TY - JOUR
AB - The cerebral cortex, the seat of our cognitive abilities, is composed of an intricate network of billions of excitatory projection and inhibitory interneurons. Postmitotic cortical neurons are generated by a diverse set of neural stem cell progenitors within dedicated zones and defined periods of neurogenesis during embryonic development. Disruptions in neurogenesis can lead to alterations in the neuronal cytoarchitecture, which is thought to represent a major underlying cause for several neurological disorders, including microcephaly, autism and epilepsy. Although a number of signaling pathways regulating neurogenesis have been described, the precise cellular and molecular mechanisms regulating the functional neural stem cell properties in cortical neurogenesis remain unclear. Here, we discuss the most up-to-date strategies to monitor the fundamental mechanistic parameters of neuronal progenitor proliferation, and recent advances deciphering the logic and dynamics of neurogenesis.
AU - Postiglione, Maria P
AU - Hippenmeyer, Simon
ID - 2175
IS - 3
JF - Future Neurology
TI - Monitoring neurogenesis in the cerebral cortex: an update
VL - 9
ER -
TY - JOUR
AB - Electron microscopy (EM) allows for the simultaneous visualization of all tissue components at high resolution. However, the extent to which conventional aldehyde fixation and ethanol dehydration of the tissue alter the fine structure of cells and organelles, thereby preventing detection of subtle structural changes induced by an experiment, has remained an issue. Attempts have been made to rapidly freeze tissue to preserve native ultrastructure. Shock-freezing of living tissue under high pressure (high-pressure freezing, HPF) followed by cryosubstitution of the tissue water avoids aldehyde fixation and dehydration in ethanol; the tissue water is immobilized in â ̂1/450 ms, and a close-to-native fine structure of cells, organelles and molecules is preserved. Here we describe a protocol for HPF that is useful to monitor ultrastructural changes associated with functional changes at synapses in the brain but can be applied to many other tissues as well. The procedure requires a high-pressure freezer and takes a minimum of 7 d but can be paused at several points.
AU - Studer, Daniel
AU - Zhao, Shanting
AU - Chai, Xuejun
AU - Jonas, Peter M
AU - Graber, Werner
AU - Nestel, Sigrun
AU - Frotscher, Michael
ID - 2176
IS - 6
JF - Nature Protocols
TI - Capture of activity-induced ultrastructural changes at synapses by high-pressure freezing of brain tissue
VL - 9
ER -
TY - CONF
AB - We give evidence for the difficulty of computing Betti numbers of simplicial complexes over a finite field. We do this by reducing the rank computation for sparse matrices with to non-zero entries to computing Betti numbers of simplicial complexes consisting of at most a constant times to simplices. Together with the known reduction in the other direction, this implies that the two problems have the same computational complexity.
AU - Edelsbrunner, Herbert
AU - Parsa, Salman
ID - 2177
T2 - Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms
TI - On the computational complexity of betti numbers reductions from matrix rank
ER -
TY - JOUR
AB - We consider the three-state toric homogeneous Markov chain model (THMC) without loops and initial parameters. At time T, the size of the design matrix is 6 × 3 · 2T-1 and the convex hull of its columns is the model polytope. We study the behavior of this polytope for T ≥ 3 and we show that it is defined by 24 facets for all T ≥ 5. Moreover, we give a complete description of these facets. From this, we deduce that the toric ideal associated with the design matrix is generated by binomials of degree at most 6. Our proof is based on a result due to Sturmfels, who gave a bound on the degree of the generators of a toric ideal, provided the normality of the corresponding toric variety. In our setting, we established the normality of the toric variety associated to the THMC model by studying the geometric properties of the model polytope.
AU - Haws, David
AU - Martin Del Campo Sanchez, Abraham
AU - Takemura, Akimichi
AU - Yoshida, Ruriko
ID - 2178
IS - 1
JF - Beitrage zur Algebra und Geometrie
TI - Markov degree of the three-state toric homogeneous Markov chain model
VL - 55
ER -
TY - JOUR
AB - We extend the proof of the local semicircle law for generalized Wigner matrices given in MR3068390 to the case when the matrix of variances has an eigenvalue -1. In particular, this result provides a short proof of the optimal local Marchenko-Pastur law at the hard edge (i.e. around zero) for sample covariance matrices X*X, where the variances of the entries of X may vary.
AU - Ajanki, Oskari H
AU - Erdös, László
AU - Krüger, Torben H
ID - 2179
JF - Electronic Communications in Probability
TI - Local semicircle law with imprimitive variance matrix
VL - 19
ER -
TY - JOUR
AB - Weighted majority votes allow one to combine the output of several classifiers or voters. MinCq is a recent algorithm for optimizing the weight of each voter based on the minimization of a theoretical bound over the risk of the vote with elegant PAC-Bayesian generalization guarantees. However, while it has demonstrated good performance when combining weak classifiers, MinCq cannot make use of the useful a priori knowledge that one may have when using a mixture of weak and strong voters. In this paper, we propose P-MinCq, an extension of MinCq that can incorporate such knowledge in the form of a constraint over the distribution of the weights, along with general proofs of convergence that stand in the sample compression setting for data-dependent voters. The approach is applied to a vote of k-NN classifiers with a specific modeling of the voters' performance. P-MinCq significantly outperforms the classic k-NN classifier, a symmetric NN and MinCq using the same voters. We show that it is also competitive with LMNN, a popular metric learning algorithm, and that combining both approaches further reduces the error.
AU - Bellet, Aurélien
AU - Habrard, Amaury
AU - Morvant, Emilie
AU - Sebban, Marc
ID - 2180
IS - 1-2
JF - Machine Learning
TI - Learning a priori constrained weighted majority votes
VL - 97
ER -
TY - JOUR
AB - We describe a simple adaptive network of coupled chaotic maps. The network reaches a stationary state (frozen topology) for all values of the coupling parameter, although the dynamics of the maps at the nodes of the network can be nontrivial. The structure of the network shows interesting hierarchical properties and in certain parameter regions the dynamics is polysynchronous: Nodes can be divided in differently synchronized classes but, contrary to cluster synchronization, nodes in the same class need not be connected to each other. These complicated synchrony patterns have been conjectured to play roles in systems biology and circuits. The adaptive system we study describes ways whereby this behavior can evolve from undifferentiated nodes.
AU - Botella Soler, Vicente
AU - Glendinning, Paul
ID - 2183
IS - 6
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
TI - Hierarchy and polysynchrony in an adaptive network
VL - 89
ER -
TY - JOUR
AB - Given topological spaces X,Y, a fundamental problem of algebraic topology is understanding the structure of all continuous maps X→ Y. We consider a computational version, where X,Y are given as finite simplicial complexes, and the goal is to compute [X,Y], that is, all homotopy classes of suchmaps.We solve this problem in the stable range, where for some d ≥ 2, we have dim X ≤ 2d-2 and Y is (d-1)-connected; in particular, Y can be the d-dimensional sphere Sd. The algorithm combines classical tools and ideas from homotopy theory (obstruction theory, Postnikov systems, and simplicial sets) with algorithmic tools from effective algebraic topology (locally effective simplicial sets and objects with effective homology). In contrast, [X,Y] is known to be uncomputable for general X,Y, since for X = S1 it includes a well known undecidable problem: testing triviality of the fundamental group of Y. In follow-up papers, the algorithm is shown to run in polynomial time for d fixed, and extended to other problems, such as the extension problem, where we are given a subspace A ⊂ X and a map A→ Y and ask whether it extends to a map X → Y, or computing the Z2-index-everything in the stable range. Outside the stable range, the extension problem is undecidable.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Matoušek, Jiří
AU - Sergeraert, Francis
AU - Vokřínek, Lukáš
AU - Wagner, Uli
ID - 2184
IS - 3
JF - Journal of the ACM
TI - Computing all maps into a sphere
VL - 61
ER -
TY - CONF
AB - We revisit the classical problem of converting an imperfect source of randomness into a usable cryptographic key. Assume that we have some cryptographic application P that expects a uniformly random m-bit key R and ensures that the best attack (in some complexity class) against P(R) has success probability at most δ. Our goal is to design a key-derivation function (KDF) h that converts any random source X of min-entropy k into a sufficiently "good" key h(X), guaranteeing that P(h(X)) has comparable security δ′ which is 'close' to δ. Seeded randomness extractors provide a generic way to solve this problem for all applications P, with resulting security δ′ = O(δ), provided that we start with entropy k ≥ m + 2 log (1/δ) - O(1). By a result of Radhakrishnan and Ta-Shma, this bound on k (called the "RT-bound") is also known to be tight in general. Unfortunately, in many situations the loss of 2 log (1/δ) bits of entropy is unacceptable. This motivates the study KDFs with less entropy waste by placing some restrictions on the source X or the application P. In this work we obtain the following new positive and negative results in this regard: - Efficient samplability of the source X does not help beat the RT-bound for general applications. This resolves the SRT (samplable RT) conjecture of Dachman-Soled et al. [DGKM12] in the affirmative, and also shows that the existence of computationally-secure extractors beating the RT-bound implies the existence of one-way functions. - We continue in the line of work initiated by Barak et al. [BDK+11] and construct new information-theoretic KDFs which beat the RT-bound for large but restricted classes of applications. Specifically, we design efficient KDFs that work for all unpredictability applications P (e.g., signatures, MACs, one-way functions, etc.) and can either: (1) extract all of the entropy k = m with a very modest security loss δ′ = O(δ·log (1/δ)), or alternatively, (2) achieve essentially optimal security δ′ = O(δ) with a very modest entropy loss k ≥ m + loglog (1/δ). In comparison, the best prior results from [BDK+11] for this class of applications would only guarantee δ′ = O(√δ) when k = m, and would need k ≥ m + log (1/δ) to get δ′ = O(δ). - The weaker bounds of [BDK+11] hold for a larger class of so-called "square- friendly" applications (which includes all unpredictability, but also some important indistinguishability, applications). Unfortunately, we show that these weaker bounds are tight for the larger class of applications. - We abstract out a clean, information-theoretic notion of (k,δ,δ′)- unpredictability extractors, which guarantee "induced" security δ′ for any δ-secure unpredictability application P, and characterize the parameters achievable for such unpredictability extractors. Of independent interest, we also relate this notion to the previously-known notion of (min-entropy) condensers, and improve the state-of-the-art parameters for such condensers.
AU - Dodis, Yevgeniy
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ED - Nguyen, Phong
ED - Oswald, Elisabeth
ID - 2185
TI - Key derivation without entropy waste
VL - 8441
ER -
TY - JOUR
AB - We prove the existence of scattering states for the defocusing cubic Gross-Pitaevskii (GP) hierarchy in ℝ3. Moreover, we show that an exponential energy growth condition commonly used in the well-posedness theory of the GP hierarchy is, in a specific sense, necessary. In fact, we prove that without the latter, there exist initial data for the focusing cubic GP hierarchy for which instantaneous blowup occurs.
AU - Chen, Thomas
AU - Hainzl, Christian
AU - Pavlović, Nataša
AU - Seiringer, Robert
ID - 2186
IS - 7
JF - Letters in Mathematical Physics
TI - On the well-posedness and scattering for the Gross-Pitaevskii hierarchy via quantum de Finetti
VL - 104
ER -
TY - JOUR
AB - Systems should not only be correct but also robust in the sense that they behave reasonably in unexpected situations. This article addresses synthesis of robust reactive systems from temporal specifications. Existing methods allow arbitrary behavior if assumptions in the specification are violated. To overcome this, we define two robustness notions, combine them, and show how to enforce them in synthesis. The first notion applies to safety properties: If safety assumptions are violated temporarily, we require that the system recovers to normal operation with as few errors as possible. The second notion requires that, if liveness assumptions are violated, as many guarantees as possible should be fulfilled nevertheless. We present a synthesis procedure achieving this for the important class of GR(1) specifications, and establish complexity bounds. We also present an implementation of a special case of robustness, and show experimental results.
AU - Bloem, Roderick
AU - Chatterjee, Krishnendu
AU - Greimel, Karin
AU - Henzinger, Thomas A
AU - Hofferek, Georg
AU - Jobstmann, Barbara
AU - Könighofer, Bettina
AU - Könighofer, Robert
ID - 2187
IS - 3-4
JF - Acta Informatica
TI - Synthesizing robust systems
VL - 51
ER -
TY - JOUR
AB - Although plant and animal cells use a similar core mechanism to deliver proteins to the plasma membrane, their different lifestyle, body organization and specific cell structures resulted in the acquisition of regulatory mechanisms that vary in the two kingdoms. In particular, cell polarity regulators do not seem to be conserved, because genes encoding key components are absent in plant genomes. In plants, the broad knowledge on polarity derives from the study of auxin transporters, the PIN-FORMED proteins, in the model plant Arabidopsis thaliana. In animals, much information is provided from the study of polarity in epithelial cells that exhibit basolateral and luminal apical polarities, separated by tight junctions. In this review, we summarize the similarities and differences of the polarization mechanisms between plants and animals and survey the main genetic approaches that have been used to characterize new genes involved in polarity establishment in plants, including the frequently used forward and reverse genetics screens as well as a novel chemical genetics approach that is expected to overcome the limitation of classical genetics methods.
AU - Kania, Urszula
AU - Fendrych, Matyas
AU - Friml, Jiřĺ
ID - 2188
IS - APRIL
JF - Open Biology
TI - Polar delivery in plants; commonalities and differences to animal epithelial cells
VL - 4
ER -
TY - CONF
AB - En apprentissage automatique, nous parlons d'adaptation de domaine lorsque les données de test (cibles) et d'apprentissage (sources) sont générées selon différentes distributions. Nous devons donc développer des algorithmes de classification capables de s'adapter à une nouvelle distribution, pour laquelle aucune information sur les étiquettes n'est disponible. Nous attaquons cette problématique sous l'angle de l'approche PAC-Bayésienne qui se focalise sur l'apprentissage de modèles définis comme des votes de majorité sur un ensemble de fonctions. Dans ce contexte, nous introduisons PV-MinCq une version adaptative de l'algorithme (non adaptatif) MinCq. PV-MinCq suit le principe suivant. Nous transférons les étiquettes sources aux points cibles proches pour ensuite appliquer MinCq sur l'échantillon cible ``auto-étiqueté'' (justifié par une borne théorique). Plus précisément, nous définissons un auto-étiquetage non itératif qui se focalise dans les régions où les distributions marginales source et cible sont les plus similaires. Dans un second temps, nous étudions l'influence de notre auto-étiquetage pour en déduire une procédure de validation des hyperparamètres. Finalement, notre approche montre des résultats empiriques prometteurs.
