TY - JOUR AB - We study multiple keyword sponsored search auctions with budgets. Each keyword has multiple ad slots with a click-through rate. The bidders have additive valuations, which are linear in the click-through rates, and budgets, which are restricting their overall payments. Additionally, the number of slots per keyword assigned to a bidder is bounded. We show the following results: (1) We give the first mechanism for multiple keywords, where click-through rates differ among slots. Our mechanism is incentive compatible in expectation, individually rational in expectation, and Pareto optimal. (2) We study the combinatorial setting, where each bidder is only interested in a subset of the keywords. We give an incentive compatible, individually rational, Pareto-optimal, and deterministic mechanism for identical click-through rates. (3) We give an impossibility result for incentive compatible, individually rational, Pareto-optimal, and deterministic mechanisms for bidders with diminishing marginal valuations. AU - Colini-Baldeschi, Riccardo AU - Leonardi, Stefano AU - Henzinger, Monika H AU - Starnberger, Martin ID - 11668 IS - 1 JF - ACM Transactions on Economics and Computation KW - Algorithms KW - Economics KW - Clinching ascending auction KW - auctions with budgets KW - Sponsored search auctions SN - 2167-8375 TI - On multiple keyword sponsored search auctions with budgets VL - 4 ER - TY - JOUR AB - We study individual rational, Pareto-optimal, and incentive compatible mechanisms for auctions with heterogeneous items and budget limits. We consider settings with multiunit demand and additive valuations. For single-dimensional valuations we prove a positive result for randomized mechanisms, and a negative result for deterministic mechanisms. While the positive result allows for private budgets, the negative result is for public budgets. For multidimensional valuations and public budgets we prove an impossibility result that applies to deterministic and randomized mechanisms. Taken together this shows the power of randomization in certain settings with heterogeneous items, but it also shows its limitations. AU - Dütting, Paul AU - Henzinger, Monika H AU - Starnberger, Martin ID - 11669 IS - 1 JF - ACM Transactions on Economics and Computation KW - Algorithmic game theory KW - auction theory KW - Clinching auction KW - Pareto optimality KW - Budget limits SN - 2167-8375 TI - Auctions for heterogeneous items and budget limits VL - 4 ER - TY - JOUR AB - Auctions are widely used on the Web. Applications range from sponsored search to platforms such as eBay. In these and in many other applications the auctions in use are single-/multi-item auctions with unit demand. The main drawback of standard mechanisms for this type of auctions, such as VCG and GSP, is the limited expressiveness that they offer to the bidders. The General Auction Mechanism (GAM) of Aggarwal et al. [2009] takes a first step toward addressing the problem of limited expressiveness by computing a bidder optimal, envy-free outcome for linear utility functions with identical slopes and a single discontinuity per bidder-item pair. We show that in many practical situations this does not suffice to adequately model the preferences of the bidders, and we overcome this problem by presenting the first mechanism for piecewise linear utility functions with nonidentical slopes and multiple discontinuities. Our mechanism runs in polynomial time. Like GAM it is incentive compatible for inputs that fulfill a certain nondegeneracy assumption, but our requirement is more general than the requirement of GAM. For discontinuous utility functions that are nondegenerate as well as for continuous utility functions the outcome of our mechanism is a competitive equilibrium. We also show how our mechanism can be used to compute approximately bidder optimal, envy-free outcomes for a general class of continuous utility functions via piecewise linear approximation. Finally, we prove hardness results for even more expressive settings. AU - Dütting, Paul AU - Henzinger, Monika H AU - Weber, Ingmar ID - 11670 IS - 1 JF - ACM Transactions on Economics and Computation KW - Computational Mathematics KW - Marketing KW - Economics and Econometrics KW - Statistics and Probability KW - Computer Science (miscellaneous) SN - 2167-8375 TI - An expressive mechanism for auctions on the web VL - 4 ER - TY - CONF AB - Combinatorial auctions (CA) are a well-studied area in algorithmic mechanism design. However, contrary to the standard model, empirical studies suggest that a bidder’s valuation often does not depend solely on the goods assigned to him. For instance, in adwords auctions an advertiser might not want his ads to be displayed next to his competitors’ ads. In this paper, we propose and analyze several natural graph-theoretic models that incorporate such negative externalities, in which bidders form a directed conflict graph with maximum out-degree Δ. We design algorithms and truthful mechanisms for social welfare maximization that attain approximation ratios depending on Δ. For CA, our results are twofold: (1) A lottery that eliminates conflicts by discarding bidders/items independent of the bids. It allows to apply any truthful 𝛼-approximation mechanism for conflict-free valuations and yields an 𝒪(𝛼Δ)-approximation mechanism. (2) For fractionally sub-additive valuations, we design a rounding algorithm via a novel combination of a semi-definite program and a linear program, resulting in a cone program; the approximation ratio is 𝒪((ΔloglogΔ)/logΔ). The ratios are almost optimal given existing hardness results. For adwords auctions, we present several algorithms for the most relevant scenario when the number of items is small. In particular, we design a truthful mechanism with approximation ratio 𝑜(Δ) when the number of items is only logarithmic in the number of bidders. AU - Cheung, Yun Kuen AU - Henzinger, Monika H AU - Hoefer, Martin AU - Starnberger, Martin ID - 11774 SN - 0302-9743 T2 - 11th International Conference on Web and Internet Economics TI - Combinatorial auctions with conflict-based externalities VL - 9470 ER - TY - CONF AB - Ad exchanges are an emerging platform for trading advertisement slots on the web with billions of dollars revenue per year. Every time a user visits a web page, the publisher of that web page can ask an ad exchange to auction off the ad slots on this page to determine which advertisements are shown at which price. Due to the high volume of traffic, ad networks typically act as mediators for individual advertisers at ad exchanges. If multiple advertisers in an ad network are interested in the ad slots of the same auction, the ad network might use a “local” auction to resell the obtained ad slots among its advertisers. In this work we want to deepen the theoretical understanding of these new markets by analyzing them from the viewpoint of combinatorial auctions. Prior work studied mostly single-item auctions, while we allow the advertisers to express richer preferences over multiple items. We develop a game-theoretic model for the entanglement of the central auction at the ad exchange with the local auctions at the ad networks. We consider the incentives of all three involved parties and suggest a three-party competitive equilibrium, an extension of the Walrasian equilibrium that ensures envy-freeness for all participants. We show the existence of a three-party competitive equilibrium and a polynomial-time algorithm to find one for gross-substitute bidder valuations. AU - Ben-Zwi, Oren AU - Henzinger, Monika H AU - Loitzenbauer, Veronika ID - 11773 SN - 0302-9743 T2 - 11th International Conference on Web and Internet Economics TI - Ad exchange: Envy-free auctions with mediators VL - 9470 ER - TY - CONF AB - Recently we presented the first algorithm for maintaining the set of nodes reachable from a source node in a directed graph that is modified by edge deletions with 𝑜(𝑚𝑛) total update time, where 𝑚 is the number of edges and 𝑛 is the number of nodes in the graph [Henzinger et al. STOC 2014]. The algorithm is a combination of several different algorithms, each for a different 𝑚 vs. 𝑛 trade-off. For the case of 𝑚=Θ(𝑛1.5) the running time is 𝑂(𝑛2.47), just barely below 𝑚𝑛=Θ(𝑛2.5). In this paper we simplify the previous algorithm using new algorithmic ideas and achieve an improved running time of 𝑂̃ (min(𝑚7/6𝑛2/3,𝑚3/4𝑛5/4+𝑜(1),𝑚2/3𝑛4/3+𝑜(1)+𝑚3/7𝑛12/7+𝑜(1))). This gives, e.g., 𝑂(𝑛2.36) for the notorious case 𝑚=Θ(𝑛1.5). We obtain the same upper bounds for the problem of maintaining the strongly connected components of a directed graph undergoing edge deletions. Our algorithms are correct with high probabililty against an oblivious adversary. AU - Henzinger, Monika H AU - Krinninger, Sebastian AU - Nanongkai, Danupon ID - 11785 SN - 0302-9743 T2 - 42nd International Colloquium on Automata, Languages and Programming TI - Improved algorithms for decremental single-source reachability on directed graphs VL - 9134 ER - TY - CONF AB - We present faster algorithms for computing the 2-edge and 2-vertex strongly connected components of a directed graph. While in undirected graphs the 2-edge and 2-vertex connected components can be found in linear time, in directed graphs with m edges and n vertices only rather simple O(m n)-time algorithms were known. We use a hierarchical sparsification technique to obtain algorithms that run in time 𝑂(𝑛2). For 2-edge strongly connected components our algorithm gives the first running time improvement in 20 years. Additionally we present an 𝑂(𝑚2/log𝑛)-time algorithm for 2-edge strongly connected components, and thus improve over the O(m n) running time also when 𝑚=𝑂(𝑛). Our approach extends to k-edge and k-vertex strongly connected components for any constant k with a running time of 𝑂(𝑛2log𝑛) for k-edge-connectivity and 𝑂(𝑛3) for k-vertex-connectivity. AU - Henzinger, Monika H AU - Krinninger, Sebastian AU - Loitzenbauer, Veronika ID - 11787 SN - 0302-9743 T2 - 2nd International Colloquium on Automata, Languages and Programming TI - Finding 2-edge and 2-vertex strongly connected components in quadratic time VL - 9134 ER - TY - CONF AB - Ad exchanges are becoming an increasingly popular way to sell advertisement slots on the internet. An ad exchange is basically a spot market for ad impressions. A publisher who has already signed contracts reserving advertisement impressions on his pages can choose between assigning a new ad impression for a new page view to a contracted advertiser or to sell it at an ad exchange. This leads to an online revenue maximization problem for the publisher. Given a new impression to sell decide whether (a) to assign it to a contracted advertiser and if so to which one or (b) to sell it at the ad exchange and if so at which reserve price. We make no assumptions about the distribution of the advertiser valuations that participate in the ad exchange and show that there exists a simple primal-dual based online algorithm, whose lower bound for the revenue converges to 𝑅𝐴𝐷𝑋+𝑅𝐴(1−1/𝑒), where 𝑅𝐴𝐷𝑋 is the revenue that the optimum algorithm achieves from the ad exchange and 𝑅𝐴 is the revenue that the optimum algorithm achieves from the contracted advertisers. AU - Dvořák, Wolfgang AU - Henzinger, Monika H ID - 11788 SN - 0302-9743 T2 - 12th International Workshop of Approximation and Online Algorithms TI - Online ad assignment with an ad exchange VL - 8952 ER - TY - CONF AB - In this paper, we develop a dynamic version of the primal-dual method for optimization problems, and apply it to obtain the following results. (1) For the dynamic set-cover problem, we maintain an 𝑂(𝑓2)-approximately optimal solution in 𝑂(𝑓⋅log(𝑚+𝑛)) amortized update time, where 𝑓 is the maximum “frequency” of an element, 𝑛 is the number of sets, and 𝑚 is the maximum number of elements in the universe at any point in time. (2) For the dynamic 𝑏-matching problem, we maintain an 𝑂(1)-approximately optimal solution in 𝑂(log3𝑛) amortized update time, where 𝑛 is the number of nodes in the graph. AU - Bhattacharya, Sayan AU - Henzinger, Monika H AU - Italiano, Giuseppe F. ID - 11786 SN - 0302-9743 T2 - 42nd International Colloquium on Automata, Languages and Programming TI - Design of dynamic algorithms via primal-dual method VL - 9134 ER - TY - JOUR AB - Phylogenetic diversity (PD) is a measure of biodiversity based on the evolutionary history of species. Here, we discuss several optimization problems related to the use of PD, and the more general measure split diversity (SD), in conservation prioritization. Depending on the conservation goal and the information available about species, one can construct optimization routines that incorporate various conservation constraints. We demonstrate how this information can be used to select sets of species for conservation action. Specifically, we discuss the use of species' geographic distributions, the choice of candidates under economic pressure, and the use of predator–prey interactions between the species in a community to define viability constraints. Despite such optimization problems falling into the area of NP hard problems, it is possible to solve them in a reasonable amount of time using integer programming. We apply integer linear programming to a variety of models for conservation prioritization that incorporate the SD measure. We exemplarily show the results for two data sets: the Cape region of South Africa and a Caribbean coral reef community. Finally, we provide user-friendly software at http://www.cibiv.at/software/pda. AU - Chernomor, Olga AU - Minh, Bui Quang AU - Forest, Félix AU - Klaere, Steffen AU - Ingram, Travis AU - Henzinger, Monika H AU - von Haeseler, Arndt ID - 11845 IS - 1 JF - Methods in Ecology and Evolution TI - Split diversity in constrained conservation prioritization using integer linear programming VL - 6 ER - TY - CONF AB - Consider the following Online Boolean Matrix-Vector Multiplication problem: We are given an n x n matrix M and will receive n column-vectors of size n, denoted by v1, ..., vn, one by one. After seeing each vector vi, we have to output the product Mvi before we can see the next vector. A naive algorithm can solve this problem using O(n3) time in total, and its running time can be slightly improved to O(n3/log2 n) [Williams SODA'07]. We show that a conjecture that there is no truly subcubic (O(n3-ε)) time algorithm for this problem can be used to exhibit the underlying polynomial time hardness shared by many dynamic problems. For a number of problems, such as subgraph connectivity, Pagh's problem, d-failure connectivity, decremental single-source shortest paths, and decremental transitive closure, this conjecture implies tight hardness results. Thus, proving or disproving this conjecture will be very interesting as it will either imply several tight unconditional lower bounds or break through a common barrier that blocks progress with these problems. This conjecture might also be considered as strong evidence against any further improvement for these problems since refuting it will imply a major breakthrough for combinatorial Boolean matrix multiplication and other long-standing problems if the term "combinatorial algorithms" is interpreted as "Strassen-like algorithms" [Ballard et al. SPAA'11]. The conjecture also leads to hardness results for problems that were previously based on diverse problems and conjectures -- such as 3SUM, combinatorial Boolean matrix multiplication, triangle detection, and multiphase -- thus providing a uniform way to prove polynomial hardness results for dynamic algorithms; some of the new proofs are also simpler or even become trivial. The conjecture also leads to stronger and new, non-trivial, hardness results, e.g., for the fully-dynamic