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
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 - 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 - 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 - Speciation results from the progressive accumulation of mutations that decrease the probability of mating between parental populations or reduce the fitness of hybrids—the so-called species barriers. The speciation genomic literature, however, is mainly a collection of case studies, each with its own approach and specificities, such that a global view of the gradual process of evolution from one to two species is currently lacking. Of primary importance is the prevalence of gene flow between diverging entities, which is central in most species concepts and has been widely discussed in recent years. Here, we explore the continuum of speciation thanks to a comparative analysis of genomic data from 61 pairs of populations/species of animals with variable levels of divergence. Gene flow between diverging gene pools is assessed under an approximate Bayesian computation (ABC) framework. We show that the intermediate "grey zone" of speciation, in which taxonomy is often controversial, spans from 0.5% to 2% of net synonymous divergence, irrespective of species life history traits or ecology. Thanks to appropriate modeling of among-locus variation in genetic drift and introgression rate, we clarify the status of the majority of ambiguous cases and uncover a number of cryptic species. Our analysis also reveals the high incidence in animals of semi-isolated species (when some but not all loci are affected by barriers to gene flow) and highlights the intrinsic difficulty, both statistical and conceptual, of delineating species in the grey zone of speciation.
AU - Roux, Camille
AU - Fraisse, Christelle
AU - Romiguier, Jonathan
AU - Anciaux, Youann
AU - Galtier, Nicolas
AU - Bierne, Nicolas
ID - 1158
IS - 12
JF - PLoS Biology
TI - Shedding light on the grey zone of speciation along a continuum of genomic divergence
VL - 14
ER -
TY - CONF
AB - A drawing of a graph G is radial if the vertices of G are placed on concentric circles C1, … , Ck with common center c, and edges are drawn radially: every edge intersects every circle centered at c at most once. G is radial planar if it has a radial embedding, that is, a crossing-free radial drawing. If the vertices of G are ordered or partitioned into ordered levels (as they are for leveled graphs), we require that the assignment of vertices to circles corresponds to the given ordering or leveling. A pair of edges e and f in a graph is independent if e and f do not share a vertex. We show that a graph G is radial planar if G has a radial drawing in which every two independent edges cross an even number of times; the radial embedding has the same leveling as the radial drawing. In other words, we establish the strong Hanani-Tutte theorem for radial planarity. This characterization yields a very simple algorithm for radial planarity testing.
AU - Fulek, Radoslav
AU - Pelsmajer, Michael
AU - Schaefer, Marcus
ID - 1164
TI - Hanani-Tutte for radial planarity II
VL - 9801
ER -
TY - CONF
AB - We show that c-planarity is solvable in quadratic time for flat clustered graphs with three clusters if the combinatorial embedding of the underlying graph is fixed. In simpler graph-theoretical terms our result can be viewed as follows. Given a graph G with the vertex set partitioned into three parts embedded on a 2-sphere, our algorithm decides if we can augment G by adding edges without creating an edge-crossing so that in the resulting spherical graph the vertices of each part induce a connected sub-graph. We proceed by a reduction to the problem of testing the existence of a perfect matching in planar bipartite graphs. We formulate our result in a slightly more general setting of cyclic clustered graphs, i.e., the simple graph obtained by contracting each cluster, where we disregard loops and multi-edges, is a cycle.
AU - Fulek, Radoslav
ID - 1165
TI - C-planarity of embedded cyclic c-graphs
VL - 9801
ER -
TY - JOUR
AB - Evolutionary pathways describe trajectories of biological evolution in the space of different variants of organisms (genotypes). The probability of existence and the number of evolutionary pathways that lead from a given genotype to a better-adapted genotype are important measures of accessibility of local fitness optima and the reproducibility of evolution. Both quantities have been studied in simple mathematical models where genotypes are represented as binary sequences of two types of basic units, and the network of permitted mutations between the genotypes is a hypercube graph. However, it is unclear how these results translate to the biologically relevant case in which genotypes are represented by sequences of more than two units, for example four nucleotides (DNA) or 20 amino acids (proteins), and the mutational graph is not the hypercube. Here we investigate accessibility of the best-adapted genotype in the general case of K > 2 units. Using computer generated and experimental fitness landscapes we show that accessibility of the global fitness maximum increases with K and can be much higher than for binary sequences. The increase in accessibility comes from the increase in the number of indirect trajectories exploited by evolution for higher K. As one of the consequences, the fraction of genotypes that are accessible increases by three orders of magnitude when the number of units K increases from 2 to 16 for landscapes of size N ∼ 106genotypes. This suggests that evolution can follow many different trajectories on such landscapes and the reconstruction of evolutionary pathways from experimental data might be an extremely difficult task.
