@misc{5436,
abstract = {Recently there has been a significant effort to handle 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, some basic system properties such as average response time cannot be expressed using weighted automata, nor in any other know decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata which makes it possible to express important quantitative properties such as average response time.
In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in run-time verification. We establish an almost complete decidability picture for the basic decision problems about nested weighted automata, and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.},
author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan},
issn = {2664-1690},
pages = {29},
publisher = {IST Austria},
title = {{Nested weighted automata}},
doi = {10.15479/AT:IST-2015-170-v2-2},
year = {2015},
}
@misc{5437,
abstract = {We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean-payoff property, the ratio property, and the minimum initial credit for energy property.
The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let $n$ denote the number of nodes of a graph, $m$ the number of edges (for constant treewidth graphs $m=O(n)$) and $W$ the largest absolute value of the weights.
Our main theoretical results are as follows.
First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a multiplicative factor of $\epsilon$ in time $O(n \cdot \log (n/\epsilon))$ and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time $O(n \cdot \log (|a\cdot b|))=O(n\cdot\log (n\cdot W))$, when the output is $\frac{a}{b}$, as compared to the previously best known algorithm with running time $O(n^2 \cdot \log (n\cdot W))$. Third, for the minimum initial credit problem we show that (i)~for general graphs the problem can be solved in $O(n^2\cdot m)$ time and the associated decision problem can be solved in $O(n\cdot m)$ time, improving the previous known $O(n^3\cdot m\cdot \log (n\cdot W))$ and $O(n^2 \cdot m)$ bounds, respectively; and (ii)~for constant treewidth graphs we present an algorithm that requires $O(n\cdot \log n)$ time, improving the previous known $O(n^4 \cdot \log (n \cdot W))$ bound.
We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks. },
author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas},
issn = {2664-1690},
pages = {27},
publisher = {IST Austria},
title = {{Faster algorithms for quantitative verification in constant treewidth graphs}},
doi = {10.15479/AT:IST-2015-330-v2-1},
year = {2015},
}
@misc{5438,
abstract = {The edit distance between two words w1, w2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w1 to w2. The edit distance generalizes to languages L1, L2, where the edit distance is the minimal number k such that for every word from L1 there exists a word in L2 with edit distance at most k. We study the edit distance computation problem between pushdown automata and their subclasses.
The problem of computing edit distance to a pushdown automaton is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for deciding whether, for a given threshold k, the edit distance from a pushdown automaton to a finite automaton is at most k. },
author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Ibsen-Jensen, Rasmus and Otop, Jan},
issn = {2664-1690},
pages = {15},
publisher = {IST Austria},
title = {{Edit distance for pushdown automata}},
doi = {10.15479/AT:IST-2015-334-v1-1},
year = {2015},
}
@misc{5439,
abstract = {The target discounted-sum problem is the following: Given a rational discount factor 0 < λ < 1 and three rational values a, b, and t, does there exist a finite or an infinite sequence w ε(a, b)∗ or w ε(a, b)w, such that Σ|w| i=0 w(i)λi equals t? The problem turns out to relate to many fields of mathematics and computer science, and its decidability question is surprisingly hard to solve. We solve the finite version of the problem, and show the hardness of the infinite version, linking it to various areas and open problems in mathematics and computer science: β-expansions, discounted-sum automata, piecewise affine maps, and generalizations of the Cantor set. We provide some partial results to the infinite version, among which are solutions to its restriction to eventually-periodic sequences and to the cases that λ λ 1/2 or λ = 1/n, for every n ε N. We use our results for solving some open problems on discounted-sum automata, among which are the exact-value problem for nondeterministic automata over finite words and the universality and inclusion problems for functional automata. },
author = {Boker, Udi and Henzinger, Thomas A and Otop, Jan},
issn = {2664-1690},
pages = {20},
publisher = {IST Austria},
title = {{The target discounted-sum problem}},
doi = {10.15479/AT:IST-2015-335-v1-1},
year = {2015},
}
@misc{5440,
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 for payoff 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 of the population. The fitness (or the reproductive rate) is a non-negative number, and depends on the payoff. 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 as follows: First, we consider a special case of the general problem, where the residents do not reproduce. We show that the qualitative question is NP-complete, and the quantitative approximation question is #P-complete, and the hardness results hold even in the special case where the interaction and the replacement graphs coincide. Second, we show that in general both the qualitative and the quantitative approximation questions are PSPACE-complete. The PSPACE-hardness result for quantitative approximation holds even when the fitness is always positive.},
author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Nowak, Martin},
issn = {2664-1690},
pages = {18},
publisher = {IST Austria},
title = {{The complexity of evolutionary games on graphs}},
doi = {10.15479/AT:IST-2015-323-v2-2},
year = {2015},
}
@misc{5441,
abstract = {We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time. Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks.},
author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Goharshady, Amir and Pavlogiannis, Andreas},
issn = {2664-1690},
pages = {24},
publisher = {IST Austria},
title = {{Algorithms for algebraic path properties in concurrent systems of constant treewidth components}},
doi = {10.15479/AT:IST-2015-340-v1-1},
year = {2015},
}
@misc{5443,
abstract = {POMDPs are standard models for probabilistic planning problems, where an agent interacts with an uncertain environment. We study the problem of almost-sure reachability, where given a set of target states, the question is to decide whether there is a policy to ensure that the target set is reached with probability 1 (almost-surely). While in general the problem is EXPTIME-complete, in many practical cases policies with a small amount of memory suffice. Moreover, the existing solution to the problem is explicit, which first requires to construct explicitly an exponential reduction to a belief-support MDP. In this work, we first study the existence of observation-stationary strategies, which is NP-complete, and then small-memory strategies. We present a symbolic algorithm by an efficient encoding to SAT and using a SAT solver for the problem. We report experimental results demonstrating the scalability of our symbolic (SAT-based) approach.},
author = {Chatterjee, Krishnendu and Chmelik, Martin and Davies, Jessica},
issn = {2664-1690},
pages = {23},
publisher = {IST Austria},
title = {{A symbolic SAT-based algorithm for almost-sure reachability with small strategies in POMDPs}},
doi = {10.15479/AT:IST-2015-325-v2-1},
year = {2015},
}
@misc{5444,
