe's sensitivity to the magnetic field is approximately equal to its sensitivity to the electric field. Through rigorous modeling of the nanowire mode as well as the aperture probe response function, we obtain a good agreement between experimentally measured signals and a numerical model. Our findings provide a better understanding of aperture-based near-field imaging of the nanoscopic plasmonic and photonic structures and are helpful for the interpretation of future near-field experiments. AU - Kabakova, Irina AU - De Hoogh, Anouk AU - Van Der Wel, Ruben AU - Wulf, Matthias AU - Le Feber, Boris AU - Kuipers, Laurens ID - 1246 JF - Scientific Reports TI - Imaging of electric and magnetic fields near plasmonic nanowires VL - 6 ER - TY - CONF AB - To facilitate collaboration in massive online classrooms, instructors must make many decisions. For instance, the following parameters need to be decided when designing a peer-feedback system where students review each others' essays: the number of students each student must provide feedback to, an algorithm to map feedback providers to receivers, constraints that ensure students do not become free-riders (receiving feedback but not providing it), the best times to receive feedback to improve learning etc. While instructors can answer these questions by running experiments or invoking past experience, game-theoretic models with data from online learning platforms can identify better initial designs for further improvements. As an example, we explore the design space of a peer feedback system by modeling it using game theory. Our simulations show that incentivizing students to provide feedback requires the value obtained from receiving a feedback to exceed the cost of providing it by a large factor (greater than 7). Furthermore, hiding feedback from low-effort students incentivizes them to provide more feedback. AU - Pandey, Vineet AU - Chatterjee, Krishnendu ID - 1245 IS - Februar-2016 T2 - Proceedings of the ACM Conference on Computer Supported Cooperative Work TI - Game-theoretic models identify useful principles for peer collaboration in online learning platforms VL - 26 ER - TY - JOUR AB - Cell polarity refers to a functional spatial organization of proteins that is crucial for the control of essential cellular processes such as growth and division. To establish polarity, cells rely on elaborate regulation networks that control the distribution of proteins at the cell membrane. In fission yeast cells, a microtubule-dependent network has been identified that polarizes the distribution of signaling proteins that restricts growth to cell ends and targets the cytokinetic machinery to the middle of the cell. Although many molecular components have been shown to play a role in this network, it remains unknown which molecular functionalities are minimally required to establish a polarized protein distribution in this system. Here we show that a membrane-binding protein fragment, which distributes homogeneously in wild-type fission yeast cells, can be made to concentrate at cell ends by attaching it to a cytoplasmic microtubule end-binding protein. This concentration results in a polarized pattern of chimera proteins with a spatial extension that is very reminiscent of natural polarity patterns in fission yeast. However, chimera levels fluctuate in response to microtubule dynamics, and disruption of microtubules leads to disappearance of the pattern. Numerical simulations confirm that the combined functionality of membrane anchoring and microtubule tip affinity is in principle sufficient to create polarized patterns. Our chimera protein may thus represent a simple molecular functionality that is able to polarize the membrane, onto which additional layers of molecular complexity may be built to provide the temporal robustness that is typical of natural polarity patterns. AU - Recouvreux, Pierre AU - Sokolowski, Thomas R AU - Grammoustianou, Aristea AU - Tenwolde, Pieter AU - Dogterom, Marileen ID - 1244 IS - 7 JF - PNAS TI - Chimera proteins with affinity for membranes and microtubule tips polarize in the membrane of fission yeast cells VL - 113 ER - TY - JOUR AB - Life depends as much on the flow of information as on the flow of energy. Here we review the many efforts to make this intuition precise. Starting with the building blocks of information theory, we explore examples where it has been possible to measure, directly, the flow of information in biological networks, or more generally where information-theoretic ideas have been used to guide the analysis of experiments. Systems of interest range from single molecules (the sequence diversity in families of proteins) to groups of organisms (the distribution of velocities in flocks of birds), and all scales in between. Many of these analyses are motivated by the idea that biological systems may have evolved to optimize the gathering and representation of information, and we review the experimental evidence for this optimization, again across a wide range of scales. AU - Tkacik, Gasper AU - Bialek, William ID - 1248 JF - Annual Review of Condensed Matter Physics TI - Information processing in living systems VL - 7 ER - TY - JOUR AB - Actin and myosin assemble into a thin layer of a highly dynamic network underneath the membrane of eukaryotic cells. This network generates the forces that drive cell- and tissue-scale morphogenetic processes. The effective material properties of this active network determine large-scale deformations and other morphogenetic events. For example, the characteristic time of stress relaxation (the Maxwell time τM) in the actomyosin sets the timescale of large-scale deformation of the cortex. Similarly, the characteristic length of stress propagation (the hydrodynamic length λ) sets the length scale of slow deformations, and a large hydrodynamic length is a prerequisite for long-ranged cortical flows. Here we introduce a method to determine physical parameters of the actomyosin cortical layer in vivo directly from laser ablation experiments. For this we investigate the cortical response to laser ablation in the one-cell-stage Caenorhabditis elegans embryo and in the gastrulating zebrafish embryo. These responses can be interpreted using a coarse-grained physical description of the cortex in terms of a two-dimensional thin