densest subgraph and diameter problems. AU - Henzinger, Monika H AU - Krinninger, Sebastian AU - Nanongkai, Danupon AU - Saranurak, Thatchaphol ID - 11868 SN - 0737.8017 T2 - 47th Annual ACM Symposium on Theory of Computing TI - Unifying and strengthening hardness for dynamic problems via the online matrix-vector multiplication conjecture ER - TY - CONF AB - While in many graph mining applications it is crucial to handle a stream of updates efficiently in terms of both time and space, not much was known about achieving such type of algorithm. In this paper we study this issue for a problem which lies at the core of many graph mining applications called densest subgraph problem. We develop an algorithm that achieves time- and space-efficiency for this problem simultaneously. It is one of the first of its kind for graph problems to the best of our knowledge. Given an input graph, the densest subgraph is the subgraph that maximizes the ratio between the number of edges and the number of nodes. For any ε>0, our algorithm can, with high probability, maintain a (4+ε)-approximate solution under edge insertions and deletions using ~O(n) space and ~O(1) amortized time per update; here, $n$ is the number of nodes in the graph and ~O hides the O(polylog_{1+ε} n) term. The approximation ratio can be improved to (2+ε) with more time. It can be extended to a (2+ε)-approximation sublinear-time algorithm and a distributed-streaming algorithm. Our algorithm is the first streaming algorithm that can maintain the densest subgraph in one pass. Prior to this, no algorithm could do so even in the special case of an incremental stream and even when there is no time restriction. The previously best algorithm in this setting required O(log n) passes [BahmaniKV12]. The space required by our algorithm is tight up to a polylogarithmic factor. AU - Bhattacharya, Sayan AU - Henzinger, Monika H AU - Nanongkai, Danupon AU - Tsourakakis, Charalampos ID - 11869 SN - 0737-8017 T2 - 47th Annual ACM Symposium on Theory of Computing TI - Space- and time-efficient algorithm for maintaining dense subgraphs on one-pass dynamic streams ER - TY - CONF AB - Online social networks allow the collection of large amounts of data about the influence between users connected by a friendship-like relationship. When distributing items among agents forming a social network, this information allows us to exploit network externalities that each agent receives from his neighbors that get the same item. In this paper we consider Friends-of-Friends (2-hop) network externalities, i.e., externalities that not only depend on the neighbors that get the same item but also on neighbors of neighbors. For these externalities we study a setting where multiple different items are assigned to unit-demand agents. Specifically, we study the problem of welfare maximization under different types of externality functions. Let n be the number of agents and m be the number of items. Our contributions are the following: (1) We show that welfare maximization is APX-hard; we show that even for step functions with 2-hop (and also with 1-hop) externalities it is NP-hard to approximate social welfare better than (1-1/e). (2) On the positive side we present (i) an O(sqrt n)-approximation algorithm for general concave externality functions, (ii) an O(\log m)-approximation algorithm for linear externality functions, and (iii) an (1-1/e)\frac{1}{6}-approximation algorithm for 2-hop step function externalities. We also improve the result from [6] for 1-hop step function externalities by giving a (1-1/e)/2-approximation algorithm. AU - Bhattacharya, Sayan AU - Dvorák, Wolfgang AU - Henzinger, Monika H AU - Starnberger, Martin ID - 11837 SN - 1868-8969 T2 - 32nd International Symposium on Theoretical Aspects of Computer Science TI - Welfare maximization with friends-of-friends network externalities VL - 30 ER - TY - JOUR AB - We consider auctions of indivisible items to unit-demand bidders with budgets. This setting was suggested as an expressive model for single sponsored search auctions. Prior work presented mechanisms that compute bidder-optimal outcomes and are truthful for a restricted set of inputs, i.e., inputs in so-called general position. This condition is easily violated. We provide the first mechanism that is truthful in expectation for all inputs and achieves for each bidder no worse utility than the bidder-optimal outcome. Additionally we give a complete characterization for which inputs mechanisms that compute bidder-optimal outcomes are truthful. AU - Henzinger, Monika H AU - Loitzenbauer, Veronika ID - 11901 JF - Theoretical Computer Science SN - 0304-3975 TI - Truthful unit-demand auctions with budgets revisited VL - 573 ER - TY - JOUR AB - One of the rare alternative reagents for the reduction of carbon–carbon double bonds is diimide (HNNH), which can be generated in situ from hydrazine hydrate (N2H4⋅H2O) and O2. Although this selective method is extremely clean and powerful, it is rarely used, as the rate-determining oxidation of hydrazine in the absence of a catalyst is relatively slow using conventional batch protocols. A continuous high-temperature/high-pressure methodology dramatically enhances the initial oxidation step, at the same time allowing for a safe and scalable processing of the hazardous reaction mixture. Simple alkenes can be selectively reduced within 10–20 min at 100–120 °C and 20 bar O2 pressure. The development of a multi-injection reactor platform for the periodic addition of N2H4⋅H2O enables the reduction of less reactive olefins even at lower reaction temperatures. This concept was utilized for the highly selective reduction of artemisinic acid to dihydroartemisinic acid, the precursor molecule for the semisynthesis of the antimalarial drug artemisinin. The industrially relevant reduction was achieved by using four consecutive liquid feeds (of N2H4⋅H2O) and residence time units resulting in a highly selective reduction within approximately 40 min at 60 °C and 20 bar O2 pressure, providing dihydroartemisinic acid in ≥93 % yield and ≥95 % selectivity. AU - Pieber, Bartholomäus AU - Glasnov, Toma AU - Kappe, C. Oliver ID - 11962 IS - 11 JF - Chemistry - A European Journal SN - 0947-6539 TI - Continuous flow reduction of artemisinic acid utilizing multi-injection strategies-closing the gap towards a fully continuous synthesis of antimalarial drugs VL - 21 ER - TY - JOUR AB - The development of a continuous flow multistep strategy for the synthesis of linear peptoids and their subsequent macrocyclization via Click chemistry is described. The central transformation of this process is an Ugi four-component reaction generating the peptidomimetic core structure. In order to avoid exposure to the often toxic and malodorous isocyanide building blocks, the continuous approach was telescoped by the dehydration of the corresponding formamide. In a concurrent operation, the highly energetic azide moiety required for the subsequent intramolecular copper-catalyzed azide–alkyne cycloaddition (Click reaction) was installed by nucleophilic substitution from a bromide precursor. All steps yielding to the linear core structures can be conveniently coupled without the need for purification steps resulting in a single process generating the desired peptidomimetics in good to excellent yields within a 25 min reaction time. The following macrocyclization was realized in a coil reactor made of copper without any additional additive. A careful process intensification study demonstrated that this transformation occurs quantitatively within 25 min at 140 °C. Depending on the resulting ring strain, either a dimeric or a monomeric form of the cyclic product was obtained. AU - Salvador, Carlos Eduardo M. AU - Pieber, Bartholomäus AU - Neu, Philipp M. AU - Torvisco, Ana AU - Kleber Z. Andrade, Carlos AU - Kappe, C. Oliver ID - 11977 IS - 9 JF - The Journal of Organic Chemistry SN - 0022-3263 TI - A sequential Ugi multicomponent/Cu-catalyzed azide–alkyne cycloaddition approach for the continuous flow generation of cyclic peptoids VL - 80 ER - TY - CHAP AB - In recent years, the high demand for sustainable processes resulted in the development of highly attractive oxidation protocols utilizing molecular oxygen or even air instead of more uneconomic and often toxic reagents. The application of these sustainable, gaseous oxidants in conventional batch reactors is often associated with severe safety risks and process challenges especially on larger scales. Continuous flow technology offers the possibility to minimize these safety hazards and concurrently allows working in high-temperature/high-pressure regimes to access highly efficient oxidation protocols. This review article critically discusses recent literature examples of flow methodologies for selective aerobic oxidations of organic compounds. Several technologies and reactor designs for biphasic gas/liquid as well as supercritical reaction media are presented in detail. © Springer International Publishing Switzerland 2015. AU - Pieber, Bartholomäus AU - Kappe, C. Oliver ED - Noël, Timothy ID - 11989 SN - 1436-6002 T2 - Organometallic Flow Chemistry TI - Aerobic oxidations in continuous flow VL - 57 ER - TY - JOUR AB - Clustering of fine particles is of crucial importance in settings ranging from the early stages of planet formation to the coagulation of industrial powders and airborne pollutants. Models of such clustering typically focus on inelastic deformation and cohesion. However, even in charge-neutral particle systems comprising grains of the same dielectric material, tribocharging can generate large amounts of net positive or negative charge on individual particles, resulting in long-range electrostatic forces. The effects of such forces on cluster formation are not well understood and have so far not been studied in situ. Here we report the first observations of individual collide-and-capture events between charged submillimetre particles, including Kepler-like orbits. Charged particles can become trapped in their mutual electrostatic energy well and aggregate via multiple bounces. This enables the initiation of clustering at relative velocities much larger than the upper limit for sticking after a head-on collision, a long-standing issue known from pre-planetary dust aggregation. Moreover, Coulomb interactions together with dielectric polarization are found to stabilize characteristic molecule-like configurations, providing new insights for the modelling of clustering dynamics in a wide range of microscopic dielectric systems, such as charged polarizable ions, biomolecules and colloids. AU - Lee, Victor AU - Waitukaitis, Scott R AU - Miskin, Marc AU - Jaeger, Heinrich ID - 120 IS - 9 JF - Nature Physics TI - Direct observation of particle interactions and clustering in charged granular streams VL - 11 ER - TY - JOUR AB - We show that the simplest building blocks of origami-based materials - rigid, degree-four vertices - are generically multistable. The existence of two distinct branches of folding motion emerging from the flat state suggests at least bistability, but we show how nonlinearities in the folding motions allow generic vertex geometries to have as many as five stable states. In special geometries with collinear folds and symmetry, more branches emerge leading to as many as six stable states. Tuning the fold energy parameters, we show how monostability is also possible. Finally, we show how to program the stability features of a single vertex into a periodic fold tessellation. The resulting metasheets provide a previously unanticipated functionality - tunable and switchable shape and size via multistability. AU - Waitukaitis, Scott R AU - Menaut, Rémi AU - Chen, Bryan AU - Van Hecke, Martin ID - 121 IS - 5 JF - APS Physics, Physical Review Letters TI - Origami multistability: From single vertices to metasheets VL - 114 ER - TY - JOUR AB - In this paper, we develop an energy method to study finite speed of propagation and waiting time phenomena for the stochastic porous media equation with linear multiplicative noise in up to three spatial dimensions. Based on a novel iteration technique and on stochastic counterparts of weighted integral estimates used in the deterministic setting, we formulate a sufficient criterion on the growth of initial data which locally guarantees a waiting time phenomenon to occur almost surely. Up to a logarithmic factor, this criterion coincides with the optimal criterion known from the deterministic setting. Our technique can be modified to prove finite speed of propagation as well. AU - Julian Fischer AU - Grün, Günther ID - 1311 IS - 1 JF - SIAM Journal on Mathematical Analysis TI - Finite speed of propagation and waiting times for the stochastic porous medium equation: A unifying approach VL - 47 ER - TY - JOUR AB - We derive a posteriori estimates for the modeling error caused by the assumption of perfect incompressibility in the incompressible Navier-Stokes equation: Real fluids are never perfectly incompressible but always feature at least some low amount of compressibility. Thus, their behavior is described by the compressible Navier-Stokes equation, the pressure being a steep function of the density. We rigorously estimate the difference between an approximate solution to the incompressible Navier-Stokes equation and any weak solution to the compressible Navier-Stokes equation in the sense of Lions (without assuming any additional regularity of solutions). Heuristics and numerical results suggest that our error estimates are of optimal order in the case of "well-behaved" flows and divergence-free approximations of the velocity field. Thus, we expect our estimates to justify the idealization of fluids as perfectly incompressible also in practical situations. AU - Fischer, Julian L ID - 1314 IS - 5 JF - SIAM Journal on Numerical Analysis TI - A posteriori modeling error estimates for the assumption of perfect incompressibility in the Navier-Stokes equation VL - 53 ER - TY - JOUR AB - We present an algorithm for the derivation of lower bounds on support propagation for a certain class of nonlinear parabolic equations. We proceed by combining the ideas in some recent papers by the author with the algorithmic construction of entropies due to Jüngel and Matthes, reducing the problem to a quantifier elimination problem. Due to its complexity, the quantifier elimination problem cannot be solved by present exact algorithms. However, by tackling the quantifier elimination problem numerically, in the case of the thin-film equation we are able to improve recent results by the author in the regime of strong slippage n ∈ (1, 2). For certain second-order doubly nonlinear parabolic equations, we are able to extend the known lower bounds on free boundary propagation to the case of irregular oscillatory initial data. Finally, we apply our method to a sixth-order quantum drift-diffusion equation, resulting in an upper bound on the time which it takes for the support to reach every point in the domain. AU - Julian Fischer ID - 1313 IS - 1 JF - Interfaces and Free Boundaries TI - Estimates on front propagation for nonlinear higher-order parabolic equations: An algorithmic approach VL - 17 ER - TY - JOUR AB - In the present work we introduce the notion of a renormalized solution for reaction–diffusion systems with entropy-dissipating reactions. We establish the global existence of renormalized solutions. In the case of integrable reaction terms our notion of a renormalized solution reduces to the usual notion of a weak solution. Our existence result in particular covers all reaction–diffusion systems involving a single reversible reaction with mass-action kinetics and (possibly species-dependent) Fick-law diffusion; more generally, it covers