AU - Morvant, Emilie
ID - 2189
TI - Adaptation de domaine de vote de majorité par auto-étiquetage non itératif
VL - 1
ER -
TY - CONF
AB - We present a new algorithm to construct a (generalized) deterministic Rabin automaton for an LTL formula φ. The automaton is the product of a master automaton and an array of slave automata, one for each G-subformula of φ. The slave automaton for G ψ is in charge of recognizing whether FG ψ holds. As opposed to standard determinization procedures, the states of all our automata have a clear logical structure, which allows for various optimizations. Our construction subsumes former algorithms for fragments of LTL. Experimental results show improvement in the sizes of the resulting automata compared to existing methods.
AU - Esparza, Javier
AU - Kretinsky, Jan
ID - 2190
TI - From LTL to deterministic automata: A safraless compositional approach
VL - 8559
ER -
TY - JOUR
AB - In two-player finite-state stochastic games of partial observation on graphs, in every state of the graph, the players simultaneously choose an action, and their joint actions determine a probability distribution over the successor states. The game is played for infinitely many rounds and thus the players construct an infinite path in the graph. We consider reachability objectives where the first player tries to ensure a target state to be visited almost-surely (i.e., with probability 1) or positively (i.e., with positive probability), no matter the strategy of the second player. We classify such games according to the information and to the power of randomization available to the players. On the basis of information, the game can be one-sided with either (a) player 1, or (b) player 2 having partial observation (and the other player has perfect observation), or two-sided with (c) both players having partial observation. On the basis of randomization, (a) the players may not be allowed to use randomization (pure strategies), or (b) they may choose a probability distribution over actions but the actual random choice is external and not visible to the player (actions invisible), or (c) they may use full randomization. Our main results for pure strategies are as follows: (1) For one-sided games with player 2 having perfect observation we show that (in contrast to full randomized strategies) belief-based (subset-construction based) strategies are not sufficient, and we present an exponential upper bound on memory both for almost-sure and positive winning strategies; we show that the problem of deciding the existence of almost-sure and positive winning strategies for player 1 is EXPTIME-complete and present symbolic algorithms that avoid the explicit exponential construction. (2) For one-sided games with player 1 having perfect observation we show that nonelementarymemory is both necessary and sufficient for both almost-sure and positive winning strategies. (3) We show that for the general (two-sided) case finite-memory strategies are sufficient for both positive and almost-sure winning, and at least nonelementary memory is required. We establish the equivalence of the almost-sure winning problems for pure strategies and for randomized strategies with actions invisible. Our equivalence result exhibit serious flaws in previous results of the literature: we show a nonelementary memory lower bound for almost-sure winning whereas an exponential upper bound was previously claimed.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 2211
IS - 2
JF - ACM Transactions on Computational Logic (TOCL)
TI - Partial-observation stochastic games: How to win when belief fails
VL - 15
ER -
TY - CONF
AB - The theory of graph games is the foundation for modeling and synthesizing reactive processes. In the synthesis of stochastic processes, we use 2 1/2-player games where some transitions of the game graph are controlled by two adversarial players, the System and the Environment, and the other transitions are determined probabilistically. We consider 2 1/2-player games where the objective of the System is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a mean-payoff condition). We establish that the problem of deciding whether the System can ensure that the probability to satisfy the mean-payoff parity objective is at least a given threshold is in NP ∩ coNP, matching the best known bound in the special case of 2-player games (where all transitions are deterministic). We present an algorithm running in time O(d·n2d·MeanGame) to compute the set of almost-sure winning states from which the objective can be ensured with probability 1, where n is the number of states of the game, d the number of priorities of the parity objective, and MeanGame is the complexity to compute the set of almost-sure winning states in 2 1/2-player mean-payoff games. Our results are useful in the synthesis of stochastic reactive systems with both functional requirement (given as a qualitative objective) and performance requirement (given as a quantitative objective).
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Gimbert, Hugo
AU - Oualhadj, Youssouf
ID - 2212
TI - Perfect-information stochastic mean-payoff parity games
VL - 8412
ER -
TY - CONF
AB - We consider two-player partial-observation stochastic games on finitestate graphs where player 1 has partial observation and player 2 has perfect observation. The winning condition we study are ε-regular conditions specified as parity objectives. The qualitative-analysis problem given a partial-observation stochastic game and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). These qualitative-analysis problems are known to be undecidable. However in many applications the relevant question is the existence of finite-memory strategies, and the qualitative-analysis problems under finite-memory strategies was recently shown to be decidable in 2EXPTIME.We improve the complexity and show that the qualitative-analysis problems for partial-observation stochastic parity games under finite-memory strategies are EXPTIME-complete; and also establish optimal (exponential) memory bounds for finite-memory strategies required for qualitative analysis.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Nain, Sumit
AU - Vardi, Moshe
ID - 2213
TI - The complexity of partial-observation stochastic parity games with finite-memory strategies
VL - 8412
ER -
TY - JOUR
AB - A hallmark of immune cell trafficking is directional guidance via gradients of soluble or surface bound chemokines. Vascular endothelial cells produce, transport and deposit either their own chemokines or chemokines produced by the underlying stroma. Endothelial heparan sulfate (HS) was suggested to be a critical scaffold for these chemokine pools, but it is unclear how steep chemokine gradients are sustained between the lumenal and ablumenal aspects of blood vessels. Addressing this question by semi-quantitative immunostaining of HS moieties around blood vessels with a pan anti-HS IgM mAb, we found a striking HS enrichment in the basal lamina of resting and inflamed post capillary skin venules, as well as in high endothelial venules (HEVs) of lymph nodes. Staining of skin vessels with a glycocalyx probe further suggested that their lumenal glycocalyx contains much lower HS density than their basolateral extracellular matrix (ECM). This polarized HS pattern was observed also in isolated resting and inflamed microvascular dermal cells. Notably, progressive skin inflammation resulted in massive ECM deposition and in further HS enrichment around skin post capillary venules and their associated pericytes. Inflammation-dependent HS enrichment was not compromised in mice deficient in the main HS degrading enzyme, heparanase. Our results suggest that the blood vasculature patterns steep gradients of HS scaffolds between their lumenal and basolateral endothelial aspects, and that inflammatory processes can further enrich the HS content nearby inflamed vessels. We propose that chemokine gradients between the lumenal and ablumenal sides of vessels could be favored by these sharp HS scaffold gradients.
AU - Stoler Barak, Liat
AU - Moussion, Christine
AU - Shezen, Elias
AU - Hatzav, Miki
AU - Sixt, Michael K
AU - Alon, Ronen
ID - 2214
IS - 1
JF - PLoS One
TI - Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects
VL - 9
ER -
TY - JOUR
AB - Homologous recombination is crucial for genome stability and for genetic exchange. Although our knowledge of the principle steps in recombination and its machinery is well advanced, homology search, the critical step of exploring the genome for homologous sequences to enable recombination, has remained mostly enigmatic. However, recent methodological advances have provided considerable new insights into this fundamental step in recombination that can be integrated into a mechanistic model. These advances emphasize the importance of genomic proximity and nuclear organization for homology search and the critical role of homology search mediators in this process. They also aid our understanding of how homology search might lead to unwanted and potentially disease-promoting recombination events.
AU - Renkawitz, Jörg
AU - Lademann, Claudio
AU - Jentsch, Stefan
ID - 2215
IS - 6
JF - Nature Reviews Molecular Cell Biology
TI - Mechanisms and principles of homology search during recombination
VL - 15
ER -
TY - CONF
AB - The edit distance between two (untimed) traces is the minimum cost of a sequence of edit operations (insertion, deletion, or substitution) needed to transform one trace to the other. Edit distances have been extensively studied in the untimed setting, and form the basis for approximate matching of sequences in different domains such as coding theory, parsing, and speech recognition. In this paper, we lift the study of edit distances from untimed languages to the timed setting. We define an edit distance between timed words which incorporates both the edit distance between the untimed words and the absolute difference in time stamps. Our edit distance between two timed words is computable in polynomial time. Further, we show that the edit distance between a timed word and a timed language generated by a timed automaton, defined as the edit distance between the word and the closest word in the language, is PSPACE-complete. While computing the edit distance between two timed automata is undecidable, we show that the approximate version, where we decide if the edit distance between two timed automata is either less than a given parameter or more than δ away from the parameter, for δ > 0, can be solved in exponential space and is EXPSPACE-hard. Our definitions and techniques can be generalized to the setting of hybrid systems, and analogous decidability results hold for rectangular automata.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Majumdar, Ritankar
ID - 2216
TI - Edit distance for timed automata
ER -
TY - CONF
AB - As hybrid systems involve continuous behaviors, they should be evaluated by quantitative methods, rather than qualitative methods. In this paper we adapt a quantitative framework, called model measuring, to the hybrid systems domain. The model-measuring problem asks, given a model M and a specification, what is the maximal distance such that all models within that distance from M satisfy (or violate) the specification. A distance function on models is given as part of the input of the problem. Distances, especially related to continuous behaviors are more natural in the hybrid case than the discrete case. We are interested in distances represented by monotonic hybrid automata, a hybrid counterpart of (discrete) weighted automata, whose recognized timed languages are monotone (w.r.t. inclusion) in the values of parameters.
The contributions of this paper are twofold. First, we give sufficient conditions under which the model-measuring problem can be solved. Second, we discuss the modeling of distances and applications of the model-measuring problem.
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 2217
T2 - Proceedings of the 17th international conference on Hybrid systems: computation and control
TI - Model measuring for hybrid systems
ER -
TY - CONF
AB - Recently, Döttling et al. (ASIACRYPT 2012) proposed the first chosen-ciphertext (IND-CCA) secure public-key encryption scheme from the learning parity with noise (LPN) assumption. In this work we give an alternative scheme which is conceptually simpler and more efficient. At the core of our construction is a trapdoor technique originally proposed for lattices by Micciancio and Peikert (EUROCRYPT 2012), which we adapt to the LPN setting. The main technical tool is a new double-trapdoor mechanism, together with a trapdoor switching lemma based on a computational variant of the leftover hash lemma.
AU - Kiltz, Eike
AU - Masny, Daniel
AU - Pietrzak, Krzysztof Z
ID - 2219
SN - 978-364254630-3
TI - Simple chosen-ciphertext security from low noise LPN
VL - 8383
ER -
TY - JOUR
AB - In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications.
AU - De Vos, Marjon
AU - Bollenbach, Mark Tobias
ID - 2220
IS - 4
JF - Chemistry and Biology
SN - 10745521
TI - Suppressive drug interactions between antifungals
VL - 21
ER -
TY - JOUR
AB - Leaf venation develops complex patterns in angiosperms, but the mechanism underlying this process is largely unknown. To elucidate the molecular mechanisms governing vein pattern formation, we previously isolated vascular network defective (van) mutants that displayed venation discontinuities. Here, we report the phenotypic analysis of van4 mutants, and we identify and characterize the VAN4 gene. Detailed phenotypic analysis shows that van4 mutants are defective in procambium cell differentiation and subsequent vascular cell differentiation. Reduced shoot and root cell growth is observed in van4 mutants, suggesting that VAN4 function is important for cell growth and the establishment of venation continuity. Consistent with these phenotypes, the VAN4 gene is strongly expressed in vascular and meristematic cells. VAN4 encodes a putative TRS120, which is a known guanine nucleotide exchange factor (GEF) for Rab GTPase involved in regulating vesicle transport, and a known tethering factor that determines the specificity of membrane fusion. VAN4 protein localizes at the trans-Golgi network/early endosome (TGN/EE). Aberrant recycling of the auxin efflux carrier PIN proteins is observed in van4 mutants. These results suggest that VAN4-mediated exocytosis at the TGN plays important roles in plant vascular development and cell growth in shoot and root. Our identification of VAN4 as a putative TRS120 shows that Rab GTPases are crucial (in addition to ARF GTPases) for continuous vascular development, and provides further evidence for the importance of vesicle transport in leaf vascular formation.
AU - Naramoto, Satoshi
AU - Nodzyński, Tomasz
AU - Dainobu, Tomoko
AU - Takatsuka, Hirotomo
AU - Okada, Teruyo
AU - Friml, Jirí
AU - Fukuda, Hiroo
ID - 2222
IS - 4
JF - Plant and Cell Physiology
SN - 00320781
TI - VAN4 encodes a putative TRS120 that is required for normal cell growth and vein development in arabidopsis
VL - 55
ER -
TY - JOUR
AB - Correct positioning of membrane proteins is an essential process in eukaryotic organisms. The plant hormone auxin is distributed through intercellular transport and triggers various cellular responses. Auxin transporters of the PIN-FORMED (PIN) family localize asymmetrically at the plasma membrane (PM) and mediate the directional transport of auxin between cells. A fungal toxin, brefeldin A (BFA), inhibits a subset of guanine nucleotide exchange factors for ADP-ribosylation factor small GTPases (ARF GEFs) including GNOM, which plays a major role in localization of PIN1 predominantly to the basal side of the PM. The Arabidopsis genome encodes 19 ARF-related putative GTPases. However, ARF components involved in PIN1 localization have been genetically poorly defined. Using a fluorescence imaging-based forward genetic approach, we identified an Arabidopsis mutant, bfa-visualized exocytic trafficking defective1 (bex1), in which PM localization of PIN1-green fluorescent protein (GFP) as well as development is hypersensitive to BFA. We found that in bex1 a member of the ARF1 gene family, ARF1A1C, was mutated. ARF1A1C localizes to the trans-Golgi network/early endosome and Golgi apparatus, acts synergistically to BEN1/MIN7 ARF GEF and is important for PIN recycling to the PM. Consistent with the developmental importance of PIN proteins, functional interference with ARF1 resulted in an impaired auxin response gradient and various developmental defects including embryonic patterning defects and growth arrest. Our results show that ARF1A1C is essential for recycling of PIN auxin transporters and for various auxin-dependent developmental processes.