abstract = {A comprehensive understanding of the clonal evolution of cancer is critical for understanding neoplasia. Genome-wide sequencing data enables evolutionary studies at unprecedented depth. However, classical phylogenetic methods often struggle with noisy sequencing data of impure DNA samples and fail to detect subclones that have different evolutionary trajectories. We have developed a tool, called Treeomics, that allows us to reconstruct the phylogeny of a cancer with commonly available sequencing technologies. Using Bayesian inference and Integer Linear Programming, robust phylogenies consistent with the biological processes underlying cancer evolution were obtained for pancreatic, ovarian, and prostate cancers. Furthermore, Treeomics correctly identified sequencing artifacts such as those resulting from low statistical power; nearly 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumor heterogeneity among distinct samples. Importantly, we show that the evolutionary trees generated with Treeomics are mathematically optimal.},
author = {Reiter, Johannes and Makohon-Moore, Alvin and Gerold, Jeffrey and Bozic, Ivana and Chatterjee, Krishnendu and Iacobuzio-Donahue, Christine and Vogelstein, Bert and Nowak, Martin},
issn = {2664-1690},
pages = {25},
publisher = {IST Austria},
title = {{Reconstructing robust phylogenies of metastatic cancers}},
doi = {10.15479/AT:IST-2015-399-v1-1},
year = {2015},
}
@article{1383,
abstract = {In plants, vacuolar H+-ATPase (V-ATPase) activity acidifies both the trans-Golgi network/early endosome (TGN/EE) and the vacuole. This dual V-ATPase function has impeded our understanding of how the pH homeostasis within the plant TGN/EE controls exo- and endocytosis. Here, we show that the weak V-ATPase mutant deetiolated3 (det3) displayed a pH increase in the TGN/EE, but not in the vacuole, strongly impairing secretion and recycling of the brassinosteroid receptor and the cellulose synthase complexes to the plasma membrane, in contrast to mutants lacking tonoplast-localized V-ATPase activity only. The brassinosteroid insensitivity and the cellulose deficiency defects in det3 were tightly correlated with reduced Golgi and TGN/EE motility. Thus, our results provide strong evidence that acidification of the TGN/EE, but not of the vacuole, is indispensable for functional secretion and recycling in plants.},
author = {Yu, Luo and Scholl, Stefan and Doering, Anett and Yi, Zhang and Irani, Niloufer and Di Rubbo, Simone and Neumetzler, Lutz and Krishnamoorthy, Praveen and Van Houtte, Isabelle and Mylle, Evelien and Bischoff, Volker and Vernhettes, Samantha and Winne, Johan and Friml, Jirí and Stierhof, York and Schumacher, Karin and Persson, Staffan and Russinova, Eugenia},
journal = {Nature Plants},
number = {7},
publisher = {Nature Publishing Group},
title = {{V-ATPase activity in the TGN/EE is required for exocytosis and recycling in Arabidopsis}},
doi = {10.1038/nplants.2015.94},
volume = {1},
year = {2015},
}
@phdthesis{1399,
abstract = {This thesis is concerned with the computation and approximation of intrinsic volumes. Given a smooth body M and a certain digital approximation of it, we develop algorithms to approximate various intrinsic volumes of M using only measurements taken from its digital approximations. The crucial idea behind our novel algorithms is to link the recent theory of persistent homology to the theory of intrinsic volumes via the Crofton formula from integral geometry and, in particular, via Euler characteristic computations. Our main contributions are a multigrid convergent digital algorithm to compute the first intrinsic volume of a solid body in R^n as well as an appropriate integration pipeline to approximate integral-geometric integrals defined over the Grassmannian manifold.},
author = {Pausinger, Florian},
pages = {144},
publisher = {IST Austria},
title = {{On the approximation of intrinsic volumes}},
year = {2015},
}
@phdthesis{1400,
abstract = {Cancer results from an uncontrolled growth of abnormal cells. Sequentially accumulated genetic and epigenetic alterations decrease cell death and increase cell replication. We used mathematical models to quantify the effect of driver gene mutations. The recently developed targeted therapies can lead to dramatic regressions. However, in solid cancers, clinical responses are often short-lived because resistant cancer cells evolve. We estimated that approximately 50 different mutations can confer resistance to a typical targeted therapeutic agent. We find that resistant cells are likely to be present in expanded subclones before the start of the treatment. The dominant strategy to prevent the evolution of resistance is combination therapy. Our analytical results suggest that in most patients, dual therapy, but not monotherapy, can result in long-term disease control. However, long-term control can only occur if there are no possible mutations in the genome that can cause cross-resistance to both drugs. Furthermore, we showed that simultaneous therapy with two drugs is much more likely to result in long-term disease control than sequential therapy with the same drugs. To improve our understanding of the underlying subclonal evolution we reconstruct the evolutionary history of a patient's cancer from next-generation sequencing data of spatially-distinct DNA samples. Using a quantitative measure of genetic relatedness, we found that pancreatic cancers and their metastases demonstrated a higher level of relatedness than that expected for any two cells randomly taken from a normal tissue. This minimal amount of genetic divergence among advanced lesions indicates that genetic heterogeneity, when quantitatively defined, is not a fundamental feature of the natural history of untreated pancreatic cancers. Our newly developed, phylogenomic tool Treeomics finds evidence for seeding patterns of metastases and can directly be used to discover rules governing the evolution of solid malignancies to transform cancer into a more predictable disease.},
author = {Reiter, Johannes},
pages = {183},
publisher = {IST Austria},
title = {{The subclonal evolution of cancer}},
year = {2015},
}
@inproceedings{1424,
abstract = {We consider the problem of statistical computations with persistence diagrams, a summary representation of topological features in data. These diagrams encode persistent homology, a widely used invariant in topological data analysis. While several avenues towards a statistical treatment of the diagrams have been explored recently, we follow an alternative route that is motivated by the success of methods based on the embedding of probability measures into reproducing kernel Hilbert spaces. In fact, a positive definite kernel on persistence diagrams has recently been proposed, connecting persistent homology to popular kernel-based learning techniques such as support vector machines. However, important properties of that kernel enabling a principled use in the context of probability measure embeddings remain to be explored. Our contribution is to close this gap by proving universality of a variant of the original kernel, and to demonstrate its effective use in twosample hypothesis testing on synthetic as well as real-world data.},
author = {Kwitt, Roland and Huber, Stefan and Niethammer, Marc and Lin, Weili and Bauer, Ulrich},
location = {Montreal, Canada},
pages = {3070 -- 3078},
publisher = {Neural Information Processing Systems},
title = {{Statistical topological data analysis-A kernel perspective}},
volume = {28},
year = {2015},
}
@inproceedings{1425,
abstract = {In this work we aim at extending the theoretical foundations of lifelong learning. Previous work analyzing this scenario is based on the assumption that learning tasks are sampled i.i.d. from a task environment or limited to strongly constrained data distributions. Instead, we study two scenarios when lifelong learning is possible, even though the observed tasks do not form an i.i.d. sample: first, when they are sampled from the same environment, but possibly with dependencies, and second, when the task environment is allowed to change over time in a consistent way. In the first case we prove a PAC-Bayesian theorem that can be seen as a direct generalization of the analogous previous result for the i.i.d. case. For the second scenario we propose to learn an inductive bias in form of a transfer procedure. We present a generalization bound and show on a toy example how it can be used to identify a beneficial transfer algorithm.},
