@article{2246,
abstract = {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. },
author = {Grinshpun, Andrey and Phalitnonkiat, Pakawat and Rubin, Sasha and Tarfulea, Andrei},
issn = {03043975},
journal = {Theoretical Computer Science},
pages = {73 -- 91},
publisher = {Elsevier},
title = {{Alternating traps in Muller and parity games}},
doi = {10.1016/j.tcs.2013.11.032},
volume = {521},
year = {2014},
}
@article{2248,
abstract = {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.},
author = {Capek, Daniel and Metscher, Brian and Müller, Gerd},
issn = {15525007},
journal = {Journal of Experimental Zoology Part B: Molecular and Developmental Evolution},
number = {1},
pages = {1 -- 12},
publisher = {Wiley-Blackwell},
title = {{Thumbs down: A molecular-morphogenetic approach to avian digit homology}},
doi = {10.1002/jez.b.22545},
volume = {322},
year = {2014},
}
@article{2249,
abstract = {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.},
author = {Chen, Yani and Aung, Kyaw and Rolčík, Jakub and Walicki, Kathryn and Friml, Jirí and Brandizzí, Federica},
issn = {09607412},
journal = {Plant Journal},
number = {1},
pages = {97 -- 107},
publisher = {Wiley-Blackwell},
title = {{Inter-regulation of the unfolded protein response and auxin signaling}},
doi = {10.1111/tpj.12373},
volume = {77},
year = {2014},
}
@article{2251,
abstract = {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.},
author = {Csicsvari, Jozsef L and Dupret, David},
issn = {09628436},
journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences},
number = {1635},
publisher = {Royal Society, The},
title = {{Sharp wave/ripple network oscillations and learning-associated hippocampal maps}},
doi = {10.1098/rstb.2012.0528},
volume = {369},
year = {2014},
}
@article{2253,
abstract = {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.},
author = {Bailly, Aurélien and Wang, Bangjun and Zwiewka, Marta and Pollmann, Stephan and Schenck, Daniel and Lüthen, Hartwig and Schulz, Alexander and Friml, Jirí and Geisler, Markus},
issn = {09607412},
journal = {Plant Journal},
number = {1},
pages = {108 -- 118},
publisher = {Wiley-Blackwell},
title = {{Expression of TWISTED DWARF1 lacking its in-plane membrane anchor leads to increased cell elongation and hypermorphic growth}},
doi = {10.1111/tpj.12369},
volume = {77},
year = {2014},
}
@article{2254,
abstract = {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.},
author = {Pernia-Andrade, Alejandro and Jonas, Peter M},
issn = {08966273},
journal = {Neuron},
number = {1},
pages = {140 -- 152},
publisher = {Elsevier},
title = {{Theta-gamma-modulated synaptic currents in hippocampal granule cells in vivo define a mechanism for network oscillations}},
doi = {10.1016/j.neuron.2013.09.046},
volume = {81},
year = {2014},
}
@article{2255,
abstract = {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.},
author = {Edelsbrunner, Herbert and Pausinger, Florian},
issn = {09249907},
journal = {Journal of Mathematical Imaging and Vision},
number = {1},
pages = {164 -- 177},
publisher = {Springer},
title = {{Stable length estimates of tube-like shapes}},
doi = {10.1007/s10851-013-0468-x},
volume = {50},
year = {2014},
}
@article{2257,
abstract = {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.},
author = {Tkacik, Gasper and Marre, Olivier and Amodei, Dario and Schneidman, Elad and Bialek, William and Berry, Michael},
issn = {1553734X},
journal = {PLoS Computational Biology},
number = {1},
publisher = {Public Library of Science},
title = {{Searching for collective behavior in a large network of sensory neurons}},
doi = {10.1371/journal.pcbi.1003408},
volume = {10},
year = {2014},
}
@article{468,
abstract = {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.},
author = {Cimadom, Arno and Ulloa, Angel and Meidl, Patrick and Zöttl, Markus and Zöttl, Elisabet and Fessl, Birgit and Nemeth, Erwin and Dvorak, Michael and Cunninghame, Francesca and Tebbich, Sabine},
journal = {PLoS One},
number = {9},
publisher = {Public Library of Science},
title = {{Invasive parasites habitat change and heavy rainfall reduce breeding success in Darwin's finches}},
doi = {10.1371/journal.pone.0107518},
volume = {9},
year = {2014},
}
@inproceedings{475,
abstract = {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. },
author = {Aminof, Benjamin and Rubin, Sasha},
booktitle = {Electronic Proceedings in Theoretical Computer Science, EPTCS},
location = {Grenoble, France},
pages = {83 -- 90},
publisher = {Open Publishing Association},
title = {{First cycle games}},
doi = {10.4204/EPTCS.146.11},
volume = {146},
year = {2014},
}
@article{535,
abstract = {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.},
author = {Chatterjee, Krishnendu and Henzinger, Monika and Krinninger, Sebastian and Nanongkai, Danupon},
journal = {Algorithmica},
number = {3},
pages = {457 -- 492},
publisher = {Springer},
title = {{Polynomial time algorithms for energy games with special weight structures}},
doi = {10.1007/s00453-013-9843-7},
volume = {70},
year = {2014},
}
@article{537,
abstract = {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.},
author = {Prizak, Roshan and Ezard, Thomas and Hoyle, Rebecca},
journal = {Ecology and Evolution},
number = {15},
pages = {3139 -- 3145},
publisher = {Wiley-Blackwell},
title = {{Fitness consequences of maternal and grandmaternal effects}},
doi = {10.1002/ece3.1150},
volume = {4},
year = {2014},
}
@misc{5411,
abstract = {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.},
author = {Daca, Przemyslaw and Henzinger, Thomas A and Krenn, Willibald and Nickovic, Dejan},
issn = {2664-1690},
pages = {20},
publisher = {IST Austria},
title = {{Compositional specifications for IOCO testing}},
doi = {10.15479/AT:IST-2014-148-v2-1},
year = {2014},
}
@misc{5412,
abstract = {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. },
author = {Chatterjee, Krishnendu and Daca, Przemyslaw and Chmelik, Martin},
issn = {2664-1690},
pages = {31},
publisher = {IST Austria},
title = {{CEGAR for qualitative analysis of probabilistic systems}},
doi = {10.15479/AT:IST-2014-153-v1-1},
year = {2014},
}
@misc{5413,
abstract = {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. },
author = {Chatterjee, Krishnendu and Daca, Przemyslaw and Chmelik, Martin},
issn = {2664-1690},
pages = {33},
publisher = {IST Austria},
title = {{CEGAR for qualitative analysis of probabilistic systems}},
doi = {10.15479/AT:IST-2014-153-v2-2},
year = {2014},
}
@misc{5414,
abstract = {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. },
author = {Chatterjee, Krishnendu and Daca, Przemyslaw and Chmelik, Martin},
issn = {2664-1690},
pages = {33},
publisher = {IST Austria},
title = {{CEGAR for qualitative analysis of probabilistic systems}},
doi = {10.15479/AT:IST-2014-153-v3-1},
year = {2014},
}
@misc{5415,
abstract = {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. },
author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan},
issn = {2664-1690},
pages = {27},
publisher = {IST Austria},
title = {{Nested weighted automata}},
doi = {10.15479/AT:IST-2014-170-v1-1},
year = {2014},
}
@misc{5416,
abstract = {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.},
author = {Henzinger, Thomas A and Otop, Jan},
issn = {2664-1690},
pages = {22},
publisher = {IST Austria},
title = {{Model measuring for hybrid systems}},
doi = {10.15479/AT:IST-2014-171-v1-1},
year = {2014},
}
@misc{5417,
abstract = {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.},
author = {Henzinger, Thomas A and Otop, Jan},
issn = {2664-1690},
pages = {14},
publisher = {IST Austria},
title = {{From model checking to model measuring}},
doi = {10.15479/AT:IST-2014-172-v1-1},
year = {2014},
}
@misc{5418,
abstract = {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.},
author = {Chatterjee, Krishnendu and Doyen, Laurent},
issn = {2664-1690},
pages = {18},
publisher = {IST Austria},
title = {{Games with a weak adversary}},
doi = {10.15479/AT:IST-2014-176-v1-1},
year = {2014},
}
@misc{5419,
abstract = {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.},
author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas},
issn = {2664-1690},
pages = {34},
publisher = {IST Austria},
title = {{Improved algorithms for reachability and shortest path on low tree-width graphs}},
doi = {10.15479/AT:IST-2014-187-v1-1},
year = {2014},
}
@misc{5420,
abstract = {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).},
author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus},
issn = {2664-1690},
pages = {49},
publisher = {IST Austria},
title = {{The value 1 problem for concurrent mean-payoff games}},
doi = {10.15479/AT:IST-2014-191-v1-1},
year = {2014},
}
@misc{5421,
abstract = {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.},
author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Nowak, Martin},
issn = {2664-1690},
pages = {27},
publisher = {IST Austria},
title = {{The complexity of evolution on graphs}},
doi = {10.15479/AT:IST-2014-190-v2-2},
year = {2014},
}
@techreport{5422,
abstract = {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.},
author = {Porsche, Jana},
publisher = {none},
title = {{Notes from Research Data Alliance Plenary Meeting in Dublin, Ireland}},
year = {2014},
}
@misc{5423,
abstract = {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. },