AU - Tanaka, Hirokazu
AU - Nodzyński, Tomasz
AU - Kitakura, Saeko
AU - Feraru, Mugurel
AU - Sasabe, Michiko
AU - Ishikawa, Tomomi
AU - Kleine Vehn, Jürgen
AU - Kakimoto, Tatsuo
AU - Friml, Jirí
ID - 2223
IS - 4
JF - Plant and Cell Physiology
SN - 00320781
TI - BEX1/ARF1A1C is required for BFA-sensitive recycling of PIN auxin transporters and auxin-mediated development in arabidopsis
VL - 55
ER -
TY - JOUR
AB - This work investigates the transition between different traveling helical waves (spirals, SPIs) in the setup of differentially independent rotating cylinders. We use direct numerical simulations to consider an infinite long and periodic Taylor-Couette apparatus with fixed axial periodicity length. We find so-called mixed-cross-spirals (MCSs), that can be seen as nonlinear superpositions of SPIs, to establish stable footbridges connecting SPI states. While bridging the bifurcation branches of SPIs, the corresponding contributions within the MCS vary continuously with the control parameters. Here discussed MCSs presenting footbridge solutions start and end in different SPI branches. Therefore they differ significantly from the already known MCSs that present bypass solutions (Altmeyer and Hoffmann 2010 New J. Phys. 12 113035). The latter start and end in the same SPI branch, while they always bifurcate out of those SPI branches with the larger mode amplitude. Meanwhile, these only appear within the coexisting region of both SPIs. In contrast, the footbridge solutions can also bifurcate out of the minor SPI contribution. We also find they exist in regions where only one of the SPIs contributions exists. In addition, MCS as footbridge solution can appear either stable or unstable. The latter detected transient solutions offer similar spatio-temporal characteristics to the flow establishing stable footbridges. Such transition processes are interesting for pattern-forming systems in general because they accomplish transitions between traveling waves of different azimuthal wave numbers and have not been described in the literature yet.
AU - Altmeyer, Sebastian
ID - 2224
IS - 2
JF - Fluid Dynamics Research
SN - 01695983
TI - On secondary instabilities generating footbridges between spiral vortex flow
VL - 46
ER -
TY - JOUR
AB - We consider sample covariance matrices of the form X∗X, where X is an M×N matrix with independent random entries. We prove the isotropic local Marchenko-Pastur law, i.e. we prove that the resolvent (X∗X−z)−1 converges to a multiple of the identity in the sense of quadratic forms. More precisely, we establish sharp high-probability bounds on the quantity ⟨v,(X∗X−z)−1w⟩−⟨v,w⟩m(z), where m is the Stieltjes transform of the Marchenko-Pastur law and v,w∈CN. We require the logarithms of the dimensions M and N to be comparable. Our result holds down to scales Iz≥N−1+ε and throughout the entire spectrum away from 0. We also prove analogous results for generalized Wigner matrices.
AU - Bloemendal, Alex
AU - Erdös, László
AU - Knowles, Antti
AU - Yau, Horng
AU - Yin, Jun
ID - 2225
JF - Electronic Journal of Probability
SN - 10836489
TI - Isotropic local laws for sample covariance and generalized Wigner matrices
VL - 19
ER -
TY - JOUR
AB - Coriolis force effects on shear flows are important in geophysical and astrophysical contexts. We report a study on the linear stability and the transient energy growth of the plane Couette flow with system rotation perpendicular to the shear direction. External rotation causes linear instability. At small rotation rates, the onset of linear instability scales inversely with the rotation rate and the optimal transient growth in the linearly stable region is slightly enhanced ∼Re2. The corresponding optimal initial perturbations are characterized by roll structures inclined in the streamwise direction and are twisted under external rotation. At large rotation rates, the transient growth is significantly inhibited and hence linear stability analysis is a reliable indicator for instability.
AU - Shi, Liang
AU - Hof, Björn
AU - Tilgner, Andreas
ID - 2226
IS - 1
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
SN - 15393755
TI - Transient growth of Ekman-Couette flow
VL - 89
ER -
TY - JOUR
AB - The Balkan Peninsula, characterized by high rates of endemism, is recognised as one of the most diverse and species-rich areas of Europe. However, little is known about the origin of Balkan endemics. The present study addresses the phylogenetic position of the Balkan endemic Ranunculus wettsteinii, as well as its taxonomic status and relationship with the widespread R. parnassiifolius, based on nuclear DNA (internal transcribed spacer, ITS) and plastid regions (rpl32-trnL, rps16-trnQ, trnK-matK and ycf6-psbM). Maximum parsimony and Bayesian inference analyses revealed a well-supported clade formed by accessions of R. wettsteinii. Furthermore, our phylogenetic and network analyses supported previous hypotheses of a likely allopolyploid origin for R. wettsteinii between R. montenegrinus and R. parnassiifolius, with the latter as the maternal parent.
AU - Cires Rodriguez, Eduardo
AU - Baltisberger, Matthias
AU - Cuesta, Candela
AU - Vargas, Pablo
AU - Prieto, José
ID - 2227
IS - 1
JF - Organisms Diversity and Evolution
SN - 14396092
TI - Allopolyploid origin of the Balkan endemic Ranunculus wettsteinii (Ranunculaceae) inferred from nuclear and plastid DNA sequences
VL - 14
ER -
TY - JOUR
AB - Fast-spiking, parvalbumin-expressing GABAergic interneurons, a large proportion of which are basket cells (BCs), have a key role in feedforward and feedback inhibition, gamma oscillations and complex information processing. For these functions, fast propagation of action potentials (APs) from the soma to the presynaptic terminals is important. However, the functional properties of interneuron axons remain elusive. We examined interneuron axons by confocally targeted subcellular patch-clamp recording in rat hippocampal slices. APs were initiated in the proximal axon ∼20 μm from the soma and propagated to the distal axon with high reliability and speed. Subcellular mapping revealed a stepwise increase of Na^+ conductance density from the soma to the proximal axon, followed by a further gradual increase in the distal axon. Active cable modeling and experiments with partial channel block revealed that low axonal Na^+ conductance density was sufficient for reliability, but high Na^+ density was necessary for both speed of propagation and fast-spiking AP phenotype. Our results suggest that a supercritical density of Na^+ channels compensates for the morphological properties of interneuron axons (small segmental diameter, extensive branching and high bouton density), ensuring fast AP propagation and high-frequency repetitive firing.
AU - Hu, Hua
AU - Jonas, Peter M
ID - 2228
IS - 5
JF - Nature Neuroscience
SN - 10976256
TI - A supercritical density of Na^+ channels ensures fast signaling in GABAergic interneuron axons
VL - 17
ER -
TY - JOUR
AB - The distance between Ca^2+ channels and release sensors determines the speed and efficacy of synaptic transmission. Tight "nanodomain" channel-sensor coupling initiates transmitter release at synapses in the mature brain, whereas loose "microdomain" coupling appears restricted to early developmental stages. To probe the coupling configuration at a plastic synapse in the mature central nervous system, we performed paired recordings between mossy fiber terminals and CA3 pyramidal neurons in rat hippocampus. Millimolar concentrations of both the fast Ca^2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane- N,N, N′,N′-tetraacetic acid] and the slow chelator EGTA efficiently suppressed transmitter release, indicating loose coupling between Ca^2+ channels and release sensors. Loose coupling enabled the control of initial release probability by fast endogenous Ca^2+ buffers and the generation of facilitation by buffer saturation. Thus, loose coupling provides the molecular framework for presynaptic plasticity.
AU - Vyleta, Nicholas
AU - Jonas, Peter M
ID - 2229
IS - 6171
JF - Science
SN - 00368075
TI - Loose coupling between Ca^2+ channels and release sensors at a plastic hippocampal synapse
VL - 343
ER -
TY - JOUR
AB - Intracellular electrophysiological recordings provide crucial insights into elementary neuronal signals such as action potentials and synaptic currents. Analyzing and interpreting these signals is essential for a quantitative understanding of neuronal information processing, and requires both fast data visualization and ready access to complex analysis routines. To achieve this goal, we have developed Stimfit, a free software package for cellular neurophysiology with a Python scripting interface and a built-in Python shell. The program supports most standard file formats for cellular neurophysiology and other biomedical signals through the Biosig library. To quantify and interpret the activity of single neurons and communication between neurons, the program includes algorithms to characterize the kinetics of presynaptic action potentials and postsynaptic currents, estimate latencies between pre- and postsynaptic events, and detect spontaneously occurring events. We validate and benchmark these algorithms, give estimation errors, and provide sample use cases, showing that Stimfit represents an efficient, accessible and extensible way to accurately analyze and interpret neuronal signals.
AU - Guzmán, José
AU - Schlögl, Alois
AU - Schmidt Hieber, Christoph
ID - 2230
IS - FEB
JF - Frontiers in Neuroinformatics
SN - 16625196
TI - Stimfit: Quantifying electrophysiological data with Python
VL - 8
ER -
TY - JOUR
AB - Based on the measurements of noise in gene expression performed during the past decade, it has become customary to think of gene regulation in terms of a two-state model, where the promoter of a gene can stochastically switch between an ON and an OFF state. As experiments are becoming increasingly precise and the deviations from the two-state model start to be observable, we ask about the experimental signatures of complex multistate promoters, as well as the functional consequences of this additional complexity. In detail, we i), extend the calculations for noise in gene expression to promoters described by state transition diagrams with multiple states, ii), systematically compute the experimentally accessible noise characteristics for these complex promoters, and iii), use information theory to evaluate the channel capacities of complex promoter architectures and compare them with the baseline provided by the two-state model. We find that adding internal states to the promoter generically decreases channel capacity, except in certain cases, three of which (cooperativity, dual-role regulation, promoter cycling) we analyze in detail.
AU - Rieckh, Georg
AU - Tkacik, Gasper
ID - 2231
IS - 5
JF - Biophysical Journal
SN - 00063495
TI - Noise and information transmission in promoters with multiple internal states
VL - 106
ER -
TY - JOUR
AB - The purpose of this contribution is to summarize and discuss recent advances regarding the onset of turbulence in shear flows. The absence of a clear-cut instability mechanism, the spatio-temporal intermittent character and extremely long lived transients are some of the major difficulties encountered in these flows and have hindered progress towards understanding the transition process. We will show for the case of pipe flow that concepts from nonlinear dynamics and statistical physics can help to explain the onset of turbulence. In particular, the turbulent structures (puffs) observed close to onset are spatially localized chaotic transients and their lifetimes increase super-exponentially with Reynolds number. At the same time fluctuations of individual turbulent puffs can (although very rarely) lead to the nucleation of new puffs. The competition between these two stochastic processes gives rise to a non-equilibrium phase transition where turbulence changes from a super-transient to a sustained state.
AU - Song, Baofang
AU - Hof, Björn
ID - 2232
IS - 2
JF - Journal of Statistical Mechanics Theory and Experiment
SN - 17425468
TI - Deterministic and stochastic aspects of the transition to turbulence
VL - 2014
ER -
TY - JOUR
AB - A discounted-sum automaton (NDA) is a nondeterministic finite automaton with edge weights, valuing a run by the discounted sum of visited edge weights. More precisely, the weight in the i-th position of the run is divided by λi, where the discount factor λ is a fixed rational number greater than 1. The value of a word is the minimal value of the automaton runs on it. Discounted summation is a common and useful measuring scheme, especially for infinite sequences, reflecting the assumption that earlier weights are more important than later weights. Unfortunately, determinization of NDAs, which is often essential in formal verification, is, in general, not possible. We provide positive news, showing that every NDA with an integral discount factor is determinizable. We complete the picture by proving that the integers characterize exactly the discount factors that guarantee determinizability: for every nonintegral rational discount factor λ, there is a nondeterminizable λ-NDA. We also prove that the class of NDAs with integral discount factors enjoys closure under the algebraic operations min, max, addition, and subtraction, which is not the case for general NDAs nor for deterministic NDAs. For general NDAs, we look into approximate determinization, which is always possible as the influence of a word's suffix decays. We show that the naive approach, of unfolding the automaton computations up to a sufficient level, is doubly exponential in the discount factor. We provide an alternative construction for approximate determinization, which is singly exponential in the discount factor, in the precision, and in the number of states. We also prove matching lower bounds, showing that the exponential dependency on each of these three parameters cannot be avoided. All our results hold equally for automata over finite words and for automata over infinite words.
AU - Boker, Udi
AU - Henzinger, Thomas A
ID - 2233
IS - 1
JF - Logical Methods in Computer Science
SN - 18605974
TI - Exact and approximate determinization of discounted-sum automata
VL - 10
ER -
TY - JOUR
AB - We study Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) functions. We consider two different objectives, namely, expectation and satisfaction objectives. Given an MDP with κ limit-average functions, in the expectation objective the goal is to maximize the expected limit-average value, and in the satisfaction objective the goal is to maximize the probability of runs such that the limit-average value stays above a given vector. We show that under the expectation objective, in contrast to the case of one limit-average function, both randomization and memory are necessary for strategies even for ε-approximation, and that finite-memory randomized strategies are sufficient for achieving Pareto optimal values. Under the satisfaction objective, in contrast to the case of one limit-average function, infinite memory is necessary for strategies achieving a specific value (i.e. randomized finite-memory strategies are not sufficient), whereas memoryless randomized strategies are sufficient for ε-approximation, for all ε > 0. We further prove that the decision problems for both expectation and satisfaction objectives can be solved in polynomial time and the trade-off curve (Pareto curve) can be ε-approximated in time polynomial in the size of the MDP and 1/ε, and exponential in the number of limit-average functions, for all ε > 0. Our analysis also reveals flaws in previous work for MDPs with multiple mean-payoff functions under the expectation objective, corrects the flaws, and allows us to obtain improved results.
AU - Brázdil, Tomáš
AU - Brožek, Václav
AU - Chatterjee, Krishnendu
AU - Forejt, Vojtěch
AU - Kučera, Antonín
ID - 2234
IS - 1
JF - Logical Methods in Computer Science
SN - 18605974
TI - Markov decision processes with multiple long-run average objectives
VL - 10
ER -
TY - JOUR
AB - Emerging infectious diseases (EIDs) pose a risk to human welfare, both directly and indirectly, by affecting managed livestock and wildlife that provide valuable resources and ecosystem services, such as the pollination of crops. Honeybees (Apis mellifera), the prevailing managed insect crop pollinator, suffer from a range of emerging and exotic high-impact pathogens, and population maintenance requires active management by beekeepers to control them. Wild pollinators such as bumblebees (Bombus spp.) are in global decline, one cause of which may be pathogen spillover from managed pollinators like honeybees or commercial colonies of bumblebees. Here we use a combination of infection experiments and landscape-scale field data to show that honeybee EIDs are indeed widespread infectious agents within the pollinator assemblage. The prevalence of deformed wing virus (DWV) and the exotic parasite Nosema ceranae in honeybees and bumblebees is linked; as honeybees have higher DWV prevalence, and sympatric bumblebees and honeybees are infected by the same DWV strains, Apis is the likely source of at least one major EID in wild pollinators. Lessons learned from vertebrates highlight the need for increased pathogen control in managed bee species to maintain wild pollinators, as declines in native pollinators may be caused by interspecies pathogen transmission originating from managed pollinators.
