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 - CONF
AB - POMDPs are standard models for probabilistic planning problems, where an agent interacts with an uncertain environment. We study the problem of almost-sure reachability, where given a set of target states, the question is to decide whether there is a policy to ensure that the target set is reached with probability 1 (almost-surely). While in general the problem is EXPTIMEcomplete, in many practical cases policies with a small amount of memory suffice. Moreover, the existing solution to the problem is explicit, which first requires to construct explicitly an exponential reduction to a belief-support MDP. In this work, we first study the existence of observation-stationary strategies, which is NP-complete, and then small-memory strategies. We present a symbolic algorithm by an efficient encoding to SAT and using a SAT solver for the problem. We report experimental results demonstrating the scalability of our symbolic (SAT-based) approach. © 2016, Association for the Advancement of Artificial Intelligence (www.aaai.org). All rights reserved.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Davies, Jessica
ID - 1166
T2 - Proceedings of the Thirtieth AAAI Conference on Artificial Intelligence
TI - A symbolic SAT based algorithm for almost sure reachability with small strategies in pomdps
VL - 2016
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 - 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 - We provide general conditions for which bosonic quadratic Hamiltonians on Fock spaces can be diagonalized by Bogoliubov transformations. Our results cover the case when quantum systems have infinite degrees of freedom and the associated one-body kinetic and paring operators are unbounded. Our sufficient conditions are optimal in the sense that they become necessary when the relevant one-body operators commute.
AU - Nam, Phan
AU - Napiórkowski, Marcin M
AU - Solovej, Jan
ID - 1545
IS - 11
JF - Journal of Functional Analysis
TI - Diagonalization of bosonic quadratic Hamiltonians by Bogoliubov transformations
VL - 270
ER -
TY - JOUR
AB - Antibiotic resistance carries a fitness cost that must be overcome in order for resistance to persist over the long term. Compensatory mutations that recover the functional defects associated with resistance mutations have been argued to play a key role in overcoming the cost of resistance, but compensatory mutations are expected to be rare relative to generally beneficial mutations that increase fitness, irrespective of antibiotic resistance. Given this asymmetry, population genetics theory predicts that populations should adapt by compensatory mutations when the cost of resistance is large, whereas generally beneficial mutations should drive adaptation when the cost of resistance is small. We tested this prediction by determining the genomic mechanisms underpinning adaptation to antibiotic-free conditions in populations of the pathogenic bacterium Pseudomonas aeruginosa that carry costly antibiotic resistance mutations. Whole-genome sequencing revealed that populations founded by high-cost rifampicin-resistant mutants adapted via compensatory mutations in three genes of the RNA polymerase core enzyme, whereas populations founded by low-cost mutants adapted by generally beneficial mutations, predominantly in the quorum-sensing transcriptional regulator gene lasR. Even though the importance of compensatory evolution in maintaining resistance has been widely recognized, our study shows that the roles of general adaptation in maintaining resistance should not be underestimated and highlights the need to understand how selection at other sites in the genome influences the dynamics of resistance alleles in clinical settings.
AU - Qi, Qin
AU - Toll Riera, Macarena
AU - Heilbron, Karl
AU - Preston, Gail
AU - Maclean, R Craig
ID - 1552
IS - 1822
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa
VL - 283
ER -
TY - JOUR
AB - A modular approach to constructing cryptographic protocols leads to simple designs but often inefficient instantiations. On the other hand, ad hoc constructions may yield efficient protocols at the cost of losing conceptual simplicity. We suggest a new design paradigm, structure-preserving cryptography, that provides a way to construct modular protocols with reasonable efficiency while retaining conceptual simplicity. A cryptographic scheme over a bilinear group is called structure-preserving if its public inputs and outputs consist of elements from the bilinear groups and their consistency can be verified by evaluating pairing-product equations. As structure-preserving schemes smoothly interoperate with each other, they are useful as building blocks in modular design of cryptographic applications. This paper introduces structure-preserving commitment and signature schemes over bilinear groups with several desirable properties. The commitment schemes include homomorphic, trapdoor and length-reducing commitments to group elements, and the structure-preserving signature schemes are the first ones that yield constant-size signatures on multiple group elements. A structure-preserving signature scheme is called automorphic if the public keys lie in the message space, which cannot be achieved by compressing inputs via a cryptographic hash function, as this would destroy the mathematical structure we are trying to preserve. Automorphic signatures can be used for building certification chains underlying privacy-preserving protocols. Among a vast number of applications of structure-preserving protocols, we present an efficient round-optimal blind-signature scheme and a group signature scheme with an efficient and concurrently secure protocol for enrolling new members.