author = {Pentina, Anastasia and Lampert, Christoph},
location = {Montreal, Canada},
pages = {1540 -- 1548},
publisher = {Neural Information Processing Systems},
title = {{Lifelong learning with non-i.i.d. tasks}},
volume = {2015},
year = {2015},
}
@inproceedings{1430,
abstract = {Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse their runtime on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.},
author = {Paixao, Tiago and Sudholt, Dirk and Heredia, Jorge and Trubenova, Barbora},
booktitle = {Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation},
location = {Madrid, Spain},
pages = {1455 -- 1462},
publisher = {ACM},
title = {{First steps towards a runtime comparison of natural and artificial evolution}},
doi = {10.1145/2739480.2754758},
year = {2015},
}
@inproceedings{1474,
abstract = {Cryptographic access control offers selective access to encrypted data via a combination of key management and functionality-rich cryptographic schemes, such as attribute-based encryption. Using this approach, publicly available meta-data may inadvertently leak information on the access policy that is enforced by cryptography, which renders cryptographic access control unusable in settings where this information is highly sensitive. We begin to address this problem by presenting rigorous definitions for policy privacy in cryptographic access control. For concreteness we set our results in the model of Role-Based Access Control (RBAC), where we identify and formalize several different flavors of privacy, however, our framework should serve as inspiration for other models of access control. Based on our insights we propose a new system which significantly improves on the privacy properties of state-of-the-art constructions. Our design is based on a novel type of privacy-preserving attribute-based encryption, which we introduce and show how to instantiate. We present our results in the context of a cryptographic RBAC system by Ferrara et al. (CSF'13), which uses cryptography to control read access to files, while write access is still delegated to trusted monitors. We give an extension of the construction that permits cryptographic control over write access. Our construction assumes that key management uses out-of-band channels between the policy enforcer and the users but eliminates completely the need for monitoring read/write access to the data.},
author = {Ferrara, Anna and Fuchsbauer, Georg and Liu, Bin and Warinschi, Bogdan},
location = {Verona, Italy},
pages = {46--60},
publisher = {IEEE},
title = {{Policy privacy in cryptographic access control}},
doi = {10.1109/CSF.2015.11},
year = {2015},
}
@inproceedings{1481,
abstract = {Simple board games, like Tic-Tac-Toe and CONNECT-4, play an important role not only in the development of mathematical and logical skills, but also in the emotional and social development. In this paper, we address the problem of generating targeted starting positions for such games. This can facilitate new approaches for bringing novice players to mastery, and also leads to discovery of interesting game variants. We present an approach that generates starting states of varying hardness levels for player 1 in a two-player board game, given rules of the board game, the desired number of steps required for player 1 to win, and the expertise levels of the two players. Our approach leverages symbolic methods and iterative simulation to efficiently search the extremely large state space. We present experimental results that include discovery of states of varying hardness levels for several simple grid-based board games. The presence of such states for standard game variants like 4×4 Tic-Tac-Toe opens up new games to be played that have never been played as the default start state is heavily biased. },
author = {Ahmed, Umair and Chatterjee, Krishnendu and Gulwani, Sumit},
booktitle = {Proceedings of the Twenty-Ninth AAAI Conference on Artificial Intelligence},
location = {Austin, TX, USA},
pages = {745 -- 752},
publisher = {AAAI Press},
title = {{Automatic generation of alternative starting positions for simple traditional board games}},
volume = {2},
year = {2015},
}
@inproceedings{1483,
abstract = {Topological data analysis offers a rich source of valuable information to study vision problems. Yet, so far we lack a theoretically sound connection to popular kernel-based learning techniques, such as kernel SVMs or kernel PCA. In this work, we establish such a connection by designing a multi-scale kernel for persistence diagrams, a stable summary representation of topological features in data. We show that this kernel is positive definite and prove its stability with respect to the 1-Wasserstein distance. Experiments on two benchmark datasets for 3D shape classification/retrieval and texture recognition show considerable performance gains of the proposed method compared to an alternative approach that is based on the recently introduced persistence landscapes.},
author = {Reininghaus, Jan and Huber, Stefan and Bauer, Ulrich and Kwitt, Roland},
location = {Boston, MA, USA},
pages = {4741 -- 4748},
publisher = {IEEE},
title = {{A stable multi-scale kernel for topological machine learning}},
doi = {10.1109/CVPR.2015.7299106},
year = {2015},
}
@inproceedings{1495,
abstract = {Motivated by biological questions, we study configurations of equal-sized disks in the Euclidean plane that neither pack nor cover. Measuring the quality by the probability that a random point lies in exactly one disk, we show that the regular hexagonal grid gives the maximum among lattice configurations. },
author = {Edelsbrunner, Herbert and Iglesias Ham, Mabel and Kurlin, Vitaliy},
booktitle = {Proceedings of the 27th Canadian Conference on Computational Geometry},
location = {Ontario, Canada},
pages = {128--135},
publisher = {Queen's University},
title = {{Relaxed disk packing}},
volume = {2015-August},
year = {2015},
}
@article{1497,
abstract = {Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide.},
author = {Andergassen, Daniel and Dotter, Christoph and Kulinski, Tomasz and Guenzl, Philipp and Bammer, Philipp and Barlow, Denise and Pauler, Florian and Hudson, Quanah},
journal = {Nucleic Acids Research},
number = {21},
publisher = {Oxford University Press},
title = {{Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data}},
doi = {10.1093/nar/gkv727},
volume = {43},
year = {2015},
}
@inproceedings{1498,
abstract = {Fault-tolerant distributed algorithms play an important role in many critical/high-availability applications. These algorithms are notoriously difficult to implement correctly, due to asynchronous communication and the occurrence of faults, such as the network dropping messages or computers crashing. Nonetheless there is surprisingly little language and verification support to build distributed systems based on fault-tolerant algorithms. In this paper, we present some of the challenges that a designer has to overcome to implement a fault-tolerant distributed system. Then we review different models that have been proposed to reason about distributed algorithms and sketch how such a model can form the basis for a domain-specific programming language. Adopting a high-level programming model can simplify the programmer's life and make the code amenable to automated verification, while still compiling to efficiently executable code. We conclude by summarizing the current status of an ongoing language design and implementation project that is based on this idea.},