film of an active viscoelastic gel. To determine the Maxwell time τM, the hydrodynamic length λ, the ratio of active stress ζΔμ, and per-area friction γ, we evaluated the response to laser ablation in two different ways: by quantifying flow and density fields as a function of space and time, and by determining the time evolution of the shape of the ablated region. Importantly, both methods provide best-fit physical parameters that are in close agreement with each other and that are similar to previous estimates in the two systems. Our method provides an accurate and robust means for measuring physical parameters of the actomyosin cortical layer. It can be useful for investigations of actomyosin mechanics at the cellular-scale, but also for providing insights into the active mechanics processes that govern tissue-scale morphogenesis. AU - Saha, Arnab AU - Nishikawa, Masatoshi AU - Behrndt, Martin AU - Heisenberg, Carl-Philipp J AU - Julicher, Frank AU - Grill, Stephan ID - 1249 IS - 6 JF - Biophysical Journal TI - Determining physical properties of the cell cortex VL - 110 ER - TY - JOUR AB - Plant growth and architecture is regulated by the polar distribution of the hormone auxin. Polarity and flexibility of this process is provided by constant cycling of auxin transporter vesicles along actin filaments, coordinated by a positive auxinactin feedback loop. Both polar auxin transport and vesicle cycling are inhibited by synthetic auxin transport inhibitors, such as 1-Nnaphthylphthalamic acid (NPA), counteracting the effect of auxin; however, underlying targets and mechanisms are unclear. Using NMR, we map the NPA binding surface on the Arabidopsis thaliana ABCB chaperone TWISTED DWARF1 (TWD1).We identify ACTIN7 as a relevant, although likely indirect, TWD1 interactor, and show TWD1-dependent regulation of actin filament organization and dynamics and that TWD1 is required for NPA-mediated actin cytoskeleton remodeling. The TWD1-ACTIN7 axis controls plasma membrane presence of efflux transporters, and as a consequence act7 and twd1 share developmental and physiological phenotypes indicative of defects in auxin transport. These can be phenocopied by NPA treatment or by chemical actin (de)stabilization. We provide evidence that TWD1 determines downstreamlocations of auxin efflux transporters by adjusting actin filament debundling and dynamizing processes and mediating NPA action on the latter. This function appears to be evolutionary conserved since TWD1 expression in budding yeast alters actin polarization and cell polarity and provides NPA sensitivity. AU - Zhu, Jinsheng AU - Bailly, Aurélien AU - Zwiewka, Marta AU - Sovero, Valpuri AU - Di Donato, Martin AU - Ge, Pei AU - Oehri, Jacqueline AU - Aryal, Bibek AU - Hao, Pengchao AU - Linnert, Miriam AU - Burgardt, Noelia AU - Lücke, Christian AU - Weiwad, Matthias AU - Michel, Max AU - Weiergräber, Oliver AU - Pollmann, Stephan AU - Azzarello, Elisa AU - Mancuso, Stefano AU - Ferro, Noel AU - Fukao, Yoichiro AU - Hoffmann, Céline AU - Wedlich Söldner, Roland AU - Friml, Jirí AU - Thomas, Clément AU - Geisler, Markus ID - 1251 IS - 4 JF - Plant Cell TI - TWISTED DWARF1 mediates the action of auxin transport inhibitors on actin cytoskeleton dynamics VL - 28 ER - TY - JOUR AB - We study the homomorphism induced in homology by a closed correspondence between topological spaces, using projections from the graph of the correspondence to its domain and codomain. We provide assumptions under which the homomorphism induced by an outer approximation of a continuous map coincides with the homomorphism induced in homology by the map. In contrast to more classical results we do not require that the projection to the domain have acyclic preimages. Moreover, we show that it is possible to retrieve correct homological information from a correspondence even if some data is missing or perturbed. Finally, we describe an application to combinatorial maps that are either outer approximations of continuous maps or reconstructions of such maps from a finite set of data points. AU - Harker, Shaun AU - Kokubu, Hiroshi AU - Mischaikow, Konstantin AU - Pilarczyk, Pawel ID - 1252 IS - 4 JF - Proceedings of the American Mathematical Society SN - 1088-6826 TI - Inducing a map on homology from a correspondence VL - 144 ER - TY - JOUR AB - We use rigorous numerical techniques to compute a lower bound for the exponent of expansivity outside a neighborhood of the critical point for thousands of intervals of parameter values in the quadratic family. We first compute a radius of the critical neighborhood outside which the map is uniformly expanding. This radius is taken as small as possible, yet large enough for our numerical procedure to succeed in proving that the expansivity exponent outside this neighborhood is positive. Then, for each of the intervals, we compute a lower bound for this expansivity exponent, valid for all the parameters in that interval. We illustrate and study the distribution of the radii and the expansivity exponents. The results of our computations are mathematically rigorous. The source code of the software and the results of the computations are made publicly available at http://www.pawelpilarczyk.com/quadratic/. AU - Golmakani, Ali AU - Luzzatto, Stefano AU - Pilarczyk, Pawel ID - 1254 IS - 2 JF - Experimental Mathematics TI - Uniform expansivity outside a critical neighborhood in the quadratic family VL - 25 ER - TY - JOUR AB - Down syndrome cell adhesion molecule 1 (Dscam1) has widereaching and vital neuronal functions although the role it plays in insect and crustacean immunity is less well understood. In this study, we combine different approaches to understand the roles that Dscam1 plays in fitness-related contexts in two model insect species. Contrary to our expectations, we found no short-term modulation of Dscam1 gene expression after haemocoelic or oral bacterial exposure in Tribolium castaneum, or after haemocoelic bacterial exposure in Drosophila melanogaster. Furthermore, RNAi-mediated Dscam1 knockdown and subsequent bacterial exposure did not reduce T. castaneum survival. However, Dscam1 knockdown in larvae resulted in adult locomotion defects, as well as dramatically reduced fecundity in males and females. We suggest that Dscam1 does not always play a straightforward role in