AU - Abe, Masayuki
AU - Fuchsbauer, Georg
AU - Groth, Jens
AU - Haralambiev, Kristiyan
AU - Ohkubo, Miyako
ID - 1592
IS - 2
JF - Journal of Cryptology
TI - Structure preserving signatures and commitments to group elements
VL - 29
ER -
TY - JOUR
AB - Chemokines are the main guidance cues directing leukocyte migration. Opposed to early assumptions, chemokines do not necessarily act as soluble cues but are often immobilized within tissues, e.g., dendritic cell migration toward lymphatic vessels is guided by a haptotactic gradient of the chemokine CCL21. Controlled assay systems to quantitatively study haptotaxis in vitro are still missing. In this chapter, we describe an in vitro haptotaxis assay optimized for the unique properties of dendritic cells. The chemokine CCL21 is immobilized in a bioactive state, using laser-assisted protein adsorption by photobleaching. The cells follow this immobilized CCL21 gradient in a haptotaxis chamber, which provides three dimensionally confined migration conditions.
AU - Schwarz, Jan
AU - Sixt, Michael K
ID - 1597
JF - Methods in Enzymology
TI - Quantitative analysis of dendritic cell haptotaxis
VL - 570
ER -
TY - JOUR
AB - The addition of polysialic acid to N- and/or O-linked glycans, referred to as polysialylation, is a rare posttranslational modification that is mainly known to control the developmental plasticity of the nervous system. Here we show that CCR7, the central chemokine receptor controlling immune cell trafficking to secondary lymphatic organs, carries polysialic acid. This modification is essential for the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited conformation, which is released upon interaction with polysialic acid. Thus, we describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic basis.
AU - Kiermaier, Eva
AU - Moussion, Christine
AU - Veldkamp, Christopher
AU - Gerardy Schahn, Rita
AU - De Vries, Ingrid
AU - Williams, Larry
AU - Chaffee, Gary
AU - Phillips, Andrew
AU - Freiberger, Friedrich
AU - Imre, Richard
AU - Taleski, Deni
AU - Payne, Richard
AU - Braun, Asolina
AU - Förster, Reinhold
AU - Mechtler, Karl
AU - Mühlenhoff, Martina
AU - Volkman, Brian
AU - Sixt, Michael K
ID - 1599
IS - 6269
JF - Science
TI - Polysialylation controls dendritic cell trafficking by regulating chemokine recognition
VL - 351
ER -
TY - JOUR
AB - We show that the Anderson model has a transition from localization to delocalization at exactly 2 dimensional growth rate on antitrees with normalized edge weights which are certain discrete graphs. The kinetic part has a one-dimensional structure allowing a description through transfer matrices which involve some Schur complement. For such operators we introduce the notion of having one propagating channel and extend theorems from the theory of one-dimensional Jacobi operators that relate the behavior of transfer matrices with the spectrum. These theorems are then applied to the considered model. In essence, in a certain energy region the kinetic part averages the random potentials along shells and the transfer matrices behave similar as for a one-dimensional operator with random potential of decaying variance. At d dimensional growth for d>2 this effective decay is strong enough to obtain absolutely continuous spectrum, whereas for some uniform d dimensional growth with d<2 one has pure point spectrum in this energy region. At exactly uniform 2 dimensional growth also some singular continuous spectrum appears, at least at small disorder. As a corollary we also obtain a change from singular spectrum (d≤2) to absolutely continuous spectrum (d≥3) for random operators of the type rΔdr+λ on ℤd, where r is an orthogonal radial projection, Δd the discrete adjacency operator (Laplacian) on ℤd and λ a random potential.
