@inproceedings{6747, abstract = {We establish connections between the problem of learning a two-layer neural network and tensor decomposition. We consider a model with feature vectors x∈ℝd, r hidden units with weights {wi}1≤i≤r and output y∈ℝ, i.e., y=∑ri=1σ(w𝖳ix), with activation functions given by low-degree polynomials. In particular, if σ(x)=a0+a1x+a3x3, we prove that no polynomial-time learning algorithm can outperform the trivial predictor that assigns to each example the response variable 𝔼(y), when d3/2≪r≪d2. Our conclusion holds for a `natural data distribution', namely standard Gaussian feature vectors x, and output distributed according to a two-layer neural network with random isotropic weights, and under a certain complexity-theoretic assumption on tensor decomposition. Roughly speaking, we assume that no polynomial-time algorithm can substantially outperform current methods for tensor decomposition based on the sum-of-squares hierarchy. We also prove generalizations of this statement for higher degree polynomial activations, and non-random weight vectors. Remarkably, several existing algorithms for learning two-layer networks with rigorous guarantees are based on tensor decomposition. Our results support the idea that this is indeed the core computational difficulty in learning such networks, under the stated generative model for the data. As a side result, we show that under this model learning the network requires accurate learning of its weights, a property that does not hold in a more general setting. }, author = {Mondelli, Marco and Montanari, Andrea}, booktitle = {Proceedings of the 22nd International Conference on Artificial Intelligence and Statistics}, location = {Naha, Okinawa, Japan}, pages = {1051--1060}, publisher = {Proceedings of Machine Learning Research}, title = {{On the connection between learning two-layers neural networks and tensor decomposition}}, volume = {89}, year = {2019}, } @article{6750, abstract = {Polar codes have gained extensive attention during the past few years and recently they have been selected for the next generation of wireless communications standards (5G). Successive-cancellation-based (SC-based) decoders, such as SC list (SCL) and SC flip (SCF), provide a reasonable error performance for polar codes at the cost of low decoding speed. Fast SC-based decoders, such as Fast-SSC, Fast-SSCL, and Fast-SSCF, identify the special constituent codes in a polar code graph off-line, produce a list of operations, store the list in memory, and feed the list to the decoder to decode the constituent codes in order efficiently, thus increasing the decoding speed. However, the list of operations is dependent on the code rate and as the rate changes, a new list is produced, making fast SC-based decoders not rate-flexible. In this paper, we propose a completely rate-flexible fast SC-based decoder by creating the list of operations directly in hardware, with low implementation complexity. We further propose a hardware architecture implementing the proposed method and show that the area occupation of the rate-flexible fast SC-based decoder in this paper is only 38% of the total area of the memory-based base-line decoder when 5G code rates are supported. }, author = {Hashemi, Seyyed Ali and Condo, Carlo and Mondelli, Marco and Gross, Warren J}, issn = {1053587X}, journal = {IEEE Transactions on Signal Processing}, number = {22}, publisher = {IEEE}, title = {{Rate-flexible fast polar decoders}}, doi = {10.1109/TSP.2019.2944738}, volume = {67}, year = {2019}, } @article{6759, abstract = {We consider the graph class Grounded-L corresponding to graphs that admit an intersection representation by L-shaped curves, where additionally the topmost points of each curve are assumed to belong to a common horizontal line. We prove that Grounded-L graphs admit an equivalent characterisation in terms of vertex ordering with forbidden patterns. We also compare this class to related intersection classes, such as the grounded segment graphs, the monotone L-graphs (a.k.a. max point-tolerance graphs), or the outer-1-string graphs. We give constructions showing that these classes are all distinct and satisfy only trivial or previously known inclusions.}, author = {Jelínek, Vít and Töpfer, Martin}, issn = {10778926}, journal = {Electronic Journal of Combinatorics}, number = {3}, publisher = {Electronic Journal of Combinatorics}, title = {{On grounded L-graphs and their relatives}}, doi = {10.37236/8096}, volume = {26}, year = {2019}, } @inproceedings{6822, abstract = {In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the qualitative winner or quantitative payoff of the game. In bidding games, in each turn, we hold an auction between the two players to determine which player moves the token. Bidding games have largely been studied with concrete bidding mechanisms that are variants of a first-price auction: in each turn both players simultaneously submit bids, the higher bidder moves the token, and pays his bid to the lower bidder in Richman bidding, to the bank in poorman bidding, and in taxman bidding, the bid is split between the other player and the bank according to a predefined constant factor. Bidding games are deterministic games. They have an intriguing connection with a fragment of stochastic games called randomturn games. We study, for the first time, a combination of bidding games with probabilistic behavior; namely, we study bidding games that are played on Markov decision processes, where the players bid for the right to choose the next action, which determines the probability distribution according to which the next vertex is chosen. We study parity and meanpayoff bidding games on MDPs and extend results from the deterministic bidding setting to the probabilistic one.}, author = {Avni, Guy and Henzinger, Thomas A and Ibsen-Jensen, Rasmus and Novotny, Petr}, booktitle = { Proceedings of the 13th International Conference of Reachability Problems}, isbn = {978-303030805-6}, issn = {0302-9743}, location = {Brussels, Belgium}, pages = {1--12}, publisher = {Springer}, title = {{Bidding games on Markov decision processes}}, doi = {10.1007/978-3-030-30806-3_1}, volume = {11674}, year = {2019}, } @inproceedings{6887, abstract = {The fundamental model-checking problem, given as input a model and a specification, asks for the algorithmic verification of whether the model satisfies the specification. Two classical models for reactive systems are graphs and Markov decision processes (MDPs). A basic specification formalism in the verification of reactive systems is the strong fairness (aka Streett) objective, where given different types of requests and corresponding grants, the requirement is that for each type, if the request event happens infinitely often, then the corresponding grant event must also happen infinitely often. All omega-regular objectives can be expressed as Streett objectives and hence they are canonical in verification. Consider graphs/MDPs with n vertices, m edges, and a Streett objectives with k pairs, and let b denote the size of the description of the Streett objective for the sets of requests and grants. The current best-known algorithm for the problem requires time O(min(n^2, m sqrt{m log n}) + b log n). In this work we present randomized near-linear time algorithms, with expected running time O~(m + b), where the O~ notation hides poly-log factors. Our randomized algorithms are near-linear in the size of the input, and hence optimal up to poly-log factors. }, author = {Chatterjee, Krishnendu and Dvorák, Wolfgang and Henzinger, Monika H and Svozil, Alexander}, booktitle = {Leibniz International Proceedings in Informatics}, location = {Amsterdam, Netherlands}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Near-linear time algorithms for Streett objectives in graphs and MDPs}}, doi = {10.4230/LIPICS.CONCUR.2019.7}, volume = {140}, year = {2019}, } @inproceedings{6888, abstract = {In this paper, we design novel liquid time-constant recurrent neural networks for robotic control, inspired by the brain of the nematode, C. elegans. In the worm's nervous system, neurons communicate through nonlinear time-varying synaptic links established amongst them by their particular wiring structure. This property enables neurons to express liquid time-constants dynamics and therefore allows the network to originate complex behaviors with a small number of neurons. We identify neuron-pair communication motifs as design operators and use them to configure compact neuronal network structures to govern sequential robotic tasks. The networks are systematically designed to map the environmental observations to motor actions, by their hierarchical topology from sensory neurons, through recurrently-wired interneurons, to motor neurons. The networks are then parametrized in a supervised-learning scheme by a search-based algorithm. We demonstrate that obtained networks realize interpretable dynamics. We evaluate their performance in controlling mobile and arm robots, and compare their attributes to other artificial neural network-based control agents. Finally, we experimentally show their superior resilience to environmental noise, compared to the existing machine learning-based methods.