immunity, but strongly influences behaviour and fecundity. This study takes a step towards understanding more about the role of this intriguing gene from different phenotypic perspectives. AU - Peuß, Robert AU - Wensing, Kristina AU - Woestmann, Luisa AU - Eggert, Hendrik AU - Milutinovic, Barbara AU - Sroka, Marlene AU - Scharsack, Jörn AU - Kurtz, Joachim AU - Armitage, Sophie ID - 1255 IS - 4 JF - Royal Society Open Science TI - Down syndrome cell adhesion molecule 1: Testing for a role in insect immunity, behaviour and reproduction VL - 3 ER - TY - CONF AB - Simulink is widely used for model driven development (MDD) of industrial software systems. Typically, the Simulink based development is initiated from Stateflow modeling, followed by simulation, validation and code generation mapped to physical execution platforms. However, recent industrial trends have raised the demands of rigorous verification on safety-critical applications, which is unfortunately challenging for Simulink. In this paper, we present an approach to bridge the Stateflow based model driven development and a well- defined rigorous verification. First, we develop a self- contained toolkit to translate Stateflow model into timed automata, where major advanced modeling features in Stateflow are supported. Taking advantage of the strong verification capability of Uppaal, we can not only find bugs in Stateflow models which are missed by Simulink Design Verifier, but also check more important temporal properties. Next, we customize a runtime verifier for the generated nonintrusive VHDL and C code of Stateflow model for monitoring. The major strength of the customization is the flexibility to collect and analyze runtime properties with a pure software monitor, which opens more opportunities for engineers to achieve high reliability of the target system compared with the traditional act that only relies on Simulink Polyspace. We incorporate these two parts into original Stateflow based MDD seamlessly. In this way, safety-critical properties are both verified at the model level, and at the consistent system implementation level with physical execution environment in consideration. We apply our approach on a train controller design, and the verified implementation is tested and deployed on a real hardware platform. AU - Jiang, Yu AU - Yang, Yixiao AU - Liu, Han AU - Kong, Hui AU - Gu, Ming AU - Sun, Jiaguang AU - Sha, Lui ID - 1256 TI - From stateflow simulation to verified implementation: A verification approach and a real-time train controller design ER - TY - JOUR AB - We consider products of random matrices that are small, independent identically distributed perturbations of a fixed matrix (Formula presented.). Focusing on the eigenvalues of (Formula presented.) of a particular size we obtain a limit to a SDE in a critical scaling. Previous results required (Formula presented.) to be a (conjugated) unitary matrix so it could not have eigenvalues of different modulus. From the result we can also obtain a limit SDE for the Markov process given by the action of the random products on the flag manifold. Applying the result to random Schrödinger operators we can improve some results by Valko and Virag showing GOE statistics for the rescaled eigenvalue process of a sequence of Anderson models on long boxes. In particular, we solve a problem posed in their work. AU - Sadel, Christian AU - Virág, Bálint ID - 1257 IS - 3 JF - Communications in Mathematical Physics TI - A central limit theorem for products of random matrices and GOE statistics for the Anderson model on long boxes VL - 343 ER - TY - JOUR AB - When plants grow in close proximity basic resources such as light can become limiting. Under such conditions plants respond to anticipate and/or adapt to the light shortage, a process known as the shade avoidance syndrome (SAS). Following genetic screening using a shade-responsive luciferase reporter line (PHYB:LUC), we identified DRACULA2 (DRA2), which encodes an Arabidopsis homolog of mammalian nucleoporin 98, a component of the nuclear pore complex (NPC). DRA2, together with other nucleoporins, participates positively in the control of the hypocotyl elongation response to plant proximity, a role that can be considered dependent on the nucleocytoplasmic transport of macromolecules (i.e. is transport dependent). In addition, our results reveal a specific role for DRA2 in controlling shade-induced gene expression. We suggest that this novel regulatory role of DRA2 is transport independent and that it might rely on its dynamic localization within and outside of the NPC. These results provide mechanistic insights in to how SAS responses are rapidly established by light conditions. They also indicate that nucleoporins have an active role in plant signaling. AU - Gallemi Rovira, Marcal AU - Galstyan, Anahit AU - Paulišić, Sandi AU - Then, Christiane AU - Ferrández Ayela, Almudena AU - Lorenzo Orts, Laura AU - Roig Villanova, Irma AU - Wang, Xuewen AU - Micol, José AU - Ponce, Maria AU - Devlin, Paul AU - Martínez García, Jaime ID - 1258 IS - 9 JF - Development TI - DRACULA2 is a dynamic nucleoporin with a role in regulating the shade avoidance syndrome in Arabidopsis VL - 143 ER - TY - JOUR AB - We consider the Bogolubov–Hartree–Fock functional for a fermionic many-body system with two-body interactions. For suitable interaction potentials that have a strong enough attractive tail in order to allow for two-body bound states, but are otherwise sufficiently repulsive to guarantee stability of the system, we show that in the low-density limit the ground state of this model consists of a Bose–Einstein condensate of fermion pairs. The latter can be described by means of the Gross–Pitaevskii energy functional. AU - Bräunlich, Gerhard AU - Hainzl, Christian AU - Seiringer, Robert ID - 1259 IS - 2 JF - Mathematical Physics, Analysis and Geometry TI - Bogolubov–Hartree–Fock theory for strongly interacting fermions in the low density limit VL - 19 ER - TY - JOUR AB - In this work, the Gardner problem of inferring interactions and fields for an Ising neural network from given patterns under a local stability hypothesis is addressed under a dual perspective. By means of duality arguments, an integer linear system is defined whose solution space is the dual of the Gardner space and whose