author = {Chatterjee, Krishnendu and Kössler, Alexander and Pavlogiannis, Andreas and Schmid, Ulrich},
issn = {2664-1690},
pages = {14},
publisher = {IST Austria},
title = {{A framework for automated competitive analysis of on-line scheduling of firm-deadline tasks}},
doi = {10.15479/AT:IST-2014-300-v1-1},
year = {2014},
}
@misc{5424,
abstract = {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.},
author = {Chatterjee, Krishnendu and Chmelik, Martin and Gupta, Raghav and Kanodia, Ayush},
issn = {2664-1690},
pages = {12},
publisher = {IST Austria},
title = {{Qualitative analysis of POMDPs with temporal logic specifications for robotics applications}},
doi = {10.15479/AT:IST-2014-305-v1-1},
year = {2014},
}
@misc{5426,
abstract = {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.},
author = {Chatterjee, Krishnendu and Chmelik, Martin and Gupta, Raghav and Kanodia, Ayush},
issn = {2664-1690},
pages = {10},
publisher = {IST Austria},
title = {{Qualitative analysis of POMDPs with temporal logic specifications for robotics applications}},
doi = {10.15479/AT:IST-2014-305-v2-1},
year = {2014},
}
@misc{5427,
abstract = {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.},
author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas},
issn = {2664-1690},
pages = {24},
publisher = {IST Austria},
title = {{Optimal tree-decomposition balancing and reachability on low treewidth graphs}},
doi = {10.15479/AT:IST-2014-314-v1-1},
year = {2014},
}
@misc{5428,
abstract = {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.},
author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan and Velner, Yaron},
issn = {2664-1690},
pages = {26},
publisher = {IST Austria},
title = {{Quantitative fair simulation games}},
doi = {10.15479/AT:IST-2014-315-v1-1},
year = {2014},
}
@inbook{6178,
abstract = {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.},
author = {Smutny, Michael and Behrndt, Martin and Campinho, Pedro and Ruprecht, Verena and Heisenberg, Carl-Philipp J},
booktitle = {Tissue Morphogenesis},
editor = {Nelson, Celeste},
isbn = {9781493911639},
issn = {1064-3745},
pages = {219--235},
publisher = {Springer},
title = {{UV laser ablation to measure cell and tissue-generated forces in the zebrafish embryo in vivo and ex vivo}},
doi = {10.1007/978-1-4939-1164-6_15},
volume = {1189},
year = {2014},
}
@book{6853,
abstract = {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.},
author = {Edelsbrunner, Herbert},
isbn = {9783319059563},
issn = {2191-530X},
pages = {IX, 110},
publisher = {Springer International Publishing},
title = {{A Short Course in Computational Geometry and Topology}},
doi = {10.1007/978-3-319-05957-0},
year = {2014},
}
@techreport{7038,
author = {Huszár, Kristóf and Rolinek, Michal},
pages = {5},
publisher = {IST Austria},
title = {{Playful Math - An introduction to mathematical games}},
year = {2014},
}
@article{1375,
abstract = {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.},
author = {Chatterjee, Krishnendu and Henzinger, Monika and Krinninger, Sebastian and Loitzenbauer, Veronika and Raskin, Michael},
journal = {Theoretical Computer Science},
number = {C},
pages = {104 -- 116},
publisher = {Elsevier},
title = {{Approximating the minimum cycle mean}},
doi = {10.1016/j.tcs.2014.06.031},
volume = {547},
year = {2014},
}
@inproceedings{1392,
abstract = {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).},
author = {Dragoi, Cezara and Henzinger, Thomas A and Veith, Helmut and Widder, Josef and Zufferey, Damien},
location = {San Diego, USA},
pages = {161 -- 181},
publisher = {Springer},
title = {{A logic-based framework for verifying consensus algorithms}},
doi = {10.1007/978-3-642-54013-4_10},
volume = {8318},
year = {2014},
}
@inproceedings{1393,
abstract = {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.},
author = {Gordon, Andrew and Henzinger, Thomas A and Nori, Aditya and Rajamani, Sriram},
booktitle = {Proceedings of the on Future of Software Engineering},
location = {Hyderabad, India},
pages = {167 -- 181},
publisher = {ACM},
title = {{Probabilistic programming}},
doi = {10.1145/2593882.2593900},
year = {2014},
}
@phdthesis{1395,
abstract = {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.},
author = {Konrad, Matthias},
pages = {131},
publisher = {IST Austria},
title = {{Immune defences in ants: Effects of social immunisation and a fungal ectosymbiont in the ant Lasius neglectus}},
year = {2014},
}
@phdthesis{1402,
abstract = {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.},
author = {Marhavá, Petra},
pages = {90},
publisher = {IST Austria},
title = {{Molecular mechanisms of patterning and subcellular trafficking in Arabidopsis thaliana}},
year = {2014},
}
@phdthesis{1403,
abstract = {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.},
author = {Behrndt, Martin},
pages = {91},
publisher = {IST Austria},
title = {{Forces driving epithelial spreading in zebrafish epiboly}},
year = {2014},
}
@phdthesis{1404,
abstract = {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.},
author = {Stock, Miriam},
pages = {101},
publisher = {IST Austria},
title = {{Evolution of a fungal pathogen towards individual versus social immunity in ants}},
year = {2014},
}
@inproceedings{1507,
abstract = {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.},
author = {Erdös, László},
location = {Seoul, Korea},
pages = {214 -- 236},
publisher = {Kyung Moon SA Co. Ltd.},
title = {{Random matrices, log-gases and Hölder regularity}},
volume = {3},
year = {2014},
}
@inproceedings{1516,
abstract = {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.
},
author = {Bräunlich, Gerhard and Hainzl, Christian and Seiringer, Robert},
booktitle = {Proceedings of the QMath12 Conference},
location = {Berlin, Germany},
pages = {127 -- 137},
publisher = {World Scientific Publishing},
title = {{On the BCS gap equation for superfluid fermionic gases}},
doi = {10.1142/9789814618144_0007},
year = {2014},
}
@article{1532,
abstract = {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.},
author = {Yang, Huaiyu and Von Der Fecht Bartenbach, Jenny and Friml, Jirí and Lohmann, Jan and Neuhäuser, Benjamin and Ludewig, Uwe},
journal = {Functional Plant Biology},
number = {3},
pages = {239 -- 251},
publisher = {CSIRO},
title = {{Auxin-modulated root growth inhibition in Arabidopsis thaliana seedlings with ammonium as the sole nitrogen source}},
doi = {10.1071/FP14171},
volume = {42},
year = {2014},
}
@article{1629,
abstract = {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.},
author = {Guerrero, Paul and Jeschke, Stefan and Wimmer, Michael and Wonka, Peter},
journal = {ACM Transactions on Graphics},
number = {2},
publisher = {ACM},
title = {{Edit propagation using geometric relationship functions}},
doi = {10.1145/2591010},
volume = {33},
year = {2014},
}
@inproceedings{1643,
abstract = {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.},
author = {Fuchsbauer, Georg},
booktitle = {SCN 2014},
editor = {Abdalla, Michel and De Prisco, Roberto},
location = {Amalfi, Italy},
pages = {95 -- 114},
publisher = {Springer},
title = {{Constrained Verifiable Random Functions }},
doi = {10.1007/978-3-319-10879-7_7},
volume = {8642},
year = {2014},
}
@article{3263,
abstract = {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.},
author = {Tkacik, Gasper and Ghosh, Anandamohan and Schneidman, Elad and Segev, Ronen},
journal = {PLoS One},
number = {1},
publisher = {Public Library of Science},
title = {{Adaptation to changes in higher-order stimulus statistics in the salamander retina}},
doi = {10.1371/journal.pone.0085841},
volume = {9},
year = {2014},
}
@inproceedings{2218,
abstract = {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.},
author = {Cerny, Pavol and Henzinger, Thomas A and Radhakrishna, Arjun and Ryzhyk, Leonid and Tarrach, Thorsten},
isbn = {978-331908866-2},
location = {Vienna, Austria},
pages = {568 -- 584},
publisher = {Springer},
title = {{Regression-free synthesis for concurrency}},
doi = {10.1007/978-3-319-08867-9_38},
volume = {8559},
year = {2014},
}
@inproceedings{2159,
abstract = {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.},
author = {Mabillard, Isaac and Wagner, Uli},
booktitle = {Proceedings of the Annual Symposium on Computational Geometry},
location = {Kyoto, Japan},
pages = {171 -- 180},
publisher = {ACM},
title = {{Eliminating Tverberg points, I. An analogue of the Whitney trick}},
doi = {10.1145/2582112.2582134},
year = {2014},
}
@article{2023,
abstract = {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.},
author = {Novak, Sebastian},
journal = {Ecology and Evolution},
number = {24},
pages = {4589 -- 4597},
publisher = {Wiley-Blackwell},
title = {{Habitat heterogeneities versus spatial type frequency variances as driving forces of dispersal evolution}},
doi = {10.1002/ece3.1289},
volume = {4},
year = {2014},
}
@article{1999,
abstract = {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.},
author = {Stroeymeyt, Nathalie and Casillas Perez, Barbara E and Cremer, Sylvia},
journal = {Current Opinion in Insect Science},
number = {1},
pages = {1 -- 15},
publisher = {Elsevier},
title = {{Organisational immunity in social insects}},
doi = {10.1016/j.cois.2014.09.001},
volume = {5},
year = {2014},
}
@inproceedings{2260,
abstract = {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.