the case of systems of reversible reactions with mass-action kinetics which satisfy the detailed balance condition. For such equations the existence of any kind of solution in general was an open problem, thereby motivating the study of renormalized solutions. AU - Julian Fischer ID - 1316 IS - 1 JF - Archive for Rational Mechanics and Analysis TI - Global existence of renormalized solutions to entropy-dissipating reaction–diffusion systems VL - 218 ER - TY - JOUR AB - In plants, vacuolar H+-ATPase (V-ATPase) activity acidifies both the trans-Golgi network/early endosome (TGN/EE) and the vacuole. This dual V-ATPase function has impeded our understanding of how the pH homeostasis within the plant TGN/EE controls exo- and endocytosis. Here, we show that the weak V-ATPase mutant deetiolated3 (det3) displayed a pH increase in the TGN/EE, but not in the vacuole, strongly impairing secretion and recycling of the brassinosteroid receptor and the cellulose synthase complexes to the plasma membrane, in contrast to mutants lacking tonoplast-localized V-ATPase activity only. The brassinosteroid insensitivity and the cellulose deficiency defects in det3 were tightly correlated with reduced Golgi and TGN/EE motility. Thus, our results provide strong evidence that acidification of the TGN/EE, but not of the vacuole, is indispensable for functional secretion and recycling in plants. AU - Yu, Luo AU - Scholl, Stefan AU - Doering, Anett AU - Yi, Zhang AU - Irani, Niloufer AU - Di Rubbo, Simone AU - Neumetzler, Lutz AU - Krishnamoorthy, Praveen AU - Van Houtte, Isabelle AU - Mylle, Evelien AU - Bischoff, Volker AU - Vernhettes, Samantha AU - Winne, Johan AU - Friml, Jirí AU - Stierhof, York AU - Schumacher, Karin AU - Persson, Staffan AU - Russinova, Eugenia ID - 1383 IS - 7 JF - Nature Plants TI - V-ATPase activity in the TGN/EE is required for exocytosis and recycling in Arabidopsis VL - 1 ER - TY - CONF AB - In this work we aim at extending the theoretical foundations of lifelong learning. Previous work analyzing this scenario is based on the assumption that learning tasks are sampled i.i.d. from a task environment or limited to strongly constrained data distributions. Instead, we study two scenarios when lifelong learning is possible, even though the observed tasks do not form an i.i.d. sample: first, when they are sampled from the same environment, but possibly with dependencies, and second, when the task environment is allowed to change over time in a consistent way. In the first case we prove a PAC-Bayesian theorem that can be seen as a direct generalization of the analogous previous result for the i.i.d. case. For the second scenario we propose to learn an inductive bias in form of a transfer procedure. We present a generalization bound and show on a toy example how it can be used to identify a beneficial transfer algorithm. AU - Pentina, Anastasia AU - Lampert, Christoph ID - 1425 TI - Lifelong learning with non-i.i.d. tasks VL - 2015 ER - TY - CONF AB - We consider the problem of statistical computations with persistence diagrams, a summary representation of topological features in data. These diagrams encode persistent homology, a widely used invariant in topological data analysis. While several avenues towards a statistical treatment of the diagrams have been explored recently, we follow an alternative route that is motivated by the success of methods based on the embedding of probability measures into reproducing kernel Hilbert spaces. In fact, a positive definite kernel on persistence diagrams has recently been proposed, connecting persistent homology to popular kernel-based learning techniques such as support vector machines. However, important properties of that kernel enabling a principled use in the context of probability measure embeddings remain to be explored. Our contribution is to close this gap by proving universality of a variant of the original kernel, and to demonstrate its effective use in twosample hypothesis testing on synthetic as well as real-world data. AU - Kwitt, Roland AU - Huber, Stefan AU - Niethammer, Marc AU - Lin, Weili AU - Bauer, Ulrich ID - 1424 TI - Statistical topological data analysis-A kernel perspective VL - 28 ER - TY - CONF AB - Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse their runtime on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient. AU - Paixao, Tiago AU - Sudholt, Dirk AU - Heredia, Jorge AU - Trubenova, Barbora ID - 1430 T2 - Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation TI - First steps towards a runtime comparison of natural and artificial evolution ER - TY - CONF AB - Cryptographic access control offers selective access to encrypted data via a combination of key management and functionality-rich cryptographic schemes, such as attribute-based encryption. Using this approach, publicly available meta-data may inadvertently leak information on the access policy that is enforced by cryptography, which renders cryptographic access control unusable in settings where this information is highly sensitive. We begin to address this problem by presenting rigorous definitions for policy privacy in cryptographic access control. For concreteness we set our results in the model of Role-Based Access Control (RBAC), where we identify and formalize several different flavors of privacy, however, our framework should serve as inspiration for other models of access control. Based on our insights we propose a new system which significantly improves on the privacy properties of state-of-the-art constructions. Our design is based on a novel type of privacy-preserving attribute-based encryption, which we introduce and show how to instantiate. We present our results in the context of a cryptographic RBAC system by Ferrara et al. (CSF'13), which uses cryptography to control read access to files, while write access is still delegated to trusted monitors. We give an extension of the construction that permits cryptographic control over write access. Our construction assumes that key management uses out-of-band channels between the policy enforcer and the users but eliminates completely the need for monitoring read/write access to the data. AU - Ferrara, Anna AU - Fuchsbauer, Georg AU - Liu, Bin AU - Warinschi, Bogdan ID - 1474 TI - Policy privacy in cryptographic access control ER - TY - GEN AB - In this paper we survey geometric and arithmetic techniques to study the cohomology of semiprojective hyperkähler manifolds including toric hyperkähler varieties, Nakajima quiver varieties and moduli spaces of Higgs bundles on Riemann surfaces. The resulting formulae for their Poincaré polynomials are combinatorial and representation theoretical in nature. In particular we will look at their Betti numbers and will establish some results and state some expectations on their asymptotic shape. AU - Tamas Hausel AU - Rodríguez Villegas, Fernando ID - 1473 IS - 370 T2 - Asterisque TI - Cohomology of large semiprojective hyperkähler varieties VL - 2015 ER - TY - CONF AB - Topological data analysis offers a rich source of valuable information to study vision problems. Yet, so far we lack a theoretically sound connection to popular kernel-based learning techniques, such as kernel SVMs or kernel PCA. In this work, we establish such a connection by designing a multi-scale kernel for persistence diagrams, a stable summary representation of topological features in data. We show that this kernel is positive definite and prove its stability with respect to the 1-Wasserstein distance. Experiments on two benchmark datasets for 3D shape classification/retrieval and texture recognition show considerable performance gains of the proposed method compared to an alternative approach that is based on the recently introduced persistence landscapes. AU - Reininghaus, Jan AU - Huber, Stefan AU - Bauer, Ulrich AU - Kwitt, Roland ID - 1483 TI - A stable multi-scale kernel for topological machine learning ER - TY - CONF AB - Fault-tolerant distributed algorithms play an important role in many critical/high-availability applications. These algorithms are notoriously difficult to implement correctly, due to asynchronous communication and the occurrence of faults, such as the network dropping messages or computers crashing. Nonetheless there is surprisingly little language and verification support to build distributed systems based on fault-tolerant algorithms. In this paper, we present some of the challenges that a designer has to overcome to implement a fault-tolerant distributed system. Then we review different models that have been proposed to reason about distributed algorithms and sketch how such a model can form the basis for a domain-specific programming language. Adopting a high-level programming model can simplify the programmer's life and make the code amenable to automated verification, while still compiling to efficiently executable code. We conclude by summarizing the current status of an ongoing language design and implementation project that is based on this idea. AU - Dragoi, Cezara AU - Henzinger, Thomas A AU - Zufferey, Damien ID - 1498 SN - 978-3-939897-80-4 TI - The need for language support for fault-tolerant distributed systems VL - 32 ER - TY - JOUR AB - Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide. AU - Andergassen, Daniel AU - Dotter, Christoph AU - Kulinski, Tomasz AU - Guenzl, Philipp AU - Bammer, Philipp AU - Barlow, Denise AU - Pauler, Florian AU - Hudson, Quanah ID - 1497 IS - 21 JF - Nucleic Acids Research TI - Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data VL - 43 ER - TY - CONF AB - We consider weighted automata with both positive and negative integer weights on edges and study the problem of synchronization using adaptive strategies that may only observe whether the current weight-level is negative or nonnegative. We show that the synchronization problem is decidable in polynomial time for deterministic weighted automata. AU - Kretinsky, Jan AU - Larsen, Kim AU - Laursen, Simon AU - Srba, Jiří ID - 1499 TI - Polynomial time decidability of weighted synchronization under partial observability VL - 42 ER - TY - CONF AB - Motivated by biological questions, we study configurations of equal-sized disks in the Euclidean plane that neither pack nor cover. Measuring the quality by the probability that a random point lies in exactly one disk, we show that the regular hexagonal grid gives the maximum among lattice configurations. AU - Edelsbrunner, Herbert AU - Iglesias Ham, Mabel AU - Kurlin, Vitaliy ID - 1495 T2 - Proceedings of the 27th Canadian Conference on Computational Geometry TI - Relaxed disk packing VL - 2015-August ER - TY - JOUR AB - Let Q = (Q1, . . . , Qn) be a random vector drawn from the uniform distribution on the set of all n! permutations of {1, 2, . . . , n}. Let Z = (Z1, . . . , Zn), where Zj is the mean zero variance one random variable obtained by centralizing and normalizing Qj , j = 1, . . . , n. Assume that Xi , i = 1, . . . ,p are i.i.d. copies of 1/√ p Z and X = Xp,n is the p × n random matrix with Xi as its ith row. Then Sn = XX is called the p × n Spearman's rank correlation matrix which can be regarded as a high dimensional extension of the classical nonparametric statistic Spearman's rank correlation coefficient between two independent random variables. In this paper, we establish a CLT for the linear spectral statistics of this nonparametric random matrix model in the scenario of high dimension, namely, p = p(n) and p/n→c ∈ (0,∞) as n→∞.We propose a novel evaluation scheme to estimate the core quantity in Anderson and Zeitouni's cumulant method in [Ann. Statist. 36 (2008) 2553-2576] to bypass the so-called joint cumulant summability. In addition, we raise a two-step comparison approach to obtain the explicit formulae for the mean and covariance functions in the CLT. Relying on this CLT, we then construct a distribution-free statistic to test complete independence for components of random vectors. Owing to the nonparametric property, we can use this test on generally distributed random variables including the heavy-tailed ones. AU - Bao, Zhigang AU - Lin, Liang AU - Pan, Guangming AU - Zhou, Wang ID - 1504 IS - 6 JF - Annals of Statistics TI - Spectral statistics of large dimensional spearman s rank correlation matrix and its application VL - 43 ER - TY - GEN AB - In this poster, we present methods for randomly generating hybrid automata with affine differential equations, invariants, guards, and assignments. Selecting an arbitrary affine function from the set of all affine functions results in a low likelihood of generating hybrid automata with diverse and interesting behaviors, as there are an uncountable number of elements in the set of all affine functions. Instead, we partition the set of all affine functions into potentially interesting classes and randomly select elements from these classes. For example, we partition the set of all affine differential equations by using restrictions on eigenvalues such as those that yield stable, unstable, etc. equilibrium points. We partition the components describing discrete behavior (guards, assignments, and invariants) to allow either time-dependent or state-dependent switching, and in particular provide the ability to generate subclasses of piecewise-affine hybrid automata. Our preliminary experimental results with a prototype tool called HyRG (Hybrid Random Generator) illustrate the feasibility of this generation method to automatically create standard hybrid automaton examples like the bouncing ball and thermostat. AU - Nguyen, Luan V AU - Christian Schilling AU - Sergiy Bogomolov AU - Johnson, Taylor T ID - 1500 T2 - HSCC: Hybrid Systems - Computation and Control TI - Poster: HyRG: A random generation tool for affine hybrid automata ER - TY - JOUR AB - A Herman-Avila-Bochi type formula is obtained for the average sum of the top d Lyapunov exponents over a one-parameter family of double-struck G-cocycles, where double-struck G is the group that leaves a certain, non-degenerate Hermitian form of signature (c, d) invariant. The generic example of such a group is the pseudo-unitary group U(c, d) or, in the case c = d, the Hermitian-symplectic group HSp(2d) which naturally appears for cocycles related to Schrödinger operators. In the case d = 1, the formula for HSp(2d) cocycles reduces to the Herman-Avila-Bochi formula for SL(2, ℝ) cocycles. AU - Sadel, Christian ID - 1503 IS - 5 JF - Ergodic Theory and Dynamical Systems TI - A Herman-Avila-Bochi formula for higher-dimensional pseudo-unitary and Hermitian-symplectic-cocycles VL - 35 ER - TY - CONF AB - The concept of well group in a special but important case captures homological properties of the zero set of a continuous map f from K to R^n on a compact space K that are invariant with respect to perturbations of f. The perturbations are arbitrary continuous maps within L_infty distance r from f for a given r > 0. The main drawback of the approach is that the computability of well groups was shown only when dim K = n or n = 1. Our contribution to the theory of well groups is twofold: on the one hand we improve on the computability issue, but on the other hand we present a range of examples where the well groups are incomplete invariants, that is, fail to capture certain important robust properties of the zero set. For the first part, we identify a computable subgroup of the well group that is obtained by cap product with the pullback of the orientation of R^n by f. In other words, well groups can be algorithmically approximated from below. When f is smooth and dim K < 2n-2, our approximation of the (dim K-n)th well group is exact. For the second part, we find examples of maps f, f' from K to R^n with all well groups isomorphic but whose perturbations have different zero sets. We discuss on a possible replacement of the well groups of vector valued maps by an invariant of a better descriptive power and computability status. AU - Franek, Peter AU - Krcál, Marek ID - 1510 TI - On computability and triviality of well groups VL - 34 ER - TY - JOUR AB - This paper is aimed at deriving the universality of the largest eigenvalue of a class of high-dimensional real or complex sample covariance matrices of the form W N =Σ 1/2XX∗Σ 1/2 . Here, X = (xij )M,N is an M× N random matrix with independent entries xij , 1 ≤ i M,≤ 1 ≤ j ≤ N such that Exij = 0, E|xij |2 = 1/N . On dimensionality, we assume that M = M(N) and N/M → d ε (0, ∞) as N ∞→. For a class of general deterministic positive-definite M × M matrices Σ , under some additional assumptions on the distribution of xij 's, we show that the limiting behavior of the largest eigenvalue of W N is universal, via pursuing a Green function comparison strategy raised in [Probab. Theory Related Fields 154 (2012) 341-407, Adv. Math. 229 (2012) 1435-1515] by Erd″os, Yau and Yin for Wigner matrices and extended by Pillai and Yin [Ann. Appl. Probab. 