AU - Fürst, Matthias
AU - Mcmahon, Dino
AU - Osborne, Juliet
AU - Paxton, Robert
AU - Brown, Mark
ID - 2235
IS - 7488
JF - Nature
SN - 00280836
TI - Disease associations between honeybees and bumblebees as a threat to wild pollinators
VL - 506
ER -
TY - CONF
AB - Consider a joint distribution (X,A) on a set. We show that for any family of distinguishers, there exists a simulator such that 1 no function in can distinguish (X,A) from (X,h(X)) with advantage ε, 2 h is only O(2 3ℓ ε -2) times less efficient than the functions in. For the most interesting settings of the parameters (in particular, the cryptographic case where X has superlogarithmic min-entropy, ε > 0 is negligible and consists of circuits of polynomial size), we can make the simulator h deterministic. As an illustrative application of our theorem, we give a new security proof for the leakage-resilient stream-cipher from Eurocrypt'09. Our proof is simpler and quantitatively much better than the original proof using the dense model theorem, giving meaningful security guarantees if instantiated with a standard blockcipher like AES. Subsequent to this work, Chung, Lui and Pass gave an interactive variant of our main theorem, and used it to investigate weak notions of Zero-Knowledge. Vadhan and Zheng give a more constructive version of our theorem using their new uniform min-max theorem.
AU - Jetchev, Dimitar
AU - Pietrzak, Krzysztof Z
ED - Lindell, Yehuda
ID - 2236
SN - 978-364254241-1
TI - How to fake auxiliary input
VL - 8349
ER -
TY - CONF
AB - The analysis of the energy consumption of software is an important goal for quantitative formal methods. Current methods, using weighted transition systems or energy games, model the energy source as an ideal resource whose status is characterized by one number, namely the amount of remaining energy. Real batteries, however, exhibit behaviors that can deviate substantially from an ideal energy resource. Based on a discretization of a standard continuous battery model, we introduce battery transition systems. In this model, a battery is viewed as consisting of two parts-the available-charge tank and the bound-charge tank. Any charge or discharge is applied to the available-charge tank. Over time, the energy from each tank diffuses to the other tank. Battery transition systems are infinite state systems that, being not well-structured, fall into no decidable class that is known to us. Nonetheless, we are able to prove that the !-regular modelchecking problem is decidable for battery transition systems. We also present a case study on the verification of control programs for energy-constrained semi-autonomous robots.
AU - Boker, Udi
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 2239
IS - 1
SN - 978-145032544-8
TI - Battery transition systems
VL - 49
ER -
TY - JOUR
AB - Clathrin-mediated endocytosis is the major mechanism for eukaryotic plasma membrane-based proteome turn-over. In plants, clathrin-mediated endocytosis is essential for physiology and development, but the identification and organization of the machinery operating this process remains largely obscure. Here, we identified an eight-core-component protein complex, the TPLATE complex, essential for plant growth via its role as major adaptor module for clathrin-mediated endocytosis. This complex consists of evolutionarily unique proteins that associate closely with core endocytic elements. The TPLATE complex is recruited as dynamic foci at the plasma membrane preceding recruitment of adaptor protein complex 2, clathrin, and dynamin-related proteins. Reduced function of different complex components severely impaired internalization of assorted endocytic cargoes, demonstrating its pivotal role in clathrin-mediated endocytosis. Taken together, the TPLATE complex is an early endocytic module representing a unique evolutionary plant adaptation of the canonical eukaryotic pathway for clathrin-mediated endocytosis.
AU - Gadeyne, Astrid
AU - Sánchez Rodríguez, Clara
AU - Vanneste, Steffen
AU - Di Rubbo, Simone
AU - Zauber, Henrik
AU - Vanneste, Kevin
AU - Van Leene, Jelle
AU - De Winne, Nancy
AU - Eeckhout, Dominique
AU - Persiau, Geert
AU - Van De Slijke, Eveline
AU - Cannoot, Bernard
AU - Vercruysse, Leen
AU - Mayers, Jonathan
AU - Adamowski, Maciek
AU - Kania, Urszula
AU - Ehrlich, Matthias
AU - Schweighofer, Alois
AU - Ketelaar, Tijs
AU - Maere, Steven
AU - Bednarek, Sebastian
AU - Friml, Jirí
AU - Gevaert, Kris
AU - Witters, Erwin
AU - Russinova, Eugenia
AU - Persson, Staffan
AU - De Jaeger, Geert
AU - Van Damme, Daniël
ID - 2240
IS - 4
JF - Cell
SN - 00928674
TI - The TPLATE adaptor complex drives clathrin-mediated endocytosis in plants
VL - 156
ER -
TY - JOUR
AB - The brain demands high-energy supply and obstruction of blood flow causes rapid deterioration of the healthiness of brain cells. Two major events occur upon ischemia: acidosis and liberation of excess glutamate, which leads to excitotoxicity. However, cellular source of glutamate and its release mechanism upon ischemia remained unknown. Here we show a causal relationship between glial acidosis and neuronal excitotoxicity. As the major cation that flows through channelrhodopsin-2 (ChR2) is proton, this could be regarded as an optogenetic tool for instant intracellular acidification. Optical activation of ChR2 expressed in glial cells led to glial acidification and to release of glutamate. On the other hand, glial alkalization via optogenetic activation of a proton pump, archaerhodopsin (ArchT), led to cessation of glutamate release and to the relief of ischemic brain damage in vivo. Our results suggest that controlling glial pH may be an effective therapeutic strategy for intervention of ischemic brain damage.
AU - Beppu, Kaoru
AU - Sasaki, Takuya
AU - Tanaka, Kenji
AU - Yamanaka, Akihiro
AU - Fukazawa, Yugo
AU - Shigemoto, Ryuichi
AU - Matsui, Ko
ID - 2241
IS - 2
JF - Neuron
SN - 08966273
TI - Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage
VL - 81
ER -
TY - JOUR
AB - MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in many cellular pathways. MiRNAs associate with members of the Argonaute protein family and bind to partially complementary sequences on mRNAs and induce translational repression or mRNA decay. Using deep sequencing and Northern blotting, we characterized miRNA expression in wild type and miR-155-deficient dendritic cells (DCs) and macrophages. Analysis of different stimuli (LPS, LDL, eLDL, oxLDL) reveals a direct influence of miR-155 on the expression levels of other miRNAs. For example, miR-455 is negatively regulated in miR-155-deficient cells possibly due to inhibition of the transcription factor C/EBPbeta by miR-155. Based on our comprehensive data sets, we propose a model of hierarchical miRNA expression dominated by miR-155 in DCs and macrophages.
AU - Dueck, Anne
AU - Eichner, Alexander
AU - Sixt, Michael K
AU - Meister, Gunter
ID - 2242
IS - 4
JF - FEBS Letters
SN - 00145793
TI - A miR-155-dependent microRNA hierarchy in dendritic cell maturation and macrophage activation
VL - 588
ER -
TY - CHAP
AB - Exogenous application of biologically important molecules for plant growth promotion and/or regulation is very common both in plant research and horticulture. Plant hormones such as auxins and cytokinins are classes of compounds which are often applied exogenously. Nevertheless, plants possess a well-established machinery to regulate the active pool of exogenously applied compounds by converting them to metabolites and conjugates. Consequently, it is often very useful to know the in vivo status of applied compounds to connect them with some of the regulatory events in plant developmental processes. The in vivo status of applied compounds can be measured by incubating plants with radiolabeled compounds, followed by extraction, purification, and HPLC metabolic profiling of plant extracts. Recently we have used this method to characterize the intracellularly localized PIN protein, PIN5. Here we explain the method in detail, with a focus on general application.
AU - Simon, Sibu
AU - Skůpa, Petr
AU - Dobrev, Petre
AU - Petrášek, Jan
AU - Zažímalová, Eva
AU - Friml, Jirí
ED - Hicks, Glenn
ED - Robert, Stéphanie
ID - 2245
SN - 10643745
T2 - Plant Chemical Genomics
TI - Analyzing the in vivo status of exogenously applied auxins: A HPLC-based method to characterize the intracellularly localized auxin transporters
VL - 1056
ER -
TY - JOUR
AB - Muller games are played by two players moving a token along a graph; the winner is determined by the set of vertices that occur infinitely often. The central algorithmic problem is to compute the winning regions for the players. Different classes and representations of Muller games lead to problems of varying computational complexity. One such class are parity games; these are of particular significance in computational complexity, as they remain one of the few combinatorial problems known to be in NP ∩ co-NP but not known to be in P. We show that winning regions for a Muller game can be determined from the alternating structure of its traps. To every Muller game we then associate a natural number that we call its trap depth; this parameter measures how complicated the trap structure is. We present algorithms for parity games that run in polynomial time for graphs of bounded trap depth, and in general run in time exponential in the trap depth.
AU - Grinshpun, Andrey
AU - Phalitnonkiat, Pakawat
AU - Rubin, Sasha
AU - Tarfulea, Andrei
ID - 2246
JF - Theoretical Computer Science
SN - 03043975
TI - Alternating traps in Muller and parity games
VL - 521
ER -
TY - JOUR
AB - Avian forelimb digit homology remains one of the standard themes in comparative biology and EvoDevo research. In order to resolve the apparent contradictions between embryological and paleontological evidence a variety of hypotheses have been presented in recent years. The proposals range from excluding birds from the dinosaur clade, to assignments of homology by different criteria, or even assuming a hexadactyl tetrapod limb ground state. At present two approaches prevail: the frame shift hypothesis and the pyramid reduction hypothesis. While the former postulates a homeotic shift of digit identities, the latter argues for a gradual bilateral reduction of phalanges and digits. Here we present a new model that integrates elements from both hypotheses with the existing experimental and fossil evidence. We start from the main feature common to both earlier concepts, the initiating ontogenetic event: reduction and loss of the anterior-most digit. It is proposed that a concerted mechanism of molecular regulation and developmental mechanics is capable of shifting the boundaries of hoxD expression in embryonic forelimb buds as well as changing the digit phenotypes. Based on a distinction between positional (topological) and compositional (phenotypic) homology criteria, we argue that the identity of the avian digits is II, III, IV, despite a partially altered phenotype. Finally, we introduce an alternative digit reduction scheme that reconciles the current fossil evidence with the presented molecular-morphogenetic model. Our approach identifies specific experiments that allow to test whether gene expression can be shifted and digit phenotypes can be altered by induced digit loss or digit gain.
AU - Capek, Daniel
AU - Metscher, Brian
AU - Müller, Gerd
ID - 2248
IS - 1
JF - Journal of Experimental Zoology Part B: Molecular and Developmental Evolution
SN - 15525007
TI - Thumbs down: A molecular-morphogenetic approach to avian digit homology
VL - 322
ER -
TY - JOUR
AB - The unfolded protein response (UPR) is a signaling network triggered by overload of protein-folding demand in the endoplasmic reticulum (ER), a condition termed ER stress. The UPR is critical for growth and development; nonetheless, connections between the UPR and other cellular regulatory processes remain largely unknown. Here, we identify a link between the UPR and the phytohormone auxin, a master regulator of plant physiology. We show that ER stress triggers down-regulation of auxin receptors and transporters in Arabidopsis thaliana. We also demonstrate that an Arabidopsis mutant of a conserved ER stress sensor IRE1 exhibits defects in the auxin response and levels. These data not only support that the plant IRE1 is required for auxin homeostasis, they also reveal a species-specific feature of IRE1 in multicellular eukaryotes. Furthermore, by establishing that UPR activation is reduced in mutants of ER-localized auxin transporters, including PIN5, we define a long-neglected biological significance of ER-based auxin regulation. We further examine the functional relationship of IRE1 and PIN5 by showing that an ire1 pin5 triple mutant enhances defects of UPR activation and auxin homeostasis in ire1 or pin5. Our results imply that the plant UPR has evolved a hormone-dependent strategy for coordinating ER function with physiological processes.
AU - Chen, Yani
AU - Aung, Kyaw
AU - Rolčík, Jakub
AU - Walicki, Kathryn
AU - Friml, Jirí
AU - Brandizzí, Federica
ID - 2249
IS - 1
JF - Plant Journal
SN - 09607412
TI - Inter-regulation of the unfolded protein response and auxin signaling
VL - 77
ER -
TY - JOUR
AB - The genome sequences of new viruses often contain many "orphan" or "taxon-specific" proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as "genus specific" by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virionsd.
AU - Kuchibhatla, Durga
AU - Sherman, Westley
AU - Chung, Betty
AU - Cook, Shelley
AU - Schneider, Georg
AU - Eisenhaber, Birgit
AU - Karlin, David
ID - 2250
IS - 1
JF - Journal of Virology
SN - 0022538X
TI - Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently "orphan" viral proteins
VL - 88
ER -
TY - JOUR
AB - Sharp wave/ripple (SWR, 150–250 Hz) hippocampal events have long been postulated to be involved in memory consolidation. However, more recent work has investigated SWRs that occur during active waking behaviour: findings that suggest that SWRs may also play a role in cell assembly strengthening or spatial working memory. Do such theories of SWR function apply to animal learning? This review discusses how general theories linking SWRs to memory-related function may explain circuit mechanisms related to rodent spatial learning and to the associated stabilization of new cognitive maps.
AU - Csicsvari, Jozsef L
AU - Dupret, David
ID - 2251
IS - 1635
JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
SN - 09628436
TI - Sharp wave/ripple network oscillations and learning-associated hippocampal maps
VL - 369
ER -
TY - JOUR
AB - The pattern of inheritance and mechanism of sex determination can have important evolutionary consequences. We studied probabilistic sex determination in the ciliate Tetrahymena thermophila, which was previously shown to cause evolution of skewed sex ratios. We find that the genetic background alters the sex determination patterns of mat alleles in heterozygotes and that allelic interaction can differentially influence the expression probability of the 7 sexes. We quantify the dominance relationships between several mat alleles and find that A-type alleles, which specify sex I, are indeed recessive to B-type alleles, which are unable to specify that sex. Our results provide additional support for the presence of modifier loci and raise implications for the dynamics of sex ratios in populations of T. thermophila.