},
author = {Bernhard, David and Fuchsbauer, Georg and Ghadafi, Essam},
location = {Banff, AB, Canada},
pages = {518 -- 533},
publisher = {Springer},
title = {{Efficient signatures of knowledge and DAA in the standard model}},
doi = {10.1007/978-3-642-38980-1_33},
volume = {7954},
year = {2013},
}
@article{2264,
abstract = {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.},
author = {Liang, Huixuan and Xiao, Guanxi and Yin, Haifeng and Hippenmeyer, Simon and Horowitz, Jonathan and Ghashghaei, Troy},
journal = {Development},
number = {3},
pages = {552 -- 561},
publisher = {Company of Biologists},
title = {{Neural development is dependent on the function of specificity protein 2 in cell cycle progression}},
doi = {10.1242/dev.085621},
volume = {140},
year = {2013},
}
@inproceedings{2270,
abstract = {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.},
author = {Bachrach, Yoram and Kohli, Pushmeet and Kolmogorov, Vladimir and Zadimoghaddam, Morteza},
location = {Bellevue, WA, United States},
pages = {81--87},
publisher = {AAAI Press},
title = {{Optimal Coalition Structures in Cooperative Graph Games}},
year = {2013},
}
@inproceedings{2272,
abstract = {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. },
author = {Takhanov, Rustem and Kolmogorov, Vladimir},
booktitle = {ICML'13 Proceedings of the 30th International Conference on International},
location = {Atlanta, GA, USA},
number = {3},
pages = {145 -- 153},
publisher = {International Machine Learning Society},
title = {{Inference algorithms for pattern-based CRFs on sequence data}},
volume = {28},
year = {2013},
}
@techreport{2273,
abstract = {We propose a new family of message passing techniques for MAP estimation in graphical models which we call Sequential Reweighted Message Passing (SRMP). Special cases include well-known techniques such as Min-Sum Diusion (MSD) and a faster Sequential Tree-Reweighted Message Passing (TRW-S). Importantly, our derivation is simpler than the original derivation of TRW-S, and does not involve a decomposition into trees. This allows easy generalizations. We present such a generalization for the case of higher-order graphical models, and test it on several real-world problems with promising results.},
author = {Vladimir Kolmogorov},
publisher = {IST Austria},
title = {{Reweighted message passing revisited}},
year = {2013},
}
@techreport{2274,
abstract = {Proofs of work (PoW) have been suggested by Dwork and Naor (Crypto'92) as protection to a shared resource. The basic idea is to ask the service requestor to dedicate some non-trivial amount of computational work to every request. The original applications included prevention of spam and protection against denial of service attacks. More recently, PoWs have been used to prevent double spending in the Bitcoin digital currency system.
In this work, we put forward an alternative concept for PoWs -- so-called proofs of space (PoS), where a service requestor must dedicate a significant amount of disk space as opposed to computation. We construct secure PoS schemes in the random oracle model, using graphs with high "pebbling complexity" and Merkle hash-trees. },
author = {Dziembowski, Stefan and Faust, Sebastian and Kolmogorov, Vladimir and Pietrzak, Krzysztof Z},
publisher = {IST Austria},
title = {{Proofs of Space}},
year = {2013},
}
@inproceedings{2276,
abstract = {The problem of minimizing the Potts energy function frequently occurs in computer vision applications. One way to tackle this NP-hard problem was proposed by Kovtun [19, 20]. It identifies a part of an optimal solution by running k maxflow computations, where k is the number of labels. The number of “labeled” pixels can be significant in some applications, e.g. 50-93% in our tests for stereo. We show how to reduce the runtime to O (log k) maxflow computations (or one parametric maxflow computation). Furthermore, the output of our algorithm allows to speed-up the subsequent alpha expansion for the unlabeled part, or can be used as it is for time-critical applications. To derive our technique, we generalize the algorithm of Felzenszwalb et al. [7] for Tree Metrics . We also show a connection to k-submodular functions from combinatorial optimization, and discuss k-submodular relaxations for general energy functions.},
author = {Gridchyn, Igor and Kolmogorov, Vladimir},
location = {Sydney, Australia},
pages = {2320 -- 2327},
publisher = {IEEE},
title = {{Potts model, parametric maxflow and k-submodular functions}},
doi = {10.1109/ICCV.2013.288},
year = {2013},
}
@article{2277,
abstract = {Redundancies and correlations in the responses of sensory neurons may seem to waste neural resources, but they can also carry cues about structured stimuli and may help the brain to correct for response errors. To investigate the effect of stimulus structure on redundancy in retina, we measured simultaneous responses from populations of retinal ganglion cells presented with natural and artificial stimuli that varied greatly in correlation structure; these stimuli and recordings are publicly available online. Responding to spatio-temporally structured stimuli such as natural movies, pairs of ganglion cells were modestly more correlated than in response to white noise checkerboards, but they were much less correlated than predicted by a non-adapting functional model of retinal response. Meanwhile, responding to stimuli with purely spatial correlations, pairs of ganglion cells showed increased correlations consistent with a static, non-adapting receptive field and nonlinearity. We found that in response to spatio-temporally correlated stimuli, ganglion cells had faster temporal kernels and tended to have stronger surrounds. These properties of individual cells, along with gain changes that opposed changes in effective contrast at the ganglion cell input, largely explained the pattern of pairwise correlations across stimuli where receptive field measurements were possible.},
author = {Simmons, Kristina and Prentice, Jason and Tkacik, Gasper and Homann, Jan and Yee, Heather and Palmer, Stephanie and Nelson, Philip and Balasubramanian, Vijay},
journal = {PLoS Computational Biology},
number = {12},
publisher = {Public Library of Science},
title = {{Transformation of stimulus correlations by the retina}},
doi = {10.1371/journal.pcbi.1003344},
volume = {9},
year = {2013},
}
@article{2278,
abstract = {It is firmly established that interactions between neurons and glia are fundamental across species for the correct establishment of a functional brain. Here, we found that the glia of the Drosophila larval brain display an essential non-autonomous role during the development of the optic lobe. The optic lobe develops from neuroepithelial cells that proliferate by dividing symmetrically until they switch to asymmetric/differentiative divisions that generate neuroblasts. The proneural gene lethal of scute (l9sc) is transiently activated by the epidermal growth factor receptor (EGFR)-Ras signal transduction pathway at the leading edge of a proneural wave that sweeps from medial to lateral neuroepithelium, promoting this switch. This process is tightly regulated by the tissue-autonomous function within the neuroepithelium of multiple signaling pathways, including EGFR-Ras and Notch. This study shows that the Notch ligand Serrate (Ser) is expressed in the glia and it forms a complex in vivo with Notch and Canoe, which colocalize at the adherens junctions of neuroepithelial cells. This complex is crucial for interactions between glia and neuroepithelial cells during optic lobe development. Ser is tissue-autonomously required in the glia where it activates Notch to regulate its proliferation, and non-autonomously in the neuroepithelium where Ser induces Notch signaling to avoid the premature activation of the EGFR-Ras pathway and hence of L9sc. Interestingly, different Notch activity reporters showed very different expression patterns in the glia and in the neuroepithelium, suggesting the existence of tissue-specific factors that promote the expression of particular Notch target genes or/and a reporter response dependent on different thresholds of Notch signaling.},
author = {Pérez Gómez, Raquel and Slovakova, Jana and Rives Quinto, Noemí and Krejčí, Alena and Carmena, Ana},
journal = {Journal of Cell Science},
number = {21},
pages = {4873 -- 4884},
publisher = {Company of Biologists},
title = {{A serrate-notch-canoe complex mediates essential interactions between glia and neuroepithelial cells during Drosophila optic lobe development}},
doi = {10.1242/jcs.125617},
volume = {126},
year = {2013},
}
@inproceedings{2279,
abstract = {We consider two-player games played on weighted directed graphs with mean-payoff and total-payoff objectives, two classical quantitative objectives. While for single-dimensional games the complexity and memory bounds for both objectives coincide, we show that in contrast to multi-dimensional mean-payoff games that are known to be coNP-complete, multi-dimensional total-payoff games are undecidable. We introduce conservative approximations of these objectives, where the payoff is considered over a local finite window sliding along a play, instead of the whole play. For single dimension, we show that (i) if the window size is polynomial, deciding the winner takes polynomial time, and (ii) the existence of a bounded window can be decided in NP ∩ coNP, and is at least as hard as solving mean-payoff games. For multiple dimensions, we show that (i) the problem with fixed window size is EXPTIME-complete, and (ii) there is no primitive-recursive algorithm to decide the existence of a bounded window.},
author = {Chatterjee, Krishnendu and Doyen, Laurent and Randour, Mickael and Raskin, Jean},
location = {Hanoi, Vietnam},
pages = {118 -- 132},
publisher = {Springer},
title = {{Looking at mean-payoff and total-payoff through windows}},
doi = {10.1007/978-3-319-02444-8_10},
volume = {8172},
year = {2013},
}
@article{2280,
abstract = {The problem of packing ellipsoids of different sizes and shapes into an ellipsoidal container so as to minimize a measure of overlap between ellipsoids is considered. A bilevel optimization formulation is given, together with an algorithm for the general case and a simpler algorithm for the special case in which all ellipsoids are in fact spheres. Convergence results are proved and computational experience is described and illustrated. The motivating application-chromosome organization in the human cell nucleus-is discussed briefly, and some illustrative results are presented.},
author = {Uhler, Caroline and Wright, Stephen},
journal = {SIAM Review},
number = {4},
pages = {671 -- 706},
publisher = {Society for Industrial and Applied Mathematics },
title = {{Packing ellipsoids with overlap}},
doi = {10.1137/120872309},
volume = {55},
year = {2013},
}
@article{2282,
abstract = {Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly.},
author = {Campinho, Pedro and Behrndt, Martin and Ranft, Jonas and Risler, Thomas and Minc, Nicolas and Heisenberg, Carl-Philipp J},
journal = {Nature Cell Biology},
pages = {1405 -- 1414},
publisher = {Nature Publishing Group},
title = {{Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly}},
doi = {10.1038/ncb2869},
volume = {15},
year = {2013},
}
@article{2283,