author = {Dragoi, Cezara and Henzinger, Thomas A and Zufferey, Damien},
isbn = {978-3-939897-80-4 },
location = {Asilomar, CA, United States},
pages = {90 -- 102},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{The need for language support for fault-tolerant distributed systems}},
doi = {10.4230/LIPIcs.SNAPL.2015.90},
volume = {32},
year = {2015},
}
@inproceedings{1499,
abstract = {We consider weighted automata with both positive and negative integer weights on edges and
study the problem of synchronization using adaptive strategies that may only observe whether
the current weight-level is negative or nonnegative. We show that the synchronization problem is decidable in polynomial time for deterministic weighted automata.},
author = {Kretinsky, Jan and Larsen, Kim and Laursen, Simon and Srba, Jiří},
location = {Madrid, Spain},
pages = {142 -- 154},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{Polynomial time decidability of weighted synchronization under partial observability}},
doi = {10.4230/LIPIcs.CONCUR.2015.142},
volume = {42},
year = {2015},
}
@article{1501,
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 algorithms with quadratic complexity to compute the simulation relation. We present an automated technique for assume-guarantee style reasoning for compositional analysis of two-player games by giving a counterexample guided abstraction-refinement approach to compute our new simulation relation. We show a tight link between two-player games and MDPs, and as a consequence the results for games are lifted to MDPs with qualitative properties. We have implemented our algorithms and show that the compositional analysis leads to significant improvements. },
author = {Chatterjee, Krishnendu and Chmelik, Martin and Daca, Przemyslaw},
journal = {Formal Methods in System Design},
number = {2},
pages = {230 -- 264},
publisher = {Springer},
title = {{CEGAR for compositional analysis of qualitative properties in Markov decision processes}},
doi = {10.1007/s10703-015-0235-2},
volume = {47},
year = {2015},
}
@inproceedings{1502,
abstract = {We extend the theory of input-output conformance with operators for merge and quotient. The former is useful when testing against multiple requirements or views. The latter can be used to generate tests for patches of an already tested system. Both operators can combine systems with different action alphabets, which is usually the case when constructing complex systems and specifications from parts, for instance different views as well as newly defined functionality of a~previous version of the system.},
author = {Beneš, Nikola and Daca, Przemyslaw and Henzinger, Thomas A and Kretinsky, Jan and Nickovic, Dejan},
isbn = {978-1-4503-3471-6},
location = {Montreal, QC, Canada},
pages = {101 -- 110},
publisher = {ACM},
title = {{Complete composition operators for IOCO-testing theory}},
doi = {10.1145/2737166.2737175},
year = {2015},
}
@article{1505,
abstract = {This paper is aimed at deriving the universality of the largest eigenvalue of a class of high-dimensional real or complex sample covariance matrices of the form W N =Σ 1/2XX∗Σ 1/2 . Here, X = (xij )M,N is an M× N random matrix with independent entries xij , 1 ≤ i M,≤ 1 ≤ j ≤ N such that Exij = 0, E|xij |2 = 1/N . On dimensionality, we assume that M = M(N) and N/M → d ε (0, ∞) as N ∞→. For a class of general deterministic positive-definite M × M matrices Σ , under some additional assumptions on the distribution of xij 's, we show that the limiting behavior of the largest eigenvalue of W N is universal, via pursuing a Green function comparison strategy raised in [Probab. Theory Related Fields 154 (2012) 341-407, Adv. Math. 229 (2012) 1435-1515] by Erd″os, Yau and Yin for Wigner matrices and extended by Pillai and Yin [Ann. Appl. Probab. 24 (2014) 935-1001] to sample covariance matrices in the null case (&Epsi = I ). Consequently, in the standard complex case (Ex2 ij = 0), combing this universality property and the results known for Gaussian matrices obtained by El Karoui in [Ann. Probab. 35 (2007) 663-714] (nonsingular case) and Onatski in [Ann. Appl. Probab. 18 (2008) 470-490] (singular case), we show that after an appropriate normalization the largest eigenvalue of W N converges weakly to the type 2 Tracy-Widom distribution TW2 . Moreover, in the real case, we show that whenΣ is spiked with a fixed number of subcritical spikes, the type 1 Tracy-Widom limit TW1 holds for the normalized largest eigenvalue of W N , which extends a result of Féral and Péché in [J. Math. Phys. 50 (2009) 073302] to the scenario of nondiagonal Σ and more generally distributed X . In summary, we establish the Tracy-Widom type universality for the largest eigenvalue of generally distributed sample covariance matrices under quite light assumptions on &Sigma . Applications of these limiting results to statistical signal detection and structure recognition of separable covariance matrices are also discussed.},
author = {Bao, Zhigang and Pan, Guangming and Zhou, Wang},
journal = {Annals of Statistics},
number = {1},
pages = {382 -- 421},
publisher = {Institute of Mathematical Statistics},
title = {{Universality for the largest eigenvalue of sample covariance matrices with general population}},
doi = {10.1214/14-AOS1281},
volume = {43},
year = {2015},
}
@article{1506,
abstract = {Consider the square random matrix An = (aij)n,n, where {aij:= a(n)ij , i, j = 1, . . . , n} is a collection of independent real random variables with means zero and variances one. Under the additional moment condition supn max1≤i,j ≤n Ea4ij <∞, we prove Girko's logarithmic law of det An in the sense that as n→∞ log | detAn| ? (1/2) log(n-1)! d/→√(1/2) log n N(0, 1).},
author = {Bao, Zhigang and Pan, Guangming and Zhou, Wang},
journal = {Bernoulli},
number = {3},
pages = {1600 -- 1628},
publisher = {Bernoulli Society for Mathematical Statistics and Probability},
title = {{The logarithmic law of random determinant}},
doi = {10.3150/14-BEJ615},
volume = {21},
year = {2015},
}
@article{1508,
abstract = {We consider generalized Wigner ensembles and general β-ensembles with analytic potentials for any β ≥ 1. The recent universality results in particular assert that the local averages of consecutive eigenvalue gaps in the bulk of the spectrum are universal in the sense that they coincide with those of the corresponding Gaussian β-ensembles. In this article, we show that local averaging is not necessary for this result, i.e. we prove that the single gap distributions in the bulk are universal. In fact, with an additional step, our result can be extended to any C4(ℝ) potential.},
author = {Erdös, László and Yau, Horng},
journal = {Journal of the European Mathematical Society},
number = {8},
pages = {1927 -- 2036},
publisher = {European Mathematical Society},
title = {{Gap universality of generalized Wigner and β ensembles}},
doi = {10.4171/JEMS/548},
volume = {17},
year = {2015},
}
@article{1509,
abstract = {The Auxin Binding Protein1 (ABP1) has been identified based on its ability to bind auxin with high affinity and studied for a long time as a prime candidate for the extracellular auxin receptor responsible for mediating in particular the fast non-transcriptional auxin responses. However, the contradiction between the embryo-lethal phenotypes of the originally described Arabidopsis T-DNA insertional knock-out alleles (abp1-1 and abp1-1s) and the wild type-like phenotypes of other recently described loss-of-function alleles (abp1-c1 and abp1-TD1) questions the biological importance of ABP1 and relevance of the previous genetic studies. Here we show that there is no hidden copy of the ABP1 gene in the Arabidopsis genome but the embryo-lethal phenotypes of abp1-1 and abp1-1s alleles are very similar to the knock-out phenotypes of the neighboring gene, BELAYA SMERT (BSM). Furthermore, the allelic complementation test between bsm and abp1 alleles shows that the embryo-lethality in the abp1-1 and abp1-1s alleles is caused by the off-target disruption of the BSM locus by the T-DNA insertions. This clarifies the controversy of different phenotypes among published abp1 knock-out alleles and asks for reflections on the developmental role of ABP1.},