24 (2014) 935-1001] to sample covariance matrices in the null case (&Epsi = I ). Consequently, in the standard complex case (Ex2 ij = 0), combing this universality property and the results known for Gaussian matrices obtained by El Karoui in [Ann. Probab. 35 (2007) 663-714] (nonsingular case) and Onatski in [Ann. Appl. Probab. 18 (2008) 470-490] (singular case), we show that after an appropriate normalization the largest eigenvalue of W N converges weakly to the type 2 Tracy-Widom distribution TW2 . Moreover, in the real case, we show that whenΣ is spiked with a fixed number of subcritical spikes, the type 1 Tracy-Widom limit TW1 holds for the normalized largest eigenvalue of W N , which extends a result of Féral and Péché in [J. Math. Phys. 50 (2009) 073302] to the scenario of nondiagonal Σ and more generally distributed X . In summary, we establish the Tracy-Widom type universality for the largest eigenvalue of generally distributed sample covariance matrices under quite light assumptions on &Sigma . Applications of these limiting results to statistical signal detection and structure recognition of separable covariance matrices are also discussed. AU - Bao, Zhigang AU - Pan, Guangming AU - Zhou, Wang ID - 1505 IS - 1 JF - Annals of Statistics TI - Universality for the largest eigenvalue of sample covariance matrices with general population VL - 43 ER - TY - JOUR AB - We consider generalized Wigner ensembles and general β-ensembles with analytic potentials for any β ≥ 1. The recent universality results in particular assert that the local averages of consecutive eigenvalue gaps in the bulk of the spectrum are universal in the sense that they coincide with those of the corresponding Gaussian β-ensembles. In this article, we show that local averaging is not necessary for this result, i.e. we prove that the single gap distributions in the bulk are universal. In fact, with an additional step, our result can be extended to any C4(ℝ) potential. AU - Erdös, László AU - Yau, Horng ID - 1508 IS - 8 JF - Journal of the European Mathematical Society TI - Gap universality of generalized Wigner and β ensembles VL - 17 ER - TY - JOUR AB - Consider the square random matrix An = (aij)n,n, where {aij:= a(n)ij , i, j = 1, . . . , n} is a collection of independent real random variables with means zero and variances one. Under the additional moment condition supn max1≤i,j ≤n Ea4ij <∞, we prove Girko's logarithmic law of det An in the sense that as n→∞ log | detAn| ? (1/2) log(n-1)! d/→√(1/2) log n N(0, 1). AU - Bao, Zhigang AU - Pan, Guangming AU - Zhou, Wang ID - 1506 IS - 3 JF - Bernoulli TI - The logarithmic law of random determinant VL - 21 ER - TY - JOUR AB - Insects of the order Hemiptera (true bugs) use a wide range of mechanisms of sex determination, including genetic sex determination, paternal genome elimination, and haplodiploidy. Genetic sex determination, the prevalent mode, is generally controlled by a pair of XY sex chromosomes or by an XX/X0 system, but different configurations that include additional sex chromosomes are also present. Although this diversity of sex determining systems has been extensively studied at the cytogenetic level, only the X chromosome of the model pea aphid Acyrthosiphon pisum has been analyzed at the genomic level, and little is known about X chromosome biology in the rest of the order. In this study, we take advantage of published DNA- and RNA-seq data from three additional Hemiptera species to perform a comparative analysis of the gene content and expression of the X chromosome throughout this clade. We find that, despite showing evidence of dosage compensation, the X chromosomes of these species show female-biased expression, and a deficit of male-biased genes, in direct contrast to the pea aphid X. We further detect an excess of shared gene content between these very distant species, suggesting that despite the diversity of sex determining systems, the same chromosomal element is used as the X throughout a large portion of the order. AU - Pal, Arka AU - Vicoso, Beatriz ID - 1513 IS - 12 JF - Genome Biology and Evolution TI - The X chromosome of hemipteran insects: Conservation, dosage compensation and sex-biased expression VL - 7 ER - TY - JOUR AB - We study the large deviation rate functional for the empirical distribution of independent Brownian particles with drift. In one dimension, it has been shown by Adams, Dirr, Peletier and Zimmer that this functional is asymptotically equivalent (in the sense of Γ-convergence) to the Jordan-Kinderlehrer-Otto functional arising in the Wasserstein gradient flow structure of the Fokker-Planck equation. In higher dimensions, part of this statement (the lower bound) has been recently proved by Duong, Laschos and Renger, but the upper bound remained open, since the proof of Duong et al relies on regularity properties of optimal transport maps that are restricted to one dimension. In this note we present a new proof of the upper bound, thereby generalising the result of Adams et al to arbitrary dimensions. AU - Erbar, Matthias AU - Maas, Jan AU - Renger, Michiel ID - 1517 JF - Electronic Communications in Probability TI - From large deviations to Wasserstein gradient flows in multiple dimensions VL - 20 ER - TY - JOUR AB - Type 1 metabotropic glutamate (mGlu1) receptors play a pivotal role in different forms of synaptic plasticity in the cerebellar cortex, e.g. long-term depression at glutamatergic synapses and rebound potentiation at GABAergic synapses. These various forms of plasticity might depend on the subsynaptic arrangement of the receptor in Purkinje cells that can be regulated by protein-protein interactions. This study investigated, by means of the freeze-fracture replica immunogold labelling method, the subcellular localization of mGlu1 receptors in the rodent cerebellum and whether Homer proteins regulate their subsynaptic distribution. We observed a widespread extrasynaptic localization of mGlu1 receptors and confirmed their peri-synaptic enrichment at glutamatergic synapses. Conversely, we detected mGlu1 receptors within the main body of GABAergic synapses onto Purkinje cell dendrites. Although Homer proteins are known to interact with the mGlu1 receptor C-terminus, we could not detect Homer3, the most abundant Homer protein in the cerebellar cortex, at GABAergic synapses by pre-embedding and post-embedding immunoelectron microscopy. We then hypothesized a critical role for Homer proteins in the peri-junctional localization of mGlu1 receptors at glutamatergic synapses. To disrupt Homer-associated protein complexes, mice were tail-vein injected with the membrane-permeable dominant-negative TAT-Homer1a. Freeze-fracture replica immunogold labelling analysis showed no significant alteration in the mGlu1 receptor distribution pattern at parallel fibre-Purkinje cell synapses, suggesting that other scaffolding proteins are involved in the peri-synaptic confinement. The identification of interactors that regulate the subsynaptic localization of the mGlu1 receptor at neurochemically distinct synapses may offer new insight into its trafficking and intracellular signalling. AU - Mansouri, Mahnaz AU - Kasugai, Yu AU - Fukazawa, Yugo AU - Bertaso, Federica AU - Raynaud, Fabrice AU - Perroy, Julie AU - Fagni, Laurent AU - Walter Kaufmann AU - Watanabe, Masahiko AU - Ryuichi Shigemoto AU - Ferraguti, Francesco ID - 1515 IS - 2 JF - European Journal of Neuroscience TI - Distinct subsynaptic localization of type 1 metabotropic glutamate receptors at glutamatergic and GABAergic synapses in the rodent cerebellar cortex VL - 41 ER - TY - JOUR AB - Endocannabinoids (eCBs) play key roles in brain function, acting as modulatory signals in synaptic transmission and plasticity. They are recognized as retrograde messengers that mediate long-term synaptic depression (LTD), but their ability to induce long-term potentiation (LTP) is poorly known. We show that eCBs induce the long-term enhancement of transmitter release at single hippocampal synapses through stimulation of astrocytes when coincident with postsynaptic activity. This LTP requires the coordinated activity of the 3 elements of the tripartite synapse: 1) eCB-evoked astrocyte calcium signal that stimulates glutamate release; 2) postsynaptic nitric oxide production; and 3) activation of protein kinase C and presynaptic group I metabotropic glutamate receptors, whose location at presynaptic sites was confirmed by immunoelectron microscopy. Hence, while eCBs act as retrograde signals to depress homoneuronal synapses, they serve as lateral messengers to induce LTP in distant heteroneuronal synapses through stimulation of astrocytes. Therefore, eCBs can trigger LTP through stimulation of astrocyte-neuron signaling, revealing novel cellular mechanisms of eCB effects on synaptic plasticity. AU - Gómez-Gonzalo, Marta AU - Navarrete, Marta AU - Perea, Gertrudis AU - Covelo, Ana AU - Martín-Fernández, Mario AU - Ryuichi Shigemoto AU - Luján, Rafael AU - Araque, Alfonso ID - 1514 IS - 10 JF - Cerebral Cortex TI - Endocannabinoids induce lateral long term potentiation of transmitter release by stimulation of gliotransmission VL - 25 ER - TY - JOUR AB - Evolutionary biologists have an array of powerful theoretical techniques that can accurately predict changes in the genetic composition of populations. Changes in gene frequencies and genetic associations between loci can be tracked as they respond to a wide variety of evolutionary forces. However, it is often less clear how to decompose these various forces into components that accurately reflect the underlying biology. Here, we present several issues that arise in the definition and interpretation of selection and selection coefficients, focusing on insights gained through the examination of selection coefficients in multilocus notation. Using this notation, we discuss how its flexibility-which allows different biological units to be identified as targets of selection-is reflected in the interpretation of the coefficients that the notation generates. In many situations, it can be difficult to agree on whether loci can be considered to be under "direct" versus "indirect" selection, or to quantify this selection. We present arguments for what the terms direct and indirect selection might best encompass, considering a range of issues, from viability and sexual selection to kin selection. We show how multilocus notation can discriminate between direct and indirect selection, and describe when it can do so. AU - Barton, Nicholas H AU - Servedio, Maria ID - 1519 IS - 5 JF - Evolution TI - The interpretation of selection coefficients VL - 69 ER - TY - JOUR AB - Based on 16 recommendations, efforts should be made to achieve the following goal: By 2025, all scholarly publication activity in Austria should be Open Access. In other words, the final versions of all scholarly publications resulting from the support of public resources must be freely accessible on the Internet without delay (Gold Open Access). The resources required to meet this obligation shall be provided to the authors, or the cost of the publication venues shall be borne directly by the research organisations. AU - Bauer, Bruno AU - Blechl, Guido AU - Bock, Christoph AU - Danowski, Patrick AU - Ferus, Andreas AU - Graschopf, Anton AU - König, Thomas AU - Mayer, Katja AU - Reckling, Falk AU - Rieck, Katharina AU - Seitz, Peter AU - Stöger, Herwig AU - Welzig, Elvira ID - 1525 IS - 3 JF - VÖB Mitteilungen TI - Arbeitsgruppe „Nationale Strategie“ des Open Access Network Austria OANA VL - 68 ER - TY - CONF AB - Creating mechanical automata that can walk in stable and pleasing manners is a challenging task that requires both skill and expertise. We propose to use computational design to offset the technical difficulties of this process. A simple drag-and-drop interface allows casual users to create personalized walking toys from a library of pre-defined template mechanisms. Provided with this input, our method leverages physical simulation and evolutionary optimization to refine the mechanical designs such that the resulting toys are able to walk. The optimization process is guided by an intuitive set of objectives that measure the quality of the walking motions. We demonstrate our approach on a set of simulated mechanical toys with different numbers of legs and various distinct gaits. Two fabricated prototypes showcase the feasibility of our designs. AU - Bharaj, Gaurav AU - Coros, Stelian AU - Thomaszewski, Bernhard AU - Tompkin, James AU - Bickel, Bernd AU - Pfister, Hanspeter ID - 1520 SN - 978-1-4503-3496-9 TI - Computational design of walking automata ER - TY - JOUR AB - Ammonium is the major nitrogen source in some plant ecosystems but is toxic at high concentrations, especially when available as the exclusive nitrogen source. Ammonium stress rapidly leads to various metabolic and hormonal imbalances that ultimately inhibit root and shoot growth in many plant species, including Arabidopsis thaliana (L.) Heynh. To identify molecular and genetic factors involved in seedling survival with prolonged exclusive NH4+ nutrition, a transcriptomic analysis with microarrays was used. Substantial transcriptional differences were most pronounced in (NH4)2SO4-grown seedlings, compared with plants grown on KNO3 or NH4NO3. Consistent with previous physiological analyses, major differences in the expression modules of photosynthesis-related genes, an altered mitochondrial metabolism, differential expression of the primary NH4+ assimilation, alteration of transporter gene expression and crucial changes in cell wall biosynthesis were found. A major difference in plant hormone responses, particularly of auxin but not cytokinin, was striking. The activity of the DR5::GUS reporter revealed a dramatically decreased auxin response in (NH4)2SO4-grown primary roots. The impaired root growth on (NH4)2SO4 was partially rescued by exogenous auxin or in specific mutants in the auxin pathway. The data suggest that NH4+-induced nutritional and metabolic imbalances can be partially overcome by elevated auxin levels. AU - Yang, Huaiyu AU - Von Der Fecht Bartenbach, Jenny AU - Friml, Jirí AU - Lohmann, Jan AU - Neuhäuser, Benjamin AU - Ludewig, Uwe ID - 1532 IS - 3 JF - Functional Plant Biology SN - 1445-4408 TI - Auxin-modulated root growth inhibition in Arabidopsis thaliana seedlings with ammonium as the sole nitrogen source VL - 42 ER - TY - CHAP AB - The Heat Kernel Signature (HKS) is a scalar quantity which is derived from the heat kernel of a given shape. Due to its robustness, isometry invariance, and multiscale nature, it has been successfully