abstract = {Pathogens exert a strong selection pressure on organisms to evolve effective immune defences. In addition to individual immunity, social organisms can act cooperatively to produce collective defences. In many ant species, queens have the option to found a colony alone or in groups with other, often unrelated, conspecifics. These associations are transient, usually lasting only as long as each queen benefits from the presence of others. In fact, once the first workers emerge, queens fight to the death for dominance. One potential advantage of co-founding may be that queens benefit from collective disease defences, such as mutual grooming, that act against common soil pathogens. We test this hypothesis by exposing single and co-founding queens to a fungal parasite, in order to assess whether queens in co-founding associations have improved survival. Surprisingly, co-foundresses exposed to the entomopathogenic fungus Metarhizium did not engage in cooperative disease defences, and consequently, we find no direct benefit of multiple queens on survival. However, an indirect benefit was observed, with parasite-exposed queens producing more brood when they co-founded, than when they were alone. We suggest this is due to a trade-off between reproduction and immunity. Additionally, we report an extraordinary ability of the queens to tolerate an infection for long periods after parasite exposure. Our study suggests that there are no social immunity benefits for co-founding ant queens, but that in parasite-rich environments, the presence of additional queens may nevertheless improve the chances of colony founding success.},
author = {Pull, Christopher and Hughes, William and Brown, Markus},
journal = {Naturwissenschaften},
number = {12},
pages = {1125 -- 1136},
publisher = {Springer},
title = {{Tolerating an infection: an indirect benefit of co-founding queen associations in the ant Lasius niger }},
doi = {10.1007/s00114-013-1115-5},
volume = {100},
year = {2013},
}
@article{2284,
abstract = {Background: The brood of ants and other social insects is highly susceptible to pathogens, particularly those that penetrate the soft larval and pupal cuticle. We here test whether the presence of a pupal cocoon, which occurs in some ant species but not in others, affects the sanitary brood care and fungal infection patterns after exposure to the entomopathogenic fungus Metarhizium brunneum. We use a) a comparative approach analysing four species with either naked or cocooned pupae and b) a within-species analysis of a single ant species, in which both pupal types co-exist in the same colony. Results: We found that the presence of a cocoon did not compromise fungal pathogen detection by the ants and that species with cocooned pupae increased brood grooming after pathogen exposure. All tested ant species further removed brood from their nests, which was predominantly expressed towards larvae and naked pupae treated with the live fungal pathogen. In contrast, cocooned pupae exposed to live fungus were not removed at higher rates than cocooned pupae exposed to dead fungus or a sham control. Consistent with this, exposure to the live fungus caused high numbers of infections and fungal outgrowth in larvae and naked pupae, but not in cocooned pupae. Moreover, the ants consistently removed the brood prior to fungal outgrowth, ensuring a clean brood chamber. Conclusion: Our study suggests that the pupal cocoon has a protective effect against fungal infection, causing an adaptive change in sanitary behaviours by the ants. It further demonstrates that brood removal-originally described for honeybees as "hygienic behaviour"-is a widespread sanitary behaviour in ants, which likely has important implications on disease dynamics in social insect colonies.},
author = {Tragust, Simon and Ugelvig, Line V and Chapuisat, Michel and Heinze, Jürgen and Cremer, Sylvia},
journal = {BMC Evolutionary Biology},
number = {1},
publisher = {BioMed Central},
title = {{Pupal cocoons affect sanitary brood care and limit fungal infections in ant colonies}},
doi = {10.1186/1471-2148-13-225},
volume = {13},
year = {2013},
}
@article{2286,
abstract = {The spatiotemporal control of cell divisions is a key factor in epithelial morphogenesis and patterning. Mao et al (2013) now describe how differential rates of proliferation within the Drosophila wing disc epithelium give rise to anisotropic tissue tension in peripheral/proximal regions of the disc. Such global tissue tension anisotropy in turn determines the orientation of cell divisions by controlling epithelial cell elongation.},
author = {Campinho, Pedro and Heisenberg, Carl-Philipp J},
journal = {EMBO Journal},
number = {21},
pages = {2783 -- 2784},
publisher = {Wiley-Blackwell},
title = {{The force and effect of cell proliferation}},
doi = {10.1038/emboj.2013.225},
volume = {32},
year = {2013},
}
@article{2287,
abstract = {Negative frequency-dependent selection should result in equal sex ratios in large populations of dioecious flowering plants, but deviations from equality are commonly reported. A variety of ecological and genetic factors can explain biased sex ratios, although the mechanisms involved are not well understood. Most dioecious species are long-lived and/or clonal complicating efforts to identify stages during the life cycle when biases develop. We investigated the demographic correlates of sex-ratio variation in two chromosome races of Rumex hastatulus, an annual, wind-pollinated colonizer of open habitats from the southern USA. We examined sex ratios in 46 populations and evaluated the hypothesis that the proximity of males in the local mating environment, through its influence on gametophytic selection, is the primary cause of female-biased sex ratios. Female-biased sex ratios characterized most populations of R. hastatulus (mean sex ratio = 0.62), with significant female bias in 89% of populations. Large, high-density populations had the highest proportion of females, whereas smaller, low-density populations had sex ratios closer to equality. Progeny sex ratios were more female biased when males were in closer proximity to females, a result consistent with the gametophytic selection hypothesis. Our results suggest that interactions between demographic and genetic factors are probably the main cause of female-biased sex ratios in R. hastatulus. The annual life cycle of this species may limit the scope for selection against males and may account for the weaker degree of bias in comparison with perennial Rumex species.},
author = {Pickup, Melinda and Barrett, Spencer},
journal = {Ecology and Evolution},
number = {3},
pages = {629 -- 639},
publisher = {Wiley-Blackwell},
title = {{The influence of demography and local mating environment on sex ratios in a wind-pollinated dioecious plant}},
doi = {10.1002/ece3.465},
volume = {3},
year = {2013},
}
@proceedings{2288,
abstract = {This book constitutes the proceedings of the 11th International Conference on Computational Methods in Systems Biology, CMSB 2013, held in Klosterneuburg, Austria, in September 2013. The 15 regular papers included in this volume were carefully reviewed and selected from 27 submissions. They deal with computational models for all levels, from molecular and cellular, to organs and entire organisms.},
editor = {Gupta, Ashutosh and Henzinger, Thomas A},
isbn = {978-3-642-40707-9},
location = {Klosterneuburg, Austria},
publisher = {Springer},
title = {{Computational Methods in Systems Biology}},
doi = {10.1007/978-3-642-40708-6},
volume = {8130},
year = {2013},
}
@article{2289,
abstract = {Formal verification aims to improve the quality of software by detecting errors before they do harm. At the basis of formal verification is the logical notion of correctness, which purports to capture whether or not a program behaves as desired. We suggest that the boolean partition of software into correct and incorrect programs falls short of the practical need to assess the behavior of software in a more nuanced fashion against multiple criteria. We therefore propose to introduce quantitative fitness measures for programs, specifically for measuring the function, performance, and robustness of reactive programs such as concurrent processes. This article describes the goals of the ERC Advanced Investigator Project QUAREM. The project aims to build and evaluate a theory of quantitative fitness measures for reactive models. Such a theory must strive to obtain quantitative generalizations of the paradigms that have been success stories in qualitative reactive modeling, such as compositionality, property-preserving abstraction and abstraction refinement, model checking, and synthesis. The theory will be evaluated not only in the context of software and hardware engineering, but also in the context of systems biology. In particular, we will use the quantitative reactive models and fitness measures developed in this project for testing hypotheses about the mechanisms behind data from biological experiments.},
author = {Henzinger, Thomas A},
journal = {Computer Science Research and Development},
number = {4},
pages = {331 -- 344},
publisher = {Springer},
title = {{Quantitative reactive modeling and verification}},
doi = {10.1007/s00450-013-0251-7},
volume = {28},
year = {2013},
}
@article{2290,
abstract = {The plant hormone indole-acetic acid (auxin) is essential for many aspects of plant development. Auxin-mediated growth regulation typically involves the establishment of an auxin concentration gradient mediated by polarly localized auxin transporters. The localization of auxin carriers and their amount at the plasma membrane are controlled by membrane trafficking processes such as secretion, endocytosis, and recycling. In contrast to endocytosis or recycling, how the secretory pathway mediates the localization of auxin carriers is not well understood. In this study we have used the differential cell elongation process during apical hook development to elucidate the mechanisms underlying the post-Golgi trafficking of auxin carriers in Arabidopsis. We show that differential cell elongation during apical hook development is defective in Arabidopsis mutant echidna (ech). ECH protein is required for the trans-Golgi network (TGN)-mediated trafficking of the auxin influx carrier AUX1 to the plasma membrane. In contrast, ech mutation only marginally perturbs the trafficking of the highly related auxin influx carrier LIKE-AUX1-3 or the auxin efflux carrier PIN-FORMED-3, both also involved in hook development. Electron tomography reveals that the trafficking defects in ech mutant are associated with the perturbation of secretory vesicle genesis from the TGN. Our results identify differential mechanisms for the post-Golgi trafficking of de novo-synthesized auxin carriers to plasma membrane from the TGN and reveal how trafficking of auxin influx carriers mediates the control of differential cell elongation in apical hook development.},
author = {Boutté, Yohann and Jonsson, Kristoffer and Mcfarlane, Heather and Johnson, Errin and Gendre, Delphine and Swarup, Ranjan and Friml, Jirí and Samuels, Lacey and Robert, Stéphanie and Bhalerao, Rishikesh},
journal = {PNAS},
number = {40},
pages = {16259 -- 16264},
publisher = {National Academy of Sciences},
title = {{ECHIDNA mediated post Golgi trafficking of auxin carriers for differential cell elongation}},
doi = {10.1073/pnas.1309057110},
volume = {110},
year = {2013},
}
@inproceedings{2291,
abstract = {Cryptographic access control promises to offer easily distributed trust and broader applicability, while reducing reliance on low-level online monitors. Traditional implementations of cryptographic access control rely on simple cryptographic primitives whereas recent endeavors employ primitives with richer functionality and security guarantees. Worryingly, few of the existing cryptographic access-control schemes come with precise guarantees, the gap between the policy specification and the implementation being analyzed only informally, if at all. In this paper we begin addressing this shortcoming. Unlike prior work that targeted ad-hoc policy specification, we look at the well-established Role-Based Access Control (RBAC) model, as used in a typical file system. In short, we provide a precise syntax for a computational version of RBAC, offer rigorous definitions for cryptographic policy enforcement of a large class of RBAC security policies, and demonstrate that an implementation based on attribute-based encryption meets our security notions. We view our main contribution as being at the conceptual level. Although we work with RBAC for concreteness, our general methodology could guide future research for uses of cryptography in other access-control models.