AU - Phadke, Sujal
AU - Paixao, Tiago
AU - Pham, Tuan
AU - Pham, Stephanie
AU - Zufall, Rebecca
ID - 2252
IS - 1
JF - Journal of Heredity
SN - 00221503
TI - Genetic background alters dominance relationships between mat alleles in the ciliate Tetrahymena Thermophila
VL - 105
ER -
TY - JOUR
AB - Plant growth is achieved predominantly by cellular elongation, which is thought to be controlled on several levels by apoplastic auxin. Auxin export into the apoplast is achieved by plasma membrane efflux catalysts of the PIN-FORMED (PIN) and ATP-binding cassette protein subfamily B/phosphor- glycoprotein (ABCB/PGP) classes; the latter were shown to depend on interaction with the FKBP42, TWISTED DWARF1 (TWD1). Here by using a transgenic approach in combination with phenotypical, biochemical and cell biological analyses we demonstrate the importance of a putative C-terminal in-plane membrane anchor of TWD1 in the regulation of ABCB-mediated auxin transport. In contrast with dwarfed twd1 loss-of-function alleles, TWD1 gain-of-function lines that lack a putative in-plane membrane anchor (HA-TWD1-Ct) show hypermorphic plant architecture, characterized by enhanced stem length and leaf surface but reduced shoot branching. Greater hypocotyl length is the result of enhanced cell elongation that correlates with reduced polar auxin transport capacity for HA-TWD1-Ct. As a consequence, HA-TWD1-Ct displays higher hypocotyl auxin accumulation, which is shown to result in elevated auxin-induced cell elongation rates. Our data highlight the importance of C-terminal membrane anchoring for TWD1 action, which is required for specific regulation of ABCB-mediated auxin transport. These data support a model in which TWD1 controls lateral ABCB1-mediated export into the apoplast, which is required for auxin-mediated cell elongation.
AU - Bailly, Aurélien
AU - Wang, Bangjun
AU - Zwiewka, Marta
AU - Pollmann, Stephan
AU - Schenck, Daniel
AU - Lüthen, Hartwig
AU - Schulz, Alexander
AU - Friml, Jirí
AU - Geisler, Markus
ID - 2253
IS - 1
JF - Plant Journal
SN - 09607412
TI - Expression of TWISTED DWARF1 lacking its in-plane membrane anchor leads to increased cell elongation and hypermorphic growth
VL - 77
ER -
TY - JOUR
AB - Theta-gamma network oscillations are thought to represent key reference signals for information processing in neuronal ensembles, but the underlying synaptic mechanisms remain unclear. To address this question, we performed whole-cell (WC) patch-clamp recordings from mature hippocampal granule cells (GCs) in vivo in the dentate gyrus of anesthetized and awake rats. GCs in vivo fired action potentials at low frequency, consistent with sparse coding in the dentate gyrus. GCs were exposed to barrages of fast AMPAR-mediated excitatory postsynaptic currents (EPSCs), primarily relayed from the entorhinal cortex, and inhibitory postsynaptic currents (IPSCs), presumably generated by local interneurons. EPSCs exhibited coherence with the field potential predominantly in the theta frequency band, whereas IPSCs showed coherence primarily in the gamma range. Action potentials in GCs were phase locked to network oscillations. Thus, theta-gamma-modulated synaptic currents may provide a framework for sparse temporal coding of information in the dentate gyrus.
AU - Pernia-Andrade, Alejandro
AU - Jonas, Peter M
ID - 2254
IS - 1
JF - Neuron
SN - 08966273
TI - Theta-gamma-modulated synaptic currents in hippocampal granule cells in vivo define a mechanism for network oscillations
VL - 81
ER -
TY - JOUR
AB - Motivated by applications in biology, we present an algorithm for estimating the length of tube-like shapes in 3-dimensional Euclidean space. In a first step, we combine the tube formula of Weyl with integral geometric methods to obtain an integral representation of the length, which we approximate using a variant of the Koksma-Hlawka Theorem. In a second step, we use tools from computational topology to decrease the dependence on small perturbations of the shape. We present computational experiments that shed light on the stability and the convergence rate of our algorithm.
AU - Edelsbrunner, Herbert
AU - Pausinger, Florian
ID - 2255
IS - 1
JF - Journal of Mathematical Imaging and Vision
SN - 09249907
TI - Stable length estimates of tube-like shapes
VL - 50
ER -
TY - JOUR
AB - Maximum entropy models are the least structured probability distributions that exactly reproduce a chosen set of statistics measured in an interacting network. Here we use this principle to construct probabilistic models which describe the correlated spiking activity of populations of up to 120 neurons in the salamander retina as it responds to natural movies. Already in groups as small as 10 neurons, interactions between spikes can no longer be regarded as small perturbations in an otherwise independent system; for 40 or more neurons pairwise interactions need to be supplemented by a global interaction that controls the distribution of synchrony in the population. Here we show that such “K-pairwise” models—being systematic extensions of the previously used pairwise Ising models—provide an excellent account of the data. We explore the properties of the neural vocabulary by: 1) estimating its entropy, which constrains the population's capacity to represent visual information; 2) classifying activity patterns into a small set of metastable collective modes; 3) showing that the neural codeword ensembles are extremely inhomogenous; 4) demonstrating that the state of individual neurons is highly predictable from the rest of the population, allowing the capacity for error correction.
AU - Tkacik, Gasper
AU - Marre, Olivier
AU - Amodei, Dario
AU - Schneidman, Elad
AU - Bialek, William
AU - Berry, Michael
ID - 2257
IS - 1
JF - PLoS Computational Biology
SN - 1553734X
TI - Searching for collective behavior in a large network of sensory neurons
VL - 10
ER -
TY - JOUR
AB - Invasive alien parasites and pathogens are a growing threat to biodiversity worldwide, which can contribute to the extinction of endemic species. On the Galápagos Islands, the invasive parasitic fly Philornis downsi poses a major threat to the endemic avifauna. Here, we investigated the influence of this parasite on the breeding success of two Darwin's finch species, the warbler finch (Certhidea olivacea) and the sympatric small tree finch (Camarhynchus parvulus), on Santa Cruz Island in 2010 and 2012. While the population of the small tree finch appeared to be stable, the warbler finch has experienced a dramatic decline in population size on Santa Cruz Island since 1997. We aimed to identify whether warbler finches are particularly vulnerable during different stages of the breeding cycle. Contrary to our prediction, breeding success was lower in the small tree finch than in the warbler finch. In both species P. downsi had a strong negative impact on breeding success and our data suggest that heavy rain events also lowered the fledging success. On the one hand parents might be less efficient in compensating their chicks' energy loss due to parasitism as they might be less efficient in foraging on days of heavy rain. On the other hand, intense rainfalls might lead to increased humidity and more rapid cooling of the nests. In the case of the warbler finch we found that the control of invasive plant species with herbicides had a significant additive negative impact on the breeding success. It is very likely that the availability of insects (i.e. food abundance) is lower in such controlled areas, as herbicide usage led to the removal of the entire understory. Predation seems to be a minor factor in brood loss.
AU - Cimadom, Arno
AU - Ulloa, Angel
AU - Meidl, Patrick
AU - Zöttl, Markus
AU - Zöttl, Elisabet
AU - Fessl, Birgit
AU - Nemeth, Erwin
AU - Dvorak, Michael
AU - Cunninghame, Francesca
AU - Tebbich, Sabine
ID - 468
IS - 9
JF - PLoS One
TI - Invasive parasites habitat change and heavy rainfall reduce breeding success in Darwin's finches
VL - 9
ER -
TY - CONF
AB - First cycle games (FCG) are played on a finite graph by two players who push a token along the edges until a vertex is repeated, and a simple cycle is formed. The winner is determined by some fixed property Y of the sequence of labels of the edges (or nodes) forming this cycle. These games are traditionally of interest because of their connection with infinite-duration games such as parity and mean-payoff games. We study the memory requirements for winning strategies of FCGs and certain associated infinite duration games. We exhibit a simple FCG that is not memoryless determined (this corrects a mistake in Memoryless determinacy of parity and mean payoff games: a simple proof by Bj⋯orklund, Sandberg, Vorobyov (2004) that claims that FCGs for which Y is closed under cyclic permutations are memoryless determined). We show that θ (n)! memory (where n is the number of nodes in the graph), which is always sufficient, may be necessary to win some FCGs. On the other hand, we identify easy to check conditions on Y (i.e., Y is closed under cyclic permutations, and both Y and its complement are closed under concatenation) that are sufficient to ensure that the corresponding FCGs and their associated infinite duration games are memoryless determined. We demonstrate that many games considered in the literature, such as mean-payoff, parity, energy, etc., satisfy these conditions. On the complexity side, we show (for efficiently computable Y) that while solving FCGs is in PSPACE, solving some families of FCGs is PSPACE-hard.
AU - Aminof, Benjamin
AU - Rubin, Sasha
ID - 475
T2 - Electronic Proceedings in Theoretical Computer Science, EPTCS
TI - First cycle games
VL - 146
ER -
TY - JOUR
AB - Energy games belong to a class of turn-based two-player infinite-duration games played on a weighted directed graph. It is one of the rare and intriguing combinatorial problems that lie in NP∩co-NP, but are not known to be in P. The existence of polynomial-time algorithms has been a major open problem for decades and apart from pseudopolynomial algorithms there is no algorithm that solves any non-trivial subclass in polynomial time. In this paper, we give several results based on the weight structures of the graph. First, we identify a notion of penalty and present a polynomial-time algorithm when the penalty is large. Our algorithm is the first polynomial-time algorithm on a large class of weighted graphs. It includes several worst-case instances on which previous algorithms, such as value iteration and random facet algorithms, require at least sub-exponential time. Our main technique is developing the first non-trivial approximation algorithm and showing how to convert it to an exact algorithm. Moreover, we show that in a practical case in verification where weights are clustered around a constant number of values, the energy game problem can be solved in polynomial time. We also show that the problem is still as hard as in general when the clique-width is bounded or the graph is strongly ergodic, suggesting that restricting the graph structure does not necessarily help.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
AU - Krinninger, Sebastian
AU - Nanongkai, Danupon
ID - 535
IS - 3
JF - Algorithmica
TI - Polynomial time algorithms for energy games with special weight structures
VL - 70
ER -
TY - JOUR
AB - Transgenerational effects are broader than only parental relationships. Despite mounting evidence that multigenerational effects alter phenotypic and life-history traits, our understanding of how they combine to determine fitness is not well developed because of the added complexity necessary to study them. Here, we derive a quantitative genetic model of adaptation to an extraordinary new environment by an additive genetic component, phenotypic plasticity, maternal and grandmaternal effects. We show how, at equilibrium, negative maternal and negative grandmaternal effects maximize expected population mean fitness. We define negative transgenerational effects as those that have a negative effect on trait expression in the subsequent generation, that is, they slow, or potentially reverse, the expected evolutionary dynamic. When maternal effects are positive, negative grandmaternal effects are preferred. As expected under Mendelian inheritance, the grandmaternal effects have a lower impact on fitness than the maternal effects, but this dual inheritance model predicts a more complex relationship between maternal and grandmaternal effects to constrain phenotypic variance and so maximize expected population mean fitness in the offspring.
AU - Prizak, Roshan
AU - Ezard, Thomas
AU - Hoyle, Rebecca
ID - 537
IS - 15
JF - Ecology and Evolution
TI - Fitness consequences of maternal and grandmaternal effects
VL - 4
ER -
TY - GEN
AB - Model-based testing is a promising technology for black-box software and hardware testing, in which test cases are generated automatically from high-level specifications. Nowadays, systems typically consist of multiple interacting components and, due to their complexity, testing presents a considerable portion of the effort and cost in the design process. Exploiting the compositional structure of system specifications can considerably reduce the effort in model-based testing. Moreover, inferring properties about the system from testing its individual components allows the designer to reduce the amount of integration testing.
In this paper, we study compositional properties of the IOCO-testing theory. We propose a new approach to composition and hiding operations, inspired by contract-based design and interface theories. These operations preserve behaviors that are compatible under composition and hiding, and prune away incompatible ones. The resulting specification characterizes the input sequences for which the unit testing of components is sufficient to infer the correctness of component integration without the need for further tests. We provide a methodology that uses these results to minimize integration testing effort, but also to detect potential weaknesses in specifications. While we focus on asynchronous models and the IOCO conformance relation, the resulting methodology can be applied to a broader class of systems.
AU - Daca, Przemyslaw
AU - Henzinger, Thomas A
AU - Krenn, Willibald
AU - Nickovic, Dejan
ID - 5411
SN - 2664-1690
TI - Compositional specifications for IOCO testing
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) which are a standard model for probabilistic systems. We focus on qualitative properties for MDPs that can express that desired behaviors of the system arise almost-surely (with probability 1) or with positive probability.
We introduce a new simulation relation to capture the refinement relation of MDPs with respect to qualitative properties, and present discrete graph theoretic algorithms with quadratic complexity to compute the simulation relation.
We present an automated technique for assume-guarantee style reasoning for compositional analysis of MDPs with qualitative properties by giving a counter-example guided abstraction-refinement approach to compute our new simulation relation. We have implemented our algorithms and show that the compositional analysis leads to significant improvements.
AU - Chatterjee, Krishnendu
AU - Daca, Przemyslaw
AU - Chmelik, Martin
ID - 5412
SN - 2664-1690
TI - CEGAR for qualitative analysis of probabilistic systems
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) which are a standard model for probabilistic systems. We focus on qualitative properties for MDPs that can express that desired behaviors of the system arise almost-surely (with probability 1) or with positive probability.
We introduce a new simulation relation to capture the refinement relation of MDPs with respect to qualitative properties, and present discrete graph theoretic algorithms with quadratic complexity to compute the simulation relation.
We present an automated technique for assume-guarantee style reasoning for compositional analysis of MDPs with qualitative properties by giving a counter-example guided abstraction-refinement approach to compute our new simulation relation. We have implemented our algorithms and show that the compositional analysis leads to significant improvements.