solutions represent mutually unstable patterns. We propose and discuss Monte Carlo methods in order to find and remove unstable patterns and uniformly sample the space of interactions thereafter. We illustrate the problem on a set of real data and perform ensemble calculation that shows how the emergence of phase dominated by unstable patterns can be triggered in a nonlinear discontinuous way. AU - De Martino, Daniele ID - 1260 IS - 6 JF - International Journal of Modern Physics C TI - The dual of the space of interactions in neural network models VL - 27 ER - TY - JOUR AB - We consider a non-standard finite-volume discretization of a strongly non-linear fourth order diffusion equation on the d-dimensional cube, for arbitrary . The scheme preserves two important structural properties of the equation: the first is the interpretation as a gradient flow in a mass transportation metric, and the second is an intimate relation to a linear Fokker-Planck equation. Thanks to these structural properties, the scheme possesses two discrete Lyapunov functionals. These functionals approximate the entropy and the Fisher information, respectively, and their dissipation rates converge to the optimal ones in the discrete-to-continuous limit. Using the dissipation, we derive estimates on the long-time asymptotics of the discrete solutions. Finally, we present results from numerical experiments which indicate that our discretization is able to capture significant features of the complex original dynamics, even with a rather coarse spatial resolution. AU - Maas, Jan AU - Matthes, Daniel ID - 1261 IS - 7 JF - Nonlinearity TI - Long-time behavior of a finite volume discretization for a fourth order diffusion equation VL - 29 ER - TY - JOUR AB - n contrast with the wealth of recent reports about the function of μ-adaptins and clathrin adaptor protein (AP) complexes, there is very little information about the motifs that determine the sorting of membrane proteins within clathrin-coated vesicles in plants. Here, we investigated putative sorting signals in the large cytosolic loop of the Arabidopsis (Arabidopsis thaliana) PIN-FORMED1 (PIN1) auxin transporter, which are involved in binding μ-adaptins and thus in PIN1 trafficking and localization. We found that Phe-165 and Tyr-280, Tyr-328, and Tyr-394 are involved in the binding of different μ-adaptins in vitro. However, only Phe-165, which binds μA(μ2)- and μD(μ3)-adaptin, was found to be essential for PIN1 trafficking and localization in vivo. The PIN1:GFP-F165A mutant showed reduced endocytosis but also localized to intracellular structures containing several layers of membranes and endoplasmic reticulum (ER) markers, suggesting that they correspond to ER or ER-derived membranes. While PIN1:GFP localized normally in a μA (μ2)-adaptin mutant, it accumulated in big intracellular structures containing LysoTracker in a μD (μ3)-adaptin mutant, consistent with previous results obtained with mutants of other subunits of the AP-3 complex. Our data suggest that Phe-165, through the binding of μA (μ2)- and μD (μ3)-adaptin, is important for PIN1 endocytosis and for PIN1 trafficking along the secretory pathway, respectively. AU - Sancho Andrés, Gloria AU - Soriano Ortega, Esther AU - Gao, Caiji AU - Bernabé Orts, Joan AU - Narasimhan, Madhumitha AU - Müller, Anna AU - Tejos, Ricardo AU - Jiang, Liwen AU - Friml, Jirí AU - Aniento, Fernando AU - Marcote, Maria ID - 1264 IS - 3 JF - Plant Physiology TI - Sorting motifs involved in the trafficking and localization of the PIN1 auxin efflux carrier VL - 171 ER - TY - JOUR AB - Extracellular matrices (ECMs) are central to the advent of multicellular life, and their mechanical propertiesare modulated by and impinge on intracellular signaling pathways that regulate vital cellular functions. High spatial-resolution mapping of mechanical properties in live cells is, however, extremely challenging. Thus, our understanding of how signaling pathways process physiological signals to generate appropriate mechanical responses is limited. We introduce fluorescence emission-Brillouin scattering imaging (FBi), a method for the parallel and all-optical measurements of mechanical properties and fluorescence at the submicrometer scale in living organisms. Using FBi, we showed thatchanges in cellular hydrostatic pressure and cytoplasm viscoelasticity modulate the mechanical signatures of plant ECMs. We further established that the measured "stiffness" of plant ECMs is symmetrically patternedin hypocotyl cells undergoing directional growth. Finally, application of this method to Arabidopsis thaliana with photoreceptor mutants revealed that red and far-red light signals are essential modulators of ECM viscoelasticity. By mapping the viscoelastic signatures of a complex ECM, we provide proof of principlefor the organism-wide applicability of FBi for measuring the mechanical outputs of intracellular signaling pathways. As such, our work has implications for investigations of mechanosignaling pathways and developmental biology. AU - Elsayad, Kareem AU - Werner, Stephanie AU - Gallemi Rovira, Marcal AU - Kong, Jixiang AU - Guajardo, Edmundo AU - Zhang, Lijuan AU - Jaillais, Yvon AU - Greb, Thomas AU - Belkhadir, Youssef ID - 1265 IS - 435 JF - Science Signaling TI - Mapping the subcellular mechanical properties of live cells in tissues with fluorescence emission-Brillouin imaging VL - 9 ER - TY - JOUR AB - Cortical networks exhibit ‘global oscillations’, in which neural spike times are entrained to an underlying oscillatory rhythm, but where individual neurons fire irregularly, on only a fraction of cycles. While the network dynamics underlying global oscillations have been well characterised, their function is debated. Here, we show that such global oscillations are a direct consequence of optimal efficient coding in spiking networks with synaptic delays and noise. To avoid firing unnecessary spikes, neurons need to share information about the network state. Ideally, membrane potentials should be strongly correlated and reflect a ‘prediction error’ while the spikes themselves are uncorrelated and occur rarely. We show that the most efficient representation is when: (i) spike times are entrained to a global Gamma rhythm (implying a consistent representation of the error); but (ii) few neurons fire