}, author = {Lechner, Mathias and Hasani, Ramin and Zimmer, Manuel and Henzinger, Thomas A and Grosu, Radu}, booktitle = {Proceedings - IEEE International Conference on Robotics and Automation}, isbn = {9781538660270}, location = {Montreal, QC, Canada}, publisher = {IEEE}, title = {{Designing worm-inspired neural networks for interpretable robotic control}}, doi = {10.1109/icra.2019.8793840}, volume = {2019-May}, year = {2019}, } @inproceedings{6886, abstract = {In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner of the game. Such games are central in formal methods since they model the interaction between a non-terminating system and its environment. In bidding games the players bid for the right to move the token: in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Bidding games are known to have a clean and elegant mathematical structure that relies on the ability of the players to submit arbitrarily small bids. Many applications, however, require a fixed granularity for the bids, which can represent, for example, the monetary value expressed in cents. We study, for the first time, the combination of discrete-bidding and infinite-duration games. Our most important result proves that these games form a large determined subclass of concurrent games, where determinacy is the strong property that there always exists exactly one player who can guarantee winning the game. In particular, we show that, in contrast to non-discrete bidding games, the mechanism with which tied bids are resolved plays an important role in discrete-bidding games. We study several natural tie-breaking mechanisms and show that, while some do not admit determinacy, most natural mechanisms imply determinacy for every pair of initial budgets. }, author = {Aghajohari, Milad and Avni, Guy and Henzinger, Thomas A}, location = {Amsterdam, Netherlands}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Determinacy in discrete-bidding infinite-duration games}}, doi = {10.4230/LIPICS.CONCUR.2019.20}, volume = {140}, year = {2019}, } @inproceedings{6885, abstract = {A vector addition system with states (VASS) consists of a finite set of states and counters. A configuration is a state and a value for each counter; a transition changes the state and each counter is incremented, decremented, or left unchanged. While qualitative properties such as state and configuration reachability have been studied for VASS, we consider the long-run average cost of infinite computations of VASS. The cost of a configuration is for each state, a linear combination of the counter values. In the special case of uniform cost functions, the linear combination is the same for all states. The (regular) long-run emptiness problem is, given a VASS, a cost function, and a threshold value, if there is a (lasso-shaped) computation such that the long-run average value of the cost function does not exceed the threshold. For uniform cost functions, we show that the regular long-run emptiness problem is (a) decidable in polynomial time for integer-valued VASS, and (b) decidable but nonelementarily hard for natural-valued VASS (i.e., nonnegative counters). For general cost functions, we show that the problem is (c) NP-complete for integer-valued VASS, and (d) undecidable for natural-valued VASS. Our most interesting result is for (c) integer-valued VASS with general cost functions, where we establish a connection between the regular long-run emptiness problem and quadratic Diophantine inequalities. The general (nonregular) long-run emptiness problem is equally hard as the regular problem in all cases except (c), where it remains open. }, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, location = {Amsterdam, Netherlands}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Long-run average behavior of vector addition systems with states}}, doi = {10.4230/LIPICS.CONCUR.2019.27}, volume = {140}, year = {2019}, } @inproceedings{6889, abstract = {We study Markov decision processes and turn-based stochastic games with parity conditions. There are three qualitative winning criteria, namely, sure winning, which requires all paths to satisfy the condition, almost-sure winning, which requires the condition to be satisfied with probability 1, and limit-sure winning, which requires the condition to be satisfied with probability arbitrarily close to 1. We study the combination of two of these criteria for parity conditions, e.g., there are two parity conditions one of which must be won surely, and the other almost-surely. The problem has been studied recently by Berthon et al. for MDPs with combination of sure and almost-sure winning, under infinite-memory strategies, and the problem has been established to be in NP cap co-NP. Even in MDPs there is a difference between finite-memory and infinite-memory strategies. Our main results for combination of sure and almost-sure winning are as follows: (a) we show that for MDPs with finite-memory strategies the problem is in NP cap co-NP; (b) we show that for turn-based stochastic games the problem is co-NP-complete, both for finite-memory and infinite-memory strategies; and (c) we present algorithmic results for the finite-memory case, both for MDPs and turn-based stochastic games, by reduction to non-stochastic parity games. In addition we show that all the above complexity results also carry over to combination of sure and limit-sure winning, and results for all other combinations can be derived from existing results in the literature. Thus we present a complete picture for the study of combinations of two qualitative winning criteria for parity conditions in MDPs and turn-based stochastic games. }, author = {Chatterjee, Krishnendu and Piterman, Nir}, location = {Amsterdam, Netherlands}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Combinations of Qualitative Winning for Stochastic Parity Games}}, doi = {10.4230/LIPICS.CONCUR.2019.6}, volume = {140}, year = {2019}, } @inproceedings{6931, abstract = {Consider a distributed system with n processors out of which f can be Byzantine faulty. In the approximate agreement task, each processor i receives an input value xi and has to decide on an output value yi such that 1. the output values are in the convex hull of the non-faulty processors’ input values, 2. the output values are within distance d of each other. Classically, the values are assumed to be from an m-dimensional Euclidean space, where m ≥ 1. In this work, we study the task in a discrete setting, where input values with some structure expressible as a graph. Namely, the input values are vertices of a finite graph G and the goal is to output vertices that are within distance d of each other in G, but still remain in the graph-induced convex hull of the input values. For d = 0, the task reduces to consensus and cannot be solved with a deterministic algorithm in an asynchronous system even with a single crash fault. For any d ≥ 1, we show that the task is solvable in asynchronous systems when G is chordal and n > (ω + 1)f, where ω is the clique number of G. In addition, we give the first Byzantine-tolerant algorithm for a variant of lattice agreement. For synchronous systems, we show tight resilience bounds for the exact variants of these and related tasks over a large class of combinatorial structures.}, author = {Nowak, Thomas and Rybicki, Joel}, booktitle = {33rd International Symposium on Distributed Computing}, keywords = {consensus, approximate agreement, Byzantine faults, chordal graphs, lattice agreement}, location = {Budapest, Hungary}, pages = {29:1----29:17}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Byzantine approximate agreement on graphs}}, doi = {10.4230/LIPICS.DISC.2019.29}, volume = {146}, year = {2019}, } @inproceedings{6985, abstract = {In this paper, we introduce a novel method to interpret recurrent neural networks (RNNs), particularly long short-term memory networks (LSTMs) at the cellular level. We propose a systematic pipeline for interpreting individual hidden state dynamics within the network using response characterization methods. The ranked contribution of individual cells to the network's output is computed by analyzing a set of interpretable metrics of their decoupled step and sinusoidal responses. As a result, our method is able to uniquely identify neurons with insightful dynamics, quantify relationships between dynamical properties and test accuracy through ablation analysis, and interpret the impact of network capacity on a network's dynamical distribution. Finally, we demonstrate the generalizability and scalability of our method by evaluating a series of different benchmark sequential datasets.