AU - Chatterjee, Krishnendu
AU - Daca, Przemyslaw
AU - Chmelik, Martin
ID - 5413
SN - 2664-1690
TI - CEGAR for qualitative analysis of probabilistic systems
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) which are a standard model for probabilistic systems. We focus on qualitative properties for MDPs that can express that desired behaviors of the system arise almost-surely (with probability 1) or with positive probability.
We introduce a new simulation relation to capture the refinement relation of MDPs with respect to qualitative properties, and present discrete graph theoretic algorithms with quadratic complexity to compute the simulation relation.
We present an automated technique for assume-guarantee style reasoning for compositional analysis of MDPs with qualitative properties by giving a counter-example guided abstraction-refinement approach to compute our new simulation relation.
We have implemented our algorithms and show that the compositional analysis leads to significant improvements.
AU - Chatterjee, Krishnendu
AU - Daca, Przemyslaw
AU - Chmelik, Martin
ID - 5414
SN - 2664-1690
TI - CEGAR for qualitative analysis of probabilistic systems
ER -
TY - GEN
AB - Recently there has been a significant effort to add quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, several basic system properties such as average response time cannot be expressed with weighted automata. In this work, we introduce nested weighted automata as a new formalism for expressing important quantitative properties such as average response time. We establish an almost complete decidability picture for the basic decision problems for nested weighted automata, and illustrate its applicability in several domains.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5415
SN - 2664-1690
TI - Nested weighted automata
ER -
TY - GEN
AB - As hybrid systems involve continuous behaviors, they should be evaluated by quantitative methods, rather than qualitative methods. In this paper we adapt a quantitative framework, called model measuring, to the hybrid systems domain. The model-measuring problem asks, given a model M and a specification, what is the maximal distance such that all models within that distance from M satisfy (or violate) the specification. A distance function on models is given as part of the input of the problem. Distances, especially related to continuous behaviors are more natural in the hybrid case than the discrete case. We are interested in distances represented by monotonic hybrid automata, a hybrid counterpart of (discrete) weighted automata, whose recognized timed languages are monotone (w.r.t. inclusion) in the values of parameters.The contributions of this paper are twofold. First, we give sufficient conditions under which the model-measuring problem can be solved. Second, we discuss the modeling of distances and applications of the model-measuring problem.
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5416
SN - 2664-1690
TI - Model measuring for hybrid systems
ER -
TY - GEN
AB - We define the model-measuring problem: given a model M and specification φ, what is the maximal distance ρ such that all models M'within distance ρ from M satisfy (or violate)φ. The model measuring problem presupposes a distance function on models. We concentrate on automatic distance functions, which are defined by weighted automata.
The model-measuring problem subsumes several generalizations of the classical model-checking problem, in particular, quantitative model-checking problems that measure the degree of satisfaction of a specification, and robustness problems that measure how much a model can be perturbed without violating the specification.
We show that for automatic distance functions, and ω-regular linear-time and branching-time specifications, the model-measuring problem can be solved.
We use automata-theoretic model-checking methods for model measuring, replacing the emptiness question for standard word and tree automata by the optimal-weight question for the weighted versions of these automata. We consider weighted automata that accumulate weights by maximizing, summing, discounting, and limit averaging.
We give several examples of using the model-measuring problem to compute various notions of robustness and quantitative satisfaction for temporal specifications.
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5417
SN - 2664-1690
TI - From model checking to model measuring
ER -
TY - GEN
AB - We consider multi-player graph games with partial-observation and parity objective. While the decision problem for three-player games with a coalition of the first and second players against the third player is undecidable, we present a decidability result for partial-observation games where the first and third player are in a coalition against the second player, thus where the second player is adversarial but weaker due to partial-observation. We establish tight complexity bounds in the case where player 1 is less informed than player 2, namely 2-EXPTIME-completeness for parity objectives. The symmetric case of player 1 more informed than player 2 is much more complicated, and we show that already in the case where player 1 has perfect observation, memory of size non-elementary is necessary in general for reachability objectives, and the problem is decidable for safety and reachability objectives. Our results have tight connections with partial-observation stochastic games for which we derive new complexity results.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 5418
SN - 2664-1690
TI - Games with a weak adversary
ER -
TY - GEN
AB - We consider the reachability and shortest path problems on low tree-width graphs, with n nodes, m edges, and tree-width t, on a standard RAM with wordsize W. We use O to hide polynomial factors of the inverse of the Ackermann function. Our main contributions are three fold:
1. For reachability, we present an algorithm that requires O(n·t2·log(n/t)) preprocessing time, O(n·(t·log(n/t))/W) space, and O(t/W) time for pair queries and O((n·t)/W) time for single-source queries. Note that for constant t our algorithm uses O(n·logn) time for preprocessing; and O(n/W) time for single-source queries, which is faster than depth first search/breath first search (after the preprocessing).
2. We present an algorithm for shortest path that requires O(n·t2) preprocessing time, O(n·t) space, and O(t2) time for pair queries and O(n·t) time single-source queries.
3. We give a space versus query time trade-off algorithm for shortest path that, given any constant >0, requires O(n·t2) preprocessing time, O(n·t2) space, and O(n1−·t2) time for pair queries.
Our algorithms improve all existing results, and use very simple data structures.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5419
SN - 2664-1690
TI - Improved algorithms for reachability and shortest path on low tree-width graphs
ER -
TY - GEN
AB - We consider concurrent mean-payoff games, a very well-studied class of two-player (player 1 vs player 2) zero-sum games on finite-state graphs where every transition is assigned a reward between 0 and 1, and the payoff function is the long-run average of the rewards. The value is the maximal expected payoff that player 1 can guarantee against all strategies of player 2. We consider the computation of the set of states with value 1 under finite-memory strategies for player 1, and our main results for the problem are as follows: (1) we present a polynomial-time algorithm; (2) we show that whenever there is a finite-memory strategy, there is a stationary strategy that does not need memory at all; and (3) we present an optimal bound (which is double exponential) on the patience of stationary strategies (where patience of a distribution is the inverse of the smallest positive probability and represents a complexity measure of a stationary strategy).
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 5420
SN - 2664-1690
TI - The value 1 problem for concurrent mean-payoff games
ER -
TY - GEN
AB - Evolution occurs in populations of reproducing individuals. The structure of the population affects the outcome of the evolutionary process. Evolutionary graph theory is a powerful approach to study this phenomenon. There are two graphs. The interaction graph specifies who interacts with whom in the context of evolution. The replacement graph specifies who competes with whom for reproduction. The vertices of the two graphs are the same, and each vertex corresponds to an individual. A key quantity is the fixation probability of a new mutant. It is defined as the probability that a newly introduced mutant (on a single vertex) generates a lineage of offspring which eventually takes over the entire population of resident individuals. The basic computational questions are as follows: (i) the qualitative question asks whether the fixation probability is positive; and (ii) the quantitative approximation question asks for an approximation of the fixation probability. Our main results are: (1) We show that the qualitative question is NP-complete and the quantitative approximation question is #P-hard in the special case when the interaction and the replacement graphs coincide and even with the restriction that the resident individuals do not reproduce (which corresponds to an invading population taking over an empty structure). (2) We show that in general the qualitative question is PSPACE-complete and the quantitative approximation question is PSPACE-hard and can be solved in exponential time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Nowak, Martin
ID - 5421
SN - 2664-1690
TI - The complexity of evolution on graphs
ER -
TY - GEN
AB - Notes from the Third Plenary for the Research Data Alliance in Dublin, Ireland on March 26 to 28, 2014 with focus on starting an institutional research data repository.
AU - Porsche, Jana
ID - 5422
TI - Notes from Research Data Alliance Plenary Meeting in Dublin, Ireland
ER -
TY - GEN
AB - We present a flexible framework for the automated competitive analysis of on-line scheduling algorithms for firm- deadline real-time tasks based on multi-objective graphs: Given a taskset and an on-line scheduling algorithm specified as a labeled transition system, along with some optional safety, liveness, and/or limit-average constraints for the adversary, we automatically compute the competitive ratio of the algorithm w.r.t. a clairvoyant scheduler. We demonstrate the flexibility and power of our approach by comparing the competitive ratio of several on-line algorithms, including D(over), that have been proposed in the past, for various tasksets. Our experimental results reveal that none of these algorithms is universally optimal, in the sense that there are tasksets where other schedulers provide better performance. Our framework is hence a very useful design tool for selecting optimal algorithms for a given application.
AU - Chatterjee, Krishnendu
AU - Kössler, Alexander
AU - Pavlogiannis, Andreas
AU - Schmid, Ulrich
ID - 5423
SN - 2664-1690
TI - A framework for automated competitive analysis of on-line scheduling of firm-deadline tasks
ER -
TY - GEN
AB - We consider partially observable Markov decision processes (POMDPs), that are a standard framework for robotics applications to model uncertainties present in the real world, with temporal logic specifications. All temporal logic specifications in linear-time temporal logic (LTL) can be expressed as parity objectives. We study the qualitative analysis problem for POMDPs with parity objectives that asks whether there is a controller (policy) to ensure that the objective holds with probability 1 (almost-surely). While the qualitative analysis of POMDPs with parity objectives is undecidable, recent results show that when restricted to finite-memory policies the problem is EXPTIME-complete. While the problem is intractable in theory, we present a practical approach to solve the qualitative analysis problem. We designed several heuristics to deal with the exponential complexity, and have used our implementation on a number of well-known POMDP examples for robotics applications. Our results provide the first practical approach to solve the qualitative analysis of robot motion planning with LTL properties in the presence of uncertainty.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Gupta, Raghav
AU - Kanodia, Ayush
ID - 5424
SN - 2664-1690
TI - Qualitative analysis of POMDPs with temporal logic specifications for robotics applications
ER -
TY - GEN
AB - We consider partially observable Markov decision processes (POMDPs) with a set of target states and every transition is associated with an integer cost. The optimization objective we study asks to minimize the expected total cost till the target set is reached, while ensuring that the target set is reached almost-surely (with probability 1). We show that for integer costs approximating the optimal cost is undecidable. For positive costs, our results are as follows: (i) we establish matching lower and upper bounds for the optimal cost and the bound is double exponential; (ii) we show that the problem of approximating the optimal cost is decidable and present approximation algorithms developing on the existing algorithms for POMDPs with finite-horizon objectives. While the worst-case running time of our algorithm is double exponential, we also present efficient stopping criteria for the algorithm and show experimentally that it performs well in many examples of interest.
AU - Anonymous, 1
AU - Anonymous, 2
AU - Anonymous, 3
AU - Anonymous, 4
ID - 5425
SN - 2664-1690
TI - Optimal cost almost-sure reachability in POMDPs
ER -
TY - GEN
AB - We consider partially observable Markov decision processes (POMDPs), that are a standard framework for robotics applications to model uncertainties present in the real world, with temporal logic specifications. All temporal logic specifications in linear-time temporal logic (LTL) can be expressed as parity objectives. We study the qualitative analysis problem for POMDPs with parity objectives that asks whether there is a controller (policy) to ensure that the objective holds with probability 1 (almost-surely). While the qualitative analysis of POMDPs with parity objectives is undecidable, recent results show that when restricted to finite-memory policies the problem is EXPTIME-complete. While the problem is intractable in theory, we present a practical approach to solve the qualitative analysis problem. We designed several heuristics to deal with the exponential complexity, and have used our implementation on a number of well-known POMDP examples for robotics applications. Our results provide the first practical approach to solve the qualitative analysis of robot motion planning with LTL properties in the presence of uncertainty.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Gupta, Raghav
AU - Kanodia, Ayush
ID - 5426
SN - 2664-1690
TI - Qualitative analysis of POMDPs with temporal logic specifications for robotics applications
ER -
TY - GEN
AB - We consider graphs with n nodes together with their tree-decomposition that has b = O ( n ) bags and width t , on the standard RAM computational model with wordsize W = Θ (log n ) . Our contributions are two-fold: Our first contribution is an algorithm that given a graph and its tree-decomposition as input, computes a binary and balanced tree-decomposition of width at most 4 · t + 3 of the graph in O ( b ) time and space, improving a long-standing (from 1992) bound of O ( n · log n ) time for constant treewidth graphs. Our second contribution is on reachability queries for low treewidth graphs. We build on our tree-balancing algorithm and present a data-structure for graph reachability that requires O ( n · t 2 ) preprocessing time, O ( n · t ) space, and O ( d t/ log n e ) time for pair queries, and O ( n · t · log t/ log n ) time for single-source queries. For constant t our data-structure uses O ( n ) time for preprocessing, O (1) time for pair queries, and O ( n/ log n ) time for single-source queries. This is (asymptotically) optimal and is faster than DFS/BFS when answering more than a constant number of single-source queries.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5427
SN - 2664-1690
TI - Optimal tree-decomposition balancing and reachability on low treewidth graphs
ER -
TY - GEN
AB - Simulation is an attractive alternative for language inclusion for automata as it is an under-approximation of language inclusion, but usually has much lower complexity. For non-deterministic automata, while language inclusion is PSPACE-complete, simulation can be computed in polynomial time. Simulation has also been extended in two orthogonal directions, namely, (1) fair simulation, for simulation over specified set of infinite runs; and (2) quantitative simulation, for simulation between weighted automata. Again, while fair trace inclusion is PSPACE-complete, fair simulation can be computed in polynomial time. For weighted automata, the (quantitative) language inclusion problem is undecidable for mean-payoff automata and the decidability is open for discounted-sum automata, whereas the (quantitative) simulation reduce to mean-payoff games and discounted-sum games, which admit pseudo-polynomial time algorithms.
In this work, we study (quantitative) simulation for weighted automata with Büchi acceptance conditions, i.e., we generalize fair simulation from non-weighted automata to weighted automata. We show that imposing Büchi acceptance conditions on weighted automata changes many fundamental properties of the simulation games. For example, whereas for mean-payoff and discounted-sum games, the players do not need memory to play optimally; we show in contrast that for simulation games with Büchi acceptance conditions, (i) for mean-payoff objectives, optimal strategies for both players require infinite memory in general, and (ii) for discounted-sum objectives, optimal strategies need not exist for both players. While the simulation games with Büchi acceptance conditions are more complicated (e.g., due to infinite-memory requirements for mean-payoff objectives) as compared to their counterpart without Büchi acceptance conditions, we still present pseudo-polynomial time algorithms to solve simulation games with Büchi acceptance conditions for both weighted mean-payoff and weighted discounted-sum automata.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Velner, Yaron
ID - 5428
SN - 2664-1690
TI - Quantitative fair simulation games
ER -
TY - CHAP
AB - Mechanically coupled cells can generate forces driving cell and tissue morphogenesis during development. Visualization and measuring of these forces is of major importance to better understand the complexity of the biomechanic processes that shape cells and tissues. Here, we describe how UV laser ablation can be utilized to quantitatively assess mechanical tension in different tissues of the developing zebrafish and in cultures of primary germ layer progenitor cells ex vivo.