on each cycle (implying high efficiency), while (iii) excitation and inhibition are tightly balanced. This suggests that cortical networks exhibiting such dynamics are tuned to achieve a maximally efficient population code. AU - Chalk, Matthew J AU - Gutkin, Boris AU - Denève, Sophie ID - 1266 IS - 2016JULY JF - eLife TI - Neural oscillations as a signature of efficient coding in the presence of synaptic delays VL - 5 ER - TY - JOUR AB - Plants are continuously exposed to a myriad of external signals such as fluctuating nutrients availability, drought, heat, cold, high salinity, or pathogen/pest attacks that can severely affect their development, growth, and fertility. As sessile organisms, plants must therefore be able to sense and rapidly react to these external inputs, activate efficient responses, and adjust development to changing conditions. In recent years, significant progress has been made towards understanding the molecular mechanisms underlying the intricate and complex communication between plants and the environment. It is now becoming increasingly evident that hormones have an important regulatory role in plant adaptation and defense mechanisms. AU - Benková, Eva ID - 1269 IS - 6 JF - Plant Molecular Biology TI - Plant hormones in interactions with the environment VL - 91 ER - TY - JOUR AB - We give a simplified proof of the nonexistence of large nuclei in the liquid drop model and provide an explicit bound. Our bound is within a factor of 2.3 of the conjectured value and seems to be the first quantitative result. AU - Frank, Rupert AU - Killip, Rowan AU - Nam, Phan ID - 1267 IS - 8 JF - Letters in Mathematical Physics TI - Nonexistence of large nuclei in the liquid drop model VL - 106 ER - TY - JOUR AU - Milutinovic, Barbara AU - Kurtz, Joachim ID - 1268 IS - 4 JF - Seminars in Immunology TI - Immune memory in invertebrates VL - 28 ER - TY - JOUR AB - Background: High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood. Results: Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision. Conclusions: Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times. AU - Diz Muñoz, Alba AU - Romanczuk, Pawel AU - Yu, Weimiao AU - Bergert, Martin AU - Ivanovitch, Kenzo AU - Salbreux, Guillame AU - Heisenberg, Carl-Philipp J AU - Paluch, Ewa ID - 1271 IS - 1 JF - BMC Biology TI - Steering cell migration by alternating blebs and actin-rich protrusions VL - 14 ER - TY - JOUR AB - Lateral root primordia (LRP) originate from pericycle stem cells located deep within parental root tissues. LRP emerge through overlying root tissues by inducing auxin-dependent cell separation and hydraulic changes in adjacent cells. The auxin-inducible auxin influx carrier LAX3 plays a key role concentrating this signal in cells overlying LRP. Delimiting LAX3 expression to two adjacent cell files overlying new LRP is crucial to ensure that auxin-regulated cell separation occurs solely along their shared walls. Multiscale modeling has predicted that this highly focused pattern of expression requires auxin to sequentially induce auxin efflux and influx carriers PIN3 and LAX3, respectively. Consistent with model predictions, we report that auxin-inducible LAX3 expression is regulated indirectly by AUXIN RESPONSE FACTOR 7 (ARF7). Yeast one-hybrid screens revealed that the LAX3 promoter is bound by the transcription factor LBD29, which is a direct target for regulation by ARF7. Disrupting auxin-inducible LBD29 expression or expressing an LBD29-SRDX transcriptional repressor phenocopied the lax3 mutant, resulting in delayed lateral root emergence. We conclude that sequential LBD29 and LAX3 induction by auxin is required to coordinate cell separation and organ emergence. AU - Porco, Silvana AU - Larrieu, Antoine AU - Du, Yujuan AU - Gaudinier, Allison AU - Goh, Tatsuaki AU - Swarup, Kamal AU - Swarup, Ranjan AU - Kuempers, Britta AU - Bishopp, Anthony AU - Lavenus, Julien AU - Casimiro, Ilda AU - Hill, Kristine AU - Benková, Eva AU - Fukaki, Hidehiro AU - Brady, Siobhan AU - Scheres, Ben AU - Peéet, Benjamin AU - Bennett, Malcolm ID - 1273 IS - 18 JF - Development TI - Lateral root emergence in Arabidopsis is dependent on transcription factor LBD29 regulation of auxin influx carrier LAX3 VL - 143 ER - TY - JOUR AB - We study different means to extend offsetting based on skeletal structures beyond the well-known constant-radius and mitered offsets supported by Voronoi diagrams and straight skeletons, for which the orthogonal distance of offset elements to their respective input elements is constant and uniform over all input elements. Our main contribution is a new geometric structure, called variable-radius Voronoi diagram, which supports the computation of variable-radius offsets, i.e., offsets whose distance to the input is allowed to vary along the input. We discuss properties of this structure and sketch a prototype implementation that supports the computation of variable-radius offsets based on this new variant of Voronoi diagrams. AU - Held, Martin AU - Huber, Stefan AU - Palfrader, Peter ID - 1272 IS - 5 JF - Computer-Aided Design and Applications TI - Generalized offsetting of planar structures using skeletons VL - 13 ER - TY - JOUR AB - During hippocampal sharp wave/ripple (SWR) events, previously occurring, sensory inputdriven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity- related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level. Therefore, we tested whether intact SWR events occurring during the sleep/rest session after the first exploration of a novel environment are needed for the stabilization of the CA1 code, which process requires plasticity. We found that the newly-formed representation in the CA1 has the same level of stability with optogenetic SWR blockade as with a control manipulation that delivered the same amount of light into the brain. Therefore our results suggest that at least in the case of passive exploratory behavior, SWR-related plasticity is dispensable for the stability of CA1 ensembles. AU - Kovács, Krisztián AU - O'Neill, Joseph AU - Schönenberger, Philipp AU - Penttonen, Markku AU - Rangel Guerrero, Dámaris K AU - Csicsvari, Jozsef L ID - 1279 IS - 10 JF - PLoS One TI - Optogenetically blocking sharp wave ripple events in sleep does not interfere with the formation of stable spatial representation in