}, author = {Hasani, Ramin and Amini, Alexander and Lechner, Mathias and Naser, Felix and Grosu, Radu and Rus, Daniela}, booktitle = {Proceedings of the International Joint Conference on Neural Networks}, isbn = {9781728119854}, location = {Budapest, Hungary}, publisher = {IEEE}, title = {{Response characterization for auditing cell dynamics in long short-term memory networks}}, doi = {10.1109/ijcnn.2019.8851954}, year = {2019}, } @article{7007, abstract = {We consider the primitive relay channel, where the source sends a message to the relay and to the destination, and the relay helps the communication by transmitting an additional message to the destination via a separate channel. Two well-known coding techniques have been introduced for this setting: decode-and-forward and compress-and-forward. In decode-and-forward, the relay completely decodes the message and sends some information to the destination; in compress-and-forward, the relay does not decode, and it sends a compressed version of the received signal to the destination using Wyner–Ziv coding. In this paper, we present a novel coding paradigm that provides an improved achievable rate for the primitive relay channel. The idea is to combine compress-and-forward and decode-and-forward via a chaining construction. We transmit over pairs of blocks: in the first block, we use compress-and-forward; and, in the second block, we use decode-and-forward. More specifically, in the first block, the relay does not decode, it compresses the received signal via Wyner–Ziv, and it sends only part of the compression to the destination. In the second block, the relay completely decodes the message, it sends some information to the destination, and it also sends the remaining part of the compression coming from the first block. By doing so, we are able to strictly outperform both compress-and-forward and decode-and-forward. Note that the proposed coding scheme can be implemented with polar codes. As such, it has the typical attractive properties of polar coding schemes, namely, quasi-linear encoding and decoding complexity, and error probability that decays at super-polynomial speed. As a running example, we take into account the special case of the erasure relay channel, and we provide a comparison between the rates achievable by our proposed scheme and the existing upper and lower bounds.}, author = {Mondelli, Marco and Hassani, S. Hamed and Urbanke, Rüdiger}, issn = {1999-4893}, journal = {Algorithms}, number = {10}, publisher = {MDPI}, title = {{A new coding paradigm for the primitive relay channel}}, doi = {10.3390/a12100218}, volume = {12}, year = {2019}, } @inproceedings{7035, abstract = {The aim of this short note is to expound one particular issue that was discussed during the talk [10] given at the symposium ”Researches on isometries as preserver problems and related topics” at Kyoto RIMS. That is, the role of Dirac masses by describing the isometry group of various metric spaces of probability measures. This article is of survey character, and it does not contain any essentially new results.From an isometric point of view, in some cases, metric spaces of measures are similar to C(K)-type function spaces. Similarity means here that their isometries are driven by some nice transformations of the underlying space. Of course, it depends on the particular choice of the metric how nice these transformations should be. Sometimes, as we will see, being a homeomorphism is enough to generate an isometry. But sometimes we need more: the transformation must preserve the underlying distance as well. Statements claiming that isometries in questions are necessarily induced by homeomorphisms are called Banach-Stone-type results, while results asserting that the underlying transformation is necessarily an isometry are termed as isometric rigidity results.As Dirac masses can be considered as building bricks of the set of all Borel measures, a natural question arises:Is it enough to understand how an isometry acts on the set of Dirac masses? Does this action extend uniquely to all measures?In what follows, we will thoroughly investigate this question.}, author = {Geher, Gyorgy Pal and Titkos, Tamas and Virosztek, Daniel}, booktitle = {Kyoto RIMS Kôkyûroku}, location = {Kyoto, Japan}, pages = {34--41}, publisher = {Research Institute for Mathematical Sciences, Kyoto University}, title = {{Dirac masses and isometric rigidity}}, volume = {2125}, year = {2019}, } @article{7055, abstract = {A recent class of topological nodal-line semimetals with the general formula MSiX (M = Zr, Hf and X = S, Se, Te) has attracted much experimental and theoretical interest due to their properties, particularly their large magnetoresistances and high carrier mobilities. The plateletlike nature of the MSiX crystals and their extremely low residual resistivities make measurements of the resistivity along the [001] direction extremely challenging. To accomplish such measurements, microstructures of single crystals were prepared using focused ion beam techniques. Microstructures prepared in this manner have very well-defined geometries and maintain their high crystal quality, verified by the observations of quantum oscillations. We present magnetoresistance and quantum oscillation data for currents applied along both [001] and [100] in ZrSiS and ZrSiSe, which are consistent with the nontrivial topology of the Dirac line-node, as determined by a measured π Berry phase. Surprisingly, we find that, despite the three dimensional nature of both the Fermi surfaces of ZrSiS and ZrSiSe, both the resistivity anisotropy under applied magnetic fields and the in-plane angular dependent magnetoresistance differ considerably between the two compounds. Finally, we discuss the role microstructuring can play in the study of these materials and our ability to make these microstructures free-standing.}, author = {Shirer, Kent R. and Modic, Kimberly A and Zimmerling, Tino and Bachmann, Maja D. and König, Markus and Moll, Philip J. W. and Schoop, Leslie and Mackenzie, Andrew P.}, issn = {2166-532X}, journal = {APL Materials}, number = {10}, publisher = {AIP}, title = {{Out-of-plane transport in ZrSiS and ZrSiSe microstructures}}, doi = {10.1063/1.5124568}, volume = {7}, year = {2019}, } @article{7057, abstract = {We present a high magnetic field study of NbP—a member of the monopnictide Weyl semimetal (WSM) family. While the monoarsenides (NbAs and TaAs) have topologically distinct left and right-handed Weyl fermi surfaces, NbP is argued to be “topologically trivial” due to the fact that all pairs of Weyl nodes are encompassed by a single Fermi surface. We use torque magnetometry to measure the magnetic response of NbP up to 60 tesla and uncover a Berry paramagnetic response, characteristic of the topological Weyl nodes, across the entire field range. At the quantum limit B* (≈32 T), τ/B experiences a change in slope when the chemical potential enters the last Landau level. Our calculations confirm that this magnetic response arises from band topology of the Weyl pocket, even though the Fermi surface encompasses both Weyl nodes at zero magnetic field. We also find that the magnetic field pulls the chemical potential to the chiral n = 0 Landau level in the quantum limit, providing a disorder-free way of accessing chiral Weyl fermions in systems that are “not quite” WSMs in zero magnetic field.}, author = {Modic, Kimberly A and Meng, Tobias and Ronning, Filip and Bauer, Eric D. and Moll, Philip J. W. and Ramshaw, B. J.}, issn = {2045-2322}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, title = {{Thermodynamic signatures of Weyl fermions in NbP}}, doi = {10.1038/s41598-018-38161-7}, volume = {9}, year = {2019}, } @article{7056, abstract = {In the Ca1−x La x FeAs2 (1 1 2) family of pnictide superconductors, we have investigated a highly overdoped composition (x  =  0.56), prepared by a high-pressure, high-temperature synthesis. Magnetic measurements show an antiferromagnetic transition at T N  =  120 K, well above the one at lower doping (0.15  <  x  <  0.27). Below the onset of long-range magnetic order at T N, the electrical resistivity is strongly reduced and is dominated by electron–electron interactions, as evident from its temperature dependence. The Seebeck coefficient shows a clear metallic behavior as in narrow band conductors. The temperature dependence of the Hall coefficient and the violation of Kohler's rule agree with the multiband character of the material. No superconductivity was observed down to 1.8 K. The success of the high-pressure synthesis encourages further investigations of the so far only partially explored phase diagram in this family of Iron-based high temperature superconductors. }, author = {Martino, Edoardo and Bachmann, Maja D and Rossi, Lidia and Modic, Kimberly A and Zivkovic, Ivica and Rønnow, Henrik M and Moll, Philip J W and Akrap, Ana and Forró, László and Katrych, Sergiy}, issn = {1361-648X}, journal = {Journal of Physics: Condensed Matter}, number = {48}, publisher = {IOP Publishing}, title = {{Persistent antiferromagnetic order in heavily overdoped Ca1−x La x FeAs2}}, doi = {10.1088/1361-648x/ab3b43}, volume = {31}, year = {2019}, } @article{7082, abstract = {Although crystals of strongly correlated metals exhibit a diverse set of electronic ground states, few approaches exist for spatially modulating their properties. In this study, we demonstrate disorder-free control, on the micrometer scale, over the superconducting state in samples of the heavy-fermion superconductor CeIrIn5. We pattern crystals by focused ion beam milling to tailor the boundary conditions for the elastic deformation upon thermal contraction during cooling. The resulting nonuniform strain fields induce complex patterns of superconductivity, owing to the strong dependence of the transition temperature on the strength and direction of strain. These results showcase a generic approach to manipulating electronic order on micrometer length scales in strongly correlated matter without compromising the cleanliness, stoichiometry, or mean free path.}, author = {Bachmann, Maja D. and Ferguson, G. M. and Theuss, Florian and Meng, Tobias and Putzke, Carsten and Helm, Toni and Shirer, K. R. and Li, You-Sheng and Modic, Kimberly A and Nicklas, Michael and König, Markus and Low, D. and Ghosh, Sayak and Mackenzie, Andrew P. and Arnold, Frank and Hassinger, Elena and McDonald, Ross D. and Winter, Laurel E. and Bauer, Eric D. and Ronning, Filip and Ramshaw, B. J. and Nowack, Katja C. and Moll, Philip J. W.