},
author = {Ferrara, Anna and Fuchsbauer, Georg and Warinschi, Bogdan},
location = {New Orleans, LA, United States},
pages = {115 -- 129},
publisher = {IEEE},
title = {{Cryptographically enforced RBAC}},
doi = {10.1109/CSF.2013.15},
year = {2013},
}
@proceedings{2292,
abstract = {This book constitutes the thoroughly refereed conference proceedings of the 38th International Symposium on Mathematical Foundations of Computer Science, MFCS 2013, held in Klosterneuburg, Austria, in August 2013. The 67 revised full papers presented together with six invited talks were carefully selected from 191 submissions. Topics covered include algorithmic game theory, algorithmic learning theory, algorithms and data structures, automata, formal languages, bioinformatics, complexity, computational geometry, computer-assisted reasoning, concurrency theory, databases and knowledge-based systems, foundations of computing, logic in computer science, models of computation, semantics and verification of programs, and theoretical issues in artificial intelligence.},
editor = {Chatterjee, Krishnendu and Sgall, Jiri},
isbn = {978-3-642-40312-5},
location = {Klosterneuburg, Austria},
pages = {VI -- 854},
publisher = {Springer},
title = {{Mathematical Foundations of Computer Science 2013}},
doi = {10.1007/978-3-642-40313-2},
volume = {8087},
year = {2013},
}
@inproceedings{2293,
abstract = {Many computer vision problems have an asymmetric distribution of information between training and test time. In this work, we study the case where we are given additional information about the training data, which however will not be available at test time. This situation is called learning using privileged information (LUPI). We introduce two maximum-margin techniques that are able to make use of this additional source of information, and we show that the framework is applicable to several scenarios that have been studied in computer vision before. Experiments with attributes, bounding boxes, image tags and rationales as additional information in object classification show promising results.},
author = {Sharmanska, Viktoriia and Quadrianto, Novi and Lampert, Christoph},
location = {Sydney, Australia},
pages = {825 -- 832},
publisher = {IEEE},
title = {{Learning to rank using privileged information}},
doi = {10.1109/ICCV.2013.107},
year = {2013},
}
@inproceedings{2294,
abstract = {In this work we propose a system for automatic classification of Drosophila embryos into developmental stages.
While the system is designed to solve an actual problem in biological research, we believe that the principle underly-
ing it is interesting not only for biologists, but also for researchers in computer vision. The main idea is to combine two orthogonal sources of information: one is a classifier trained on strongly invariant features, which makes it applicable to images of very different conditions, but also leads to rather noisy predictions. The other is a label propagation step based on a more powerful similarity measure that however is only consistent within specific subsets of the data at a time.
In our biological setup, the information sources are the shape and the staining patterns of embryo images. We show
experimentally that while neither of the methods can be used by itself to achieve satisfactory results, their combina-
tion achieves prediction quality comparable to human performance.},
author = {Kazmar, Tomas and Kvon, Evgeny and Stark, Alexander and Lampert, Christoph},
location = {Sydney, Australia},
publisher = {IEEE},
title = {{Drosophila Embryo Stage Annotation using Label Propagation}},
doi = {10.1109/ICCV.2013.139},
year = {2013},
}
@inproceedings{2295,
abstract = {We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, we establish decidability (with optimal EXPTIME-complete complexity) of the qualitative analysis problems for POMDPs with all parity objectives under finite-memory strategies. We also establish asymptotically optimal (exponential) memory bounds.},
author = {Chatterjee, Krishnendu and Chmelik, Martin and Tracol, Mathieu},
location = {Torino, Italy},
pages = {165 -- 180},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{What is decidable about partially observable Markov decision processes with omega-regular objectives}},
doi = {10.4230/LIPIcs.CSL.2013.165},
volume = {23},
year = {2013},
}
@article{2297,
abstract = {We present an overview of mathematical results on the low temperature properties of dilute quantum gases, which have been obtained in the past few years. The presentation includes a discussion of Bose-Einstein condensation, the excitation spectrum for trapped gases and its relation to superfluidity, as well as the appearance of quantized vortices in rotating systems. All these properties are intensely being studied in current experiments on cold atomic gases. We will give a description of the mathematics involved in understanding these phenomena, starting from the underlying many-body Schrödinger equation.},
author = {Seiringer, Robert},
journal = {Japanese Journal of Mathematics},
number = {2},
pages = {185 -- 232},
publisher = {Springer},
title = {{Hot topics in cold gases: A mathematical physics perspective}},
doi = {10.1007/s11537-013-1264-5},
volume = {8},
year = {2013},
}
@inproceedings{2298,
abstract = {We present a shape analysis for programs that manipulate overlaid data structures which share sets of objects. The abstract domain contains Separation Logic formulas that (1) combine a per-object separating conjunction with a per-field separating conjunction and (2) constrain a set of variables interpreted as sets of objects. The definition of the abstract domain operators is based on a notion of homomorphism between formulas, viewed as graphs, used recently to define optimal decision procedures for fragments of the Separation Logic. Based on a Frame Rule that supports the two versions of the separating conjunction, the analysis is able to reason in a modular manner about non-overlaid data structures and then, compose information only at a few program points, e.g., procedure returns. We have implemented this analysis in a prototype tool and applied it on several interesting case studies that manipulate overlaid and nested linked lists.
},
author = {Dragoi, Cezara and Enea, Constantin and Sighireanu, Mihaela},
location = {Seattle, WA, United States},
pages = {150 -- 171},
publisher = {Springer},
title = {{Local shape analysis for overlaid data structures}},
doi = {10.1007/978-3-642-38856-9_10},
volume = {7935},
year = {2013},
}
@article{2299,
abstract = {The standard hardware design flow involves: (a) design of an integrated circuit using a hardware description language, (b) extensive functional and formal verification, and (c) logical synthesis. However, the above-mentioned processes consume significant effort and time. An alternative approach is to use a formal specification language as a high-level hardware description language and synthesize hardware from formal specifications. Our work is a case study of the synthesis of the widely and industrially used AMBA AHB protocol from formal specifications. Bloem et al. presented the first formal specifications for the AMBA AHB Arbiter and synthesized the AHB Arbiter circuit. However, in the first formal specification some important assumptions were missing. Our contributions are as follows: (a) We present detailed formal specifications for the AHB Arbiter incorporating the missing details, and obtain significant improvements in the synthesis results (both with respect to the number of gates in the synthesized circuit and with respect to the time taken to synthesize the circuit), and (b) we present formal specifications to generate compact circuits for the remaining two main components of AMBA AHB, namely, AHB Master and AHB Slave. Thus with systematic description we are able to automatically and completely synthesize an important and widely used industrial protocol.},
author = {Godhal, Yashdeep and Chatterjee, Krishnendu and Henzinger, Thomas A},
journal = {International Journal on Software Tools for Technology Transfer},
number = {5-6},
pages = {585 -- 601},
publisher = {Springer},
title = {{Synthesis of AMBA AHB from formal specification: A case study}},
doi = {10.1007/s10009-011-0207-9},
volume = {15},
year = {2013},
}
@article{2300,
abstract = {We consider Ising models in two and three dimensions with nearest neighbor ferromagnetic interactions and long-range, power law decaying, antiferromagnetic interactions. If the strength of the ferromagnetic coupling J is larger than a critical value Jc, then the ground state is homogeneous and ferromagnetic. As the critical value is approached from smaller values of J, it is believed that the ground state consists of a periodic array of stripes (d=2) or slabs (d=3), all of the same size and alternating magnetization. Here we prove rigorously that the ground state energy per site converges to that of the optimal periodic striped or slabbed state, in the limit that J tends to the ferromagnetic transition point. While this theorem does not prove rigorously that the ground state is precisely striped or slabbed, it does prove that in any suitably large box the ground state is striped or slabbed with high probability.},
author = {Giuliani, Alessandro and Lieb, Élliott and Seiringer, Robert},
journal = {Physical Review B},
number = {6},
publisher = {American Physical Society},
title = {{Realization of stripes and slabs in two and three dimensions}},
doi = {10.1103/PhysRevB.88.064401},
volume = {88},
year = {2013},
}
@inproceedings{2301,