the CA1 area of the hippocampus VL - 11 ER - TY - JOUR AB - Adaptations of vestibulo-ocular and optokinetic response eye movements have been studied as an experimental model of cerebellum-dependent motor learning. Several previous physiological and pharmacological studies have consistently suggested that the cerebellar flocculus (FL) Purkinje cells (P-cells) and the medial vestibular nucleus (MVN) neurons targeted by FL (FL-targeted MVN neurons) may respectively maintain the memory traces of short- and long-term adaptation. To study the basic structures of the FL-MVN synapses by light microscopy (LM) and electron microscopy (EM), we injected green florescence protein (GFP)-expressing lentivirus into FL to anterogradely label the FL P-cell axons in C57BL/6J mice. The FL P-cell axonal boutons were distributed in the magnocellular MVN and in the border region of parvocellular MVN and prepositus hypoglossi (PrH). In the magnocellular MVN, the FL-P cell axons mainly terminated on somata and proximal dendrites. On the other hand, in the parvocellular MVN/PrH, the FL P-cell axonal synaptic boutons mainly terminated on the relatively small-diameter (< 1 μm) distal dendrites of MVN neurons, forming symmetrical synapses. The majority of such parvocellular MVN/PrH neurons were determined to be glutamatergic by immunocytochemistry and in-situ hybridization of GFP expressing transgenic mice. To further examine the spatial relationship between the synapses of FL P-cells and those of vestibular nerve on the neurons of the parvocellular MVN/ PrH, we added injections of biotinylated dextran amine into the semicircular canal and anterogradely labeled vestibular nerve axons in some mice. The MVN dendrites receiving the FL P-cell axonal synaptic boutons often closely apposed vestibular nerve synaptic boutons in both LM and EM studies. Such a partial overlap of synaptic boutons of FL P-cell axons with those of vestibular nerve axons in the distal dendrites of MVN neurons suggests that inhibitory synapses of FL P-cells may influence the function of neighboring excitatory synapses of vestibular nerve in the parvocellular MVN/PrH neurons. AU - Matsuno, Hitomi AU - Kudoh, Moeko AU - Watakabe, Akiya AU - Yamamori, Tetsuo AU - Shigemoto, Ryuichi AU - Nagao, Soichi ID - 1278 IS - 10 JF - PLoS One TI - Distribution and structure of synapses on medial vestibular nuclear neurons targeted by cerebellar flocculus purkinje cells and vestibular nerve in mice: Light and electron microscopy studies VL - 11 ER - TY - JOUR AB - The cytochrome (cyt) bc 1 complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme's substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Q i-site of the cyt bc 1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Q i-site to facilitate binding of half-protonated semiquinone-a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Q i-site. AU - Postila, Pekka AU - Kaszuba, Karol AU - Kuleta, Patryk AU - Vattulainen, Ilpo AU - Sarewicz, Marcin AU - Osyczka, Artur AU - Róg, Tomasz ID - 1276 JF - Scientific Reports TI - Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex VL - 6 ER - TY - JOUR AB - The Arabidopsis thaliana endogenous elicitor peptides (AtPeps) are released into the apoplast after cellular damage caused by pathogens or wounding to induce innate immunity by direct binding to the membrane-localized leucine-rich repeat receptor kinases, PEP RECEPTOR1 (PEPR1) and PEPR2. Although the PEPR-mediated signaling components and responses have been studied extensively, the contributions of the subcellular localization and dynamics of the active PEPRs remain largely unknown. We used live-cell imaging of the fluorescently labeled and bioactive pep1 to visualize the intracellular behavior of the PEPRs in the Arabidopsis root meristem. We found that AtPep1 decorated the plasma membrane (PM) in a receptor-dependent manner and cointernalized with PEPRs. Trafficking of the AtPep1-PEPR1 complexes to the vacuole required neither the trans-Golgi network/early endosome (TGN/EE)-localized vacuolar H+ -ATPase activity nor the function of the brefeldin A-sensitive ADP-ribosylation factor-guanine exchange factors (ARF-GEFs). In addition, AtPep1 and different TGN/EE markers colocalized only rarely, implying that the intracellular route of this receptor-ligand pair is largely independent of the TGN/EE. Inducible overexpression of the Arabidopsis clathrin coat disassembly factor, Auxilin2, which inhibits clathrin-mediated endocytosis (CME), impaired the AtPep1-PEPR1 internalization and compromised AtPep1-mediated responses. Our results show that clathrin function at the PM is required to induce plant defense responses, likely through CME of cell surface-located signaling components. AU - Ortiz Morea, Fausto AU - Savatin, Daniel AU - Dejonghe, Wim AU - Kumar, Rahul AU - Luo, Yu AU - Adamowski, Maciek AU - Van Begin, Jos AU - Dressano, Keini AU - De Oliveira, Guilherme AU - Zhao, Xiuyang AU - Lu, Qing AU - Madder, Annemieke AU - Friml, Jirí AU - De Moura, Daniel AU - Russinova, Eugenia ID - 1277 IS - 39 JF - PNAS TI - Danger-associated peptide signaling in Arabidopsis requires clathrin VL - 113 ER - TY - JOUR AB - Plants are able to modulate root growth and development to optimize their nitrogen nutrition. In Arabidopsis (Arabidopsis thaliana), the adaptive root response to nitrate (NO3 -) depends on the NRT1.1/NPF6.3 transporter/sensor. NRT1.1 represses emergence of lateral root primordia (LRPs) at low concentration or absence of NO3 - through its auxin transport activity that lowers auxin accumulation in LR. However, these functional data strongly contrast with the known transcriptional regulation of NRT1.1, which is markedly repressed in LRPs in the absence of NO3 -. To explain this discrepancy, we investigated in detail the spatiotemporal expression pattern of the NRT1.1 protein during LRP development and combined local transcript analysis with the use of transgenic lines expressing tagged NRT1.1 proteins. Our results show that although NO3 - stimulates NRT1.1 transcription and probably mRNA stability both in primary root tissues and in LRPs, it acts differentially on protein accumulation, depending on the tissues considered with stimulation in cortex and epidermis of the primary root and a strong repression in LRPs and to a lower extent at the primary