}, issn = {1095-9203}, journal = {Science}, number = {6462}, pages = {221--226}, publisher = {AAAS}, title = {{Spatial control of heavy-fermion superconductivity in CeIrIn5}}, doi = {10.1126/science.aao6640}, volume = {366}, year = {2019}, } @article{7128, abstract = {Loss of functional cardiomyocytes is a major determinant of heart failure after myocardial infarction. Previous high throughput screening studies have identified a few microRNAs (miRNAs) that can induce cardiomyocyte proliferation and stimulate cardiac regeneration in mice. Here, we show that all of the most effective of these miRNAs activate nuclear localization of the master transcriptional cofactor Yes-associated protein (YAP) and induce expression of YAP-responsive genes. In particular, miR-199a-3p directly targets two mRNAs coding for proteins impinging on the Hippo pathway, the upstream YAP inhibitory kinase TAOK1, and the E3 ubiquitin ligase β-TrCP, which leads to YAP degradation. Several of the pro-proliferative miRNAs (including miR-199a-3p) also inhibit filamentous actin depolymerization by targeting Cofilin2, a process that by itself activates YAP nuclear translocation. Thus, activation of YAP and modulation of the actin cytoskeleton are major components of the pro-proliferative action of miR-199a-3p and other miRNAs that induce cardiomyocyte proliferation.}, author = {Torrini, Consuelo and Cubero, Ryan J and Dirkx, Ellen and Braga, Luca and Ali, Hashim and Prosdocimo, Giulia and Gutierrez, Maria Ines and Collesi, Chiara and Licastro, Danilo and Zentilin, Lorena and Mano, Miguel and Zacchigna, Serena and Vendruscolo, Michele and Marsili, Matteo and Samal, Areejit and Giacca, Mauro}, issn = {2211-1247}, journal = {Cell Reports}, keywords = {cardiomyocyte, cell cycle, Cofilin2, cytoskeleton, Hippo, microRNA, regeneration, YAP}, number = {9}, pages = {2759--2771.e5}, publisher = {Elsevier}, title = {{Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation}}, doi = {10.1016/j.celrep.2019.05.005}, volume = {27}, year = {2019}, } @article{7130, abstract = {We show that statistical criticality, i.e. the occurrence of power law frequency distributions, arises in samples that are maximally informative about the underlying generating process. In order to reach this conclusion, we first identify the frequency with which different outcomes occur in a sample, as the variable carrying useful information on the generative process. The entropy of the frequency, that we call relevance, provides an upper bound to the number of informative bits. This differs from the entropy of the data, that we take as a measure of resolution. Samples that maximise relevance at a given resolution—that we call maximally informative samples—exhibit statistical criticality. In particular, Zipf's law arises at the optimal trade-off between resolution (i.e. compression) and relevance. As a byproduct, we derive a bound of the maximal number of parameters that can be estimated from a dataset, in the absence of prior knowledge on the generative model. Furthermore, we relate criticality to the statistical properties of the representation of the data generating process. We show that, as a consequence of the concentration property of the asymptotic equipartition property, representations that are maximally informative about the data generating process are characterised by an exponential distribution of energy levels. This arises from a principle of minimal entropy, that is conjugate of the maximum entropy principle in statistical mechanics. This explains why statistical criticality requires no parameter fine tuning in maximally informative samples.}, author = {Cubero, Ryan J and Jo, Junghyo and Marsili, Matteo and Roudi, Yasser and Song, Juyong}, issn = {1742-5468}, journal = {Journal of Statistical Mechanics: Theory and Experiment}, keywords = {optimization under uncertainty, source coding, large deviation}, number = {6}, publisher = {IOP Publishing}, title = {{Statistical criticality arises in most informative representations}}, doi = {10.1088/1742-5468/ab16c8}, volume = {2019}, year = {2019}, } @article{7150, abstract = {In this work, we use algebraic methods for studying distance computation and subgraph detection tasks in the congested clique model. Specifically, we adapt parallel matrix multiplication implementations to the congested clique, obtaining an O(n1−2/ω) round matrix multiplication algorithm, where ω<2.3728639 is the exponent of matrix multiplication. In conjunction with known techniques from centralised algorithmics, this gives significant improvements over previous best upper bounds in the congested clique model. The highlight results include: 1. triangle and 4-cycle counting in O(n0.158) rounds, improving upon the O(n1/3) algorithm of Dolev et al. [DISC 2012], 2. a (1+o(1))-approximation of all-pairs shortest paths in O(n0.158) rounds, improving upon the O~(n1/2)-round (2+o(1))-approximation algorithm given by Nanongkai [STOC 2014], and 3. computing the girth in O(n0.158) rounds, which is the first non-trivial solution in this model. In addition, we present a novel constant-round combinatorial algorithm for detecting 4-cycles.}, author = {Censor-Hillel, Keren and Kaski, Petteri and Korhonen, Janne and Lenzen, Christoph and Paz, Ami and Suomela, Jukka}, issn = {0178-2770}, journal = {Distributed Computing}, number = {6}, pages = {461--478}, publisher = {Springer Nature}, title = {{Algebraic methods in the congested clique}}, doi = {10.1007/s00446-016-0270-2}, volume = {32}, year = {2019}, } @book{7171, abstract = {Wissen Sie, was sich hinter künstlicher Intelligenz und maschinellem Lernen verbirgt? Dieses Sachbuch erklärt Ihnen leicht verständlich und ohne komplizierte Formeln die grundlegenden Methoden und Vorgehensweisen des maschinellen Lernens. Mathematisches Vorwissen ist dafür nicht nötig. Kurzweilig und informativ illustriert Lisa, die Protagonistin des Buches, diese anhand von Alltagssituationen. Ein Buch für alle, die in Diskussionen über Chancen und Risiken der aktuellen Entwicklung der künstlichen Intelligenz und des maschinellen Lernens mit Faktenwissen punkten möchten. Auch für Schülerinnen und Schüler geeignet!}, editor = {Kersting, Kristian and Lampert, Christoph and Rothkopf, Constantin}, isbn = {978-3-658-26762-9}, pages = {XIV, 245}, publisher = {Springer Nature}, title = {{Wie Maschinen Lernen: Künstliche Intelligenz Verständlich Erklärt}}, doi = {10.1007/978-3-658-26763-6}, year = {2019}, } @article{7275, abstract = {Aprotic alkali metal–oxygen batteries require reversible formation of metal superoxide or peroxide on cycling. Severe parasitic reactions cause poor rechargeability, efficiency, and cycle life and have been shown to be caused by singlet oxygen (1O2) that forms at all stages of cycling. However, its formation mechanism remains unclear. We show that disproportionation of superoxide, the product or intermediate on discharge and charge, to peroxide and oxygen is responsible for 1O2 formation. While the overall reaction is driven by the stability of peroxide and thus favored by stronger Lewis acidic cations such as Li+, the 1O2 fraction is enhanced by weak Lewis acids such as organic cations. Concurrently, the metal peroxide yield drops with increasing 1O2. The results explain a major parasitic pathway during cell cycling and the growing severity in K–, Na–, and Li–O2 cells based on the growing propensity for disproportionation. High capacities and rates with peroxides are now realized to require solution processes, which form peroxide or release O2via disproportionation. The results therefore establish the central dilemma that disproportionation is required for high capacity but also responsible for irreversible reactions. Highly reversible cell operation requires hence finding reaction routes that avoid disproportionation.}, author = {Mourad, Eléonore and Petit, Yann K. and Spezia, Riccardo and Samojlov, Aleksej and Summa, Francesco F. and Prehal, Christian and Leypold, Christian and Mahne, Nika and Slugovc, Christian and Fontaine, Olivier and Brutti, Sergio and Freunberger, Stefan Alexander}, issn = {1754-5692}, journal = {Energy & Environmental Science}, number = {8}, pages = {2559--2568}, publisher = {RSC}, title = {{Singlet oxygen from cation driven superoxide disproportionation and consequences for aprotic metal–O2 batteries}}, doi = {10.1039/c9ee01453e}, volume = {12}, year = {2019}, } @article{7280, abstract = {Non-aqueous lithium-oxygen batteries cycle by forming lithium peroxide during discharge and oxidizing it during recharge. The significant problem of oxidizing the solid insulating lithium peroxide can greatly be facilitated by incorporating redox mediators that shuttle electron-holes between the porous substrate and lithium peroxide. Redox mediator stability is thus key for energy efficiency, reversibility, and cycle life. However, the gradual deactivation of redox mediators during repeated cycling has not conclusively been explained. Here, we show that organic redox mediators are predominantly decomposed by singlet oxygen that forms during cycling. Their reaction with superoxide, previously assumed to mainly trigger their degradation, peroxide, and dioxygen, is orders of magnitude slower in comparison. The reduced form of the mediator is markedly more reactive towards singlet oxygen than the oxidized form, from which we derive reaction mechanisms supported by density functional theory calculations. Redox mediators must thus be designed for stability against singlet oxygen.