abstract = {We describe the design and implementation of P, a domain-specific language to write asynchronous event driven code. P allows the programmer to specify the system as a collection of interacting state machines, which communicate with each other using events. P unifies modeling and programming into one activity for the programmer. Not only can a P program be compiled into executable code, but it can also be tested using model checking techniques. P allows the programmer to specify the environment, used to "close" the system during testing, as nondeterministic ghost machines. Ghost machines are erased during compilation to executable code; a type system ensures that the erasure is semantics preserving. The P language is designed so that a P program can be checked for responsiveness-the ability to handle every event in a timely manner. By default, a machine needs to handle every event that arrives in every state. But handling every event in every state is impractical. The language provides a notion of deferred events where the programmer can annotate when she wants to delay processing an event. The default safety checker looks for presence of unhan-dled events. The language also provides default liveness checks that an event cannot be potentially deferred forever. P was used to implement and verify the core of the USB device driver stack that ships with Microsoft Windows 8. The resulting driver is more reliable and performs better than its prior incarnation (which did not use P); we have more confidence in the robustness of its design due to the language abstractions and verification provided by P.},
author = {Desai, Ankush and Gupta, Vivek and Jackson, Ethan and Qadeer, Shaz and Rajamani, Sriram and Zufferey, Damien},
booktitle = {Proceedings of the 34th ACM SIGPLAN Conference on Programming Language Design and Implementation},
location = {Seattle, WA, United States},
pages = {321 -- 331},
publisher = {ACM},
title = {{P: Safe asynchronous event-driven programming}},
doi = {10.1145/2491956.2462184},
year = {2013},
}
@article{2303,
abstract = {MADM (Mosaic Analysis with Double Markers) technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cre recombinase/loxP-dependent interchromosomal mitotic recombination to reconstitute two split marker genes—green GFP and red tdTomato—and can label sparse clones of homozygous mutant cells in one color and wild-type cells in the other color in an otherwise unlabeled background. At present, major MADM applications include lineage tracing, single cell labeling, conditional knockouts in small populations of cells and induction of uniparental chromosome disomy to assess effects of genomic imprinting. MADM can be applied universally in the mouse with the sole limitation being the specificity of the promoter controlling Cre recombinase expression. Here I review recent developments and extensions of the MADM technique and give an overview of the major discoveries and progresses enabled by the implementation of the novel genetic MADM tools.},
author = {Hippenmeyer, Simon},
journal = {Frontiers in Biology},
number = {6},
pages = {557 -- 568},
publisher = {Springer},
title = {{Dissection of gene function at clonal level using mosaic analysis with double markers}},
doi = {10.1007/s11515-013-1279-6},
volume = {8},
year = {2013},
}
@article{2304,
abstract = {This extended abstract is concerned with the irregularities of distribution of one-dimensional permuted van der Corput sequences that are generated from linear permutations. We show how to obtain upper bounds for the discrepancy and diaphony of these sequences, by relating them to Kronecker sequences and applying earlier results of Faure and Niederreiter.},
author = {Pausinger, Florian},
journal = {Electronic Notes in Discrete Mathematics},
pages = {43 -- 50},
publisher = {Elsevier},
title = {{Van der Corput sequences and linear permutations}},
doi = {10.1016/j.endm.2013.07.008},
volume = {43},
year = {2013},
}
@inproceedings{2305,
abstract = {We study the complexity of central controller synthesis problems for finite-state Markov decision processes, where the objective is to optimize both the expected mean-payoff performance of the system and its stability. e argue that the basic theoretical notion of expressing the stability in terms of the variance of the mean-payoff (called global variance in our paper) is not always sufficient, since it ignores possible instabilities on respective runs. For this reason we propose alernative definitions of stability, which we call local and hybrid variance, and which express how rewards on each run deviate from the run's own mean-payoff and from the expected mean-payoff, respectively. We show that a strategy ensuring both the expected mean-payoff and the variance below given bounds requires randomization and memory, under all the above semantics of variance. We then look at the problem of determining whether there is a such a strategy. For the global variance, we show that the problem is in PSPACE, and that the answer can be approximated in pseudo-polynomial time. For the hybrid variance, the analogous decision problem is in NP, and a polynomial-time approximating algorithm also exists. For local variance, we show that the decision problem is in NP. Since the overall performance can be traded for stability (and vice versa), we also present algorithms for approximating the associated Pareto curve in all the three cases. Finally, we study a special case of the decision problems, where we require a given expected mean-payoff together with zero variance. Here we show that the problems can be all solved in polynomial time.},
author = {Brázdil, Tomáš and Chatterjee, Krishnendu and Forejt, Vojtěch and Kučera, Antonín},
booktitle = {28th Annual ACM/IEEE Symposium},
location = {New Orleans, LA, United States},
pages = {331 -- 340},
publisher = {IEEE},
title = {{Trading performance for stability in Markov decision processes}},
doi = {10.1109/LICS.2013.39},
year = {2013},
}
@book{2306,
abstract = {Das Buch ist sowohl eine Einführung in die Themen Linked Data, Open Data und Open Linked Data als es auch den konkreten Bezug auf Bibliotheken behandelt. Hierzu werden konkrete Anwendungsprojekte beschrieben. Der Band wendet sich dabei sowohl an Personen aus der Bibliothekspraxis als auch an Personen aus dem Bibliotheksmanagement, die noch nicht mit dem Thema vertraut sind.},
author = {Danowski, Patrick and Pohl, Adrian},
publisher = {De Gruyter},
title = {{(Open) Linked Data in Bibliotheken}},
doi = {10.1515/9783110278736},
volume = {50},
year = {2013},
}
@inproceedings{2327,
abstract = {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.},
author = {Henzinger, Thomas A and Otop, Jan},
location = {Buenos Aires, Argentina},
pages = {273 -- 287},
publisher = {Springer},
title = {{From model checking to model measuring}},
doi = {10.1007/978-3-642-40184-8_20},
volume = {8052},
year = {2013},
}
@inproceedings{2328,
abstract = {Linearizability of concurrent data structures is usually proved by monolithic simulation arguments relying on identifying the so-called linearization points. Regrettably, such proofs, whether manual or automatic, are often complicated and scale poorly to advanced non-blocking concurrency patterns, such as helping and optimistic updates.
In response, we propose a more modular way of checking linearizability of concurrent queue algorithms that does not involve identifying linearization points. We reduce the task of proving linearizability with respect to the queue specification to establishing four basic properties, each of which can be proved independently by simpler arguments. As a demonstration of our approach, we verify the Herlihy and Wing queue, an algorithm that is challenging to verify by a simulation proof.},
author = {Henzinger, Thomas A and Sezgin, Ali and Vafeiadis, Viktor},
location = {Buenos Aires, Argentina},
pages = {242 -- 256},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Aspect-oriented linearizability proofs}},
doi = {10.1007/978-3-642-40184-8_18},
volume = {8052},
year = {2013},
}
@inproceedings{2329,
abstract = {Two-player games on graphs are central in many problems in formal verification and program analysis such as synthesis and verification of open systems. In this work, we consider both finite-state game graphs, and recursive game graphs (or pushdown game graphs) that model the control flow of sequential programs with recursion. The objectives we study are multidimensional mean-payoff objectives, where the goal of player 1 is to ensure that the mean-payoff is non-negative in all dimensions. In pushdown games two types of strategies are relevant: (1) global strategies, that depend on the entire global history; and (2) modular strategies, that have only local memory and thus do not depend on the context of invocation. Our main contributions are as follows: (1) We show that finite-state multidimensional mean-payoff games can be solved in polynomial time if the number of dimensions and the maximal absolute value of the weights are fixed; whereas if the number of dimensions is arbitrary, then the problem is known to be coNP-complete. (2) We show that pushdown graphs with multidimensional mean-payoff objectives can be solved in polynomial time. For both (1) and (2) our algorithms are based on hyperplane separation technique. (3) For pushdown games under global strategies both one and multidimensional mean-payoff objectives problems are known to be undecidable, and we show that under modular strategies the multidimensional problem is also undecidable; under modular strategies the one-dimensional problem is NP-complete. We show that if the number of modules, the number of exits, and the maximal absolute value of the weights are fixed, then pushdown games under modular strategies with one-dimensional mean-payoff objectives can be solved in polynomial time, and if either the number of exits or the number of modules is unbounded, then the problem is NP-hard. (4) Finally we show that a fixed parameter tractable algorithm for finite-state multidimensional mean-payoff games or pushdown games under modular strategies with one-dimensional mean-payoff objectives would imply the fixed parameter tractability of parity games.},
author = {Chatterjee, Krishnendu and Velner, Yaron},
location = {Buenos Aires, Argentinia},
pages = {500 -- 515},
publisher = {Springer},
title = {{Hyperplane separation technique for multidimensional mean-payoff games}},
doi = {10.1007/978-3-642-40184-8_35},
volume = {8052},
year = {2013},
}
@article{2410,
abstract = {Here, we describe a novel virulent bacteriophage that infects Bacillus weihenstephanensis, isolated from soil in Austria. It is the first phage to be discovered that infects this species. Here, we present the complete genome sequence of this podovirus. },