AU - Sadel, Christian
ID - 1608
IS - 7
JF - Annales Henri Poincare
TI - Anderson transition at 2 dimensional growth rate on antitrees and spectral theory for operators with one propagating channel
VL - 17
ER -
TY - JOUR
AB - We prove that whenever A is a 3-conservative relational structure with only binary and unary relations,then the algebra of polymorphisms of A either has no Taylor operation (i.e.,CSP(A)is NP-complete),or it generates an SD(∧) variety (i.e.,CSP(A)has bounded width).
AU - Kazda, Alexandr
ID - 1612
IS - 1
JF - Algebra Universalis
TI - CSP for binary conservative relational structures
VL - 75
ER -
TY - JOUR
AB - The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo. In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired action potentials spontaneously, with a frequency of ∼3–6 Hz, whereas GCs were silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine the underlying mechanisms, we quantitatively assessed the frequency of spontaneous excitatory synaptic input, the passive membrane properties, and the active membrane characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3 and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition. Thus, differential synaptic excitation is not responsible for differences in firing. Moreover, the three types of hippocampal neurons markedly differed in their passive properties. While GCs showed the most negative membrane potential, CA3 pyramidal neurons had the highest input resistance and the slowest membrane time constant. The three types of neurons also differed in the active membrane characteristics. GCs showed the highest action potential threshold, but displayed the largest gain of the input-output curves. In conclusion, our results reveal that differential firing of the three main types of hippocampal principal neurons in vivo is not primarily caused by differences in the characteristics of the synaptic input, but by the distinct properties of synaptic integration and input-output transformation.
AU - Kowalski, Janina
AU - Gan, Jian
AU - Jonas, Peter M
AU - Pernia-Andrade, Alejandro
ID - 1616
IS - 5
JF - Hippocampus
TI - Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats
VL - 26
ER -
TY - JOUR
AB - We study the discrepancy of jittered sampling sets: such a set P⊂ [0,1]d is generated for fixed m∈ℕ by partitioning [0,1]d into md axis aligned cubes of equal measure and placing a random point inside each of the N=md cubes. We prove that, for N sufficiently large, 1/10 d/N1/2+1/2d ≤EDN∗(P)≤ √d(log N) 1/2/N1/2+1/2d, where the upper bound with an unspecified constant Cd was proven earlier by Beck. Our proof makes crucial use of the sharp Dvoretzky-Kiefer-Wolfowitz inequality and a suitably taylored Bernstein inequality; we have reasons to believe that the upper bound has the sharp scaling in N. Additional heuristics suggest that jittered sampling should be able to improve known bounds on the inverse of the star-discrepancy in the regime N≳dd. We also prove a partition principle showing that every partition of [0,1]d combined with a jittered sampling construction gives rise to a set whose expected squared L2-discrepancy is smaller than that of purely random points.
AU - Pausinger, Florian
AU - Steinerberger, Stefan
ID - 1617
JF - Journal of Complexity
TI - On the discrepancy of jittered sampling
VL - 33
ER -
TY - JOUR
AB - We consider the Bardeen–Cooper–Schrieffer free energy functional for particles interacting via a two-body potential on a microscopic scale and in the presence of weak external fields varying on a macroscopic scale. We study the influence of the external fields on the critical temperature. We show that in the limit where the ratio between the microscopic and macroscopic scale tends to zero, the next to leading order of the critical temperature is determined by the lowest eigenvalue of the linearization of the Ginzburg–Landau equation.