AU - Zagórski, Marcin P
AU - Burda, Zdzisław
AU - Wacław, Bartłomiej
ID - 1167
IS - 12
JF - PLoS Computational Biology
TI - Beyond the hypercube evolutionary accessibility of fitness landscapes with realistic mutational networks
VL - 12
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 - 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 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 - CONF
AB - We consider the recent formulation of the Algorithmic Lovász Local Lemma [1], [2] for finding objects that avoid "bad features", or "flaws". It extends the Moser-Tardos resampling algorithm [3] to more general discrete spaces. At each step the method picks a flaw present in the current state and "resamples" it using a "resampling oracle" provided by the user. However, it is less flexible than the Moser-Tardos method since [1], [2] require a specific flaw selection rule, whereas [3] allows an arbitrary rule (and thus can potentially be implemented more efficiently). We formulate a new "commutativity" condition, and prove that it is sufficient for an arbitrary rule to work. It also enables an efficient parallelization under an additional assumption. We then show that existing resampling oracles for perfect matchings and permutations do satisfy this condition. Finally, we generalize the precondition in [2] (in the case of symmetric potential causality graphs). This unifies special cases that previously were treated separately.
AU - Kolmogorov, Vladimir
ID - 1193
T2 - Proceedings - Annual IEEE Symposium on Foundations of Computer Science
TI - Commutativity in the algorithmic Lovasz local lemma
VL - 2016-December
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
AB - Across the nervous system, certain population spiking patterns are observed far more frequently than others. A hypothesis about this structure is that these collective activity patterns function as population codewords–collective modes–carrying information distinct from that of any single cell. We investigate this phenomenon in recordings of ∼150 retinal ganglion cells, the retina’s output. We develop a novel statistical model that decomposes the population response into modes; it predicts the distribution of spiking activity in the ganglion cell population with high accuracy. We found that the modes represent localized features of the visual stimulus that are distinct from the features represented by single neurons. Modes form clusters of activity states that are readily discriminated from one another. When we repeated the same visual stimulus, we found that the same mode was robustly elicited. These results suggest that retinal ganglion cells’ collective signaling is endowed with a form of error-correcting code–a principle that may hold in brain areas beyond retina.
AU - Prentice, Jason
AU - Marre, Olivier
AU - Ioffe, Mark
AU - Loback, Adrianna
AU - Tkacik, Gasper
AU - Berry, Michael
ID - 1197
IS - 11
JF - PLoS Computational Biology
TI - Error-robust modes of the retinal population code
VL - 12
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
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 - CONF
AB - In this paper, we present a formal model-driven engineering approach to establishing a safety-assured implementation of Multifunction vehicle bus controller (MVBC) based on the generic reference models and requirements described in the International Electrotechnical Commission (IEC) standard IEC-61375. First, the generic models described in IEC-61375 are translated into a network of timed automata, and some safety requirements tested in IEC-61375 are formalized as timed computation tree logic (TCTL) formulas. With the help of Uppaal, we check and debug whether the timed automata satisfy the formulas or not. Within this step, several logic inconsistencies in the original standard are detected and corrected. Then, we apply the tool Times to generate C code from the verified model, which was later synthesized into a real MVBC chip. Finally, the runtime verification tool RMOR is applied to verify some safety requirements at the implementation level. We set up a real platform with worldwide mostly used MVBC D113, and verify the correctness and the scalability of the synthesized MVBC chip more comprehensively. The errors in the standard has been confirmed and the resulted MVBC has been deployed in real train communication network.
AU - Jiang, Yu
AU - Liu, Han
AU - Song, Houbing
AU - Kong, Hui
AU - Gu, Ming
AU - Sun, Jiaguang
AU - Sha, Lui
ID - 1205
TI - Safety assured formal model driven design of the multifunction vehicle bus controller
VL - 9995
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 - 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 - 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 - 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 - CONF
AB - At Crypto 2015 Fuchsbauer, Hanser and Slamanig (FHS) presented the first standard-model construction of efficient roundoptimal blind signatures that does not require complexity leveraging. It is conceptually simple and builds on the primitive of structure-preserving signatures on equivalence classes (SPS-EQ). FHS prove the unforgeability of their scheme assuming EUF-CMA security of the SPS-EQ scheme and hardness of a version of the DH inversion problem. Blindness under adversarially chosen keys is proven under an interactive variant of the DDH assumption. We propose a variant of their scheme whose blindness can be proven under a non-interactive assumption, namely a variant of the bilinear DDH assumption. We moreover prove its unforgeability assuming only unforgeability of the underlying SPS-EQ but no additional assumptions as needed for the FHS scheme.
AU - Fuchsbauer, Georg
AU - Hanser, Christian
AU - Kamath Hosdurg, Chethan
AU - Slamanig, Daniel
ID - 1225
TI - Practical round-optimal blind signatures in the standard model from weaker assumptions
VL - 9841
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 - Witness encryption (WE) was introduced by Garg et al. [GGSW13]. A WE scheme is defined for some NP language L and lets a sender encrypt messages relative to instances x. A ciphertext for x can be decrypted using w witnessing x ∈ L, but hides the message if x ∈ L. Garg et al. construct WE from multilinear maps and give another construction [GGH+13b] using indistinguishability obfuscation (iO) for circuits. Due to the reliance on such heavy tools, WE can cur- rently hardly be implemented on powerful hardware and will unlikely be realizable on constrained devices like smart cards any time soon. We construct a WE scheme where encryption is done by simply computing a Naor-Yung ciphertext (two CPA encryptions and a NIZK proof). To achieve this, our scheme has a setup phase, which outputs public parameters containing an obfuscated circuit (only required for decryption), two encryption keys and a common reference string (used for encryption). This setup need only be run once, and the parame- ters can be used for arbitrary many encryptions. Our scheme can also be turned into a functional WE scheme, where a message is encrypted w.r.t. a statement and a function f, and decryption with a witness w yields f (m, w). Our construction is inspired by the functional encryption scheme by Garg et al. and we prove (selective) security assuming iO and statistically simulation-sound NIZK. We give a construction of the latter in bilinear groups and combining it with ElGamal encryption, our ciphertexts are of size 1.3 kB at a 128-bit security level and can be computed on a smart card.
