TY - CONF AB - Various kinds of data are routinely represented as discrete probability distributions. Examples include text documents summarized by histograms of word occurrences and images represented as histograms of oriented gradients. Viewing a discrete probability distribution as a point in the standard simplex of the appropriate dimension, we can understand collections of such objects in geometric and topological terms. Importantly, instead of using the standard Euclidean distance, we look into dissimilarity measures with information-theoretic justification, and we develop the theory needed for applying topological data analysis in this setting. In doing so, we emphasize constructions that enable the usage of existing computational topology software in this context. AU - Edelsbrunner, Herbert AU - Virk, Ziga AU - Wagner, Hubert ID - 6648 SN - 9783959771047 T2 - 35th International Symposium on Computational Geometry TI - Topological data analysis in information space VL - 129 ER - TY - JOUR AB - Chemical labeling of proteins with synthetic molecular probes offers the possibility to probe the functions of proteins of interest in living cells. However, the methods for covalently labeling targeted proteins using complementary peptide tag-probe pairs are still limited, irrespective of the versatility of such pairs in biological research. Herein, we report the new CysHis tag-Ni(II) probe pair for the specific covalent labeling of proteins. A broad-range evaluation of the reactivity profiles of the probe and the CysHis peptide tag afforded a tag-probe pair with an optimized and high labeling selectivity and reactivity. In particular, the labeling specificity of this pair was notably improved compared to the previously reported one. This pair was successfully utilized for the fluorescence imaging of membrane proteins on the surfaces of living cells, demonstrating its potential utility in biological research. AU - Zenmyo, Naoki AU - Tokumaru, Hiroki AU - Uchinomiya, Shohei AU - Fuchida, Hirokazu AU - Tabata, Shigekazu AU - Hamachi, Itaru AU - Shigemoto, Ryuichi AU - Ojida, Akio ID - 6659 IS - 5 JF - Bulletin of the Chemical Society of Japan SN - 00092673 TI - Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins VL - 92 ER - TY - JOUR AB - In phase retrieval, we want to recover an unknown signal đ‘„âˆˆâ„‚đ‘‘ from n quadratic measurements of the form 𝑩𝑖=|⟹𝑎𝑖,đ‘„âŸ©|2+đ‘€đ‘–, where 𝑎𝑖∈ℂ𝑑 are known sensing vectors and đ‘€đ‘– is measurement noise. We ask the following weak recovery question: What is the minimum number of measurements n needed to produce an estimator đ‘„^(𝑩) that is positively correlated with the signal đ‘„? We consider the case of Gaussian vectors 𝑎𝑎𝑖. We prove that—in the high-dimensional limit—a sharp phase transition takes place, and we locate the threshold in the regime of vanishingly small noise. For đ‘›â‰€đ‘‘âˆ’đ‘œ(𝑑), no estimator can do significantly better than random and achieve a strictly positive correlation. For đ‘›â‰„đ‘‘+𝑜(𝑑), a simple spectral estimator achieves a positive correlation. Surprisingly, numerical simulations with the same spectral estimator demonstrate promising performance with realistic sensing matrices. Spectral methods are used to initialize non-convex optimization algorithms in phase retrieval, and our approach can boost the performance in this setting as well. Our impossibility result is based on classical information-theoretic arguments. The spectral algorithm computes the leading eigenvector of a weighted empirical covariance matrix. We obtain a sharp characterization of the spectral properties of this random matrix using tools from free probability and generalizing a recent result by Lu and Li. Both the upper bound and lower bound generalize beyond phase retrieval to measurements 𝑩𝑖 produced according to a generalized linear model. As a by-product of our analysis, we compare the threshold of the proposed spectral method with that of a message passing algorithm. AU - Mondelli, Marco AU - Montanari, Andrea ID - 6662 IS - 3 JF - Foundations of Computational Mathematics TI - Fundamental limits of weak recovery with applications to phase retrieval VL - 19 ER - TY - JOUR AB - The construction of anisotropic triangulations is desirable for various applications, such as the numerical solving of partial differential equations and the representation of surfaces in graphics. To solve this notoriously difficult problem in a practical way, we introduce the discrete Riemannian Voronoi diagram, a discrete structure that approximates the Riemannian Voronoi diagram. This structure has been implemented