author = {Michalko, Jaroslav and Dravecka, Marta and Bollenbach, Tobias and Friml, Jirí},
journal = {F1000 Research },
publisher = {F1000 Research Ltd. },
title = {{Embryo-lethal phenotypes in early abp1 mutants are due to disruption of the neighboring BSM gene}},
doi = {10.12688/f1000research.7143.1},
volume = {4},
year = {2015},
}
@inproceedings{1510,
abstract = {The concept of well group in a special but important case captures homological properties of the zero set of a continuous map f from K to R^n on a compact space K that are invariant with respect to perturbations of f. The perturbations are arbitrary continuous maps within L_infty distance r from f for a given r > 0. The main drawback of the approach is that the computability of well groups was shown only when dim K = n or n = 1. Our contribution to the theory of well groups is twofold: on the one hand we improve on the computability issue, but on the other hand we present a range of examples where the well groups are incomplete invariants, that is, fail to capture certain important robust properties of the zero set. For the first part, we identify a computable subgroup of the well group that is obtained by cap product with the pullback of the orientation of R^n by f. In other words, well groups can be algorithmically approximated from below. When f is smooth and dim K < 2n-2, our approximation of the (dim K-n)th well group is exact. For the second part, we find examples of maps f, f' from K to R^n with all well groups isomorphic but whose perturbations have different zero sets. We discuss on a possible replacement of the well groups of vector valued maps by an invariant of a better descriptive power and computability status. },
author = {Franek, Peter and Krcál, Marek},
location = {Eindhoven, Netherlands},
pages = {842 -- 856},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{On computability and triviality of well groups}},
doi = {10.4230/LIPIcs.SOCG.2015.842},
volume = {34},
year = {2015},
}
@inproceedings{1511,
abstract = {The fact that the complete graph K_5 does not embed in the plane has been generalized in two independent directions. On the one hand, the solution of the classical Heawood problem for graphs on surfaces established that the complete graph K_n embeds in a closed surface M if and only if (n-3)(n-4) is at most 6b_1(M), where b_1(M) is the first Z_2-Betti number of M. On the other hand, Van Kampen and Flores proved that the k-skeleton of the n-dimensional simplex (the higher-dimensional analogue of K_{n+1}) embeds in R^{2k} if and only if n is less or equal to 2k+2. Two decades ago, Kuhnel conjectured that the k-skeleton of the n-simplex embeds in a compact, (k-1)-connected 2k-manifold with kth Z_2-Betti number b_k only if the following generalized Heawood inequality holds: binom{n-k-1}{k+1} is at most binom{2k+1}{k+1} b_k. This is a common generalization of the case of graphs on surfaces as well as the Van Kampen--Flores theorem. In the spirit of Kuhnel's conjecture, we prove that if the k-skeleton of the n-simplex embeds in a 2k-manifold with kth Z_2-Betti number b_k, then n is at most 2b_k binom{2k+2}{k} + 2k + 5. This bound is weaker than the generalized Heawood inequality, but does not require the assumption that M is (k-1)-connected. Our proof uses a result of Volovikov about maps that satisfy a certain homological triviality condition.},
author = {Goaoc, Xavier and Mabillard, Isaac and Paták, Pavel and Patakova, Zuzana and Tancer, Martin and Wagner, Uli},
location = {Eindhoven, Netherlands},
pages = {476 -- 490},
publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik},
title = {{On generalized Heawood inequalities for manifolds: A Van Kampen–Flores-type nonembeddability result}},
doi = {10.4230/LIPIcs.SOCG.2015.476},
volume = {34 },
year = {2015},
}
@inproceedings{1512,
abstract = {We show that very weak topological assumptions are enough to ensure the existence of a Helly-type theorem. More precisely, we show that for any non-negative integers b and d there exists an integer h(b,d) such that the following holds. If F is a finite family of subsets of R^d such that the ith reduced Betti number (with Z_2 coefficients in singular homology) of the intersection of any proper subfamily G of F is at most b for every non-negative integer i less or equal to (d-1)/2, then F has Helly number at most h(b,d). These topological conditions are sharp: not controlling any of these first Betti numbers allow for families with unbounded Helly number. Our proofs combine homological non-embeddability results with a Ramsey-based approach to build, given an arbitrary simplicial complex K, some well-behaved chain map from C_*(K) to C_*(R^d). Both techniques are of independent interest.},
author = {Goaoc, Xavier and Paták, Pavel and Patakova, Zuzana and Tancer, Martin and Wagner, Uli},
location = {Eindhoven, Netherlands},
pages = {507 -- 521},
publisher = {ACM},
title = {{Bounding Helly numbers via Betti numbers}},
doi = {10.4230/LIPIcs.SOCG.2015.507},
volume = {34},
year = {2015},
}
@article{1513,
abstract = {Insects of the order Hemiptera (true bugs) use a wide range of mechanisms of sex determination, including genetic sex determination, paternal genome elimination, and haplodiploidy. Genetic sex determination, the prevalent mode, is generally controlled by a pair of XY sex chromosomes or by an XX/X0 system, but different configurations that include additional sex chromosomes are also present. Although this diversity of sex determining systems has been extensively studied at the cytogenetic level, only the X chromosome of the model pea aphid Acyrthosiphon pisum has been analyzed at the genomic level, and little is known about X chromosome biology in the rest of the order.
In this study, we take advantage of published DNA- and RNA-seq data from three additional Hemiptera species to perform a comparative analysis of the gene content and expression of the X chromosome throughout this clade. We find that, despite showing evidence of dosage compensation, the X chromosomes of these species show female-biased expression, and a deficit of male-biased genes, in direct contrast to the pea aphid X. We further detect an excess of shared gene content between these very distant species, suggesting that despite the diversity of sex determining systems, the same chromosomal element is used as the X throughout a large portion of the order. },
author = {Pal, Arka and Vicoso, Beatriz},
journal = {Genome Biology and Evolution},
number = {12},
pages = {3259 -- 3268},
publisher = {Oxford University Press},
title = {{The X chromosome of hemipteran insects: Conservation, dosage compensation and sex-biased expression}},
doi = {10.1093/gbe/evv215},
volume = {7},
year = {2015},
}
@article{1517,
abstract = {We study the large deviation rate functional for the empirical distribution of independent Brownian particles with drift. In one dimension, it has been shown by Adams, Dirr, Peletier and Zimmer that this functional is asymptotically equivalent (in the sense of Γ-convergence) to the Jordan-Kinderlehrer-Otto functional arising in the Wasserstein gradient flow structure of the Fokker-Planck equation. In higher dimensions, part of this statement (the lower bound) has been recently proved by Duong, Laschos and Renger, but the upper bound remained open, since the proof of Duong et al relies on regularity properties of optimal transport maps that are restricted to one dimension. In this note we present a new proof of the upper bound, thereby generalising the result of Adams et al to arbitrary dimensions.