AU - Abusalah, Hamza M
AU - Fuchsbauer, Georg
AU - Pietrzak, Krzysztof Z
ID - 1229
TI - Offline witness encryption
VL - 9696
ER -
TY - CONF
AB - Concolic testing is a promising method for generating test suites for large programs. However, it suffers from the path-explosion problem and often fails to find tests that cover difficult-to-reach parts of programs. In contrast, model checkers based on counterexample-guided abstraction refinement explore programs exhaustively, while failing to scale on large programs with precision. In this paper, we present a novel method that iteratively combines concolic testing and model checking to find a test suite for a given coverage criterion. If concolic testing fails to cover some test goals, then the model checker refines its program abstraction to prove more paths infeasible, which reduces the search space for concolic testing. We have implemented our method on top of the concolictesting tool Crest and the model checker CpaChecker. We evaluated our tool on a collection of programs and a category of SvComp benchmarks. In our experiments, we observed an improvement in branch coverage compared to Crest from 48% to 63% in the best case, and from 66% to 71% on average.
AU - Daca, Przemyslaw
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
ID - 1230
TI - Abstraction-driven concolic testing
VL - 9583
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 - 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 - CONF
AB - We present a new algorithm for the statistical model checking of Markov chains with respect to unbounded temporal properties, including full linear temporal logic. The main idea is that we monitor each simulation run on the fly, in order to detect quickly if a bottom strongly connected component is entered with high probability, in which case the simulation run can be terminated early. As a result, our simulation runs are often much shorter than required by termination bounds that are computed a priori for a desired level of confidence on a large state space. In comparison to previous algorithms for statistical model checking our method is not only faster in many cases but also requires less information about the system, namely, only the minimum transition probability that occurs in the Markov chain. In addition, our method can be generalised to unbounded quantitative properties such as mean-payoff bounds.
AU - Daca, Przemyslaw
AU - Henzinger, Thomas A
AU - Kretinsky, Jan
AU - Petrov, Tatjana
ID - 1234
TI - Faster statistical model checking for unbounded temporal properties
VL - 9636
ER -
TY - CONF
AB - A constrained pseudorandom function (CPRF) F: K×X → Y for a family T of subsets of χ is a function where for any key k ∈ K and set S ∈ T one can efficiently compute a short constrained key kS, which allows to evaluate F(k, ·) on all inputs x ∈ S, while the outputs on all inputs x /∈ S look random even given kS. Abusalah et al. recently constructed the first constrained PRF for inputs of arbitrary length whose sets S are decided by Turing machines. They use their CPRF to build broadcast encryption and the first ID-based non-interactive key exchange for an unbounded number of users. Their constrained keys are obfuscated circuits and are therefore large. In this work we drastically reduce the key size and define a constrained key for a Turing machine M as a short signature on M. For this, we introduce a new signature primitive with constrained signing keys that let one only sign certain messages, while forging a signature on others is hard even when knowing the coins for key generation.
AU - Abusalah, Hamza M
AU - Fuchsbauer, Georg
ID - 1235
TI - Constrained PRFs for unbounded inputs with short keys
VL - 9696
ER -
TY - CONF
AB - A constrained pseudorandom function F: K × X → Y for a family T ⊆ 2X of subsets of X is a function where for any key k ∈ K and set S ∈ T one can efficiently compute a constrained key kS which allows to evaluate F (k, ·) on all inputs x ∈ S, while even given this key, the outputs on all inputs x ∉ S look random. At Asiacrypt’13 Boneh and Waters gave a construction which supports the most general set family so far. Its keys kc are defined for sets decided by boolean circuits C and enable evaluation of the PRF on any x ∈ X where C(x) = 1. In their construction the PRF input length and the size of the circuits C for which constrained keys can be computed must be fixed beforehand during key generation. We construct a constrained PRF that has an unbounded input length and whose constrained keys can be defined for any set recognized by a Turing machine. The only a priori bound we make is on the description size of the machines. We prove our construction secure assuming publiccoin differing-input obfuscation. As applications of our constrained PRF we build a broadcast encryption scheme where the number of potential receivers need not be fixed at setup (in particular, the length of the keys is independent of the number of parties) and the first identity-based non-interactive key exchange protocol with no bound on the number of parties that can agree on a shared key.
AU - Abusalah, Hamza M
AU - Fuchsbauer, Georg
AU - Pietrzak, Krzysztof Z
ID - 1236
TI - Constrained PRFs for unbounded inputs
VL - 9610
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 - 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 -