AU - Frank, Rupert
AU - Hainzl, Christian
AU - Seiringer, Robert
AU - Solovej, Jan
ID - 1620
IS - 1
JF - Communications in Mathematical Physics
TI - The external field dependence of the BCS critical temperature
VL - 342
ER -
TY - JOUR
AB - We prove analogues of the Lieb–Thirring and Hardy–Lieb–Thirring inequalities for many-body quantum systems with fractional kinetic operators and homogeneous interaction potentials, where no anti-symmetry on the wave functions is assumed. These many-body inequalities imply interesting one-body interpolation inequalities, and we show that the corresponding one- and many-body inequalities are actually equivalent in certain cases.
AU - Lundholm, Douglas
AU - Nam, Phan
AU - Portmann, Fabian
ID - 1622
IS - 3
JF - Archive for Rational Mechanics and Analysis
TI - Fractional Hardy–Lieb–Thirring and related Inequalities for interacting systems
VL - 219
ER -
TY - JOUR
AB - Ancestral processes are fundamental to modern population genetics and spatial structure has been the subject of intense interest for many years. Despite this interest, almost nothing is known about the distribution of the locations of pedigree or genetic ancestors. Using both spatially continuous and stepping-stone models, we show that the distribution of pedigree ancestors approaches a travelling wave, for which we develop two alternative approximations. The speed and width of the wave are sensitive to the local details of the model. After a short time, genetic ancestors spread far more slowly than pedigree ancestors, ultimately diffusing out with radius ## rather than spreading at constant speed. In contrast to the wave of pedigree ancestors, the spread of genetic ancestry is insensitive to the local details of the models.
AU - Kelleher, Jerome
AU - Etheridge, Alison
AU - Véber, Amandine
AU - Barton, Nicholas H
ID - 1631
JF - Theoretical Population Biology
TI - Spread of pedigree versus genetic ancestry in spatially distributed populations
VL - 108
ER -
TY - JOUR
AB - The plant hormone auxin (indole-3-acetic acid) is a major regulator of plant growth and development including embryo and root patterning, lateral organ formation and growth responses to environmental stimuli. Auxin is directionally transported from cell to cell by the action of specific auxin influx [AUXIN-RESISTANT1 (AUX1)] and efflux [PIN-FORMED (PIN)] transport regulators, whose polar, subcellular localizations are aligned with the direction of the auxin flow. Auxin itself regulates its own transport by modulation of the expression and subcellular localization of the auxin transporters. Increased auxin levels promote the transcription of PIN2 and AUX1 genes as well as stabilize PIN proteins at the plasma membrane, whereas prolonged auxin exposure increases the turnover of PIN proteins and their degradation in the vacuole. In this study, we applied a forward genetic approach, to identify molecular components playing a role in the auxin-mediated degradation. We generated EMS-mutagenized Arabidopsis PIN2::PIN2:GFP, AUX1::AUX1:YFP eir1aux1 populations and designed a screen for mutants with persistently strong fluorescent signals of the tagged PIN2 and AUX1 after prolonged treatment with the synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D). This approach yielded novel auxin degradation mutants defective in trafficking and degradation of PIN2 and AUX1 proteins and established a role for auxin-mediated degradation in plant development.
AU - Zemová, Radka
AU - Zwiewka, Marta
AU - Bielach, Agnieszka
AU - Robert, Hélène
AU - Friml, Jirí
ID - 1641
IS - 2
JF - Journal of Plant Growth Regulation
TI - A forward genetic screen for new regulators of auxin mediated degradation of auxin transport proteins in Arabidopsis thaliana
VL - 35
ER -
TY - CONF
AB - A somewhere statistically binding (SSB) hash, introduced by Hubáček and Wichs (ITCS ’15), can be used to hash a long string x to a short digest y = H hk (x) using a public hashing-key hk. Furthermore, there is a way to set up the hash key hk to make it statistically binding on some arbitrary hidden position i, meaning that: (1) the digest y completely determines the i’th bit (or symbol) of x so that all pre-images of y have the same value in the i’th position, (2) it is computationally infeasible to distinguish the position i on which hk is statistically binding from any other position i’. Lastly, the hash should have a local opening property analogous to Merkle-Tree hashing, meaning that given x and y = H hk (x) it should be possible to create a short proof π that certifies the value of the i’th bit (or symbol) of x without having to provide the entire input x. A similar primitive called a positional accumulator, introduced by Koppula, Lewko and Waters (STOC ’15) further supports dynamic updates of the hashed value. These tools, which are interesting in their own right, also serve as one of the main technical components in several recent works building advanced applications from indistinguishability obfuscation (iO).