},
author = {Erbar, Matthias and Maas, Jan and Renger, Michiel},
journal = {Electronic Communications in Probability},
publisher = {Institute of Mathematical Statistics},
title = {{From large deviations to Wasserstein gradient flows in multiple dimensions}},
doi = {10.1214/ECP.v20-4315},
volume = {20},
year = {2015},
}
@article{1519,
abstract = {Evolutionary biologists have an array of powerful theoretical techniques that can accurately predict changes in the genetic composition of populations. Changes in gene frequencies and genetic associations between loci can be tracked as they respond to a wide variety of evolutionary forces. However, it is often less clear how to decompose these various forces into components that accurately reflect the underlying biology. Here, we present several issues that arise in the definition and interpretation of selection and selection coefficients, focusing on insights gained through the examination of selection coefficients in multilocus notation. Using this notation, we discuss how its flexibility-which allows different biological units to be identified as targets of selection-is reflected in the interpretation of the coefficients that the notation generates. In many situations, it can be difficult to agree on whether loci can be considered to be under "direct" versus "indirect" selection, or to quantify this selection. We present arguments for what the terms direct and indirect selection might best encompass, considering a range of issues, from viability and sexual selection to kin selection. We show how multilocus notation can discriminate between direct and indirect selection, and describe when it can do so.},
author = {Barton, Nicholas H and Servedio, Maria},
journal = {Evolution},
number = {5},
pages = {1101 -- 1112},
publisher = {Wiley},
title = {{The interpretation of selection coefficients}},
doi = {10.1111/evo.12641},
volume = {69},
year = {2015},
}
@inproceedings{1520,
abstract = {Creating mechanical automata that can walk in stable and pleasing manners is a challenging task that requires both skill and expertise. We propose to use computational design to offset the technical difficulties of this process. A simple drag-and-drop interface allows casual users to create personalized walking toys from a library of pre-defined template mechanisms. Provided with this input, our method leverages physical simulation and evolutionary optimization to refine the mechanical designs such that the resulting toys are able to walk. The optimization process is guided by an intuitive set of objectives that measure the quality of the walking motions. We demonstrate our approach on a set of simulated mechanical toys with different numbers of legs and various distinct gaits. Two fabricated prototypes showcase the feasibility of our designs.},
author = {Bharaj, Gaurav and Coros, Stelian and Thomaszewski, Bernhard and Tompkin, James and Bickel, Bernd and Pfister, Hanspeter},
isbn = {978-1-4503-3496-9},
location = {Los Angeles, CA, United States},
pages = {93 -- 100},
publisher = {ACM},
title = {{Computational design of walking automata}},
doi = {10.1145/2786784.2786803},
year = {2015},
}
@article{1525,
abstract = {Based on 16 recommendations, efforts should be made to achieve the following goal: By 2025, all scholarly publication activity in Austria should be Open Access. In other words, the final versions of all scholarly publications resulting from the support of public resources must be freely accessible on the Internet without delay (Gold Open Access). The resources required to meet this obligation shall be provided to the authors, or the cost of the publication venues shall be borne directly by the research organisations.},
author = {Bauer, Bruno and Blechl, Guido and Bock, Christoph and Danowski, Patrick and Ferus, Andreas and Graschopf, Anton and König, Thomas and Mayer, Katja and Reckling, Falk and Rieck, Katharina and Seitz, Peter and Stöger, Herwig and Welzig, Elvira},
journal = {VÖB Mitteilungen},
number = {3},
pages = {580 -- 607},
publisher = {Verein Österreichischer Bibliothekare},
title = {{Arbeitsgruppe „Nationale Strategie“ des Open Access Network Austria OANA}},
doi = {10.5281/zenodo.33178},
volume = {68},
year = {2015},
}
@article{1530,
abstract = {In growing cells, protein synthesis and cell growth are typically not synchronous, and, thus, protein concentrations vary over the cell division cycle. We have developed a theoretical description of genetic regulatory systems in bacteria that explicitly considers the cell division cycle to investigate its impact on gene expression. We calculate the cell-to-cell variations arising from cells being at different stages in the division cycle for unregulated genes and for basic regulatory mechanisms. These variations contribute to the extrinsic noise observed in single-cell experiments, and are most significant for proteins with short lifetimes. Negative autoregulation buffers against variation of protein concentration over the division cycle, but the effect is found to be relatively weak. Stronger buffering is achieved by an increased protein lifetime. Positive autoregulation can strongly amplify such variation if the parameters are set to values that lead to resonance-like behaviour. For cooperative positive autoregulation, the concentration variation over the division cycle diminishes the parameter region of bistability and modulates the switching times between the two stable states. The same effects are seen for a two-gene mutual-repression toggle switch. By contrast, an oscillatory circuit, the repressilator, is only weakly affected by the division cycle.},
author = {Bierbaum, Veronika and Klumpp, Stefan},
journal = {Physical Biology},
number = {6},
publisher = {IOP Publishing Ltd.},
title = {{Impact of the cell division cycle on gene circuits}},
doi = {10.1088/1478-3975/12/6/066003},
volume = {12},
year = {2015},
}
@article{1531,
abstract = {The Heat Kernel Signature (HKS) is a scalar quantity which is derived from the heat kernel of a given shape. Due to its robustness, isometry invariance, and multiscale nature, it has been successfully applied in many geometric applications. From a more general point of view, the HKS can be considered as a descriptor of the metric of a Riemannian manifold. Given a symmetric positive definite tensor field we may interpret it as the metric of some Riemannian manifold and thereby apply the HKS to visualize and analyze the given tensor data. In this paper, we propose a generalization of this approach that enables the treatment of indefinite tensor fields, like the stress tensor, by interpreting them as a generator of a positive definite tensor field. To investigate the usefulness of this approach we consider the stress tensor from the two-point-load model example and from a mechanical work piece.},
author = {Zobel, Valentin and Jan Reininghaus and Hotz, Ingrid},
journal = {Mathematics and Visualization},
pages = {257 -- 267},
publisher = {Springer},
title = {{Visualizing symmetric indefinite 2D tensor fields using The Heat Kernel Signature}},
doi = {10.1007/978-3-319-15090-1_13},
volume = {40},
year = {2015},
}
@article{1533,
abstract = {This paper addresses the problem of semantic segmentation, where the possible class labels are from a predefined set. We exploit top-down guidance, i.e., the coarse localization of the objects and their class labels provided by object detectors. For each detected bounding box, figure-ground segmentation is performed and the final result is achieved by merging the figure-ground segmentations. The main idea of the proposed approach, which is presented in our preliminary work, is to reformulate the figure-ground segmentation problem as sparse reconstruction pursuing the object mask in a nonparametric manner. The latent segmentation mask should be coherent subject to sparse error caused by intra-category diversity; thus, the object mask is inferred by making use of sparse representations over the training set. To handle local spatial deformations, local patch-level masks are also considered and inferred by sparse representations over the spatially nearby patches. The sparse reconstruction coefficients and the latent mask are alternately optimized by applying the Lasso algorithm and the accelerated proximal gradient method. The proposed formulation results in a convex optimization problem; thus, the global optimal solution is achieved. In this paper, we provide theoretical analysis of the convergence and optimality. We also give an extended numerical analysis of the proposed algorithm and a comprehensive comparison with the related semantic segmentation methods on the challenging PASCAL visual object class object segmentation datasets and the Weizmann horse dataset. The experimental results demonstrate that the proposed algorithm achieves a competitive performance when compared with the state of the arts.},