root tip. This demonstrates that NRT1.1 is strongly regulated at the posttranscriptional level by tissue-specific mechanisms. These mechanisms are crucial for controlling the large palette of adaptive responses to NO3 - mediated by NRT1.1 as they ensure that the protein is present in the proper tissue under the specific conditions where it plays a signaling role in this particular tissue. AU - Bouguyon, Eléonore AU - Perrine Walker, Francine AU - Pervent, Marjorie AU - Rochette, Juliette AU - Cuesta, Candela AU - Benková, Eva AU - Martinière, Alexandre AU - Bach, Lien AU - Krouk, Gabriel AU - Gojon, Alain AU - Nacry, Philippe ID - 1281 IS - 2 JF - Plant Physiology TI - Nitrate controls root development through posttranscriptional regulation of the NRT1.1/NPF6.3 transporter sensor VL - 172 ER - TY - JOUR AB - We consider higher-dimensional generalizations of the normalized Laplacian and the adjacency matrix of graphs and study their eigenvalues for the Linial–Meshulam model Xk(n, p) of random k-dimensional simplicial complexes on n vertices. We show that for p = Ω(logn/n), the eigenvalues of each of the matrices are a.a.s. concentrated around two values. The main tool, which goes back to the work of Garland, are arguments that relate the eigenvalues of these matrices to those of graphs that arise as links of (k - 2)-dimensional faces. Garland’s result concerns the Laplacian; we develop an analogous result for the adjacency matrix. The same arguments apply to other models of random complexes which allow for dependencies between the choices of k-dimensional simplices. In the second part of the paper, we apply this to the question of possible higher-dimensional analogues of the discrete Cheeger inequality, which in the classical case of graphs relates the eigenvalues of a graph and its edge expansion. It is very natural to ask whether this generalizes to higher dimensions and, in particular, whether the eigenvalues of the higher-dimensional Laplacian capture the notion of coboundary expansion—a higher-dimensional generalization of edge expansion that arose in recent work of Linial and Meshulam and of Gromov; this question was raised, for instance, by Dotterrer and Kahle. We show that this most straightforward version of a higher-dimensional discrete Cheeger inequality fails, in quite a strong way: For every k ≥ 2 and n ∈ N, there is a k-dimensional complex Yn k on n vertices that has strong spectral expansion properties (all nontrivial eigenvalues of the normalised k-dimensional Laplacian lie in the interval [1−O(1/√1), 1+0(1/√1]) but whose coboundary expansion is bounded from above by O(log n/n) and so tends to zero as n → ∞; moreover, Yn k can be taken to have vanishing integer homology in dimension less than k. AU - Gundert, Anna AU - Wagner, Uli ID - 1282 IS - 2 JF - Israel Journal of Mathematics TI - On eigenvalues of random complexes VL - 216 ER - TY - JOUR AB - We prove the Wigner-Dyson-Mehta conjecture at fixed energy in the bulk of the spectrum for generalized symmetric and Hermitian Wigner matrices. Previous results concerning the universality of random matrices either require an averaging in the energy parameter or they hold only for Hermitian matrices if the energy parameter is fixed. We develop a homogenization theory of the Dyson Brownian motion and show that microscopic universality follows from mesoscopic statistics. AU - Bourgade, Paul AU - Erdös, László AU - Yau, Horngtzer AU - Yin, Jun ID - 1280 IS - 10 JF - Communications on Pure and Applied Mathematics TI - Fixed energy universality for generalized wigner matrices VL - 69 ER - TY - JOUR AU - Callan Jones, Andrew AU - Ruprecht, Verena AU - Wieser, Stefan AU - Heisenberg, Carl-Philipp J AU - Voituriez, Raphaël ID - 1275 IS - 13 JF - Physical Review Letters TI - Callan-Jones et al. Reply VL - 117 ER - TY - JOUR AB - The impact of the plant hormone ethylene on seedling development has long been recognized; however, its ecophysiological relevance is unexplored. Three recent studies demonstrate that ethylene is a critical endogenous integrator of various environmental signals including mechanical stress, light, and oxygen availability during seedling germination and growth through the soil. AU - Zhu, Qiang AU - Benková, Eva ID - 1283 IS - 10 JF - Trends in Plant Science TI - Seedlings’ strategy to overcome a soil barrier VL - 21 ER - TY - JOUR AB - We use recently developed angulon theory [R. Schmidt and M. Lemeshko, Phys. Rev. Lett. 114, 203001 (2015)PRLTAO0031-900710.1103/PhysRevLett.114.203001] to study the rotational spectrum of a cyanide molecular anion immersed into Bose-Einstein condensates of rubidium and strontium. Based on ab initio potential energy surfaces, we provide a detailed study of the rotational Lamb shift and many-body-induced fine structure which arise due to dressing of molecular rotation by a field of phonon excitations. We demonstrate that the magnitude of these effects is large enough in order to be observed in modern experiments on cold molecular ions. Furthermore, we introduce a novel method to construct pseudopotentials starting from the ab initio potential energy surfaces, which provides a means to obtain effective coupling constants for low-energy polaron models. AU - Midya, Bikashkali AU - Tomza, Michał AU - Schmidt, Richard AU - Lemeshko, Mikhail ID - 1286 IS - 4 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Rotation of cold molecular ions inside a Bose-Einstein condensate VL - 94 ER - TY - JOUR AB - Cell migration is central to a multitude of physiological processes, including embryonic development, immune surveillance, and wound healing, and deregulated migration is key to cancer dissemination. Decades of investigations have uncovered many of the molecular and physical mechanisms underlying cell migration. Together with protrusion extension and cell body retraction, adhesion to the substrate via specific focal adhesion points has long been considered an essential step in cell migration. Although this is true for cells moving on two-dimensional substrates, recent studies have demonstrated that focal adhesions are not required for cells moving in three dimensions, in which confinement is sufficient to maintain a cell in contact with its substrate. Here, we review the investigations that have led to challenging the requirement of