The prior constructions of SSB hashing and positional accumulators required fully homomorphic encryption (FHE) and iO respectively. In this work, we give new constructions of these tools based on well studied number-theoretic assumptions such as DDH, Phi-Hiding and DCR, as well as a general construction from lossy/injective functions.
AU - Okamoto, Tatsuaki
AU - Pietrzak, Krzysztof Z
AU - Waters, Brent
AU - Wichs, Daniel
ID - 1653
TI - New realizations of somewhere statistically binding hashing and positional accumulators
VL - 9452
ER -
TY - JOUR
AB - We introduce a modification of the classic notion of intrinsic volume using persistence moments of height functions. Evaluating the modified first intrinsic volume on digital approximations of a compact body with smoothly embedded boundary in Rn, we prove convergence to the first intrinsic volume of the body as the resolution of the approximation improves. We have weaker results for the other modified intrinsic volumes, proving they converge to the corresponding intrinsic volumes of the n-dimensional unit ball.
AU - Edelsbrunner, Herbert
AU - Pausinger, Florian
ID - 1662
JF - Advances in Mathematics
TI - Approximation and convergence of the intrinsic volume
VL - 287
ER -
TY - JOUR
AB - Hybrid systems represent an important and powerful formalism for modeling real-world applications such as embedded systems. A verification tool like SpaceEx is based on the exploration of a symbolic search space (the region space). As a verification tool, it is typically optimized towards proving the absence of errors. In some settings, e.g., when the verification tool is employed in a feedback-directed design cycle, one would like to have the option to call a version that is optimized towards finding an error trajectory in the region space. A recent approach in this direction is based on guided search. Guided search relies on a cost function that indicates which states are promising to be explored, and preferably explores more promising states first. In this paper, we propose an abstraction-based cost function based on coarse-grained space abstractions for guiding the reachability analysis. For this purpose, a suitable abstraction technique that exploits the flexible granularity of modern reachability analysis algorithms is introduced. The new cost function is an effective extension of pattern database approaches that have been successfully applied in other areas. The approach has been implemented in the SpaceEx model checker. The evaluation shows its practical potential.
AU - Bogomolov, Sergiy
AU - Donzé, Alexandre
AU - Frehse, Goran
AU - Grosu, Radu
AU - Johnson, Taylor
AU - Ladan, Hamed
AU - Podelski, Andreas
AU - Wehrle, Martin
ID - 1705
IS - 4
JF - International Journal on Software Tools for Technology Transfer
TI - Guided search for hybrid systems based on coarse-grained space abstractions
VL - 18
ER -
TY - CONF
AB - Volunteer supporters play an important role in modern crisis and disaster management. In the times of mobile Internet devices, help from thousands of volunteers can be requested within a short time span, thus relieving professional helpers from minor chores or geographically spread-out tasks. However, the simultaneous availability of many volunteers also poses new problems. In particular, the volunteer efforts must be well coordinated, or otherwise situations might emerge in which too many idle volunteers at one location become more of a burden than a relief to the professionals.
In this work, we study the task of optimally assigning volunteers to selected locations, e.g. in order to perform regular measurements, to report on damage, or to distribute information or resources to the population in a crisis situation. We formulate the assignment tasks as an optimization problem and propose an effective and efficient solution procedure. Experiments on real data of the Team Österreich, consisting of over 36,000 Austrian volunteers, show the effectiveness and efficiency of our approach.