author = {Xia, Wei and Domokos, Csaba and Xiong, Junjun and Cheong, Loongfah and Yan, Shuicheng},
journal = {IEEE Transactions on Circuits and Systems for Video Technology},
number = {8},
pages = {1295 -- 1308},
publisher = {IEEE},
title = {{Segmentation over detection via optimal sparse reconstructions}},
doi = {10.1109/TCSVT.2014.2379972},
volume = {25},
year = {2015},
}
@article{1534,
abstract = {PIN proteins are auxin export carriers that direct intercellular auxin flow and in turn regulate many aspects of plant growth and development including responses to environmental changes. The Arabidopsis R2R3-MYB transcription factor FOUR LIPS (FLP) and its paralogue MYB88 regulate terminal divisions during stomatal development, as well as female reproductive development and stress responses. Here we show that FLP and MYB88 act redundantly but differentially in regulating the transcription of PIN3 and PIN7 in gravity-sensing cells of primary and lateral roots. On the one hand, FLP is involved in responses to gravity stimulation in primary roots, whereas on the other, FLP and MYB88 function complementarily in establishing the gravitropic set-point angles of lateral roots. Our results support a model in which FLP and MYB88 expression specifically determines the temporal-spatial patterns of PIN3 and PIN7 transcription that are closely associated with their preferential functions during root responses to gravity.},
author = {Wang, Hongzhe and Yang, Kezhen and Zou, Junjie and Zhu, Lingling and Xie, Zidian and Morita, Miyoterao and Tasaka, Masao and Friml, Jirí and Grotewold, Erich and Beeckman, Tom and Vanneste, Steffen and Sack, Fred and Le, Jie},
journal = {Nature Communications},
publisher = {Nature Publishing Group},
title = {{Transcriptional regulation of PIN genes by FOUR LIPS and MYB88 during Arabidopsis root gravitropism}},
doi = {10.1038/ncomms9822},
volume = {6},
year = {2015},
}
@article{1535,
abstract = {Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuronlike” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress.},
author = {Vandael, David H and Marcantoni, Andrea and Carbone, Emilio},
journal = {Current Molecular Pharmacology},
number = {2},
pages = {149 -- 161},
publisher = {Bentham Science Publishers},
title = {{Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells}},
doi = {10.2174/1874467208666150507105443},
volume = {8},
year = {2015},
}
@article{1536,
abstract = {Strigolactones, first discovered as germination stimulants for parasitic weeds [1], are carotenoid-derived phytohormones that play major roles in inhibiting lateral bud outgrowth and promoting plant-mycorrhizal symbiosis [2-4]. Furthermore, strigolactones are involved in the regulation of lateral and adventitious root development, root cell division [5, 6], secondary growth [7], and leaf senescence [8]. Recently, we discovered the strigolactone transporter Petunia axillaris PLEIOTROPIC DRUG RESISTANCE 1 (PaPDR1), which is required for efficient mycorrhizal colonization and inhibition of lateral bud outgrowth [9]. However, how strigolactones are transported through the plant remained unknown. Here we show that PaPDR1 exhibits a cell-type-specific asymmetric localization in different root tissues. In root tips, PaPDR1 is co-expressed with the strigolactone biosynthetic gene DAD1 (CCD8), and it is localized at the apical membrane of root hypodermal cells, presumably mediating the shootward transport of strigolactone. Above the root tip, in the hypodermal passage cells that form gates for the entry of mycorrhizal fungi, PaPDR1 is present in the outer-lateral membrane, compatible with its postulated function as strigolactone exporter from root to soil. Transport studies are in line with our localization studies since (1) a papdr1 mutant displays impaired transport of strigolactones out of the root tip to the shoot as well as into the rhizosphere and (2) DAD1 expression and PIN1/PIN2 levels change in plants deregulated for PDR1 expression, suggestive of variations in endogenous strigolactone contents. In conclusion, our results indicate that the polar localizations of PaPDR1 mediate directional shootward strigolactone transport as well as localized exudation into the soil.},
author = {Sasse, Joëlle and Simon, Sibu and Gübeli, Christian and Liu, Guowei and Cheng, Xi and Friml, Jirí and Bouwmeester, Harro and Martinoia, Enrico and Borghi, Lorenzo},
journal = {Current Biology},
number = {5},
pages = {647 -- 655},
publisher = {Cell Press},
title = {{Asymmetric localizations of the ABC transporter PaPDR1 trace paths of directional strigolactone transport}},
doi = {10.1016/j.cub.2015.01.015},
volume = {25},
year = {2015},
}
@article{1537,
abstract = {3D amoeboid cell migration is central to many developmental and disease-related processes such as cancer metastasis. Here, we identify a unique prototypic amoeboid cell migration mode in early zebrafish embryos, termed stable-bleb migration. Stable-bleb cells display an invariant polarized balloon-like shape with exceptional migration speed and persistence. Progenitor cells can be reversibly transformed into stable-bleb cells irrespective of their primary fate and motile characteristics by increasing myosin II activity through biochemical or mechanical stimuli. Using a combination of theory and experiments, we show that, in stable-bleb cells, cortical contractility fluctuations trigger a stochastic switch into amoeboid motility, and a positive feedback between cortical flows and gradients in contractility maintains stable-bleb cell polarization. We further show that rearward cortical flows drive stable-bleb cell migration in various adhesive and non-adhesive environments, unraveling a highly versatile amoeboid migration phenotype.},
author = {Ruprecht, Verena and Wieser, Stefan and Callan Jones, Andrew and Smutny, Michael and Morita, Hitoshi and Sako, Keisuke and Barone, Vanessa and Ritsch Marte, Monika and Sixt, Michael K and Voituriez, Raphaël and Heisenberg, Carl-Philipp J},
journal = {Cell},
number = {4},
pages = {673 -- 685},
publisher = {Cell Press},
title = {{Cortical contractility triggers a stochastic switch to fast amoeboid cell motility}},
doi = {10.1016/j.cell.2015.01.008},
volume = {160},
year = {2015},
}
@article{1538,
abstract = {Systems biology rests on the idea that biological complexity can be better unraveled through the interplay of modeling and experimentation. However, the success of this approach depends critically on the informativeness of the chosen experiments, which is usually unknown a priori. Here, we propose a systematic scheme based on iterations of optimal experiment design, flow cytometry experiments, and Bayesian parameter inference to guide the discovery process in the case of stochastic biochemical reaction networks. To illustrate the benefit of our methodology, we apply it to the characterization of an engineered light-inducible gene expression circuit in yeast and compare the performance of the resulting model with models identified from nonoptimal experiments. In particular, we compare the parameter posterior distributions and the precision to which the outcome of future experiments can be predicted. Moreover, we illustrate how the identified stochastic model can be used to determine light induction patterns that make either the average amount of protein or the variability in a population of cells follow a desired profile. Our results show that optimal experiment design allows one to derive models that are accurate enough to precisely predict and regulate the protein expression in heterogeneous cell populations over extended periods of time.},
author = {Ruess, Jakob and Parise, Francesca and Milias Argeitis, Andreas and Khammash, Mustafa and Lygeros, John},
journal = {PNAS},
number = {26},
pages = {8148 -- 8153},
publisher = {National Academy of Sciences},
title = {{Iterative experiment design guides the characterization of a light-inducible gene expression circuit}},
doi = {10.1073/pnas.1423947112},
volume = {112},
year = {2015},
}
@article{1539,