specific adhesions for migration, discuss the physical mechanisms proposed for cell body translocation during focal adhesion-independent migration, and highlight the remaining open questions for the future. AU - Paluch, Ewa AU - Aspalter, Irene AU - Sixt, Michael K ID - 1285 JF - Annual Review of Cell and Developmental Biology TI - Focal adhesion-independent cell migration VL - 32 ER - TY - JOUR AB - Respiratory complex I transfers electrons from NADH to quinone, utilizing the reaction energy to translocate protons across the membrane. It is a key enzyme of the respiratory chain of many prokaryotic and most eukaryotic organisms. The reversible NADH oxidation reaction is facilitated in complex I by non-covalently bound flavin mononucleotide (FMN). Here we report that the catalytic activity of E. coli complex I with artificial electron acceptors potassium ferricyanide (FeCy) and hexaamineruthenium (HAR) is significantly inhibited in the enzyme pre-reduced by NADH. Further, we demonstrate that the inhibition is caused by reversible dissociation of FMN. The binding constant (Kd) for FMN increases from the femto- or picomolar range in oxidized complex I to the nanomolar range in the NADH reduced enzyme, with an FMN dissociation time constant of ~ 5 s. The oxidation state of complex I, rather than that of FMN, proved critical to the dissociation. Such dissociation is not observed with the T. thermophilus enzyme and our analysis suggests that the difference may be due to the unusually high redox potential of Fe-S cluster N1a in E. coli. It is possible that the enzyme attenuates ROS production in vivo by releasing FMN under highly reducing conditions. AU - Holt, Peter AU - Efremov, Rouslan AU - Nakamaru Ogiso, Eiko AU - Sazanov, Leonid A ID - 1288 IS - 11 JF - Biochimica et Biophysica Acta - Bioenergetics TI - Reversible FMN dissociation from Escherichia coli respiratory complex I VL - 1857 ER - TY - JOUR AB - We consider Ising models in two and three dimensions, with short range ferromagnetic and long range, power-law decaying, antiferromagnetic interactions. We let J be the ratio between the strength of the ferromagnetic to antiferromagnetic interactions. The competition between these two kinds of interactions induces the system to form domains of minus spins in a background of plus spins, or vice versa. If the decay exponent p of the long range interaction is larger than d + 1, with d the space dimension, this happens for all values of J smaller than a critical value Jc(p), beyond which the ground state is homogeneous. In this paper, we give a characterization of the infinite volume ground states of the system, for p > 2d and J in a left neighborhood of Jc(p). In particular, we prove that the quasi-one-dimensional states consisting of infinite stripes (d = 2) or slabs (d = 3), all of the same optimal width and orientation, and alternating magnetization, are infinite volume ground states. Our proof is based on localization bounds combined with reflection positivity. AU - Giuliani, Alessandro AU - Seiringer, Robert ID - 1291 IS - 3 JF - Communications in Mathematical Physics TI - Periodic striped ground states in Ising models with competing interactions VL - 347 ER - TY - JOUR AB - For a graph G with p vertices the closed convex cone S⪰0(G) consists of all real positive semidefinite p×p matrices whose sparsity pattern is given by G, that is, those matrices with zeros in the off-diagonal entries corresponding to nonedges of G. The extremal rays of this cone and their associated ranks have applications to matrix completion problems, maximum likelihood estimation in Gaussian graphical models in statistics, and Gauss elimination for sparse matrices. While the maximum rank of an extremal ray in S⪰0(G), known as the sparsity order of G, has been characterized for different classes of graphs, we here study all possible extremal ranks of S⪰0(G). We investigate when the geometry of the (±1)-cut polytope of G yields a polyhedral characterization of the set of extremal ranks of S⪰0(G). For a graph G without K5 minors, we show that appropriately chosen normal vectors to the facets of the (±1)-cut polytope of G specify the off-diagonal entries of extremal matrices in S⪰0(G). We also prove that for appropriately chosen scalars the constant term of the linear equation of each facet-supporting hyperplane is the rank of its corresponding extremal matrix in S⪰0(G). Furthermore, we show that if G is series-parallel then this gives a complete characterization of all possible extremal ranks of S⪰0(G). Consequently, the sparsity order problem for series-parallel graphs can be solved in terms of polyhedral geometry. AU - Solus, Liam T AU - Uhler, Caroline AU - Yoshida, Ruriko ID - 1293 JF - Linear Algebra and Its Applications TI - Extremal positive semidefinite matrices whose sparsity pattern is given by graphs without K5 minors VL - 509 ER - TY - JOUR AB - We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline. AU - Stone, Laura AU - Baym, Michael AU - Lieberman, Tami AU - Chait, Remy P AU - Clardy, Jon AU - Kishony, Roy ID - 1290 IS - 11 JF - Nature Chemical Biology TI - Compounds that select against the tetracycline-resistance efflux pump VL - 12 ER - TY - JOUR AB - Voronoi diagrams and Delaunay triangulations have been extensively used to represent and compute geometric features of point configurations. We introduce a generalization to poset diagrams and poset complexes, which contain order-k and degree-k Voronoi diagrams and their duals as special cases. Extending a result of Aurenhammer from 1990, we show how to construct poset diagrams as weighted Voronoi diagrams of average balls. AU - Edelsbrunner, Herbert AU - Iglesias Ham, Mabel ID - 1295 JF - Electronic Notes in Discrete Mathematics TI - Multiple covers with balls II: Weighted averages VL - 54 ER - TY - JOUR AB - We give explicit formulas and algorithms for the computation of the Thurston–Bennequin invariant of a nullhomologous Legendrian knot on a page of a contact open book and on Heegaard surfaces in convex position. Furthermore, we extend the results to rationally nullhomologous knots in arbitrary 3-manifolds. AU - Durst, Sebastian AU - Kegel, Marc AU - Klukas, Mirko D ID - 1292 IS - 2 JF - Acta Mathematica Hungarica TI - Computing the Thurston–Bennequin invariant in open books VL - 150 ER -