AU - Smutny, Michael
AU - Behrndt, Martin
AU - Campinho, Pedro
AU - Ruprecht, Verena
AU - Heisenberg, Carl-Philipp J
ED - Nelson, Celeste
ID - 6178
SN - 1064-3745
T2 - Tissue Morphogenesis
TI - UV laser ablation to measure cell and tissue-generated forces in the zebrafish embryo in vivo and ex vivo
VL - 1189
ER -
TY - BOOK
AB - This monograph presents a short course in computational geometry and topology. In the first part the book covers Voronoi diagrams and Delaunay triangulations, then it presents the theory of alpha complexes which play a crucial role in biology. The central part of the book is the homology theory and their computation, including the theory of persistence which is indispensable for applications, e.g. shape reconstruction. The target audience comprises researchers and practitioners in mathematics, biology, neuroscience and computer science, but the book may also be beneficial to graduate students of these fields.
AU - Edelsbrunner, Herbert
ID - 6853
SN - 2191-530X
TI - A Short Course in Computational Geometry and Topology
ER -
TY - GEN
AU - Huszár, Kristóf
AU - Rolinek, Michal
ID - 7038
TI - Playful Math - An introduction to mathematical games
ER -
TY - JOUR
AB - We consider directed graphs where each edge is labeled with an integer weight and study the fundamental algorithmic question of computing the value of a cycle with minimum mean weight. Our contributions are twofold: (1) First we show that the algorithmic question is reducible to the problem of a logarithmic number of min-plus matrix multiplications of n×n-matrices, where n is the number of vertices of the graph. (2) Second, when the weights are nonnegative, we present the first (1+ε)-approximation algorithm for the problem and the running time of our algorithm is Õ(nωlog3(nW/ε)/ε),1 where O(nω) is the time required for the classic n×n-matrix multiplication and W is the maximum value of the weights. With an additional O(log(nW/ε)) factor in space a cycle with approximately optimal weight can be computed within the same time bound.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
AU - Krinninger, Sebastian
AU - Loitzenbauer, Veronika
AU - Raskin, Michael
ID - 1375
IS - C
JF - Theoretical Computer Science
TI - Approximating the minimum cycle mean
VL - 547
ER -
TY - CONF
AB - Fault-tolerant distributed algorithms play an important role in ensuring the reliability of many software applications. In this paper we consider distributed algorithms whose computations are organized in rounds. To verify the correctness of such algorithms, we reason about (i) properties (such as invariants) of the state, (ii) the transitions controlled by the algorithm, and (iii) the communication graph. We introduce a logic that addresses these points, and contains set comprehensions with cardinality constraints, function symbols to describe the local states of each process, and a limited form of quantifier alternation to express the verification conditions. We show its use in automating the verification of consensus algorithms. In particular, we give a semi-decision procedure for the unsatisfiability problem of the logic and identify a decidable fragment. We successfully applied our framework to verify the correctness of a variety of consensus algorithms tolerant to both benign faults (message loss, process crashes) and value faults (message corruption).
AU - Dragoi, Cezara
AU - Henzinger, Thomas A
AU - Veith, Helmut
AU - Widder, Josef
AU - Zufferey, Damien
ID - 1392
TI - A logic-based framework for verifying consensus algorithms
VL - 8318
ER -
TY - CONF
AB - Probabilistic programs are usual functional or imperative programs with two added constructs: (1) the ability to draw values at random from distributions, and (2) the ability to condition values of variables in a program via observations. Models from diverse application areas such as computer vision, coding theory, cryptographic protocols, biology and reliability analysis can be written as probabilistic programs. Probabilistic inference is the problem of computing an explicit representation of the probability distribution implicitly specified by a probabilistic program. Depending on the application, the desired output from inference may vary-we may want to estimate the expected value of some function f with respect to the distribution, or the mode of the distribution, or simply a set of samples drawn from the distribution. In this paper, we describe connections this research area called \Probabilistic Programming" has with programming languages and software engineering, and this includes language design, and the static and dynamic analysis of programs. We survey current state of the art and speculate on promising directions for future research.
AU - Gordon, Andrew
AU - Henzinger, Thomas A
AU - Nori, Aditya
AU - Rajamani, Sriram
ID - 1393
T2 - Proceedings of the on Future of Software Engineering
TI - Probabilistic programming
ER -
TY - THES
AB - In this thesis I studied various individual and social immune defences employed by the invasive garden ant Lasius neglectus mostly against entomopathogenic fungi. The first two chapters of this thesis address the phenomenon of 'social immunisation'. Social immunisation, that is the immunological protection of group members due to social contact to a pathogen-exposed nestmate, has been described in various social insect species against different types of pathogens. However, in the case of entomopathogenic fungi it has, so far, only been demonstrated that social immunisation exists at all. Its underlying mechanisms r any other properties were, however, unknown. In the first chapter of this thesis I identified the mechanistic basis of social immunisation in L. neglectus against the entomopathogenous fungus Metarhizium. I could show that nestmates of a pathogen-exposed individual contract low-level infections due to social interactions. These low-level infections are, however, non-lethal and cause an active stimulation of the immune system, which protects the nestmates upon subsequent pathogen encounters. In the second chapter of this thesis I investigated the specificity and colony level effects of social immunisation. I demonstrated that the protection conferred by social immunisation is highly specific, protecting ants only against the same pathogen strain. In addition, depending on the respective context, social immunisation may even cause fitness costs. I further showed that social immunisation crucially affects sanitary behaviour and disease dynamics within ant groups. In the third chapter of this thesis I studied the effects of the ectosymbiotic fungus Laboulbenia formicarum on its host L. neglectus. Although Laboulbeniales are the largest order of insect-parasitic fungi, research concerning host fitness consequence is sparse. I showed that highly Laboulbenia-infected ants sustain fitness costs under resource limitation, however, gain fitness benefits when exposed to an entomopathogenus fungus. These effects are probably cause by a prophylactic upregulation of behavioural as well as physiological immune defences in highly infected ants.
AU - Konrad, Matthias
ID - 1395
TI - Immune defences in ants: Effects of social immunisation and a fungal ectosymbiont in the ant Lasius neglectus
ER -
TY - THES
AB - Phosphatidylinositol (Ptdlns) is a structural phospholipid that can be phosphorylated into various lipid signaling molecules, designated polyphosphoinositides (PPIs). The reversible phosphorylation of PPIs on the 3, 4, or 5 position of inositol is performed by a set of organelle-specific kinases and phosphatases, and the characteristic head groups make these molecules ideal for regulating biological processes in time and space. In yeast and mammals, Ptdlns3P and Ptdlns(3,5)P2 play crucial roles in trafficking toward the lytic compartments, whereas the role in plants is not yet fully understood. Here we identified the role of a land plant-specific subgroup of PPI phosphatases, the suppressor of actin 2 (SAC2) to SAC5, during vauolar trafficking and morphogenesis in Arabidopsis thaliana. SAC2-SAC5 localize to the tonoplast along with Ptdlns3P, the presumable product of their activity. in SAC gain- and loss-of-function mutants, the levels of Ptdlns monophosphates and bisphosphates were changed, with opposite effects on the morphology of storage and lytic vacuoles, and the trafficking toward the vacuoles was defective. Moreover, multiple sac knockout mutants had an increased number of smaller storage and lytic vacuoles, whereas extralarge vacuoles were observed in the overexpression lines, correlating with various growth and developmental defects. The fragmented vacuolar phenotype of sac mutants could be mimicked by treating wild-type seedlings with Ptdlns(3,5)P2, corroborating that this PPI is important for vacuole morphology. Taken together, these results provide evidence that PPIs, together with their metabolic enzymes SAC2-SAC5, are crucial for vacuolar trafficking and for vacuolar morphology and function in plants.
AU - Marhavá, Petra
ID - 1402
TI - Molecular mechanisms of patterning and subcellular trafficking in Arabidopsis thaliana
ER -
TY - THES
AB - A variety of developmental and disease related processes depend on epithelial cell sheet spreading. In order to gain insight into the biophysical mechanism(s) underlying the tissue morphogenesis we studied the spreading of an epithelium during the early development of the zebrafish embryo. In zebrafish epiboly the enveloping cell layer (EVL), a simple squamous epithelium, spreads over the yolk cell to completely engulf it at the end of gastrulation. Previous studies have proposed that an actomyosin ring forming within the yolk syncytial layer (YSL) acts as purse string that through constriction along its circumference pulls on the margin of the EVL. Direct biophysical evidence for this hypothesis has however been missing. The aim of the thesis was to understand how the actomyosin ring may generate pulling forces onto the EVL and what cellular mechanism(s) may facilitate the spreading of the epithelium. Using laser ablation to measure cortical tension within the actomyosin ring we found an anisotropic tension distribution, which was highest along the circumference of the ring. However the low degree of anisotropy was incompatible with the actomyosin ring functioning as a purse string only. Additionally, we observed retrograde cortical flow from vegetal parts of the ring into the EVL margin. Interpreting the experimental data using a theoretical distribution that models the tissues as active viscous gels led us to proposen that the actomyosin ring has a twofold contribution to EVL epiboly. It not only acts as a purse string through constriction along its circumference, but in addition constriction along the width of the ring generates pulling forces through friction-resisted cortical flow. Moreover, when rendering the purse string mechanism unproductive EVL epiboly proceeded normally indicating that the flow-friction mechanism is sufficient to drive the process. Aiming to understand what cellular mechanism(s) may facilitate the spreading of the epithelium we found that tension-oriented EVL cell divisions limit tissue anisotropy by releasing tension along the division axis and promote epithelial spreading. Notably, EVL cells undergo ectopic cell fusion in conditions in which oriented-cell division is impaired or the epithelium is mechanically challenged. Taken together our study of EVL epiboly suggests a novel mechanism of force generation for actomyosin rings through friction-resisted cortical flow and highlights the importance of tension-oriented cell divisions in epithelial morphogenesis.
AU - Behrndt, Martin
ID - 1403
TI - Forces driving epithelial spreading in zebrafish epiboly
ER -
TY - THES
AB - The co-evolution of hosts and pathogens is characterized by continuous adaptations of both parties. Pathogens of social insects need to adapt towards disease defences at two levels: 1) individual immunity of each colony member consisting of behavioural defence strategies as well as humoral and cellular immune responses and 2) social immunity that is collectively performed by all group members comprising behavioural, physiological and organisational defence strategies.
To disentangle the selection pressure on pathogens by the collective versus individual level of disease defence in social insects, we performed an evolution experiment using the Argentine Ant, Linepithema humile, as a host and a mixture of the general insect pathogenic fungus Metarhizium spp. (6 strains) as a pathogen. We allowed pathogen evolution over 10 serial host passages to two different evolution host treatments: (1) only individual host immunity in a single host treatment, and (2) simultaneously acting individual and social immunity in a social host treatment, in which an exposed ant was accompanied by two untreated nestmates.
Before starting the pathogen evolution experiment, the 6 Metarhizium spp. strains were characterised concerning conidiospore size killing rates in singly and socially reared ants, their competitiveness under coinfecting conditions and their influence on ant behaviour. We analysed how the ancestral atrain mixture changed in conidiospere size, killing rate and strain composition dependent on host treatment (single or social hosts) during 10 passages and found that killing rate and conidiospere size of the pathogen increased under both evolution regimes, but different depending on host treatment.
Testing the evolved strain mixtures that evolved under either the single or social host treatment under both single and social current rearing conditions in a full factorial design experiment revealed that the additional collective defences in insect societies add new selection pressure for their coevolving pathogens that compromise their ability to adapt to its host at the group level. To our knowledge, this is the first study directly measuring the influence of social immunity on pathogen evolution.
AU - Stock, Miriam
ID - 1404
TI - Evolution of a fungal pathogen towards individual versus social immunity in ants
ER -
TY - CONF
AB - The Wigner-Dyson-Gaudin-Mehta conjecture asserts that the local eigenvalue statistics of large real and complex Hermitian matrices with independent, identically distributed entries are universal in a sense that they depend only on the symmetry class of the matrix and otherwise are independent of the details of the distribution. We present the recent solution to this half-century old conjecture. We explain how stochastic tools, such as the Dyson Brownian motion, and PDE ideas, such as De Giorgi-Nash-Moser regularity theory, were combined in the solution. We also show related results for log-gases that represent a universal model for strongly correlated systems. Finally, in the spirit of Wigner’s original vision, we discuss the extensions of these universality results to more realistic physical systems such as random band matrices.
AU - Erdös, László
ID - 1507
TI - Random matrices, log-gases and Hölder regularity
VL - 3
ER -
TY - CONF
AB - We present a rigorous derivation of the BCS gap equation for superfluid fermionic gases with point interactions. Our starting point is the BCS energy functional, whose minimizer we investigate in the limit when the range of the interaction potential goes to zero.
AU - Bräunlich, Gerhard
AU - Hainzl, Christian
AU - Seiringer, Robert
ID - 1516
T2 - Proceedings of the QMath12 Conference
TI - On the BCS gap equation for superfluid fermionic gases
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
TI - Auxin-modulated root growth inhibition in Arabidopsis thaliana seedlings with ammonium as the sole nitrogen source
VL - 42
ER -
TY - JOUR
AB - We propose a method for propagating edit operations in 2D vector graphics, based on geometric relationship functions. These functions quantify the geometric relationship of a point to a polygon, such as the distance to the boundary or the direction to the closest corner vertex. The level sets of the relationship functions describe points with the same relationship to a polygon. For a given query point, we first determine a set of relationships to local features, construct all level sets for these relationships, and accumulate them. The maxima of the resulting distribution are points with similar geometric relationships. We show extensions to handle mirror symmetries, and discuss the use of relationship functions as local coordinate systems. Our method can be applied, for example, to interactive floorplan editing, and it is especially useful for large layouts, where individual edits would be cumbersome. We demonstrate populating 2D layouts with tens to hundreds of objects by propagating relatively few edit operations.