}, author = {Kwak, Won-Jin and Kim, Hun and Petit, Yann K. and Leypold, Christian and Nguyen, Trung Thien and Mahne, Nika and Redfern, Paul and Curtiss, Larry A. and Jung, Hun-Gi and Borisov, Sergey M. and Freunberger, Stefan Alexander and Sun, Yang-Kook}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Deactivation of redox mediators in lithium-oxygen batteries by singlet oxygen}}, doi = {10.1038/s41467-019-09399-0}, volume = {10}, year = {2019}, } @article{7276, abstract = {Singlet oxygen (1O2) causes a major fraction of the parasitic chemistry during the cycling of non‐aqueous alkali metal‐O2 batteries and also contributes to interfacial reactivity of transition‐metal oxide intercalation compounds. We introduce DABCOnium, the mono alkylated form of 1,4‐diazabicyclo[2.2.2]octane (DABCO), as an efficient 1O2 quencher with an unusually high oxidative stability of ca. 4.2 V vs. Li/Li+. Previous quenchers are strongly Lewis basic amines with too low oxidative stability. DABCOnium is an ionic liquid, non‐volatile, highly soluble in the electrolyte, stable against superoxide and peroxide, and compatible with lithium metal. The electrochemical stability covers the required range for metal–O2 batteries and greatly reduces 1O2 related parasitic chemistry as demonstrated for the Li–O2 cell.}, author = {Petit, Yann K. and Leypold, Christian and Mahne, Nika and Mourad, Eléonore and Schafzahl, Lukas and Slugovc, Christian and Borisov, Sergey M. and Freunberger, Stefan Alexander}, issn = {1433-7851}, journal = {Angewandte Chemie International Edition}, number = {20}, pages = {6535--6539}, publisher = {Wiley}, title = {{DABCOnium: An efficient and high-voltage stable singlet oxygen quencher for metal-O2 cells}}, doi = {10.1002/anie.201901869}, volume = {58}, year = {2019}, } @article{7281, abstract = {Li–O2 batteries are plagued by side reactions that cause poor rechargeability and efficiency. These reactions were recently revealed to be predominantly caused by singlet oxygen, which can be neutralized by chemical traps or physical quenchers. However, traps are irreversibly consumed and thus only active for a limited time, and so far identified quenchers lack oxidative stability to be suitable for typically required recharge potentials. Thus, reducing the charge potential within the stability limit of the quencher and/or finding more stable quenchers is required. Here, we show that dimethylphenazine as a redox mediator decreases the charge potential well within the stability limit of the quencher 1,4-diazabicyclo[2.2.2]octane. The quencher can thus mitigate the parasitic reactions without being oxidatively decomposed. At the same time the quencher protects the redox mediator from singlet oxygen attack. The mutual conservation of the redox mediator and the quencher is rational for stable and effective Li–O2 batteries.}, author = {Kwak, Won-Jin and Freunberger, Stefan Alexander and Kim, Hun and Park, Jiwon and Nguyen, Trung Thien and Jung, Hun-Gi and Byon, Hye Ryung and Sun, Yang-Kook}, issn = {2155-5435}, journal = {ACS Catalysis}, number = {11}, pages = {9914--9922}, publisher = {ACS}, title = {{Mutual conservation of redox mediator and singlet oxygen quencher in Lithium–Oxygen batteries}}, doi = {10.1021/acscatal.9b01337}, volume = {9}, year = {2019}, } @article{7282, abstract = {Interphases that form on the anode surface of lithium-ion batteries are critical for performance and lifetime, but are poorly understood. Now, a decade-old misconception regarding a main component of the interphase has been revealed, which could potentially lead to improved devices.}, author = {Freunberger, Stefan Alexander}, issn = {1755-4330}, journal = {Nature Chemistry}, number = {9}, pages = {761--763}, publisher = {Springer Nature}, title = {{Interphase identity crisis}}, doi = {10.1038/s41557-019-0311-0}, volume = {11}, year = {2019}, } @article{7283, abstract = {Potassium–air batteries, which suffer from oxygen cathode and potassium metal anode degradation, can be cycled thousands of times when an organic anode replaces the metal.}, author = {Petit, Yann K. and Freunberger, Stefan Alexander}, issn = {1476-1122}, journal = {Nature Materials}, number = {4}, pages = {301--302}, publisher = {Springer Nature}, title = {{Thousands of cycles}}, doi = {10.1038/s41563-019-0313-8}, volume = {18}, year = {2019}, } @article{7284, abstract = {In this issue of Joule, Dongmin Im and coworkers from Samsung in South Korea describe a prototype lithium-O2 battery that reaches ∼700 Wh kg–1 and ∼600 Wh L–1 on the cell level. They cut all components to the minimum to reach this value. Difficulties filling the pores with discharge product and inhomogeneous cell utilization turn out to limit the achievable energy. Their work underlines the importance of reporting performance with respect to full cell weight and volume.}, author = {Prehal, Christian and Freunberger, Stefan Alexander}, issn = {2542-4351}, journal = {Joule}, number = {2}, pages = {321--323}, publisher = {Elsevier}, title = {{Li-O2 cell-scale energy densities}}, doi = {10.1016/j.joule.2019.01.020}, volume = {3}, year = {2019}, } @unpublished{7358, abstract = {Telencephalic organoids generated from human pluripotent stem cells (hPSCs) are emerging as an effective system to study the distinct features of the developing human brain and the underlying causes of many neurological disorders. While progress in organoid technology has been steadily advancing, many challenges remain including rampant batch-to-batch and cell line-to-cell line variability and irreproducibility. Here, we demonstrate that a major contributor to successful cortical organoid production is the manner in which hPSCs are maintained prior to differentiation. Optimal results were achieved using fibroblast-feeder-supported hPSCs compared to feeder-independent cells, related to differences in their transcriptomic states. Feeder-supported hPSCs display elevated activation of diverse TGFβ superfamily signaling pathways and increased expression of genes associated with naïve pluripotency. We further identify combinations of TGFβ-related growth factors that are necessary and together sufficient to impart broad telencephalic organoid competency to feeder-free hPSCs and enable reproducible formation of brain structures suitable for disease modeling.}, author = {Watanabe, Momoko and Haney, Jillian R. and Vishlaghi, Neda and Turcios, Felix and Buth, Jessie E. and Gu, Wen and Collier, Amanda J. and Miranda, Osvaldo and Chen, Di and Sabri, Shan and Clark, Amander T. and Plath, Kathrin and Christofk, Heather R. and Gandal, Michael J. and Novitch, Bennett G.}, booktitle = {bioRxiv}, pages = {75}, publisher = {Cold Spring Harbor Laboratory}, title = {{TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids}}, doi = {10.1101/2019.12.13.875773}, year = {2019}, } @inproceedings{7401, abstract = {The genus g(G) of a graph G is the minimum g such that G has an embedding on the orientable surface M_g of genus g. A drawing of a graph on a surface is independently even if every pair of nonadjacent edges in the drawing crosses an even number of times. The Z_2-genus of a graph G, denoted by g_0(G), is the minimum g such that G has an independently even drawing on M_g. By a result of Battle, Harary, Kodama and Youngs from 1962, the graph genus is additive over 2-connected blocks. In 2013, Schaefer and Stefankovic proved that the Z_2-genus of a graph is additive over 2-connected blocks as well, and asked whether this result can be extended to so-called 2-amalgamations, as an analogue of results by Decker, Glover, Huneke, and Stahl for the genus. We give the following partial answer. If G=G_1 cup G_2, G_1 and G_2 intersect in two vertices u and v, and G-u-v has k connected components (among which we count the edge uv if present), then |g_0(G)-(g_0(G_1)+g_0(G_2))|<=k+1. For complete bipartite graphs K_{m,n}, with n >= m >= 3, we prove that g_0(K_{m,n})/g(K_{m,n})=1-O(1/n). Similar results are proved also for the Euler Z_2-genus. We express the Z_2-genus of a graph using the minimum rank of partial symmetric matrices over Z_2; a problem that might be of independent interest. }, author = {Fulek, Radoslav and Kyncl, Jan}, booktitle = {35th International Symposium on Computational Geometry (SoCG 2019)}, isbn = {978-3-95977-104-7}, issn = {1868-8969}, location = {Portland, OR, United States}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Z_2-Genus of graphs and minimum rank of partial symmetric matrices}}, doi = {10.4230/LIPICS.SOCG.2019.39}, volume = {129}, year = {2019}, } @inbook{7453, abstract = {We illustrate the ingredients of the state-of-the-art of model-based approach for the formal design and verification of cyber-physical systems. To capture the interaction between a discrete controller and its continuously evolving environment, we use the formal models of timed and hybrid automata. We explain the steps of modeling and verification in the tools Uppaal and SpaceEx using a case study based on a dual-chamber implantable pacemaker monitoring a human heart. We show how to design a model as a composition of components, how to construct models at varying levels of detail, how to establish that one model is an abstraction of another, how to specify correctness requirements using temporal logic, and how to verify that a model satisfies a logical requirement.