abstract = {Many stochastic models of biochemical reaction networks contain some chemical species for which the number of molecules that are present in the system can only be finite (for instance due to conservation laws), but also other species that can be present in arbitrarily large amounts. The prime example of such networks are models of gene expression, which typically contain a small and finite number of possible states for the promoter but an infinite number of possible states for the amount of mRNA and protein. One of the main approaches to analyze such models is through the use of equations for the time evolution of moments of the chemical species. Recently, a new approach based on conditional moments of the species with infinite state space given all the different possible states of the finite species has been proposed. It was argued that this approach allows one to capture more details about the full underlying probability distribution with a smaller number of equations. Here, I show that the result that less moments provide more information can only stem from an unnecessarily complicated description of the system in the classical formulation. The foundation of this argument will be the derivation of moment equations that describe the complete probability distribution over the finite state space but only low-order moments over the infinite state space. I will show that the number of equations that is needed is always less than what was previously claimed and always less than the number of conditional moment equations up to the same order. To support these arguments, a symbolic algorithm is provided that can be used to derive minimal systems of unconditional moment equations for models with partially finite state space. },
author = {Ruess, Jakob},
journal = {Journal of Chemical Physics},
number = {24},
publisher = {American Institute of Physics},
title = {{Minimal moment equations for stochastic models of biochemical reaction networks with partially finite state space}},
doi = {10.1063/1.4937937},
volume = {143},
year = {2015},
}
@article{1540,
abstract = {Plant sexual reproduction involves highly structured and specialized organs: stamens (male) and gynoecia (female, containing ovules). These organs synchronously develop within protective flower buds, until anthesis, via tightly coordinated mechanisms that are essential for effective fertilization and production of viable seeds. The phytohormone auxin is one of the key endogenous signalling molecules controlling initiation and development of these, and other, plant organs. In particular, its uneven distribution, resulting from tightly controlled production, metabolism and directional transport, is an important morphogenic factor. In this review we discuss how developmentally controlled and localized auxin biosynthesis and transport contribute to the coordinated development of plants' reproductive organs, and their fertilized derivatives (embryos) via the regulation of auxin levels and distribution within and around them. Current understanding of the links between de novo local auxin biosynthesis, auxin transport and/or signalling is presented to highlight the importance of the non-cell autonomous action of auxin production on development and morphogenesis of reproductive organs and embryos. An overview of transcription factor families, which spatiotemporally define local auxin production by controlling key auxin biosynthetic enzymes, is also presented.},
author = {Robert, Hélène and Crhák Khaitová, Lucie and Mroue, Souad and Benková, Eva},
journal = {Journal of Experimental Botany},
number = {16},
pages = {5029 -- 5042},
publisher = {Oxford University Press},
title = {{The importance of localized auxin production for morphogenesis of reproductive organs and embryos in Arabidopsis}},
doi = {10.1093/jxb/erv256},
volume = {66},
year = {2015},
}
@inproceedings{1541,
abstract = {We present XSpeed a parallel state-space exploration algorithm for continuous systems with linear dynamics and nondeterministic inputs. The motivation of having parallel algorithms is to exploit the computational power of multi-core processors to speed-up performance. The parallelization is achieved on two fronts. First, we propose a parallel implementation of the support function algorithm by sampling functions in parallel. Second, we propose a parallel state-space exploration by slicing the time horizon and computing the reachable states in the time slices in parallel. The second method can be however applied only to a class of linear systems with invertible dynamics and fixed input. A GP-GPU implementation is also presented following a lazy evaluation strategy on support functions. The parallel algorithms are implemented in the tool XSpeed. We evaluated the performance on two benchmarks including an 28 dimension Helicopter model. Comparison with the sequential counterpart shows a maximum speed-up of almost 7× on a 6 core, 12 thread Intel Xeon CPU E5-2420 processor. Our GP-GPU implementation shows a maximum speed-up of 12× over the sequential implementation and 53× over SpaceEx (LGG scenario), the state of the art tool for reachability analysis of linear hybrid systems. Experiments illustrate that our parallel algorithm with time slicing not only speeds-up performance but also improves precision.},
author = {Ray, Rajarshi and Gurung, Amit and Das, Binayak and Bartocci, Ezio and Bogomolov, Sergiy and Grosu, Radu},
location = {Haifa, Israel},
pages = {3 -- 18},
publisher = {Springer},
title = {{XSpeed: Accelerating reachability analysis on multi-core processors}},
doi = {10.1007/978-3-319-26287-1_1},
volume = {9434},
year = {2015},
}
@article{1542,
abstract = {The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. },
author = {Paixao, Tiago and Badkobeh, Golnaz and Barton, Nicholas H and Çörüş, Doğan and Dang, Duccuong and Friedrich, Tobias and Lehre, Per and Sudholt, Dirk and Sutton, Andrew and Trubenova, Barbora},
journal = { Journal of Theoretical Biology},
pages = {28 -- 43},
publisher = {Elsevier},
title = {{Toward a unifying framework for evolutionary processes}},
doi = {10.1016/j.jtbi.2015.07.011},
volume = {383},
year = {2015},
}
@article{1543,
abstract = {A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta.},
author = {Olvera Carrillo, Yadira and Van Bel, Michiel and Van Hautegem, Tom and Fendrych, Matyas and Huysmans, Marlies and Šimášková, Mária and Van Durme, Matthias and Buscaill, Pierre and Rivas, Susana and Coll, Núria and Coppens, Frederik and Maere, Steven and Nowack, Moritz},
journal = {Plant Physiology},
number = {4},
pages = {2684 -- 2699},
publisher = {American Society of Plant Biologists},
title = {{A conserved core of programmed cell death indicator genes discriminates developmentally and environmentally induced programmed cell death in plants}},
doi = {10.1104/pp.15.00769},
volume = {169},
year = {2015},
}
@inbook{1544,
abstract = {Cell division in prokaryotes and eukaryotes is commonly initiated by the well-controlled binding of proteins to the cytoplasmic side of the cell membrane. However, a precise characterization of the spatiotemporal dynamics of membrane-bound proteins is often difficult to achieve in vivo. Here, we present protocols for the use of supported lipid bilayers to rebuild the cytokinetic machineries of cells with greatly different dimensions: the bacterium Escherichia coli and eggs of the vertebrate Xenopus laevis. Combined with total internal reflection fluorescence microscopy, these experimental setups allow for precise quantitative analyses of membrane-bound proteins. The protocols described to obtain glass-supported membranes from bacterial and vertebrate lipids can be used as starting points for other reconstitution experiments. We believe that similar biochemical assays will be instrumental to study the biochemistry and biophysics underlying a variety of complex cellular tasks, such as signaling, vesicle trafficking, and cell motility.},
author = {Nguyen, Phuong and Field, Christine and Groen, Aaron and Mitchison, Timothy and Loose, Martin},
booktitle = {Building a Cell from its Components Parts},
pages = {223 -- 241},
publisher = {Academic Press},
title = {{Using supported bilayers to study the spatiotemporal organization of membrane-bound proteins}},
doi = {10.1016/bs.mcb.2015.01.007},
volume = {128},
year = {2015},
}
@article{1546,
abstract = {Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.},
author = {Nakamura, Yukihiro and Harada, Harumi and Kamasawa, Naomi and Matsui, Ko and Rothman, Jason and Shigemoto, Ryuichi and Silver, R Angus and Digregorio, David and Takahashi, Tomoyuki},
journal = {Neuron},
number = {1},
pages = {145 -- 158},
publisher = {Elsevier},
title = {{Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development}},
doi = {10.1016/j.neuron.2014.11.019},
volume = {85},
year = {2015},
}