applied in many geometric applications. From a more general point of view, the HKS can be considered as a descriptor of the metric of a Riemannian manifold. Given a symmetric positive definite tensor field we may interpret it as the metric of some Riemannian manifold and thereby apply the HKS to visualize and analyze the given tensor data. In this paper, we propose a generalization of this approach that enables the treatment of indefinite tensor fields, like the stress tensor, by interpreting them as a generator of a positive definite tensor field. To investigate the usefulness of this approach we consider the stress tensor from the two-point-load model example and from a mechanical work piece. AU - Zobel, Valentin AU - Reininghaus, Jan AU - Hotz, Ingrid ED - Hotz, Ingrid ED - Schultz, Thomas ID - 1531 SN - 978-3-319-15089-5 T2 - Visualization and Processing of Higher Order Descriptors for Multi-Valued Data TI - Visualizing symmetric indefinite 2D tensor fields using The Heat Kernel Signature VL - 40 ER - TY - JOUR AB - In growing cells, protein synthesis and cell growth are typically not synchronous, and, thus, protein concentrations vary over the cell division cycle. We have developed a theoretical description of genetic regulatory systems in bacteria that explicitly considers the cell division cycle to investigate its impact on gene expression. We calculate the cell-to-cell variations arising from cells being at different stages in the division cycle for unregulated genes and for basic regulatory mechanisms. These variations contribute to the extrinsic noise observed in single-cell experiments, and are most significant for proteins with short lifetimes. Negative autoregulation buffers against variation of protein concentration over the division cycle, but the effect is found to be relatively weak. Stronger buffering is achieved by an increased protein lifetime. Positive autoregulation can strongly amplify such variation if the parameters are set to values that lead to resonance-like behaviour. For cooperative positive autoregulation, the concentration variation over the division cycle diminishes the parameter region of bistability and modulates the switching times between the two stable states. The same effects are seen for a two-gene mutual-repression toggle switch. By contrast, an oscillatory circuit, the repressilator, is only weakly affected by the division cycle. AU - Bierbaum, Veronika AU - Klumpp, Stefan ID - 1530 IS - 6 JF - Physical Biology TI - Impact of the cell division cycle on gene circuits VL - 12 ER - TY - JOUR AB - Many stochastic models of biochemical reaction networks contain some chemical species for which the number of molecules that are present in the system can only be finite (for instance due to conservation laws), but also other species that can be present in arbitrarily large amounts. The prime example of such networks are models of gene expression, which typically contain a small and finite number of possible states for the promoter but an infinite number of possible states for the amount of mRNA and protein. One of the main approaches to analyze such models is through the use of equations for the time evolution of moments of the chemical species. Recently, a new approach based on conditional moments of the species with infinite state space given all the different possible states of the finite species has been proposed. It was argued that this approach allows one to capture more details about the full underlying probability distribution with a smaller number of equations. Here, I show that the result that less moments provide more information can only stem from an unnecessarily complicated description of the system in the classical formulation. The foundation of this argument will be the derivation of moment equations that describe the complete probability distribution over the finite state space but only low-order moments over the infinite state space. I will show that the number of equations that is needed is always less than what was previously claimed and always less than the number of conditional moment equations up to the same order. To support these arguments, a symbolic algorithm is provided that can be used to derive minimal systems of unconditional moment equations for models with partially finite state space. AU - Ruess, Jakob ID - 1539 IS - 24 JF - Journal of Chemical Physics TI - Minimal moment equations for stochastic models of biochemical reaction networks with partially finite state space VL - 143 ER - TY - JOUR AB - PIN proteins are auxin export carriers that direct intercellular auxin flow and in turn regulate many aspects of plant growth and development including responses to environmental changes. The Arabidopsis R2R3-MYB transcription factor FOUR LIPS (FLP) and its paralogue MYB88 regulate terminal divisions during stomatal development, as well as female reproductive development and stress responses. Here we show that FLP and MYB88 act redundantly but differentially in regulating the transcription of PIN3 and PIN7 in gravity-sensing cells of primary and lateral roots. On the one hand, FLP is involved in responses to gravity stimulation in primary roots, whereas on the other, FLP and MYB88 function complementarily in establishing the gravitropic set-point angles of lateral roots. Our results support a model in which FLP and MYB88 expression specifically determines the temporal-spatial patterns of PIN3 and PIN7 transcription that are closely associated with their preferential functions during root responses to gravity. AU - Wang, Hongzhe AU - Yang, Kezhen AU - Zou, Junjie AU - Zhu, Lingling AU - Xie, Zidian AU - Morita, Miyoterao AU - Tasaka, Masao AU - Friml, Jirí AU - Grotewold, Erich AU - Beeckman, Tom AU - Vanneste, Steffen AU - Sack, Fred AU - Le, Jie ID - 1534 JF - Nature Communications TI - Transcriptional regulation of PIN genes by FOUR LIPS and MYB88 during Arabidopsis root gravitropism VL - 6 ER - TY - JOUR AB - Systems biology rests on the idea that biological complexity can be better unraveled through the interplay of modeling and experimentation. However, the success of this approach depends critically on the informativeness of the chosen experiments, which is usually unknown a priori. Here, we propose a systematic scheme based on iterations of optimal experiment design, flow cytometry experiments, and Bayesian parameter inference to guide the discovery process in the case of stochastic biochemical reaction networks. To illustrate the benefit of our methodology, we apply it to the characterization of an engineered light-inducible gene expression circuit in yeast and compare the performance of the resulting model with models identified from nonoptimal experiments. In particular, we compare the parameter posterior distributions and the precision to which the outcome of future experiments can be predicted. Moreover, we illustrate how the identified stochastic model can be used to determine light induction patterns that make either the average amount of protein or the variability in a population of cells follow a desired profile. Our results show that optimal experiment design allows one to derive models that are accurate enough to precisely predict and regulate the protein expression in heterogeneous cell populations over extended periods of time. AU - Ruess, Jakob AU - Parise, Francesca AU - Milias Argeitis, Andreas AU - Khammash, Mustafa AU - Lygeros, John ID - 1538 IS - 26 JF - PNAS TI - Iterative experiment design guides the characterization of a light-inducible gene expression circuit VL - 112 ER - TY - JOUR AB - Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuronlike” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress. AU - Vandael, David H AU - Marcantoni, Andrea AU - Carbone, Emilio ID - 1535 IS - 2 JF - Current Molecular Pharmacology TI - Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells VL - 8 ER - TY - JOUR AB - Strigolactones, first discovered as germination stimulants for parasitic weeds [1], are carotenoid-derived phytohormones that play major roles in inhibiting lateral bud outgrowth and promoting plant-mycorrhizal symbiosis [2-4]. Furthermore, strigolactones are involved in the regulation of lateral and adventitious root development, root cell division [5, 6], secondary growth [7], and leaf senescence [8]. Recently, we discovered the strigolactone transporter Petunia axillaris PLEIOTROPIC DRUG RESISTANCE 1 (PaPDR1), which is required for efficient mycorrhizal colonization and inhibition of lateral bud outgrowth [9]. However, how strigolactones are transported through the plant remained unknown. Here we show that PaPDR1 exhibits a cell-type-specific asymmetric localization in different root tissues. In root tips, PaPDR1 is co-expressed with the strigolactone biosynthetic gene DAD1 (CCD8), and it is localized at the apical membrane of root hypodermal cells, presumably mediating the shootward transport of strigolactone. Above the root tip, in the hypodermal passage cells that form gates for the entry of mycorrhizal fungi, PaPDR1 is present in the outer-lateral membrane, compatible with its postulated function as strigolactone exporter from root to soil. Transport studies are in line with our localization studies since (1) a papdr1 mutant displays impaired transport of strigolactones out of the root tip to the shoot as well as into the rhizosphere and (2) DAD1 expression and PIN1/PIN2 levels change in plants deregulated for PDR1 expression, suggestive of variations in endogenous strigolactone contents. In conclusion, our results indicate that the polar localizations of PaPDR1 mediate directional shootward strigolactone transport as well as localized exudation into the soil. AU - Sasse, Joëlle AU - Simon, Sibu AU - Gübeli, Christian AU - Liu, Guowei AU - Cheng, Xi AU - Friml, Jirí AU - Bouwmeester, Harro AU - Martinoia, Enrico AU - Borghi, Lorenzo ID - 1536 IS - 5 JF - Current Biology TI - Asymmetric localizations of the ABC transporter PaPDR1 trace paths of directional strigolactone transport VL - 25 ER - TY - JOUR AB - This paper addresses the problem of semantic segmentation, where the possible class labels are from a predefined set. We exploit top-down guidance, i.e., the coarse localization of the objects and their class labels provided by object detectors. For each detected bounding box, figure-ground segmentation is performed and the final result is achieved by merging the figure-ground segmentations. The main idea of the proposed approach, which is presented in our preliminary work, is to reformulate the figure-ground segmentation problem as sparse reconstruction pursuing the object mask in a nonparametric manner. The latent segmentation mask should be coherent subject to sparse error caused by intra-category diversity; thus, the object mask is inferred by making use of sparse representations over the training set. To handle local spatial deformations, local patch-level masks are also considered and inferred by sparse representations over the spatially nearby patches. The sparse reconstruction coefficients and the latent mask are alternately optimized by applying the Lasso algorithm and the accelerated proximal gradient method. The proposed formulation results in a convex optimization problem; thus, the global optimal solution is achieved. In this paper, we provide theoretical analysis of the convergence and optimality. We also give an extended numerical analysis of the proposed algorithm and a comprehensive comparison with the related semantic segmentation methods on the challenging PASCAL visual object class object segmentation datasets and the Weizmann horse dataset. The experimental results demonstrate that the proposed algorithm achieves a competitive performance when compared with the state of the arts. AU - Xia, Wei AU - Domokos, Csaba AU - Xiong, Junjun AU - Cheong, Loongfah AU - Yan, Shuicheng ID - 1533 IS - 8 JF - IEEE Transactions on Circuits and Systems for Video Technology TI - Segmentation over detection via optimal sparse reconstructions VL - 25 ER - TY - JOUR AB - The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. AU - Paixao, Tiago AU - Badkobeh, Golnaz AU - Barton, Nicholas H AU - Çörüş, Doğan AU - Dang, Duccuong AU - Friedrich, Tobias AU - Lehre, Per AU - Sudholt, Dirk AU - Sutton, Andrew AU - Trubenova, Barbora ID - 1542 JF - Journal of Theoretical Biology TI - Toward a unifying framework for evolutionary processes VL - 383 ER - TY - JOUR AB - Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course. AU - Nakamura, Yukihiro AU - Harada, Harumi AU - Kamasawa, Naomi AU - Matsui, Ko AU - Rothman, Jason AU - Shigemoto, Ryuichi AU - Silver, R Angus AU - Digregorio, David AU - Takahashi, Tomoyuki ID - 1546 IS - 1 JF - Neuron TI - Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development VL - 85 ER - TY - CONF AB - We present XSpeed a parallel state-space exploration algorithm for continuous systems with linear dynamics and nondeterministic inputs. The motivation of having parallel algorithms is to exploit the computational power of multi-core processors to speed-up performance. The parallelization is achieved on two fronts. First, we propose a parallel implementation of the support function algorithm by sampling functions in parallel. Second, we propose a parallel state-space exploration by slicing the time horizon and computing the reachable states in the time slices in parallel. The second method can be however applied only to a class of linear systems with invertible dynamics and fixed input. A GP-GPU implementation is also presented following a lazy evaluation strategy on support functions. The parallel algorithms are implemented in the tool XSpeed. We evaluated the performance on two benchmarks including an 28 dimension Helicopter model. Comparison with the sequential counterpart shows a maximum speed-up of almost 7× on a 6 core, 12 thread Intel Xeon CPU E5-2420 processor. Our GP-GPU implementation shows a maximum speed-up of 12× over the sequential implementation and 53× over SpaceEx (LGG scenario), the state of the art tool for reachability analysis of linear hybrid systems. Experiments illustrate that our parallel algorithm with time slicing not only speeds-up performance but also improves precision. AU - Ray, Rajarshi AU - Gurung, Amit AU - Das, Binayak AU - Bartocci, Ezio AU - Bogomolov, Sergiy AU - Grosu, Radu ID - 1541 TI - XSpeed: Accelerating reachability analysis on multi-core processors VL - 9434 ER - TY - JOUR AB - A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta. AU - Olvera Carrillo, Yadira AU - Van Bel, Michiel AU - Van Hautegem, Tom AU - Fendrych, Matyas AU - Huysmans, Marlies AU - Šimášková, Mária AU - Van Durme, Matthias AU - Buscaill, Pierre AU - Rivas, Susana AU - Coll, Núria AU - Coppens, Frederik AU - Maere, Steven AU - Nowack, Moritz ID - 1543 IS - 4 JF - Plant Physiology TI - A conserved core of programmed cell death indicator genes discriminates developmentally and environmentally induced programmed cell death in plants VL - 169 ER - TY - CHAP AB - Cell division in prokaryotes and eukaryotes is commonly initiated by the well-controlled binding of proteins to the cytoplasmic side of the cell membrane. However, a precise characterization of the spatiotemporal dynamics of membrane-bound proteins is often difficult to achieve in vivo. Here, we present protocols for the use of supported lipid bilayers to rebuild the cytokinetic machineries of cells with greatly different dimensions: the bacterium Escherichia coli and eggs of the vertebrate Xenopus laevis. Combined with total internal reflection fluorescence microscopy, these experimental setups allow for precise quantitative analyses of membrane-bound proteins. The protocols described to obtain glass-supported membranes from bacterial and