}, author = {Alur, Rajeev and Giacobbe, Mirco and Henzinger, Thomas A and Larsen, Kim G. and Mikučionis, Marius}, booktitle = {Computing and Software Science}, editor = {Steffen, Bernhard and Woeginger, Gerhard}, isbn = {9783319919072}, issn = {0302-9743}, pages = {452--477}, publisher = {Springer Nature}, title = {{Continuous-time models for system design and analysis}}, doi = {10.1007/978-3-319-91908-9_22}, volume = {10000}, year = {2019}, } @article{7459, abstract = {We report the fabrication of BaTiO3-Ni magnetoelectric nanocomposites comprising of BaTiO3 nanotubes surrounded by Ni matrix. BaTiO3 nanotubes obtained from the hydrothermal transformation of TiO2 have both inner and outer surfaces, which facilitates greater magnetoelectric coupling with the surrounding Ni matrix. The magnetoelectric coupling was studied by measuring the piezoelectric behavior in the presence of an in-plane direct magnetic field. A higher magnetoelectric voltage coefficient of 110 mV/cm·Oe was obtained, because of better coupling between Ni and BaTiO3 through the walls of the nanotubes. Such nanocomposite developed directly on Ti substrate may lead to efficient fabrication of magnetoelectric devices.}, author = {Vadla, Samba Siva and Costanzo, Tommaso and John, Subish and Caruntu, Gabriel and Roy, Somnath C.}, issn = {1359-6462}, journal = {Scripta Materialia}, pages = {33--36}, publisher = {Elsevier}, title = {{Local probing of magnetoelectric coupling in BaTiO3-Ni 1–3 composites}}, doi = {10.1016/j.scriptamat.2018.09.003}, volume = {159}, year = {2019}, } @article{7476, abstract = {The sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating1,2. Yet, the cellular bases for its origin, development and subsequent maintenance remain poorly understood. Here, we apply large-scale quantitative fate mapping to define the patterns of cell fate behaviour during SG development and maintenance. We show that the SG develops from a defined number of lineage-restricted progenitors that undergo a programme of independent and stochastic cell fate decisions. Following an expansion phase, equipotent progenitors transition into a phase of homeostatic turnover, which is correlated with changes in the mechanical properties of the stroma and spatial restrictions on gland size. Expression of the oncogene KrasG12D results in a release from these constraints and unbridled gland expansion. Quantitative clonal fate analysis reveals that, during this phase, the primary effect of the Kras oncogene is to drive a constant fate bias with little effect on cell division rates. These findings provide insight into the developmental programme of the SG, as well as the mechanisms that drive tumour progression and gland dysfunction.}, author = {Andersen, Marianne Stemann and Hannezo, Edouard B and Ulyanchenko, Svetlana and Estrach, Soline and Antoku, Yasuko and Pisano, Sabrina and Boonekamp, Kim E. and Sendrup, Sarah and Maimets, Martti and Pedersen, Marianne Terndrup and Johansen, Jens V. and Clement, Ditte L. and Feral, Chloe C. and Simons, Benjamin D. and Jensen, Kim B.}, issn = {1465-7392}, journal = {Nature Cell Biology}, number = {8}, pages = {924--932}, publisher = {Springer Nature}, title = {{Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states}}, doi = {10.1038/s41556-019-0362-x}, volume = {21}, year = {2019}, } @article{7548, abstract = {Although the aggregation of the amyloid-β peptide (Aβ) into amyloid fibrils is a well-established hallmark of Alzheimer’s disease, the complex mechanisms linking this process to neurodegeneration are still incompletely understood. The nematode worm C. elegans is a valuable model organism through which to study these mechanisms because of its simple nervous system and its relatively short lifespan. Standard Aβ-based C. elegans models of Alzheimer’s disease are designed to study the toxic effects of the overexpression of Aβ in the muscle or nervous systems. However, the wide variety of effects associated with the tissue-level overexpression of Aβ makes it difficult to single out and study specific cellular mechanisms related to the onset of Alzheimer’s disease. Here, to better understand how to investigate the early events affecting neuronal signalling, we created a C. elegans model expressing Aβ42, the 42-residue form of Aβ, from a single-copy gene insertion in just one pair of glutamatergic sensory neurons, the BAG neurons. In behavioural assays, we found that the Aβ42-expressing animals displayed a subtle modulation of the response to CO2, compared to controls. Ca2+ imaging revealed that the BAG neurons in young Aβ42-expressing nematodes were activated more strongly than in control animals, and that neuronal activation remained intact until old age. Taken together, our results suggest that Aβ42-expression in this very subtle model of AD is sufficient to modulate the behavioural response but not strong enough to generate significant neurotoxicity, suggesting that slightly more aggressive perturbations will enable effectively studies of the links between the modulation of a physiological response and its associated neurotoxicity.}, author = {Sinnige, Tessa and Ciryam, Prashanth and Casford, Samuel and Dobson, Christopher M. and de Bono, Mario and Vendruscolo, Michele}, issn = {1932-6203}, journal = {PLOS ONE}, number = {5}, publisher = {Public Library of Science}, title = {{Expression of the amyloid-β peptide in a single pair of C. elegans sensory neurons modulates the associated behavioural response}}, doi = {10.1371/journal.pone.0217746}, volume = {14}, year = {2019}, } @article{7547, abstract = {The BH3-only family of proteins is key for initiating apoptosis in a variety of contexts, and may also contribute to non-apoptotic cellular processes. Historically, the nematode Caenorhabditis elegans has provided a powerful system for studying and identifying conserved regulators of BH3-only proteins. In C. elegans, the BH3-only protein egl-1 is expressed during development to cell-autonomously trigger most developmental cell deaths. Here we provide evidence that egl-1 is also transcribed after development in the sensory neuron pair URX without inducing apoptosis. We used genetic screening and epistasis analysis to determine that its transcription is regulated in URX by neuronal activity and/or in parallel by orthologs of Protein Kinase G and the Salt-Inducible Kinase family. Because several BH3-only family proteins are also expressed in the adult nervous system of mammals, we suggest that studying egl-1 expression in URX may shed light on mechanisms that regulate conserved family members in higher organisms.}, author = {Cohn, Jesse and Dwivedi, Vivek and Valperga, Giulio and Zarate, Nicole and de Bono, Mario and Horvitz, H. Robert and Pierce, Jonathan T.}, issn = {2160-1836}, journal = {G3: Genes, Genomes, Genetics}, number = {11}, pages = {3703--3714}, publisher = {Genetics Society of America}, title = {{Activity-dependent regulation of the proapoptotic BH3-only gene egl-1 in a living neuron pair in Caenorhabditis elegans}}, doi = {10.1534/g3.119.400654}, volume = {9}, year = {2019}, } @article{7550, abstract = {We consider an optimal control problem for an abstract nonlinear dissipative evolution equation. The differential constraint is penalized by augmenting the target functional by a nonnegative global-in-time functional which is null-minimized in the evolution equation is satisfied. Different variational settings are presented, leading to the convergence of the penalization method for gradient flows, noncyclic and semimonotone flows, doubly nonlinear evolutions, and GENERIC systems. }, author = {Portinale, Lorenzo and Stefanelli, Ulisse}, issn = {1343-4373}, journal = {Advances in Mathematical Sciences and Applications}, number = {2}, pages = {425--447}, publisher = {Gakko Tosho}, title = {{Penalization via global functionals of optimal-control problems for dissipative evolution}}, volume = {28}, year = {2019}, } @unpublished{7552, abstract = {There is increasing evidence that protein binding to specific sites along DNA can activate the reading out of genetic information without coming into direct physical contact with the gene. There also is evidence that these distant but interacting sites are embedded in a liquid droplet of proteins which condenses out of the surrounding solution. We argue that droplet-mediated interactions can account for crucial features of gene regulation only if the droplet is poised at a non-generic point in its phase diagram. We explore a minimal model that embodies this idea, show that this model has a natural mechanism for self-tuning, and suggest direct experimental tests. }, author = {Bialek, William and Gregor, Thomas and Tkačik, Gašper}, booktitle = {arXiv:1912.08579}, pages = {5}, publisher = {ArXiv}, title = {{Action at a distance in transcriptional regulation}}, year = {2019}, } @inproceedings{7576, abstract = {We present the results of a friendly competition for formal verification of continuous and hybrid systems with nonlinear continuous dynamics. The friendly competition took place as part of the workshop Applied Verification for Continuous and Hybrid Systems (ARCH) in 2019. In this year, 6 tools Ariadne, CORA, DynIbex, Flow*, Isabelle/HOL, and JuliaReach (in alphabetic order) participated. They are applied to solve reachability analysis problems on four benchmark problems, one of them with hybrid dynamics. We do not rank the tools based on the results, but show the current status and discover the potential advantages of different tools.