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 -