and was shown to lead to good triangulations in $\mathbb{R}^2$ and on surfaces embedded in $\mathbb{R}^3$ as detailed in our experimental companion paper. In this paper, we study theoretical aspects of our structure. Given a finite set of points $\mathcal{P}$ in a domain $\Omega$ equipped with a Riemannian metric, we compare the discrete Riemannian Voronoi diagram of $\mathcal{P}$ to its Riemannian Voronoi diagram. Both diagrams have dual structures called the discrete Riemannian Delaunay and the Riemannian Delaunay complex. We provide conditions that guarantee that these dual structures are identical. It then follows from previous results that the discrete Riemannian Delaunay complex can be embedded in $\Omega$ under sufficient conditions, leading to an anisotropic triangulation with curved simplices. Furthermore, we show that, under similar conditions, the simplices of this triangulation can be straightened. AU - Boissonnat, Jean-Daniel AU - Rouxel-LabbĂ©, Mael AU - Wintraecken, Mathijs ID - 6672 IS - 3 JF - SIAM Journal on Computing SN - 0097-5397 TI - Anisotropic triangulations via discrete Riemannian Voronoi diagrams VL - 48 ER - TY - CONF AB - A Valued Constraint Satisfaction Problem (VCSP) provides a common framework that can express a wide range of discrete optimization problems. A VCSP instance is given by a finite set of variables, a finite domain of labels, and an objective function to be minimized. This function is represented as a sum of terms where each term depends on a subset of the variables. To obtain different classes of optimization problems, one can restrict all terms to come from a fixed set Γ of cost functions, called a language. Recent breakthrough results have established a complete complexity classification of such classes with respect to language Γ: if all cost functions in Γ satisfy a certain algebraic condition then all Γ-instances can be solved in polynomial time, otherwise the problem is NP-hard. Unfortunately, testing this condition for a given language Γ is known to be NP-hard. We thus study exponential algorithms for this meta-problem. We show that the tractability condition of a finite-valued language Γ can be tested in O(3‟√3|D|⋅poly(size(Γ))) time, where D is the domain of Γ and poly(⋅) is some fixed polynomial. We also obtain a matching lower bound under the Strong Exponential Time Hypothesis (SETH). More precisely, we prove that for any constant ÎŽ<1 there is no O(3‟√3ÎŽ|D|) algorithm, assuming that SETH holds. AU - Kolmogorov, Vladimir ID - 6725 SN - 1868-8969 T2 - 46th International Colloquium on Automata, Languages and Programming TI - Testing the complexity of a valued CSP language VL - 132 ER - TY - CHAP AB - Randomness is an essential part of any secure cryptosystem, but many constructions rely on distributions that are not uniform. This is particularly true for lattice based cryptosystems, which more often than not make use of discrete Gaussian distributions over the integers. For practical purposes it is crucial to evaluate the impact that approximation errors have on the security of a scheme to provide the best possible trade-off between security and performance. Recent years have seen surprising results allowing to use relatively low precision while maintaining high levels of security. A key insight in these results is that sampling a distribution with low relative error can provide very strong security guarantees. Since floating point numbers provide guarantees on the relative approximation error, they seem a suitable tool in this setting, but it is not obvious which sampling algorithms can actually profit from them. While previous works have shown that inversion sampling can be adapted to provide a low relative error (Pöppelmann et al., CHES 2014; Prest, ASIACRYPT 2017), other works have called into question if this is possible for other sampling techniques (Zheng et al., Eprint report 2018/309). In this work, we consider all sampling algorithms that are popular in the cryptographic setting and analyze the relationship of floating point precision and the resulting relative error. We show that all of the algorithms either natively achieve a low relative error or can be adapted to do so. AU - Walter, Michael ED - Buchmann, J ED - Nitaj, A ED - Rachidi, T ID - 6726 SN - 0302-9743 T2 - Progress in Cryptology – AFRICACRYPT 2019 TI - Sampling the integers with low relative error VL - 11627 ER - TY - JOUR AB - Consider the problem of constructing a polar code of block length N for a given transmission channel W. Previous approaches require one to compute the reliability of the N synthetic