author = {Fernandes Redondo, Rodrigo A and Kupczok, Anne and Stift, Gertraud and Bollback, Jonathan P},
journal = {Genome Announcements},
number = {3},
publisher = {American Society for Microbiology},
title = {{Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis}},
doi = {10.1128/genomeA.00216-13},
volume = {1},
year = {2013},
}
@article{2412,
abstract = {Background: The CRISPR/Cas system is known to act as an adaptive and heritable immune system in Eubacteria and Archaea. Immunity is encoded in an array of spacer sequences. Each spacer can provide specific immunity to invasive elements that carry the same or a similar sequence. Even in closely related strains, spacer content is very dynamic and evolves quickly. Standard models of nucleotide evolutioncannot be applied to quantify its rate of change since processes other than single nucleotide changes determine its evolution.Methods We present probabilistic models that are specific for spacer content evolution. They account for the different processes of insertion and deletion. Insertions can be constrained to occur on one end only or are allowed to occur throughout the array. One deletion event can affect one spacer or a whole fragment of adjacent spacers. Parameters of the underlying models are estimated for a pair of arrays by maximum likelihood using explicit ancestor enumeration.Results Simulations show that parameters are well estimated on average under the models presented here. There is a bias in the rate estimation when including fragment deletions. The models also estimate times between pairs of strains. But with increasing time, spacer overlap goes to zero, and thus there is an upper bound on the distance that can be estimated. Spacer content similarities are displayed in a distance based phylogeny using the estimated times.We use the presented models to analyze different Yersinia pestis data sets and find that the results among them are largely congruent. The models also capture the variation in diversity of spacers among the data sets. A comparison of spacer-based phylogenies and Cas gene phylogenies shows that they resolve very different time scales for this data set.Conclusions The simulations and data analyses show that the presented models are useful for quantifying spacer content evolution and for displaying spacer content similarities of closely related strains in a phylogeny. This allows for comparisons of different CRISPR arrays or for comparisons between CRISPR arrays and nucleotide substitution rates.},
author = {Kupczok, Anne and Bollback, Jonathan P},
journal = {BMC Evolutionary Biology},
number = {1},
pages = {54 -- 54},
publisher = {BioMed Central},
title = {{Probabilistic models for CRISPR spacer content evolution }},
doi = {10.1186/1471-2148-13-54},
volume = {13},
year = {2013},
}
@inbook{2413,
abstract = {Progress in understanding the global brain dynamics has remained slow to date in large part because of the highly multiscale nature of brain activity. Indeed, normal brain dynamics is characterized by complex interactions between multiple levels: from the microscopic scale of single neurons to the mesoscopic level of local groups of neurons, and finally to the macroscopic level of the whole brain. Among the most difficult tasks are those of identifying which scales are significant for a given particular function and describing how the scales affect each other. It is important to realize that the scales of time and space are linked together, or even intertwined, and that causal inference is far more ambiguous between than within levels. We approach this problem from the perspective of our recent work on simultaneous recording from micro- and macroelectrodes in the human brain. We propose a physiological description of these multilevel interactions, based on phase–amplitude coupling of neuronal oscillations that operate at multiple frequencies and on different spatial scales. Specifically, the amplitude of the oscillations on a particular spatial scale is modulated by phasic variations in neuronal excitability induced by lower frequency oscillations that emerge on a larger spatial scale. Following this general principle, it is possible to scale up or scale down the multiscale brain dynamics. It is expected that large-scale network oscillations in the low-frequency range, mediating downward effects, may play an important role in attention and consciousness.},
author = {Valderrama, Mario and Botella Soler, Vicente and Le Van Quyen, Michel},
booktitle = {Multiscale Analysis and Nonlinear Dynamics: From Genes to the Brain},
editor = {Meyer, Misha and Pesenson, Z.},
isbn = {9783527411986 },
publisher = {Wiley-VCH},
title = {{Neuronal oscillations scale up and scale down the brain dynamics }},
doi = {10.1002/9783527671632.ch08},
year = {2013},
}
@article{2443,
abstract = {The mode of action of auxin is based on its non-uniform distribution within tissues and organs. Despite the wide use of several auxin analogues in research and agriculture, little is known about the specificity of different auxin-related transport and signalling processes towards these compounds. Using seedlings of Arabidopsis thaliana and suspension-cultured cells of Nicotiana tabacum (BY-2), the physiological activity of several auxin analogues was investigated, together with their capacity to induce auxin-dependent gene expression, to inhibit endocytosis and to be transported across the plasma membrane. This study shows that the specificity criteria for different auxin-related processes vary widely. Notably, the special behaviour of some synthetic auxin analogues suggests that they might be useful tools in investigations of the molecular mechanism of auxin action. Thus, due to their differential stimulatory effects on DR5 expression, indole-3-propionic (IPA) and 2,4,5-trichlorophenoxy acetic (2,4,5-T) acids can serve in studies of TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALLING F-BOX (TIR1/AFB)-mediated auxin signalling, and 5-fluoroindole-3-acetic acid (5-F-IAA) can help to discriminate between transcriptional and non-transcriptional pathways of auxin signalling. The results demonstrate that the major determinants for the auxin-like physiological potential of a particular compound are very complex and involve its chemical and metabolic stability, its ability to distribute in tissues in a polar manner and its activity towards auxin signalling machinery.},
author = {Simon, Sibu and Kubeš, Martin and Baster, Pawel and Robert, Stéphanie and Dobrev, Petre and Friml, Jirí and Petrášek, Jan and Zažímalová, Eva},
journal = {New Phytologist},
number = {4},
pages = {1034 -- 1048},
publisher = {Wiley-Blackwell},
title = {{Defining the selectivity of processes along the auxin response chain: A study using auxin analogues}},
doi = {10.1111/nph.12437},
volume = {200},
year = {2013},
}
@inproceedings{2444,
abstract = {We consider two core algorithmic problems for probabilistic verification: the maximal end-component decomposition and the almost-sure reachability set computation for Markov decision processes (MDPs). For MDPs with treewidth k, we present two improved static algorithms for both the problems that run in time O(n·k 2.38·2k ) and O(m·logn· k), respectively, where n is the number of states and m is the number of edges, significantly improving the previous known O(n·k·√n· k) bound for low treewidth. We also present decremental algorithms for both problems for MDPs with constant treewidth that run in amortized logarithmic time, which is a huge improvement over the previously known algorithms that require amortized linear time.},
author = {Chatterjee, Krishnendu and Ła̧Cki, Jakub},
location = {St. Petersburg, Russia},
pages = {543 -- 558},
publisher = {Springer},
title = {{Faster algorithms for Markov decision processes with low treewidth}},
doi = {10.1007/978-3-642-39799-8_36},
volume = {8044},
year = {2013},
}
@inproceedings{2446,
abstract = {The model-checking problem for probabilistic systems crucially relies on the translation of LTL to deterministic Rabin automata (DRW). Our recent Safraless translation [KE12, GKE12] for the LTL(F,G) fragment produces smaller automata as compared to the traditional approach. In this work, instead of DRW we consider deterministic automata with acceptance condition given as disjunction of generalized Rabin pairs (DGRW). The Safraless translation of LTL(F,G) formulas to DGRW results in smaller automata as compared to DRW. We present algorithms for probabilistic model-checking as well as game solving for DGRW conditions. Our new algorithms lead to improvement both in terms of theoretical bounds as well as practical evaluation. We compare PRISM with and without our new translation, and show that the new translation leads to significant improvements.},
author = {Chatterjee, Krishnendu and Gaiser, Andreas and Kretinsky, Jan},
location = {St. Petersburg, Russia},
pages = {559 -- 575},
publisher = {Springer},
title = {{Automata with generalized Rabin pairs for probabilistic model checking and LTL synthesis}},
doi = {10.1007/978-3-642-39799-8_37},
volume = {8044},
year = {2013},
}
@inproceedings{2447,
abstract = {Separation logic (SL) has gained widespread popularity because of its ability to succinctly express complex invariants of a program’s heap configurations. Several specialized provers have been developed for decidable SL fragments. However, these provers cannot be easily extended or combined with solvers for other theories that are important in program verification, e.g., linear arithmetic. In this paper, we present a reduction of decidable SL fragments to a decidable first-order theory that fits well into the satisfiability modulo theories (SMT) framework. We show how to use this reduction to automate satisfiability, entailment, frame inference, and abduction problems for separation logic using SMT solvers. Our approach provides a simple method of integrating separation logic into existing verification tools that provide SMT backends, and an elegant way of combining SL fragments with other decidable first-order theories. We implemented this approach in a verification tool and applied it to heap-manipulating programs whose verification involves reasoning in theory combinations.