AU - Pielorz, Jasmin
AU - Lampert, Christoph
ID - 1707
TI - Optimal geospatial allocation of volunteers for crisis management
ER -
TY - JOUR
AB - We consider Conditional random fields (CRFs) with pattern-based potentials defined on a chain. In this model the energy of a string (labeling) (Formula presented.) is the sum of terms over intervals [i, j] where each term is non-zero only if the substring (Formula presented.) equals a prespecified pattern w. Such CRFs can be naturally applied to many sequence tagging problems. We present efficient algorithms for the three standard inference tasks in a CRF, namely computing (i) the partition function, (ii) marginals, and (iii) computing the MAP. Their complexities are respectively (Formula presented.), (Formula presented.) and (Formula presented.) where L is the combined length of input patterns, (Formula presented.) is the maximum length of a pattern, and D is the input alphabet. This improves on the previous algorithms of Ye et al. (NIPS, 2009) whose complexities are respectively (Formula presented.), (Formula presented.) and (Formula presented.), where (Formula presented.) is the number of input patterns. In addition, we give an efficient algorithm for sampling, and revisit the case of MAP with non-positive weights.
AU - Kolmogorov, Vladimir
AU - Takhanov, Rustem
ID - 1794
IS - 1
JF - Algorithmica
TI - Inference algorithms for pattern-based CRFs on sequence data
VL - 76
ER -
TY - JOUR
AB - Relational models for contingency tables are generalizations of log-linear models, allowing effects associated with arbitrary subsets of cells in the table, and not necessarily containing the overall effect, that is, a common parameter in every cell. Similarly to log-linear models, relational models can be extended to non-negative distributions, but the extension requires more complex methods. An extended relational model is defined as an algebraic variety, and it turns out to be the closure of the original model with respect to the Bregman divergence. In the extended relational model, the MLE of the cell parameters always exists and is unique, but some of its properties may be different from those of the MLE under log-linear models. The MLE can be computed using a generalized iterative scaling procedure based on Bregman projections.
AU - Klimova, Anna
AU - Rudas, Tamás
ID - 1833
JF - Journal of Multivariate Analysis
TI - On the closure of relational models
VL - 143
ER -
TY - JOUR
AB - We consider random matrices of the form H=W+λV, λ∈ℝ+, where W is a real symmetric or complex Hermitian Wigner matrix of size N and V is a real bounded diagonal random matrix of size N with i.i.d.\ entries that are independent of W. We assume subexponential decay for the matrix entries of W and we choose λ∼1, so that the eigenvalues of W and λV are typically of the same order. Further, we assume that the density of the entries of V is supported on a single interval and is convex near the edges of its support. In this paper we prove that there is λ+∈ℝ+ such that the largest eigenvalues of H are in the limit of large N determined by the order statistics of V for λ>λ+. In particular, the largest eigenvalue of H has a Weibull distribution in the limit N→∞ if λ>λ+. Moreover, for N sufficiently large, we show that the eigenvectors associated to the largest eigenvalues are partially localized for λ>λ+, while they are completely delocalized for λ<λ+. Similar results hold for the lowest eigenvalues.
AU - Lee, Jioon
AU - Schnelli, Kevin
ID - 1881
IS - 1-2
JF - Probability Theory and Related Fields
TI - Extremal eigenvalues and eigenvectors of deformed Wigner matrices
VL - 164
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 - 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
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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Restriction-modification (RM) systems represent a minimal and ubiquitous biological system of self/non-self discrimination in prokaryotes [1], which protects hosts from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase (M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by methylating short specific DNA sequences called restriction sites, whereas R recognizes unmethylated restriction sites as non-self and introduces a double-stranded DNA break [3]. Restriction sites are significantly underrepresented in prokaryotic genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore, RM systems can promote DNA recombination [9] and contribute to genetic variation in microbial populations, thus facilitating adaptive evolution [10]. However, cleavage of self-DNA by RM systems as elements shaping prokaryotic genomes has not been directly detected, and its cause, frequency, and outcome are unknown. We quantify self-restriction caused by two RM systems of Escherichia coli and find that, in agreement with levels of restriction site avoidance, EcoRI, but not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic process, which temporarily induces the SOS response, and is followed by DNA repair, maintaining cell viability. We find that RM systems with higher restriction efficiency against bacteriophage infections exhibit a higher rate of self-restriction, and that this rate can be further increased by stochastic imbalance between R and M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic genomes.