}, author = {Immler, Fabian and Althoff, Matthias and Benet, Luis and Chapoutot, Alexandre and Chen, Xin and Forets, Marcelo and Geretti, Luca and Kochdumper, Niklas and Sanders, David P. and Schilling, Christian}, booktitle = {EPiC Series in Computing}, issn = {23987340}, location = {Montreal, Canada}, pages = {41--61}, publisher = {EasyChair Publications}, title = {{ARCH-COMP19 Category Report: Continuous and hybrid systems with nonlinear dynamics}}, doi = {10.29007/m75b}, volume = {61}, year = {2019}, } @unpublished{7627, abstract = {Electrodepositing insulating and insoluble Li2O2 is the key process during discharge of aprotic Li-O2 batteries and determines rate, capacity, and reversibility. Current understanding states that the partition between surface adsorbed and solvated LiO2 governs whether Li2O2 grows as surface film, leading to low capacity even at low rates, or in solution, leading to particles and high capacities. Here we show that Li2O2 forms to the widest extent as particles via solution mediated LiO2 disproportionation. We describe a unified Li2O2 growth model that conclusively explains capacity limitations across the whole range of electrolytes. Deciding for particle morphology, achievable rate and capacities are species mobilities, electrode specific surface area (determining true areal rate) and the concentration distribution of associated LiO2 in solution. Provided that species mobilities and surface are high, high, capacities are possible even with low-donor-number electrolytes, previously considered prototypical for low capacity via surface growth. The tools for these insights are microscopy, hydrodynamic voltammetry, a numerical reaction model, and in situ small/wide angle X-ray scattering (SAXS/WAXS). Combined with sophisticated data analysis, SAXS allows retrieving rich quantitative information from complex multi-phase systems. On a wider perspective, this SAXS method is a powerful in situ metrology with atomic to sub-micron resolution to study mechanisms in complex electrochemical systems and beyond. }, author = {Prehal, Christian and Samojlov, Aleksej and Nachtnebel, Manfred and Kriechbaum, Manfred and Amenitsch, Heinz and Freunberger, Stefan Alexander}, pages = {50}, publisher = {ChemRxiv}, title = {{A revised O2 reduction model in Li-O2 batteries as revealed by in situ small angle X-ray scattering}}, year = {2019}, } @article{7710, abstract = {The number of human genomes being genotyped or sequenced increases exponentially and efficient haplotype estimation methods able to handle this amount of data are now required. Here we present a method, SHAPEIT4, which substantially improves upon other methods to process large genotype and high coverage sequencing datasets. It notably exhibits sub-linear running times with sample size, provides highly accurate haplotypes and allows integrating external phasing information such as large reference panels of haplotypes, collections of pre-phased variants and long sequencing reads. We provide SHAPEIT4 in an open source format and demonstrate its performance in terms of accuracy and running times on two gold standard datasets: the UK Biobank data and the Genome In A Bottle.}, author = {Delaneau, Olivier and Zagury, Jean-François and Robinson, Matthew Richard and Marchini, Jonathan L. and Dermitzakis, Emmanouil T.}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Accurate, scalable and integrative haplotype estimation}}, doi = {10.1038/s41467-019-13225-y}, volume = {10}, year = {2019}, } @article{7711, abstract = {The nature and extent of mitochondrial DNA variation in a population and how it affects traits is poorly understood. Here we resequence the mitochondrial genomes of 169 Drosophila Genetic Reference Panel lines, identifying 231 variants that stratify along 12 mitochondrial haplotypes. We identify 1,845 cases of mitonuclear allelic imbalances, thus implying that mitochondrial haplotypes are reflected in the nuclear genome. However, no major fitness effects are associated with mitonuclear imbalance, suggesting that such imbalances reflect population structure at the mitochondrial level rather than genomic incompatibilities. Although mitochondrial haplotypes have no direct impact on mitochondrial respiration, some haplotypes are associated with stress- and metabolism-related phenotypes, including food intake in males. Finally, through reciprocal swapping of mitochondrial genomes, we demonstrate that a mitochondrial haplotype associated with high food intake can rescue a low food intake phenotype. Together, our findings provide new insight into population structure at the mitochondrial level and point to the importance of incorporating mitochondrial haplotypes in genotype–phenotype relationship studies.}, author = {Bevers, Roel P. J. and Litovchenko, Maria and Kapopoulou, Adamandia and Braman, Virginie S. and Robinson, Matthew Richard and Auwerx, Johan and Hollis, Brian and Deplancke, Bart}, issn = {2522-5812}, journal = {Nature Metabolism}, number = {12}, pages = {1226--1242}, publisher = {Springer Nature}, title = {{Mitochondrial haplotypes affect metabolic phenotypes in the Drosophila Genetic Reference Panel}}, doi = {10.1038/s42255-019-0147-3}, volume = {1}, year = {2019}, } @unpublished{7782, abstract = {As genome-wide association studies (GWAS) increased in size, numerous gene-environment interactions (GxE) have been discovered, many of which however explore only one environment at a time and may suffer from statistical artefacts leading to biased interaction estimates. Here we propose a maximum likelihood method to estimate the contribution of GxE to complex traits taking into account all interacting environmental variables at the same time, without the need to measure any. This is possible because GxE induces fluctuations in the conditional trait variance, the extent of which depends on the strength of GxE. The approach can be applied to continuous outcomes and for single SNPs or genetic risk scores (GRS). Extensive simulations demonstrated that our method yields unbiased interaction estimates and excellent confidence interval coverage. We also offer a strategy to distinguish specific GxE from general heteroscedasticity (scale effects). Applying our method to 32 complex traits in the UK Biobank reveals that for body mass index (BMI) the GRSxE explains an additional 1.9% variance on top of the 5.2% GRS contribution. However, this interaction is not specific to the GRS and holds for any variable similarly correlated with BMI. On the contrary, the GRSxE interaction effect for leg impedance Embedded Image is significantly (P < 10−56) larger than it would be expected for a similarly correlated variable Embedded Image. We showed that our method could robustly detect the global contribution of GxE to complex traits, which turned out to be substantial for certain obesity measures.}, author = {Sulc, Jonathan and Mounier, Ninon and Günther, Felix and Winkler, Thomas and Wood, Andrew R. and Frayling, Timothy M. and Heid, Iris M. and Robinson, Matthew Richard and Kutalik, Zoltán}, booktitle = {bioRxiv}, pages = {20}, publisher = {Cold Spring Harbor Laboratory}, title = {{Maximum likelihood method quantifies the overall contribution of gene-environment interaction to continuous traits: An application to complex traits in the UK Biobank}}, year = {2019}, } @article{8013, author = {Currin, Christopher B. and Khoza, Phumlani N. and Antrobus, Alexander D. and Latham, Peter E. and Vogels, Tim P and Raimondo, Joseph V.}, issn = {1553-7358}, journal = {PLOS Computational Biology}, number = {7}, publisher = {Public Library of Science}, title = {{Think: Theory for Africa}}, doi = {10.1371/journal.pcbi.1007049}, volume = {15}, year = {2019}, } @article{8014, abstract = {Working memory, the ability to keep recently accessed information available for immediate manipulation, has been proposed to rely on two mechanisms that appear difficult to reconcile: self-sustained neural firing, or the opposite—activity-silent synaptic traces. Here we review and contrast models of these two mechanisms, and then show that both phenomena can co-exist within a unified system in which neurons hold information in both activity and synapses. Rapid plasticity in flexibly-coding neurons allows features to be bound together into objects, with an important emergent property being the focus of attention. One memory item is held by persistent activity in an attended or “focused” state, and is thus remembered better than other items. Other, previously attended items can remain in memory but in the background, encoded in activity-silent synaptic traces. This dual functional architecture provides a unified common mechanism accounting for a diversity of perplexing attention and memory effects that have been hitherto difficult to explain in a single theoretical framework.}, author = {Manohar, Sanjay G. and Zokaei, Nahid and Fallon, Sean J. and Vogels, Tim P and Husain, Masud}, issn = {0149-7634}, journal = {Neuroscience and Biobehavioral Reviews}, pages = {1--12}, publisher = {Elsevier }, title = {{Neural mechanisms of attending to items in working memory}}, doi = {10.1016/j.neubiorev.2019.03.017}, volume = {101}, year = {2019}, } @inproceedings{8175, abstract = {We study edge asymptotics of poissonized Plancherel-type measures on skew Young diagrams (integer partitions). These measures can be seen as generalizations of those studied by Baik--Deift--Johansson and Baik--Rains in resolving Ulam's problem on longest increasing subsequences of random permutations and the last passage percolation (corner growth) discrete versions thereof. Moreover they interpolate between said measures and the uniform measure on partitions. In the new KPZ-like 1/3 exponent edge scaling limit with logarithmic corrections, we find new probability distributions generalizing the classical Tracy--Widom GUE, GOE and GSE distributions from the theory of random matrices.