},
author = {Piskac, Ruzica and Wies, Thomas and Zufferey, Damien},
location = {St. Petersburg, Russia},
pages = {773 -- 789},
publisher = {Springer},
title = {{Automating separation logic using SMT}},
doi = {10.1007/978-3-642-39799-8_54},
volume = {8044},
year = {2013},
}
@article{2448,
abstract = {Cell-to-cell directional flow of the phytohormone auxin is primarily established by polar localization of the PIN auxin transporters, a process tightly regulated at multiple levels by auxin itself. We recently reported that, in the context of strong auxin flows, activity of the vacuolar ZIFL1.1 transporter is required for fine-tuning of polar auxin transport rates in the Arabidopsis root. In particular, ZIFL1.1 function protects plasma-membrane stability of the PIN2 carrier in epidermal root tip cells under conditions normally triggering PIN2 degradation. Here, we show that ZIFL1.1 activity at the root tip also promotes PIN1 plasma-membrane abundance in central cylinder cells, thus supporting the notion that ZIFL1.1 acts as a general positive modulator of polar auxin transport in roots.},
author = {Remy, Estelle and Baster, Pawel and Friml, Jirí and Duque, Paula},
journal = {Plant Signaling & Behavior},
number = {10},
publisher = {Landes Bioscience},
title = {{ZIFL1.1 transporter modulates polar auxin transport by stabilizing membrane abundance of multiple PINs in Arabidopsis root tip}},
doi = {10.4161/psb.25688},
volume = {8},
year = {2013},
}
@article{2449,
abstract = {Intracellular protein routing is mediated by vesicular transport which is tightly regulated in eukaryotes. The protein and lipid homeostasis depends on coordinated delivery of de novo synthesized or recycled cargoes to the plasma membrane by exocytosis and their subsequent removal by rerouting them for recycling or degradation. Here, we report the characterization of protein affected trafficking 3 (pat3) mutant that we identified by an epifluorescence-based forward genetic screen for mutants defective in subcellular distribution of Arabidopsis auxin transporter PIN1–GFP. While pat3 displays largely normal plant morphology and development in nutrient-rich conditions, it shows strong ectopic intracellular accumulations of different plasma membrane cargoes in structures that resemble prevacuolar compartments (PVC) with an aberrant morphology. Genetic mapping revealed that pat3 is defective in vacuolar protein sorting 35A (VPS35A), a putative subunit of the retromer complex that mediates retrograde trafficking between the PVC and trans-Golgi network. Similarly, a mutant defective in another retromer subunit, vps29, shows comparable subcellular defects in PVC morphology and protein accumulation. Thus, our data provide evidence that the retromer components VPS35A and VPS29 are essential for normal PVC morphology and normal trafficking of plasma membrane proteins in plants. In addition, we show that, out of the three VPS35 retromer subunits present in Arabidopsis thaliana genome, the VPS35 homolog A plays a prevailing role in trafficking to the lytic vacuole, presenting another level of complexity in the retromer-dependent vacuolar sorting. },
author = {Nodzyński, Tomasz and Feraru, Murguel and Hirsch, Sibylle and De Rycke, Riet and Nicuales, Claudiu and Van Leene, Jelle and De Jaeger, Geert and Vanneste, Steffen and Friml, Jirí},
journal = {Molecular Plant},
number = {6},
pages = {1849 -- 1862},
publisher = {Cell Press},
title = {{Retromer subunits VPS35A and VPS29 mediate prevacuolar compartment (PVC) function in Arabidopsis}},
doi = {10.1093/mp/sst044},
volume = {6},
year = {2013},
}
@article{2466,
abstract = {We introduce a new method for efficiently simulating liquid with extreme amounts of spatial adaptivity. Our method combines several key components to drastically speed up the simulation of large-scale fluid phenomena: We leverage an alternative Eulerian tetrahedral mesh discretization to significantly reduce the complexity of the pressure solve while increasing the robustness with respect to element quality and removing the possibility of locking. Next, we enable subtle free-surface phenomena by deriving novel second-order boundary conditions consistent with our discretization. We couple this discretization with a spatially adaptive Fluid-Implicit Particle (FLIP) method, enabling efficient, robust, minimally-dissipative simulations that can undergo sharp changes in spatial resolution while minimizing artifacts. Along the way, we provide a new method for generating a smooth and detailed surface from a set of particles with variable sizes. Finally, we explore several new sizing functions for determining spatially adaptive simulation resolutions, and we show how to couple them to our simulator. We combine each of these elements to produce a simulation algorithm that is capable of creating animations at high maximum resolutions while avoiding common pitfalls like inaccurate boundary conditions and inefficient computation.},
author = {Ando, Ryoichi and Thuerey, Nils and Wojtan, Christopher J},
journal = {ACM Transactions on Graphics},
number = {4},
publisher = {ACM},
title = {{Highly adaptive liquid simulations on tetrahedral meshes}},
doi = {10.1145/2461912.2461982},
volume = {32},
year = {2013},
}
@article{2467,
abstract = {This paper presents a method for computing topology changes for triangle meshes in an interactive geometric modeling environment. Most triangle meshes in practice do not exhibit desirable geometric properties, so we develop a solution that is independent of standard assumptions and robust to geometric errors. Specifically, we provide the first method for topology change applicable to arbitrary non-solid, non-manifold, non-closed, self-intersecting surfaces. We prove that this new method for topology change produces the expected conventional results when applied to solid (closed, manifold, non-self-intersecting) surfaces---that is, we prove a backwards-compatibility property relative to prior work. Beyond solid surfaces, we present empirical evidence that our method remains tolerant to a variety of surface aberrations through the incorporation of a novel error correction scheme. Finally, we demonstrate how topology change applied to non-solid objects enables wholly new and useful behaviors.},
author = {Bernstein, Gilbert and Wojtan, Christopher J},
journal = {ACM Transactions on Graphics},
number = {4},
publisher = {ACM},
title = {{Putting holes in holey geometry: Topology change for arbitrary surfaces}},
doi = {10.1145/2461912.2462027},
volume = {32},
year = {2013},
}
@article{2468,
abstract = {Our work concerns the combination of an Eulerian liquid simulation with a high-resolution surface tracker (e.g. the level set method or a Lagrangian triangle mesh). The naive application of a high-resolution surface tracker to a low-resolution velocity field can produce many visually disturbing physical and topological artifacts that limit their use in practice. We address these problems by defining an error function which compares the current state of the surface tracker to the set of physically valid surface states. By reducing this error with a gradient descent technique, we introduce a novel physics-based surface fairing method. Similarly, by treating this error function as a potential energy, we derive a new surface correction force that mimics the vortex sheet equations. We demonstrate our results with both level set and mesh-based surface trackers.},
author = {Bojsen-Hansen, Morten and Wojtan, Christopher J},
journal = {ACM Transactions on Graphics},
number = {4},
publisher = {ACM},
title = {{Liquid surface tracking with error compensation}},
doi = {10.1145/2461912.2461991},
volume = {32},
year = {2013},
}
@article{2469,
abstract = {Cadherins are transmembrane proteins that mediate cell–cell adhesion in animals. By regulating contact formation and stability, cadherins play a crucial role in tissue morphogenesis and homeostasis. Here, we review the three major unctions of cadherins in cell–cell contact formation and stability. Two of those functions lead to a decrease in interfacial ension at the forming cell–cell contact, thereby promoting contact expansion — first, by providing adhesion tension that lowers interfacial tension at the cell–cell contact, and second, by signaling to the actomyosin cytoskeleton in order to reduce cortex tension and thus interfacial tension at the contact. The third function of cadherins in cell–cell contact formation is to stabilize the contact by resisting mechanical forces that pull on the contact.},
author = {Maître, Jean-Léon and Heisenberg, Carl-Philipp J},
journal = {Current Biology},
number = {14},
pages = {R626 -- R633},
publisher = {Cell Press},
title = {{Three functions of cadherins in cell adhesion}},
doi = {10.1016/j.cub.2013.06.019},
volume = {23},
year = {2013},
}
@article{2470,
abstract = {Background:Auxin binding protein 1 (ABP1) is a putative auxin receptor and its function is indispensable for plant growth and development. ABP1 has been shown to be involved in auxin-dependent regulation of cell division and expansion, in plasma-membrane-related processes such as changes in transmembrane potential, and in the regulation of clathrin-dependent endocytosis. However, the ABP1-regulated downstream pathway remains elusive.Methodology/Principal Findings:Using auxin transport assays and quantitative analysis of cellular morphology we show that ABP1 regulates auxin efflux from tobacco BY-2 cells. The overexpression of ABP1can counterbalance increased auxin efflux and auxin starvation phenotypes caused by the overexpression of PIN auxin efflux carrier. Relevant mechanism involves the ABP1-controlled vesicle trafficking processes, including positive regulation of endocytosis of PIN auxin efflux carriers, as indicated by fluorescence recovery after photobleaching (FRAP) and pharmacological manipulations.Conclusions/Significance:The findings indicate the involvement of ABP1 in control of rate of auxin transport across plasma membrane emphasizing the role of ABP1 in regulation of PIN activity at the plasma membrane, and highlighting the relevance of ABP1 for the formation of developmentally important, PIN-dependent auxin gradients.},
author = {Čovanová, Milada and Sauer, Michael and Rychtář, Jan and Friml, Jirí and Petrášek, Jan and Zažímalová, Eva},
journal = {PLoS One},
number = {7},
publisher = {Public Library of Science},
title = {{Overexpression of the auxin binding PROTEIN1 modulates PIN-dependent auxin transport in tobacco cells}},
doi = {10.1371/journal.pone.0070050},
volume = {8},
year = {2013},
}
@article{2471,
abstract = {The impact of disulfide bonds on protein stability goes beyond simple equilibrium thermodynamics effects associated with the conformational entropy of the unfolded state. Indeed, disulfide crosslinks may play a role in the prevention of dysfunctional association and strongly affect the rates of irreversible enzyme inactivation, highly relevant in biotechnological applications. While these kinetic-stability effects remain poorly understood, by analogy with proposed mechanisms for processes of protein aggregation and fibrillogenesis, we propose that they may be determined by the properties of sparsely-populated, partially-unfolded intermediates. Here we report the successful design, on the basis of high temperature molecular-dynamics simulations, of six thermodynamically and kinetically stabilized variants of phytase from Citrobacter braakii (a biotechnologically important enzyme) with one, two or three engineered disulfides. Activity measurements and 3D crystal structure determination demonstrate that the engineered crosslinks do not cause dramatic alterations in the native structure. The inactivation kinetics for all the variants displays a strongly non-Arrhenius temperature dependence, with the time-scale for the irreversible denaturation process reaching a minimum at a given temperature within the range of the denaturation transition. We show this striking feature to be a signature of a key role played by a partially unfolded, intermediate state/ensemble. Energetic and mutational analyses confirm that the intermediate is highly unfolded (akin to a proposed critical intermediate in the misfolding of the prion protein), a result that explains the observed kinetic stabilization. Our results provide a rationale for the kinetic-stability consequences of disulfide-crosslink engineering and an experimental methodology to arrive at energetic/structural descriptions of the sparsely populated and elusive intermediates that play key roles in irreversible protein denaturation.},
author = {Sanchez Romero, Inmaculada and Ariza, Antonio and Wilson, Keith and Skjøt, Michael and Vind, Jesper and De Maria, Leonardo and Skov, Lars and Sánchez Ruiz, Jose},
journal = {PLoS One},
number = {7},
publisher = {Public Library of Science},
title = {{Mechanism of protein kinetic stabilization by engineered disulfide crosslinks}},
doi = {10.1371/journal.pone.0070013},
volume = {8},
year = {2013},
}