vertebrate lipids can be used as starting points for other reconstitution experiments. We believe that similar biochemical assays will be instrumental to study the biochemistry and biophysics underlying a variety of complex cellular tasks, such as signaling, vesicle trafficking, and cell motility. AU - Nguyen, Phuong AU - Field, Christine AU - Groen, Aaron AU - Mitchison, Timothy AU - Loose, Martin ID - 1544 T2 - Building a Cell from its Components Parts TI - Using supported bilayers to study the spatiotemporal organization of membrane-bound proteins VL - 128 ER - TY - JOUR AB - Plant sexual reproduction involves highly structured and specialized organs: stamens (male) and gynoecia (female, containing ovules). These organs synchronously develop within protective flower buds, until anthesis, via tightly coordinated mechanisms that are essential for effective fertilization and production of viable seeds. The phytohormone auxin is one of the key endogenous signalling molecules controlling initiation and development of these, and other, plant organs. In particular, its uneven distribution, resulting from tightly controlled production, metabolism and directional transport, is an important morphogenic factor. In this review we discuss how developmentally controlled and localized auxin biosynthesis and transport contribute to the coordinated development of plants' reproductive organs, and their fertilized derivatives (embryos) via the regulation of auxin levels and distribution within and around them. Current understanding of the links between de novo local auxin biosynthesis, auxin transport and/or signalling is presented to highlight the importance of the non-cell autonomous action of auxin production on development and morphogenesis of reproductive organs and embryos. An overview of transcription factor families, which spatiotemporally define local auxin production by controlling key auxin biosynthetic enzymes, is also presented. AU - Robert, Hélène AU - Crhák Khaitová, Lucie AU - Mroue, Souad AU - Benková, Eva ID - 1540 IS - 16 JF - Journal of Experimental Botany TI - The importance of localized auxin production for morphogenesis of reproductive organs and embryos in Arabidopsis VL - 66 ER - TY - JOUR AB - Reciprocal coevolution between host and pathogen is widely seen as a major driver of evolution and biological innovation. Yet, to date, the underlying genetic mechanisms and associated trait functions that are unique to rapid coevolutionary change are generally unknown. We here combined experimental evolution of the bacterial biocontrol agent Bacillus thuringiensis and its nematode host Caenorhabditis elegans with large-scale phenotyping, whole genome analysis, and functional genetics to demonstrate the selective benefit of pathogen virulence and the underlying toxin genes during the adaptation process. We show that: (i) high virulence was specifically favoured during pathogen–host coevolution rather than pathogen one-sided adaptation to a nonchanging host or to an environment without host; (ii) the pathogen genotype BT-679 with known nematocidal toxin genes and high virulence specifically swept to fixation in all of the independent replicate populations under coevolution but only some under one-sided adaptation; (iii) high virulence in the BT-679-dominated populations correlated with elevated copy numbers of the plasmid containing the nematocidal toxin genes; (iv) loss of virulence in a toxin-plasmid lacking BT-679 isolate was reconstituted by genetic reintroduction or external addition of the toxins.We conclude that sustained coevolution is distinct from unidirectional selection in shaping the pathogen's genome and life history characteristics. To our knowledge, this study is the first to characterize the pathogen genes involved in coevolutionary adaptation in an animal host–pathogen interaction system. AU - El Masri, Leila AU - Branca, Antoine AU - Sheppard, Anna AU - Papkou, Andrei AU - Laehnemann, David AU - Guenther, Patrick AU - Prahl, Swantje AU - Saebelfeld, Manja AU - Hollensteiner, Jacqueline AU - Liesegang, Heiko AU - Brzuszkiewicz, Elzbieta AU - Daniel, Rolf AU - Michiels, Nico AU - Schulte, Rebecca AU - Kurtz, Joachim AU - Rosenstiel, Philip AU - Telschow, Arndt AU - Bornberg Bauer, Erich AU - Schulenburg, Hinrich ID - 1551 IS - 6 JF - PLoS Biology TI - Host–pathogen coevolution: The selective advantage of Bacillus thuringiensis virulence and its cry toxin genes VL - 13 ER - TY - CHAP AB - Nature has incorporated small photochromic molecules, colloquially termed 'photoswitches', in photoreceptor proteins to sense optical cues in photo-taxis and vision. While Nature's ability to employ light-responsive functionalities has long been recognized, it was not until recently that scientists designed, synthesized and applied synthetic photochromes to manipulate many of which open rapidly and locally in their native cell types, biological processes with the temporal and spatial resolution of light. Ion channels in particular have come to the forefront of proteins that can be put under the designer control of synthetic photochromes. Photochromic ion channel controllers are comprised of three classes, photochromic soluble ligands (PCLs), photochromic tethered ligands (PTLs) and photochromic crosslinkers (PXs), and in each class ion channel functionality is controlled through reversible changes in photochrome structure. By acting as light-dependent ion channel agonists, antagonist or modulators, photochromic controllers effectively converted a wide range of ion channels, including voltage-gated ion channels, 'leak channels', tri-, tetra- and pentameric ligand-gated ion channels, and temperaturesensitive ion channels, into man-made photoreceptors. Control by photochromes can be reversible, unlike in the case of 'caged' compounds, and non-invasive with high spatial precision, unlike pharmacology and electrical manipulation. Here, we introduce design principles of emerging photochromic molecules that act on ion channels and discuss the impact that these molecules are beginning to have on ion channel biophysics and neuronal physiology. AU - Mckenzie, Catherine AU - Sanchez Romero, Inmaculada AU - Janovjak, Harald L ID - 1549 SN - 978-1-4939-2844-6 T2 - Novel chemical tools to study ion channel biology TI - Flipping the photoswitch: Ion channels under light control VL - 869 ER - TY - JOUR AB - Reproduction within a host and transmission to the next host are crucial for the virulence and fitness of pathogens. Nevertheless, basic knowledge about such parameters is often missing from the literature, even for well-studied bacteria, such as Bacillus thuringiensis, an endospore-forming insect pathogen, which infects its hosts via the oral route. To characterize bacterial replication success, we made use of an experimental oral infection system for the red flour beetle Tribolium castaneum and developed a flow cytometric assay for the quantification of both spore ingestion by the individual beetle larvae and the resulting spore load after bacterial replication and resporulation within cadavers. On average, spore numbers increased 460-fold, showing that Bacillus thuringiensis grows and replicates successfully in insect cadavers. By inoculating cadaver-derived spores and spores from bacterial stock cultures into nutrient medium, we next investigated outgrowth characteristics of vegetative cells and found that cadaver- derived bacteria showed reduced growth compared to bacteria from the stock cultures. Interestingly, this reduced growth was a consequence of inhibited spore germination, probably originating from the host and resulting in reduced host mortality in subsequent infections by cadaver-derived spores. Nevertheless, we further showed that Bacillus thuringiensis transmission was possible via larval cannibalism when no other food was offered. These results contribute to our understanding of the ecology of Bacillus thuringiensis as an insect pathogen. AU - Milutinovic, Barbara AU - Höfling, Christina AU - Futo, Momir AU - Scharsack, Jörn AU - Kurtz, Joachim ID - 1548 IS - 23 JF - Applied and Environmental Microbiology TI - Infection of Tribolium castaneum with Bacillus thuringiensis: Quantification of bacterial replication within cadavers, transmission via cannibalism, and inhibition of spore germination VL - 81 ER - TY - JOUR AB - Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, we show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns. AU - Maiuri, Paolo AU - Rupprecht, Jean AU - Wieser, Stefan AU - Ruprecht, Verena AU - Bénichou, Olivier AU - Carpi, Nicolas AU - Coppey, Mathieu AU - De Beco, Simon AU - Gov, Nir AU - Heisenberg, Carl-Philipp J AU - Lage Crespo, Carolina AU - Lautenschlaeger, Franziska AU - Le Berre, Maël AU - Lennon Duménil, Ana AU - Raab, Matthew AU - Thiam, Hawa AU - Piel, Matthieu AU - Sixt, Michael K AU - Voituriez, Raphaël ID - 1553 IS - 2 JF - Cell TI - Actin flows mediate a universal coupling between cell speed and cell persistence VL - 161 ER - TY - JOUR AB - The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute. AU - Mayer, Christian AU - Jaglin, Xavier AU - Cobbs, Lucy AU - Bandler, Rachel AU - Streicher, Carmen AU - Cepko, Constance AU - Hippenmeyer, Simon AU - Fishell, Gord ID - 1550 IS - 5 JF - Neuron TI - Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries VL - 87 ER - TY - JOUR AB - Let G be a graph on the vertex set V(G) = {x1,…,xn} with the edge set E(G), and let R = K[x1,…, xn] be the polynomial ring over a field K. Two monomial ideals are associated to G, the edge ideal I(G) generated by all monomials xixj with {xi,xj} ∈ E(G), and the vertex cover ideal IG generated by monomials ∏xi∈Cxi for all minimal vertex covers C of G. A minimal vertex cover of G is a subset C ⊂ V(G) such that each edge has at least one vertex in C and no proper subset of C has the same property. Indeed, the vertex cover ideal of G is the Alexander dual of the edge ideal of G. In this paper, for an unmixed bipartite graph G we consider the lattice of vertex covers LG and we explicitly describe the minimal free resolution of the ideal associated to LG which is exactly the vertex cover ideal of G. Then we compute depth, projective dimension, regularity and extremal Betti numbers of R/I(G) in terms of the associated lattice. AU - Mohammadi, Fatemeh AU - Moradi, Somayeh ID - 1547 IS - 3 JF - Bulletin of the Korean Mathematical Society TI - Resolution of unmixed bipartite graphs VL - 52 ER - TY - JOUR AB - The elongator complex subunit 2 (ELP2) protein, one subunit of an evolutionarily conserved histone acetyltransferase complex, has been shown to participate in leaf patterning, plant immune and abiotic stress responses in Arabidopsis thaliana. Here, its role in root development was explored. Compared to the wild type, the elp2 mutant exhibited an accelerated differentiation of its root stem cells and cell division was more active in its quiescent centre (QC). The key transcription factors responsible for maintaining root stem cell and QC identity, such as AP2 transcription factors PLT1 (PLETHORA1) and PLT2 (PLETHORA2), GRAS transcription factors such as SCR (SCARECROW) and SHR (SHORT ROOT) and WUSCHEL-RELATED HOMEOBOX5 transcription factor WOX5, were all strongly down-regulated in the mutant. On the other hand, expression of the G2/M transition activator CYCB1 was substantially induced in elp2. The auxin efflux transporters PIN1 and PIN2 showed decreased protein levels and PIN1 also displayed mild polarity alterations in elp2, which resulted in a reduced auxin content in the root tip. Either the acetylation or methylation level of each of these genes differed between the mutant and the wild type, suggesting that the ELP2 regulation of root development involves the epigenetic modification of a range of transcription factors and other developmental regulators. AU - Jia, Yuebin AU - Tian, Huiyu AU - Li, Hongjiang AU - Yu, Qianqian AU - Wang, Lei AU - Friml, Jirí AU - Ding, Zhaojun ID - 1556 IS - 15 JF - Journal of Experimental Botany TI - The Arabidopsis thaliana elongator complex subunit 2 epigenetically affects root development VL - 66 ER - TY - JOUR AB - We show that incorporating spatial dispersal of individuals into a simple vaccination epidemic model may give rise to a model that exhibits rich dynamical behavior. Using an SIVS (susceptible-infected-vaccinated-susceptible) model as a basis, we describe the spread of an infectious disease in a population split into two regions. In each subpopulation, both forward and backward bifurcations can occur. This implies that for disconnected regions the two-patch system may admit several steady states. We consider traveling between the regions and investigate the impact of spatial dispersal of individuals on the model dynamics. We establish conditions for the existence of multiple nontrivial steady states in the system, and we study the structure of the equilibria. The mathematical analysis reveals an unusually rich dynamical behavior, not normally found in the simple epidemic models. In addition to the disease-free equilibrium, eight endemic equilibria emerge from backward transcritical and saddle-node bifurcation points, forming an interesting bifurcation diagram. Stability of steady states, their bifurcations, and the global dynamics are investigated with analytical tools, numerical simulations, and rigorous set-oriented numerical computations. AU - Knipl, Diána AU - Pilarczyk, Pawel AU - Röst, Gergely ID - 1555 IS - 2 JF - SIAM Journal on Applied Dynamical Systems TI - Rich bifurcation structure in a two patch vaccination model VL - 14 ER - TY - JOUR AB - CyclophilinAis a conserved peptidyl-prolyl cis-trans isomerase (PPIase) best known as the cellular receptor of the immunosuppressant cyclosporine A. Despite significant effort, evidence of developmental functions of cyclophilin A in non-plant systems has remained obscure. Mutations in a tomato (Solanum lycopersicum) cyclophilin A ortholog, DIAGEOTROPICA (DGT), have been shown to abolish the organogenesis of lateral roots; however, a mechanistic explanation of the phenotype is lacking. Here, we show that the dgt mutant lacks auxin maxima relevant to priming and specification of lateral root founder cells. DGT is expressed in shoot and root, and localizes to both the nucleus and cytoplasm during lateral root organogenesis. Mutation of ENTIRE/ IAA9, a member of the auxin-responsive Aux/IAA protein family of transcriptional repressors, partially restores the inability of dgt to initiate lateral root primordia but not the primordia outgrowth. By comparison, grafting of a wild-type scion restores the process of lateral root formation, consistent with participation of a mobile signal. Antibodies do not detect movement of the DGT protein into the dgt rootstock; however, experiments with radiolabeled auxin and an auxin-specific microelectrode demonstrate abnormal auxin fluxes. Functional studies of DGT in heterologous yeast and tobacco-leaf auxin-transport systems demonstrate that DGT negatively regulates PIN-FORMED (PIN) auxin efflux transporters by affecting their plasma membrane localization. Studies in tomato support complex effects of the dgt mutation on PIN expression level, expression domain and plasma membrane localization. Our data demonstrate that DGT regulates auxin transport in lateral root formation. AU - Ivanchenko, Maria AU - Zhu, Jinsheng AU - Wang, Bangjun AU - Medvecka, Eva AU - Du, Yunlong AU - Azzarello, Elisa AU - Mancuso, Stefano AU - Megraw, Molly AU - Filichkin, Sergei AU - Dubrovsky, Joseph AU - Friml, Jirí AU - Geisler, Markus ID - 1558 IS - 4 JF - Development TI - The cyclophilin a DIAGEOTROPICA gene affects auxin transport in both root and shoot to control lateral root formation VL - 142 ER - TY - JOUR AB - γ-Aminobutyric acid (GABA)- and glycine-mediated hyperpolarizing inhibition is associated with a chloride influx that depends on the inwardly directed chloride electrochemical gradient. In neurons, the extrusion of chloride from the cytosol primarily depends on the expression of an isoform of potassium-chloride cotransporters (KCC2s). KCC2 is crucial in the regulation of the inhibitory tone of neural circuits, including pain processing neural assemblies. Thus we investigated the cellular distribution of KCC2 in neurons underlying pain processing in the superficial spinal dorsal horn of rats by using high-resolution immunocytochemical methods. We demonstrated that perikarya and dendrites widely expressed KCC2, but axon terminals proved to be negative for KCC2. In single ultrathin sections, silver deposits labeling KCC2 molecules showed different densities on the surface of dendritic profiles, some of which were negative for KCC2. In freeze fracture replicas and tissue sections double stained for the β3-subunit of GABAA receptors and KCC2, GABAA receptors were revealed on dendritic segments with high and also with low KCC2 densities. By measuring the distances between spots immunoreactive for gephyrin (a scaffolding protein of GABAA and glycine receptors) and KCC2 on the surface of neurokinin 1 (NK1) receptor-immunoreactive dendrites, we found that gephyrin-immunoreactive spots were located at various distances from KCC2 cotransporters; 5.7 % of them were recovered in the middle of 4-10-μm-long dendritic segments that were free of KCC2 immunostaining. The variable local densities of KCC2 may result in variable postsynaptic potentials evoked by the activation of GABAA and glycine receptors along the dendrites of spinal neurons. AU - Javdani, Fariba AU - Holló, Krisztina AU - Hegedűs, Krisztina AU - Kis, Gréta AU - Hegyi, Zoltán AU - Dócs, Klaudia AU - Kasugai, Yu AU - Fukazawa, Yugo AU - Shigemoto, Ryuichi AU - Antal, Miklós ID - 1557 IS - 13 JF - Journal of Comparative Neurology TI - Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats VL - 523 ER - TY - JOUR AB - There are deep, yet largely unexplored, connections between computer science and biology. Both disciplines examine how information proliferates in time and space. Central results in computer science describe the complexity of algorithms that solve certain classes of problems. An algorithm is deemed efficient if it can solve a problem in polynomial time, which means the running time of the algorithm is a polynomial function of the length of the input. There are classes of harder problems for which the fastest possible algorithm requires exponential time. Another criterion is the space requirement of the algorithm. There is a crucial distinction between algorithms that can find a solution, verify a solution, or list several distinct solutions in given time and space. The complexity hierarchy that is generated in this way is the foundation of theoretical computer science. Precise complexity results can be notoriously difficult. The famous question whether polynomial time equals nondeterministic polynomial time (i.e., P = NP) is one of the hardest open problems in computer science and all of mathematics. Here, we consider simple processes of ecological and evolutionary spatial dynamics. The basic question is: What is the probability that a new invader (or a new mutant)will take over a resident population?We derive precise complexity results for a variety of scenarios. We therefore show that some fundamental questions in this area cannot be answered by simple equations (assuming that P is not equal to NP). AU - Ibsen-Jensen, Rasmus AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 1559 IS - 51 JF - PNAS TI - Computational complexity of ecological and evolutionary spatial dynamics VL - 112 ER - TY - JOUR AB - Replication-deficient recombinant adenoviruses are potent vectors for the efficient transient expression of exogenous genes in resting immune cells. However, most leukocytes are refractory to efficient adenoviral transduction as they lack expression of the coxsackie/adenovirus receptor (CAR). To circumvent this obstacle, we generated the R26/CAG-CARΔ1StopF (where R26 is ROSA26 and CAG is CMV early enhancer/chicken β actin promoter) knock-in mouse line. This strain allows monitoring of in situ Cre recombinase activity through expression of CARΔ1. Simultaneously, CARΔ1 expression permits selective and highly efficient adenoviral transduction of immune cell populations, such as mast cells or T cells, directly ex vivo in bulk cultures without prior cell purification or activation. Furthermore, we show that CARΔ1 expression dramatically improves adenoviral infection of in vitro differentiated conventional and plasmacytoid dendritic cells (DCs), basophils, mast cells, as well as Hoxb8-immortalized hematopoietic progenitor cells. This novel dual function mouse strain will hence be a valuable tool to rapidly dissect the function of specific genes in leukocyte physiology. AU - Heger, Klaus AU - Kober, Maike AU - Rieß, David AU - Drees, Christoph AU - De Vries, Ingrid AU - Bertossi, Arianna AU - Roers, Axel AU - Sixt, Michael K AU - Schmidt Supprian, Marc ID - 1561 IS - 6 JF - European Journal of Immunology TI - A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors VL - 45 ER - TY - JOUR AB - The visualization of hormonal signaling input and output is key to understanding how multicellular development is regulated. The plant signaling molecule auxin triggers many growth and developmental responses, but current tools lack the sensitivity or precision to visualize these. We developed a set of fluorescent reporters that allow sensitive and semiquantitative readout of auxin responses at cellular resolution in Arabidopsis thaliana. These generic tools are suitable for any transformable plant species. AU - Liao, Cheyang AU - Smet, Wouter AU - Brunoud, Géraldine AU - Yoshida, Saiko AU - Vernoux, Teva AU - Weijers, Dolf ID - 1554 IS - 3 JF - Nature Methods TI - Reporters for sensitive and quantitative measurement of auxin response VL - 12 ER - TY - JOUR AB - Stromal cells in the subcapsular sinus of the lymph node 'decide' which cells and molecules are allowed access to the deeper parenchyma. The glycoprotein PLVAP is a crucial component of this selector function. AU - Hons, Miroslav AU - Sixt, Michael K ID - 1560 IS - 4 JF - Nature Immunology TI - The lymph node filter revealed VL - 16 ER - TY - JOUR AB - Leptin is an adipokine produced by the adipose tissue regulating body weight through its appetite-suppressing effect. Besides being expressed in the hypothalamus and hippocampus, leptin receptors (ObRs) are also present in chromaffin cells of the adrenal medulla. In the present study, we report the effect of leptin on mouse chromaffin cell (MCC) functionality, focusing on cell excitability and catecholamine secretion. Acute application of leptin (1 nm) on spontaneously firing MCCs caused a slowly developing membrane hyperpolarization followed by complete blockade of action potential (AP) firing. This inhibitory effect at rest was abolished by the BK channel blocker paxilline (1 μm), suggesting the involvement of BK potassium channels. Single-channel recordings in 'perforated microvesicles' confirmed that leptin increased BK channel open probability without altering its unitary conductance. BK channel up-regulation was associated with the phosphoinositide 3-kinase (PI3K) signalling cascade because the PI3K specific inhibitor wortmannin (100 nm) fully prevented BK current increase. We also tested the effect of leptin on evoked AP firing and Ca2+-driven exocytosis. Although leptin preserves well-adapted AP trains of lower frequency, APs are broader and depolarization-evoked exocytosis is increased as a result of the larger size of the ready-releasable pool and higher frequency of vesicle release. The kinetics and quantal size of single secretory events remained unaltered. Leptin had no effect on firing and secretion in db-/db- mice lacking the ObR gene, confirming its specificity. In conclusion, leptin exhibits a dual action on MCC activity. It dampens AP firing at rest but preserves AP firing and increases catecholamine secretion during sustained stimulation, highlighting the importance of the adipo-adrenal axis in the leptin-mediated increase of sympathetic tone and catecholamine release. AU - Gavello, Daniela AU - Vandael, David H AU - Gosso, Sara AU - Carbone, Emilio AU - Carabelli, Valentina ID - 1565 IS - 22 JF - Journal of Physiology TI - Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells VL - 593 ER - TY - JOUR AB - The plant hormone auxin is a key regulator of plant growth and development. Auxin levels are sensed and interpreted by distinct receptor systems that activate a broad range of cellular responses. The Auxin-Binding Protein1 (ABP1) that has been identified based on its ability to bind auxin with high affinity is a prime candidate for the extracellular receptor responsible for mediating a range of auxin effects, in particular, the fast non-transcriptional ones. Contradictory genetic studies suggested prominent or no importance of ABP1 in many developmental processes. However, how crucial the role of auxin binding to ABP1 is for its functions has not been addressed. Here, we show that the auxin-binding pocket of ABP1 is essential for its gain-of-function cellular and developmental roles. In total, 16 different abp1 mutants were prepared that possessed substitutions in the metal core or in the hydrophobic amino acids of the auxin-binding pocket as well as neutral mutations. Their analysis revealed that an intact auxin-binding pocket is a prerequisite for ABP1 to activate downstream components of the ABP1 signalling pathway, such as Rho of Plants (ROPs) and to mediate the clathrin association with membranes for endocytosis regulation. In planta analyses demonstrated the importance of the auxin binding pocket for all known ABP1-mediated postembryonic developmental processes, including morphology of leaf epidermal cells, root growth and root meristem activity, and vascular tissue differentiation. Taken together, these findings suggest that auxin binding to ABP1 is central to its function, supporting the role of ABP1 as auxin receptor. AU - Grones, Peter AU - Chen, Xu AU - Simon, Sibu AU - Kaufmann, Walter AU - De Rycke, Riet AU - Nodzyński, Tomasz AU - Zažímalová, Eva AU - Friml, Jirí ID - 1562 IS - 16 JF - Journal of Experimental Botany TI - Auxin-binding pocket of ABP1 is crucial for its gain-of-function cellular and developmental roles VL - 66 ER - TY - JOUR AU - Gilson, Matthieu AU - Savin, Cristina AU - Zenke, Friedemann ID - 1564 IS - 11 JF - Frontiers in Computational Neuroscience TI - Editorial: Emergent neural computation from the interaction of different forms of plasticity VL - 9 ER - TY - CONF AB - Aiming at the automatic diagnosis of tumors from narrow band imaging (NBI) magnifying endoscopy (ME) images of the stomach, we combine methods from image processing, computational topology, and machine learning to classify patterns into normal, tubular, vessel. Training the algorithm on a small number of images of each type, we achieve a high rate of correct classifications. The analysis of the learning algorithm reveals that a handful of geometric and topological features are responsible for the overwhelming majority of decisions. AU - Dunaeva, Olga AU - Edelsbrunner, Herbert AU - Lukyanov, Anton AU - Machin, Michael AU - Malkova, Daria ID - 1568 T2 - Proceedings - 16th International Symposium on Symbolic and Numeric Algorithms for Scientific Computing TI - The classification of endoscopy images with persistent homology ER - TY - CONF AB - My personal journey to the fascinating world of geometric forms started more than 30 years ago with the invention of alpha shapes in the plane. It took about 10 years before we generalized the concept to higher dimensions, we produced working software with a graphics interface for the three-dimensional case. At the same time, we added homology to the computations. Needless to say that this foreshadowed the inception of persistent homology, because it suggested the study of filtrations to capture the scale of a shape or data set. Importantly, this method has fast algorithms. The arguably most useful result on persistent homology is the stability of its diagrams under perturbations. AU - Edelsbrunner, Herbert ID - 1567 T2 - 23rd International Symposium TI - Shape, homology, persistence, and stability VL - 9411 ER - TY - JOUR AB - For a given self-map $f$ of $M$, a closed smooth connected and simply-connected manifold of dimension $m\geq 4$, we provide an algorithm for estimating the values of the topological invariant $D^m_r[f]$, which equals the minimal number of $r$-periodic points in the smooth homotopy class of $f$. Our results are based on the combinatorial scheme for computing $D^m_r[f]$ introduced by G. Graff and J. Jezierski [J. Fixed Point Theory Appl. 13 (2013), 63-84]. An open-source implementation of the algorithm programmed in C++ is publicly available at {\tt http://www.pawelpilarczyk.com/combtop/}. AU - Graff, Grzegorz AU - Pilarczyk, Pawel ID - 1563 IS - 1 JF - Topological Methods in Nonlinear Analysis TI - An algorithmic approach to estimating the minimal number of periodic points for smooth self-maps of simply-connected manifolds VL - 45 ER - TY - JOUR AB - Multiple plant developmental processes, such as lateral root development, depend on auxin distribution patterns that are in part generated by the PIN-formed family of auxin-efflux transporters. Here we propose that AUXIN RESPONSE FACTOR7 (ARF7) and the ARF7-regulated FOUR LIPS/MYB124 (FLP) transcription factors jointly form a coherent feed-forward motif that mediates the auxin-responsive PIN3 transcription in planta to steer the early steps of lateral root formation. This regulatory mechanism might endow the PIN3 circuitry with a temporal 'memory' of auxin stimuli, potentially maintaining and enhancing the robustness of the auxin flux directionality during lateral root development. The cooperative action between canonical auxin signalling and other transcription factors might constitute a general mechanism by which transcriptional auxin-sensitivity can be regulated at a tissue-specific level. AU - Chen, Qian AU - Liu, Yang AU - Maere, Steven AU - Lee, Eunkyoung AU - Van Isterdael, Gert AU - Xie, Zidian AU - Xuan, Wei AU - Lucas, Jessica AU - Vassileva, Valya AU - Kitakura, Saeko AU - Marhavy, Peter AU - Wabnik, Krzysztof T AU - Geldner, Niko AU - Benková, Eva AU - Le, Jie AU - Fukaki, Hidehiro AU - Grotewold, Erich AU - Li, Chuanyou AU - Friml, Jirí AU - Sack, Fred AU - Beeckman, Tom AU - Vanneste, Steffen ID - 1574 JF - Nature Communications TI - A coherent transcriptional feed-forward motif model for mediating auxin-sensitive PIN3 expression during lateral root development VL - 6 ER - TY - JOUR AB - The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space. AU - Chabaud, Mélanie AU - Heuzé, Mélina AU - Bretou, Marine AU - Vargas, Pablo AU - Maiuri, Paolo AU - Solanes, Paola AU - Maurin, Mathieu AU - Terriac, Emmanuel AU - Le Berre, Maël AU - Lankar, Danielle AU - Piolot, Tristan AU - Adelstein, Robert AU - Zhang, Yingfan AU - Sixt, Michael K AU - Jacobelli, Jordan AU - Bénichou, Olivier AU - Voituriez, Raphaël AU - Piel, Matthieu AU - Lennon Duménil, Ana ID - 1575 JF - Nature Communications TI - Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells VL - 6 ER - TY - JOUR AB - Spatial regulation of the plant hormone indole-3-acetic acid (IAA, or auxin) is essential for plant development. Auxin gradient establishment is mediated by polarly localized auxin transporters, including PIN-FORMED (PIN) proteins. Their localization and abundance at the plasma membrane