AU - Pleska, Maros
AU - Qian, Long
AU - Okura, Reiko
AU - Bergmiller, Tobias
AU - Wakamoto, Yuichi
AU - Kussell, Edo
AU - Guet, Calin C
ID - 1243
IS - 3
JF - Current Biology
TI - Bacterial autoimmunity due to a restriction-modification system
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 - 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 - 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 - 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 - 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 - In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles. We found that certain changes in the regulation of the carbohydrate metabolism can affect aging. A mutation in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative lifespan; csrA mutants stop dividing once their pole exceeds an age of about five divisions. These old-pole cells accumulate glycogen at their old cell poles; after their last division, they do not contain a chromosome, presumably because of spatial exclusion by the glycogen aggregates. The new-pole daughters produced by these aging mothers are born young; they only express the deleterious phenotype once their pole is old. These results demonstrate how manipulations of nutrient allocation can lead to the exclusion of the chromosome and limit replicative lifespan in E. coli, and illustrate how mutations can have phenotypic effects that are specific for cells with old poles. This raises the question how bacteria can avoid the accumulation of such mutations in their genomes over evolutionary times, and how they can achieve the long replicative lifespans that have recently been reported.
AU - Boehm, Alex
AU - Arnoldini, Markus
AU - Bergmiller, Tobias
AU - Röösli, Thomas
AU - Bigosch, Colette
AU - Ackermann, Martin
ID - 1250
IS - 4
JF - PLoS Genetics
TI - Genetic manipulation of glycogen allocation affects replicative lifespan in E coli
VL - 12
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 - This article provides an introduction to the role of microRNAs in the nervous system and outlines their potential involvement in the pathophysiology of schizophrenia, which is hypothesized to arise owing to environmental factors and genetic predisposition.
AU - Tsai, Lihuei
AU - Siegert, Sandra
ID - 1253
IS - 4
JF - JAMA Psychiatry
TI - How MicroRNAs Are involved in splitting the mind
VL - 73
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 - Linking classical microwave electrical circuits to the optical telecommunication band is at the core of modern communication. Future quantum information networks will require coherent microwave-to-optical conversion to link electronic quantum processors and memories via low-loss optical telecommunication networks. Efficient conversion can be achieved with electro-optical modulators operating at the single microwave photon level. In the standard electro-optic modulation scheme, this is impossible because both up- and down-converted sidebands are necessarily present. Here, we demonstrate true single-sideband up- or down-conversion in a triply resonant whispering gallery mode resonator by explicitly addressing modes with asymmetric free spectral range. Compared to previous experiments, we show a 3 orders of magnitude improvement of the electro-optical conversion efficiency, reaching 0.1% photon number conversion for a 10 GHz microwave tone at 0.42 mW of optical pump power. The presented scheme is fully compatible with existing superconducting 3D circuit quantum electrodynamics technology and can be used for nonclassical state conversion and communication. Our conversion bandwidth is larger than 1 MHz and is not fundamentally limited.
AU - Rueda, Alfredo
AU - Sedlmeir, Florian
AU - Collodo, Michele
AU - Vogl, Ulrich
AU - Stiller, Birgit
AU - Schunk, Gerhard
AU - Strekalov, Dmitry
AU - Marquardt, Christoph
AU - Fink, Johannes M
AU - Painter, Oskar
AU - Leuchs, Gerd
AU - Schwefel, Harald
ID - 1263
IS - 6
JF - Optica
TI - Efficient microwave to optical photon conversion: An electro-optical realization
VL - 3
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 - 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 -