}, author = {Betea, Dan and Bouttier, Jérémie and Nejjar, Peter and Vuletíc, Mirjana}, booktitle = {Proceedings on the 31st International Conference on Formal Power Series and Algebraic Combinatorics}, location = {Ljubljana, Slovenia}, publisher = {Formal Power Series and Algebraic Combinatorics}, title = {{New edge asymptotics of skew Young diagrams via free boundaries}}, year = {2019}, } @article{8228, abstract = {Background: Atopics have a lower risk for malignancies, and IgE targeted to tumors is superior to IgG in fighting cancer. Whether IgE-mediated innate or adaptive immune surveillance can confer protection against tumors remains unclear. Objective: We aimed to investigate the effects of active and passive immunotherapy to the tumor-associated antigen HER-2 in three murine models differing in Epsilon-B-cell-receptor expression affecting the levels of expressed IgE. Methods: We compared the levels of several serum specific anti-HER-2 antibodies (IgE, IgG1, IgG2a, IgG2b, IgA) and the survival rates in low-IgE ΔM1M2 mice lacking the transmembrane/cytoplasmic domain of Epsilon-B-cell-receptors expressing reduced IgE levels, high-IgE KN1 mice expressing chimeric Epsilon-Gamma1-B-cell receptors with 4-6-fold elevated serum IgE levels, and wild type (WT) BALB/c. Prior engrafting mice with D2F2/E2 mammary tumors overexpressing HER-2, mice were vaccinated with HER-2 or vehicle control PBS using the Th2-adjuvant Al(OH)3 (active immunotherapy), or treated with the murine anti-HER-2 IgG1 antibody 4D5 (passive immunotherapy). Results: Overall, among the three strains of mice, HER-2 vaccination induced significantly higher levels of HER-2 specific IgE and IgG1 in high-IgE KN1, while low-IgE ΔM1M2 mice had higher IgG2a levels. HER-2 vaccination and passive immunotherapy prolonged the survival in tumor-grafted WT and low-IgE ΔM1M2 strains compared with treatment controls; active vaccination provided the highest benefit. Notably, untreated high-IgE KN1 mice displayed the longest survival of all strains, which could not be further extended by active or passive immunotherapy. Conclusion: Active and passive immunotherapies prolong survival in wild type and low-IgE ΔM1M2 mice engrafted with mammary tumors. High-IgE KN1 mice have an innate survival benefit following tumor challenge.}, author = {Singer, Josef and Achatz-Straussberger, Gertrude and Bentley-Lukschal, Anna and Fazekas-Singer, Judit and Achatz, Gernot and Karagiannis, Sophia N. and Jensen-Jarolim, Erika}, issn = {1939-4551}, journal = {World Allergy Organization Journal}, number = {7}, publisher = {Elsevier}, title = {{AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice}}, doi = {10.1016/j.waojou.2019.100044}, volume = {12}, year = {2019}, } @article{8229, abstract = {Food proteins may get nitrated by various exogenous or endogenous mechanisms. As individuals might get recurrently exposed to nitrated proteins via daily diet, we aimed to investigate the effect of repeatedly ingested nitrated food proteins on the subsequent immune response in non-allergic and allergic mice using the milk allergen beta-lactoglobulin (BLG) as model food protein in a mouse model. Evaluating the presence of nitrated proteins in food, we could detect 3-nitrotyrosine (3-NT) in extracts of different foods and in stomach content extracts of non-allergic mice under physiological conditions. Chemically nitrated BLG (BLGn) exhibited enhanced susceptibility to degradation in simulated gastric fluid experiments compared to untreated BLG (BLGu). Gavage of BLGn to non-allergic animals increased interferon-γ and interleukin-10 release of stimulated spleen cells and led to the formation of BLG-specific serum IgA. Allergic mice receiving three oral gavages of BLGn had higher levels of mouse mast cell protease-1 (mMCP-1) compared to allergic mice receiving BLGu. Regardless of the preceding immune status, non-allergic or allergic, repeatedly ingested nitrated food proteins seem to considerably influence the subsequent immune response.}, author = {Ondracek, Anna S. and Heiden, Denise and Oostingh, Gertie J. and Fuerst, Elisabeth and Fazekas-Singer, Judit and Bergmayr, Cornelia and Rohrhofer, Johanna and Jensen-Jarolim, Erika and Duschl, Albert and Untersmayr, Eva}, issn = {2072-6643}, journal = {Nutrients}, number = {10}, publisher = {MDPI}, title = {{Immune effects of the nitrated food allergen beta-lactoglobulin in an experimental food allergy model}}, doi = {10.3390/nu11102463}, volume = {11}, year = {2019}, } @article{8227, author = {Ilieva, Kristina M. and Fazekas-Singer, Judit and Bax, Heather J. and Crescioli, Silvia and Montero‐Morales, Laura and Mele, Silvia and Sow, Heng Sheng and Stavraka, Chara and Josephs, Debra H. and Spicer, James F. and Steinkellner, Herta and Jensen‐Jarolim, Erika and Tutt, Andrew N. J. and Karagiannis, Sophia N.}, issn = {0105-4538}, journal = {Allergy}, number = {10}, pages = {1985--1989}, publisher = {Wiley}, title = {{AllergoOncology: Expression platform development and functional profiling of an anti‐HER2 IgE antibody}}, doi = {10.1111/all.13818}, volume = {74}, year = {2019}, } @article{8263, abstract = {Background: The genus Streptococcus comprises pathogens that strongly influence the health of humans and animals. Genome sequencing of multiple Streptococcus strains demonstrated high variability in gene content and order even in closely related strains of the same species and created a newly emerged object for genomic analysis, the pan-genome. Here we analysed the genome evolution of 25 strains of Streptococcus suis, 50 strains of Streptococcus pyogenes and 28 strains of Streptococcus pneumoniae. Results: Fractions of the pan-genome, unique, periphery, and universal genes differ in size, functional composition, the level of nucleotide substitutions, and predisposition to horizontal gene transfer and genomic rearrangements. The density of substitutions in intergenic regions appears to be correlated with selection acting on adjacent genes, implying that more conserved genes tend to have more conserved regulatory regions. The total pan-genome of the genus is open, but only due to strain-specific genes, whereas other pan-genome fractions reach saturation. We have identified the set of genes with phylogenies inconsistent with species and non-conserved location in the chromosome; these genes are rare in at least one species and have likely experienced recent horizontal transfer between species. The strain-specific fraction is enriched with mobile elements and hypothetical proteins, but also contains a number of candidate virulence-related genes, so it may have a strong impact on adaptability and pathogenicity. Mapping the rearrangements to the phylogenetic tree revealed large parallel inversions in all species. A parallel inversion of length 15 kB with breakpoints formed by genes encoding surface antigen proteins PhtD and PhtB in S. pneumoniae leads to replacement of gene fragments that likely indicates the action of an antigen variation mechanism. Conclusions: Members of genus Streptococcus have a highly dynamic, open pan-genome, that potentially confers them with the ability to adapt to changing environmental conditions, i.e. antibiotic resistance or transmission between different hosts. Hence, integrated analysis of all aspects of genome evolution is important for the identification of potential pathogens and design of drugs and vaccines.}, author = {Shelyakin, Pavel V. and Bochkareva, Olga and Karan, Anna A. and Gelfand, Mikhail S.}, issn = {1471-2148}, journal = {BMC Evolutionary Biology}, publisher = {Springer Nature}, title = {{Micro-evolution of three Streptococcus species: Selection, antigenic variation, and horizontal gene inflow}}, doi = {10.1186/s12862-019-1403-6}, volume = {19}, year = {2019}, } @inproceedings{8296, abstract = {While showing great promise, smart contracts are difficult to program correctly, as they need a deep understanding of cryptography and distributed algorithms, and offer limited functionality, as they have to be deterministic and cannot operate on secret data. In this paper we present Protean, a general-purpose decentralized computing platform that addresses these limitations by moving from a monolithic execution model, where all participating nodes store all the state and execute every computation, to a modular execution-model. Protean employs secure specialized modules, called functional units, for building decentralized applications that are currently insecure or impossible to implement with smart contracts. Each functional unit is a distributed system that provides a special-purpose functionality by exposing atomic transactions to the smart-contract developer. Combining these transactions into arbitrarily-defined workflows, developers can build a larger class of decentralized applications, such as provably-secure and fair lotteries or e-voting.}, author = {Alp, Enis Ceyhun and Kokoris Kogias, Eleftherios and Fragkouli, Georgia and Ford, Bryan}, booktitle = {Proceedings of the Workshop on Hot Topics in Operating Systems}, isbn = {9781450367271}, location = {Bertinoro, Italy}, pages = {105--112}, publisher = {ACM}, title = {{Rethinking general-purpose decentralized computing}}, doi = {10.1145/3317550.3321448}, year = {2019}, }