are tightly regulated by endomembrane machinery, especially the endocytic and recycling pathways mediated by the ADP ribosylation factor guanine nucleotide exchange factor (ARF-GEF) GNOM. We assessed the role of the early secretory pathway in establishing PIN1 polarity in Arabidopsis thaliana by pharmacological and genetic approaches. We identified the compound endosidin 8 (ES8), which selectively interferes with PIN1 basal polarity without altering the polarity of apical proteins. ES8 alters the auxin distribution pattern in the root and induces a strong developmental phenotype, including reduced root length. The ARF-GEF- defective mutants gnom-like 1 ( gnl1-1) and gnom ( van7) are significantly resistant to ES8. The compound does not affect recycling or vacuolar trafficking of PIN1 but leads to its intracellular accumulation, resulting in loss of PIN1 basal polarity at the plasma membrane. Our data confirm a role for GNOM in endoplasmic reticulum (ER) - Golgi trafficking and reveal that a GNL1/GNOM-mediated early secretory pathway selectively regulates PIN1 basal polarity establishment in a manner essential for normal plant development. AU - Doyle, Siamsa AU - Haegera, Ash AU - Vain, Thomas AU - Rigala, Adeline AU - Viotti, Corrado AU - Łangowskaa, Małgorzata AU - Maa, Qian AU - Friml, Jirí AU - Raikhel, Natasha AU - Hickse, Glenn AU - Robert, Stéphanie ID - 1569 IS - 7 JF - PNAS TI - An early secretory pathway mediated by gnom-like 1 and gnom is essential for basal polarity establishment in Arabidopsis thaliana VL - 112 ER - TY - JOUR AB - Grounding autonomous behavior in the nervous system is a fundamental challenge for neuroscience. In particular, self-organized behavioral development provides more questions than answers. Are there special functional units for curiosity, motivation, and creativity? This paper argues that these features can be grounded in synaptic plasticity itself, without requiring any higher-level constructs. We propose differential extrinsic plasticity (DEP) as a new synaptic rule for self-learning systems and apply it to a number of complex robotic systems as a test case. Without specifying any purpose or goal, seemingly purposeful and adaptive rhythmic behavior is developed, displaying a certain level of sensorimotor intelligence. These surprising results require no systemspecific modifications of the DEP rule. They rather arise from the underlying mechanism of spontaneous symmetry breaking,which is due to the tight brain body environment coupling. The new synaptic rule is biologically plausible and would be an interesting target for neurobiological investigation. We also argue that this neuronal mechanism may have been a catalyst in natural evolution. AU - Der, Ralf AU - Martius, Georg S ID - 1570 IS - 45 JF - PNAS TI - Novel plasticity rule can explain the development of sensorimotor intelligence VL - 112 ER - TY - JOUR AB - Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may fail to evolve when essential mutations are only accessible through positive selection if they are fixed simultaneously. How environmental variability affects such constraints is poorly understood. Here, we studied genetic constraints in fixed and fluctuating environments using the Escherichia coli lac operon as a model system for genotype-environment interactions. We found that, in different fixed environments, all trajectories that were reconstructed by applying point mutations within the transcription factor-operator interface became trapped at suboptima, where no additional improvements were possible. Paradoxically, repeated switching between these same environments allows unconstrained adaptation by continuous improvements. This evolutionary mode is explained by pervasive cross-environmental tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach, we developed a mathematical framework to quantify the landscape-crossing rates and show that this ratchet-like adaptive mechanism is robust in a wide spectrum of fluctuating environments. Overall, this study shows that genetic constraints can be overcome by environmental change and that crossenvironmental tradeoffs do not necessarily impede but also, can facilitate adaptive evolution. Because tradeoffs and environmental variability are ubiquitous in nature, we speculate this evolutionary mode to be of general relevance. AU - De Vos, Marjon AU - Dawid, Alexandre AU - Šunderlíková, Vanda AU - Tans, Sander ID - 1571 IS - 48 JF - PNAS TI - Breaking evolutionary constraint with a tradeoff ratchet VL - 112 ER - TY - JOUR AB - We consider the quantum ferromagnetic Heisenberg model in three dimensions, for all spins S ≥ 1/2. We rigorously prove the validity of the spin-wave approximation for the excitation spectrum, at the level of the first non-trivial contribution to the free energy at low temperatures. Our proof comes with explicit, constructive upper and lower bounds on the error term. It uses in an essential way the bosonic formulation of the model in terms of the Holstein-Primakoff representation. In this language, the model describes interacting bosons with a hard-core on-site repulsion and a nearest-neighbor attraction. This attractive interaction makes the lower bound on the free energy particularly tricky: the key idea there is to prove a differential inequality for the two-particle density, which is thereby shown to be smaller than the probability density of a suitably weighted two-particle random process on the lattice. AU - Correggi, Michele AU - Giuliani, Alessandro AU - Seiringer, Robert ID - 1572 IS - 1 JF - Communications in Mathematical Physics TI - Validity of the spin-wave approximation for the free energy of the Heisenberg ferromagnet VL - 339 ER - TY - JOUR AB - We present a new, simpler proof of the unconditional uniqueness of solutions to the cubic Gross-Pitaevskii hierarchy in ℝ3. One of the main tools in our analysis is the quantum de Finetti theorem. Our uniqueness result is equivalent to the one established in the celebrated works of Erdos, Schlein, and Yau. AU - Chen, Thomas AU - Hainzl, Christian AU - Pavlović, Nataša AU - Seiringer, Robert ID - 1573 IS - 10 JF - Communications on Pure and Applied Mathematics TI - Unconditional uniqueness for the cubic gross pitaevskii hierarchy via quantum de finetti VL - 68 ER - TY - JOUR AB - Synapsins (Syns) are an evolutionarily conserved family of presynaptic proteins crucial for the fine-tuning of synaptic function. A large amount of experimental evidences has shown that Syns are involved in the development of epileptic phenotypes and several mutations in Syn genes have been associated with epilepsy in humans and animal models. Syn mutations induce alterations in circuitry and neurotransmitter release, differentially affecting excitatory and inhibitory synapses, thus causing an excitation/inhibition imbalance in network excitability toward hyperexcitability that may be a determinant with regard to the development of epilepsy. Another approach to investigate epileptogenic mechanisms is to understand how silencing Syn affects the cellular behavior of single neurons and is associated with the hyperexcitable phenotypes observed in epilepsy. Here, we examined the functional effects of antisense-RNA inhibition of Syn expression on individually identified and isolated serotonergic cells of the Helix land snail. We found that Helix synapsin silencing increases cell excitability characterized by a slightly depolarized resting membrane potential, decreases the rheobase, reduces the threshold for action potential (AP) firing and increases the mean and instantaneous firing rates, with respect to control cells. The observed increase of Ca2+ and BK currents in Syn-silenced cells seems to be related to changes in the shape of the AP waveform. These currents sustain the faster spiking in Syn-deficient cells by increasing the after hyperpolarization and limiting the Na+ and Ca2+ channel inactivation during repetitive firing. This in turn speeds up the depolarization phase by reaching the AP threshold faster. Our results provide evidence that Syn silencing increases intrinsic cell excitability associated with increased Ca2+ and Ca2+-dependent BK currents in the absence of excitatory or inhibitory inputs. AU - Brenes, Oscar AU - Vandael, David H AU - Carbone, Emilio AU - Montarolo, Pier AU - Ghirardi, Mirella ID - 1580 JF - Neuroscience TI - Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons VL - 311 ER - TY - JOUR AB - Contrary to the pattern seen in mammalian sex chromosomes, where most Y-linked genes have X-linked homologs, the Drosophila X and Y chromosomes appear to be unrelated. Most of the Y-linked genes have autosomal paralogs, so autosome-to-Y transposition must be the main source of Drosophila Y-linked genes. Here we show how these genes were acquired. We found a previously unidentified gene (flagrante delicto Y, FDY) that originated from a recent duplication of the autosomal gene vig2 to the Y chromosome of Drosophila melanogaster. Four contiguous genes were duplicated along with vig2, but they became pseudogenes through the accumulation of deletions and transposable element insertions, whereas FDY remained functional, acquired testis-specific expression, and now accounts for ∼20% of the vig2-like mRNA in testis. FDY is absent in the closest relatives of D. melanogaster, and DNA sequence divergence indicates that the duplication to the Y chromosome occurred ∼2 million years ago. Thus, FDY provides a snapshot of the early stages of the establishment of a Y-linked gene and demonstrates how the Drosophila Y has been accumulating autosomal genes. AU - Carvalho, Antonio AU - Vicoso, Beatriz AU - Russo, Claudia AU - Swenor, Bonnielin AU - Clark, Andrew ID - 1577 IS - 40 JF - PNAS TI - Birth of a new gene on the Y chromosome of Drosophila melanogaster VL - 112 ER - TY - JOUR AB - We show that the Galois group of any Schubert problem involving lines in projective space contains the alternating group. This constitutes the largest family of enumerative problems whose Galois groups have been largely determined. Using a criterion of Vakil and a special position argument due to Schubert, our result follows from a particular inequality among Kostka numbers of two-rowed tableaux. In most cases, a combinatorial injection proves the inequality. For the remaining cases, we use the Weyl integral formulas to obtain an integral formula for these Kostka numbers. This rewrites the inequality as an integral, which we estimate to establish the inequality. AU - Brooks, Christopher AU - Martin Del Campo Sanchez, Abraham AU - Sottile, Frank ID - 1579 IS - 6 JF - Transactions of the American Mathematical Society TI - Galois groups of Schubert problems of lines are at least alternating VL - 367 ER - TY - JOUR AB - We prove that the dual of the digital Voronoi diagram constructed by flooding the plane from the data points gives a geometrically and topologically correct dual triangulation. This provides the proof of correctness for recently developed GPU algorithms that outperform traditional CPU algorithms for constructing two-dimensional Delaunay triangulations. AU - Cao, Thanhtung AU - Edelsbrunner, Herbert AU - Tan, Tiowseng ID - 1578 IS - 7 JF - Computational Geometry TI - Triangulations from topologically correct digital Voronoi diagrams VL - 48 ER - TY - JOUR AB - In animal embryos, morphogen gradients determine tissue patterning and morphogenesis. Shyer et al. provide evidence that, during vertebrate gut formation, tissue folding generates graded activity of signals required for subsequent steps of gut growth and differentiation, thereby revealing an intriguing link between tissue morphogenesis and morphogen gradient formation. AU - Bollenbach, Mark Tobias AU - Heisenberg, Carl-Philipp J ID - 1581 IS - 3 JF - Cell TI - Gradients are shaping up VL - 161 ER - TY - JOUR AB - We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices. AU - Altmeyer, Sebastian AU - Do, Younghae AU - Lai, Ying ID - 1589 JF - Scientific Reports TI - Magnetic field induced flow pattern reversal in a ferrofluidic Taylor-Couette system VL - 5 ER - TY - JOUR AB - We investigate weighted straight skeletons from a geometric, graph-theoretical, and combinatorial point of view. We start with a thorough definition and shed light on some ambiguity issues in the procedural definition. We investigate the geometry, combinatorics, and topology of faces and the roof model, and we discuss in which cases a weighted straight skeleton is connected. Finally, we show that the weighted straight skeleton of even a simple polygon may be non-planar and may contain cycles, and we discuss under which restrictions on the weights and/or the input polygon the weighted straight skeleton still behaves similar to its unweighted counterpart. In particular, we obtain a non-procedural description and a linear-time construction algorithm for the straight skeleton of strictly convex polygons with arbitrary weights. AU - Biedl, Therese AU - Held, Martin AU - Huber, Stefan AU - Kaaser, Dominik AU - Palfrader, Peter ID - 1584 IS - 5 JF - Computational Geometry: Theory and Applications TI - Reprint of: Weighted straight skeletons in the plane VL - 48 ER - TY - JOUR AB - We investigate weighted straight skeletons from a geometric, graph-theoretical, and combinatorial point of view. We start with a thorough definition and shed light on some ambiguity issues in the procedural definition. We investigate the geometry, combinatorics, and topology of faces and the roof model, and we discuss in which cases a weighted straight skeleton is connected. Finally, we show that the weighted straight skeleton of even a simple polygon may be non-planar and may contain cycles, and we discuss under which restrictions on the weights and/or the input polygon the weighted straight skeleton still behaves similar to its unweighted counterpart. In particular, we obtain a non-procedural description and a linear-time construction algorithm for the straight skeleton of strictly convex polygons with arbitrary weights. AU - Biedl, Therese AU - Held, Martin AU - Huber, Stefan AU - Kaaser, Dominik AU - Palfrader, Peter ID - 1582 IS - 2 JF - Computational Geometry: Theory and Applications TI - Weighted straight skeletons in the plane VL - 48 ER - TY - JOUR AB - We study the characteristics of straight skeletons of monotone polygonal chains and use them to devise an algorithm for computing positively weighted straight skeletons of monotone polygons. Our algorithm runs in O(nlogn) time and O(n) space, where n denotes the number of vertices of the polygon. AU - Biedl, Therese AU - Held, Martin AU - Huber, Stefan AU - Kaaser, Dominik AU - Palfrader, Peter ID - 1583 IS - 2 JF - Information Processing Letters TI - A simple algorithm for computing positively weighted straight skeletons of monotone polygons VL - 115 ER - TY - JOUR AB - We investigate the quantum interference shifts between energetically close states, where the state structure is observed by laser spectroscopy. We report a compact and analytical expression that models the quantum interference induced shift for any admixture of circular polarization of the incident laser and angle of observation. An experimental scenario free of quantum interference can thus be predicted with this formula. Although this study is exemplified here for muonic deuterium, it can be applied to any other laser spectroscopy measurement of ns-n′p frequencies of a nonrelativistic atomic system, via an ns→n′p→n′′s scheme. AU - Amaro, Pedro AU - Fratini, Filippo AU - Safari, Laleh AU - Antognini, Aldo AU - Indelicato, Paul AU - Pohl, Randolf AU - Santos, José ID - 1587 IS - 6 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Quantum interference shifts in laser spectroscopy with elliptical polarization VL - 92 ER -