AU - Guerrero, Paul
AU - Jeschke, Stefan
AU - Wimmer, Michael
AU - Wonka, Peter
ID - 1629
IS - 2
JF - ACM Transactions on Graphics
TI - Edit propagation using geometric relationship functions
VL - 33
ER -
TY - CONF
AB - We extend the notion of verifiable random functions (VRF) to constrained VRFs, which generalize the concept of constrained pseudorandom functions, put forward by Boneh and Waters (Asiacrypt’13), and independently by Kiayias et al. (CCS’13) and Boyle et al. (PKC’14), who call them delegatable PRFs and functional PRFs, respectively. In a standard VRF the secret key sk allows one to evaluate a pseudorandom function at any point of its domain; in addition, it enables computation of a non-interactive proof that the function value was computed correctly. In a constrained VRF from the key sk one can derive constrained keys skS for subsets S of the domain, which allow computation of function values and proofs only at points in S. After formally defining constrained VRFs, we derive instantiations from the multilinear-maps-based constrained PRFs by Boneh and Waters, yielding a VRF with constrained keys for any set that can be decided by a polynomial-size circuit. Our VRFs have the same function values as the Boneh-Waters PRFs and are proved secure under the same hardness assumption, showing that verifiability comes at no cost. Constrained (functional) VRFs were stated as an open problem by Boyle et al.
AU - Fuchsbauer, Georg
ED - Abdalla, Michel
ED - De Prisco, Roberto
ID - 1643
T2 - SCN 2014
TI - Constrained Verifiable Random Functions
VL - 8642
ER -
TY - JOUR
AB - Adaptation in the retina is thought to optimize the encoding of natural light signals into sequences of spikes sent to the brain. While adaptive changes in retinal processing to the variations of the mean luminance level and second-order stimulus statistics have been documented before, no such measurements have been performed when higher-order moments of the light distribution change. We therefore measured the ganglion cell responses in the tiger salamander retina to controlled changes in the second (contrast), third (skew) and fourth (kurtosis) moments of the light intensity distribution of spatially uniform temporally independent stimuli. The skew and kurtosis of the stimuli were chosen to cover the range observed in natural scenes. We quantified adaptation in ganglion cells by studying linear-nonlinear models that capture well the retinal encoding properties across all stimuli. We found that the encoding properties of retinal ganglion cells change only marginally when higher-order statistics change, compared to the changes observed in response to the variation in contrast. By analyzing optimal coding in LN-type models, we showed that neurons can maintain a high information rate without large dynamic adaptation to changes in skew or kurtosis. This is because, for uncorrelated stimuli, spatio-temporal summation within the receptive field averages away non-gaussian aspects of the light intensity distribution.
AU - Tkacik, Gasper
AU - Ghosh, Anandamohan
AU - Schneidman, Elad
AU - Segev, Ronen
ID - 3263
IS - 1
JF - PLoS One
TI - Adaptation to changes in higher-order stimulus statistics in the salamander retina
VL - 9
ER -
TY - CONF
AB - While fixing concurrency bugs, program repair algorithms may introduce new concurrency bugs. We present an algorithm that avoids such regressions. The solution space is given by a set of program transformations we consider in the repair process. These include reordering of instructions within a thread and inserting atomic sections. The new algorithm learns a constraint on the space of candidate solutions, from both positive examples (error-free traces) and counterexamples (error traces). From each counterexample, the algorithm learns a constraint necessary to remove the errors. From each positive examples, it learns a constraint that is necessary in order to prevent the repair from turning the trace into an error trace. We implemented the algorithm and evaluated it on simplified Linux device drivers with known bugs.
AU - Cerny, Pavol
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Ryzhyk, Leonid
AU - Tarrach, Thorsten
ID - 2218
SN - 978-331908866-2
TI - Regression-free synthesis for concurrency
VL - 8559
ER -
TY - CONF
AB - Motivated by topological Tverberg-type problems, we consider multiple (double, triple, and higher multiplicity) selfintersection points of maps from finite simplicial complexes (compact polyhedra) into ℝd and study conditions under which such multiple points can be eliminated. The most classical case is that of embeddings (i.e., maps without double points) of a κ-dimensional complex K into ℝ2κ. For this problem, the work of van Kampen, Shapiro, and Wu provides an efficiently testable necessary condition for embeddability (namely, vanishing of the van Kampen ob-struction). For κ ≥ 3, the condition is also sufficient, and yields a polynomial-time algorithm for deciding embeddability: One starts with an arbitrary map f : K→ℝ2κ, which generically has finitely many double points; if k ≥ 3 and if the obstruction vanishes then one can successively remove these double points by local modifications of the map f. One of the main tools is the famous Whitney trick that permits eliminating pairs of double points of opposite intersection sign. We are interested in generalizing this approach to intersection points of higher multiplicity. We call a point y 2 ℝd an r-fold Tverberg point of a map f : Kκ →ℝd if y lies in the intersection f(σ1)∩. ∩f(σr) of the images of r pairwise disjoint simplices of K. The analogue of (non-)embeddability that we study is the problem Tverbergκ r→d: Given a κ-dimensional complex K, does it satisfy a Tverberg-type theorem with parameters r and d, i.e., does every map f : K κ → ℝd have an r-fold Tverberg point? Here, we show that for fixed r, κ and d of the form d = rm and k = (r-1)m, m ≥ 3, there is a polynomial-time algorithm for deciding this (based on the vanishing of a cohomological obstruction, as in the case of embeddings). Our main tool is an r-fold analogue of the Whitney trick: Given r pairwise disjoint simplices of K such that the intersection of their images contains two r-fold Tverberg points y+ and y- of opposite intersection sign, we can eliminate y+ and y- by a local isotopy of f. In a subsequent paper, we plan to develop this further and present a generalization of the classical Haeiger-Weber Theorem (which yields a necessary and sufficient condition for embeddability of κ-complexes into ℝd for a wider range of dimensions) to intersection points of higher multiplicity.
AU - Mabillard, Isaac
AU - Wagner, Uli
ID - 2159
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - Eliminating Tverberg points, I. An analogue of the Whitney trick
ER -
TY - JOUR
AB - Understanding the evolution of dispersal is essential for understanding and predicting the dynamics of natural populations. Two main factors are known to influence dispersal evolution: spatio-temporal variation in the environment and relatedness between individuals. However, the relation between these factors is still poorly understood, and they are usually treated separately. In this article, I present a theoretical framework that contains and connects effects of both environmental variation and relatedness, and reproduces and extends their known features. Spatial habitat variation selects for balanced dispersal strategies, whereby the population is kept at an ideal free distribution. Within this class of dispersal strategies, I explain how increased dispersal is promoted by perturbations to the dispersal type frequencies. An explicit formula shows the magnitude of the selective advantage of increased dispersal in terms of the spatial variability in the frequencies of the different dispersal strategies present. These variances are capable of capturing various sources of stochasticity and hence establish a common scale for their effects on the evolution of dispersal. The results furthermore indicate an alternative approach to identifying effects of relatedness on dispersal evolution.
AU - Novak, Sebastian
ID - 2023
IS - 24
JF - Ecology and Evolution
TI - Habitat heterogeneities versus spatial type frequency variances as driving forces of dispersal evolution
VL - 4
ER -
TY - JOUR
AB - Deposits of phosphorylated tau protein and convergence of pathology in the hippocampus are the hallmarks of neurodegenerative tauopathies. Thus we aimed to evaluate whether regional and cellular vulnerability patterns in the hippocampus distinguish tauopathies or are influenced by their concomitant presence. Methods: We created a heat map of phospho-tau (AT8) immunoreactivity patterns in 24 hippocampal subregions/layers in individuals with Alzheimer's disease (AD)-related neurofibrillary degeneration (n = 40), Pick's disease (n = 8), progressive supranuclear palsy (n = 7), corticobasal degeneration (n = 6), argyrophilic grain disease (AGD, n = 18), globular glial tauopathy (n = 5), and tau-astrogliopathy of the elderly (n = 10). AT8 immunoreactivity patterns were compared by mathematical analysis. Results: Our study reveals disease-specific hot spots and regional selective vulnerability for these disorders. The pattern of hippocampal AD-related tau pathology is strongly influenced by concomitant AGD. Mathematical analysis reveals that hippocampal involvement in primary tauopathies is distinguishable from early-stage AD-related neurofibrillary degeneration. Conclusion: Our data demonstrate disease-specific AT8 immunoreactivity patterns and hot spots in the hippocampus even in tauopathies, which primarily do not affect the hippocampus. These hot spots can be shifted to other regions by the co-occurrence of tauopathies like AGD. Our observations support the notion that globular glial tauopathies and tau-astrogliopathy of the elderly are distinct entities.
AU - Milenković, Ivan
AU - Petrov, Tatjana
AU - Kovács, Gábor
ID - 1913
IS - 5-6
JF - Dementia and Geriatric Cognitive Disorders
TI - Patterns of hippocampal tau pathology differentiate neurodegenerative dementias
VL - 38
ER -
TY - JOUR
AB - Selection for disease control is believed to have contributed to shape the organisation of insect societies — leading to interaction patterns that mitigate disease transmission risk within colonies, conferring them ‘organisational immunity’. Recent studies combining epidemiological models with social network analysis have identified general properties of interaction networks that may hinder propagation of infection within groups. These can be prophylactic and/or induced upon pathogen exposure. Here we review empirical evidence for these two types of organisational immunity in social insects and describe the individual-level behaviours that underlie it. We highlight areas requiring further investigation, and emphasise the need for tighter links between theory and empirical research and between individual-level and collective-level analyses.
AU - Stroeymeyt, Nathalie
AU - Casillas Perez, Barbara E
AU - Cremer, Sylvia
ID - 1999
IS - 1
JF - Current Opinion in Insect Science
TI - Organisational immunity in social insects
VL - 5
ER -
TY - CONF
AB - Direct Anonymous Attestation (DAA) is one of the most complex cryptographic protocols deployed in practice. It allows an embedded secure processor known as a Trusted Platform Module (TPM) to attest to the configuration of its host computer without violating the owner’s privacy. DAA has been standardized by the Trusted Computing Group and ISO/IEC.
The security of the DAA standard and all existing schemes is analyzed in the random-oracle model. We provide the first constructions of DAA in the standard model, that is, without relying on random oracles. Our constructions use new building blocks, including the first efficient signatures of knowledge in the standard model, which have many applications beyond DAA.
AU - Bernhard, David
AU - Fuchsbauer, Georg
AU - Ghadafi, Essam
ID - 2260
TI - Efficient signatures of knowledge and DAA in the standard model
VL - 7954
ER -
TY - JOUR
AB - Faithful progression through the cell cycle is crucial to the maintenance and developmental potential of stem cells. Here, we demonstrate that neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs) employ a zinc-finger transcription factor specificity protein 2 (Sp2) as a cell cycle regulator in two temporally and spatially distinct progenitor domains. Differential conditional deletion of Sp2 in early embryonic cerebral cortical progenitors, and perinatal olfactory bulb progenitors disrupted transitions through G1, G2 and M phases, whereas DNA synthesis appeared intact. Cell-autonomous function of Sp2 was identified by deletion of Sp2 using mosaic analysis with double markers, which clearly established that conditional Sp2-null NSCs and NPCs are M phase arrested in vivo. Importantly, conditional deletion of Sp2 led to a decline in the generation of NPCs and neurons in the developing and postnatal brains. Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain.
AU - Liang, Huixuan
AU - Xiao, Guanxi
AU - Yin, Haifeng
AU - Hippenmeyer, Simon
AU - Horowitz, Jonathan
AU - Ghashghaei, Troy
ID - 2264
IS - 3
JF - Development
TI - Neural development is dependent on the function of specificity protein 2 in cell cycle progression
VL - 140
ER -
TY - CONF
AB - Representation languages for coalitional games are a key research area in algorithmic game theory. There is an inher-
ent tradeoff between how general a language is, allowing it to capture more elaborate games, and how hard it is computationally to optimize and solve such games. One prominent such language is the simple yet expressive
Weighted Graph Games (WGGs) representation (Deng and Papadimitriou 1994), which maintains knowledge about synergies between agents in the form of an edge weighted graph. We consider the problem of finding the optimal coalition structure in WGGs. The agents in such games are vertices in a graph, and the value of a coalition is the sum of the weights of the edges present between coalition members. The optimal coalition structure is a partition of the agents to coalitions, that maximizes the sum of utilities obtained by the coalitions. We show that finding the optimal coalition structure is not only hard for general graphs, but is also intractable for restricted families such as planar graphs which are amenable for many other combinatorial problems. We then provide algorithms with constant factor approximations for planar, minorfree and bounded degree graphs.
AU - Bachrach, Yoram
AU - Kohli, Pushmeet
AU - Kolmogorov, Vladimir
AU - Zadimoghaddam, Morteza
ID - 2270
TI - Optimal Coalition Structures in Cooperative Graph Games
ER -
TY - CONF
AB - We consider Conditional Random Fields (CRFs) with pattern-based potentials defined on a chain. In this model the energy of a string (labeling) x1...xn is the sum of terms over intervals [i,j] where each term is non-zero only if the substring xi...xj equals a prespecified pattern α. Such CRFs can be naturally applied to many sequence tagging problems.
We present efficient algorithms for the three standard inference tasks in a CRF, namely computing (i) the partition function, (ii) marginals, and (iii) computing the MAP. Their complexities are respectively O(nL), O(nLℓmax) and O(nLmin{|D|,log(ℓmax+1)}) where L is the combined length of input patterns, ℓmax is the maximum length of a pattern, and D is the input alphabet. This improves on the previous algorithms of (Ye et al., 2009) whose complexities are respectively O(nL|D|), O(n|Γ|L2ℓ2max) and O(nL|D|), where |Γ| is the number of input patterns.
In addition, we give an efficient algorithm for sampling. Finally, we consider the case of non-positive weights. (Komodakis & Paragios, 2009) gave an O(nL) algorithm for computing the MAP. We present a modification that has the same worst-case complexity but can beat it in the best case.
AU - Takhanov, Rustem
AU - Kolmogorov, Vladimir
ID - 2272
IS - 3
T2 - ICML'13 Proceedings of the 30th International Conference on International
TI - Inference algorithms for pattern-based CRFs on sequence data
VL - 28
ER -