channels and then use only those that are sufficiently reliable. However, we know from two independent works by SchĂŒrch and by Bardet et al. that the synthetic channels are partially ordered with respect to degradation. Hence, it is natural to ask whether the partial order can be exploited to reduce the computational burden of the construction problem. We show that, if we take advantage of the partial order, we can construct a polar code by computing the reliability of roughly a fraction 1/ log 3/2 N of the synthetic channels. In particular, we prove that N/ log 3/2 N is a lower bound on the number of synthetic channels to be considered and such a bound is tight up to a multiplicative factor log log N. This set of roughly N/ log 3/2 N synthetic channels is universal, in the sense that it allows one to construct polar codes for any W, and it can be identified by solving a maximum matching problem on a bipartite graph. Our proof technique consists of reducing the construction problem to the problem of computing the maximum cardinality of an antichain for a suitable partially ordered set. As such, this method is general, and it can be used to further improve the complexity of the construction problem, in case a refined partial order on the synthetic channels of polar codes is discovered. AU - Mondelli, Marco AU - Hassani, Hamed AU - Urbanke, Rudiger ID - 6663 IS - 5 JF - IEEE TI - Construction of polar codes with sublinear complexity VL - 65 ER - TY - CONF AB - 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 đ”Œ(y), when d3/2â‰Șrâ‰Șd2. 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. AU - Mondelli, Marco AU - Montanari, Andrea ID - 6747 T2 - Proceedings of the 22nd International Conference on Artificial Intelligence and Statistics TI - On the connection between learning two-layers neural networks and tensor decomposition VL - 89 ER - TY - JOUR AB - 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. AU - Hashemi, Seyyed Ali AU - Condo, Carlo AU - Mondelli, Marco AU - Gross, Warren J ID - 6750 IS - 22 JF - IEEE Transactions on Signal Processing SN - 1053587X TI - Rate-flexible fast polar decoders VL - 67 ER - TY - JOUR AB - 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. AU - JelĂ­nek, VĂ­t AU - Töpfer, Martin ID - 6759 IS - 3 JF - Electronic Journal of Combinatorics TI - On grounded L-graphs and their relatives VL - 26 ER - TY - CONF AB - 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. AU - Avni, Guy AU - Henzinger, Thomas A AU - Ibsen-Jensen, Rasmus AU - Novotny, Petr ID - 6822 SN - 0302-9743 T2 - Proceedings of the 13th International Conference of Reachability Problems TI - Bidding games on Markov decision processes VL - 11674 ER - TY - CONF AB - 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. AU - Chatterjee, Krishnendu AU - DvorĂĄk, Wolfgang AU - Henzinger, Monika H AU - Svozil, Alexander ID - 6887 T2 - Leibniz International Proceedings in Informatics TI - Near-linear time algorithms for Streett objectives in graphs and MDPs VL - 140 ER - TY - CONF AB - 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. AU - Lechner, Mathias AU - Hasani, Ramin AU - Zimmer, Manuel AU - Henzinger, Thomas A AU - Grosu, Radu ID - 6888 SN - 9781538660270 T2 - Proceedings - IEEE International Conference on Robotics and Automation TI - Designing worm-inspired neural networks for interpretable robotic control VL - 2019-May ER - TY - CONF AB - 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. AU - Aghajohari, Milad AU - Avni, Guy AU - Henzinger, Thomas A ID - 6886 TI - Determinacy in discrete-bidding infinite-duration games VL - 140 ER - TY - CONF AB - 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. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Otop, Jan ID - 6885 TI - Long-run average behavior of vector addition systems with states VL - 140 ER - TY - CONF AB - 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. AU - Chatterjee, Krishnendu AU - Piterman, Nir ID - 6889 TI - Combinations of Qualitative Winning for Stochastic Parity Games VL - 140 ER - TY - CONF AB - 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. AU - Nowak, Thomas AU - Rybicki, Joel ID - 6931 KW - consensus KW - approximate agreement KW - Byzantine faults KW - chordal graphs KW - lattice agreement T2 - 33rd International Symposium on Distributed Computing TI - Byzantine approximate agreement on graphs VL - 146 ER - TY - CONF AB - 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. AU - Hasani, Ramin AU - Amini, Alexander AU - Lechner, Mathias AU - Naser, Felix AU - Grosu, Radu AU - Rus, Daniela ID - 6985 SN - 9781728119854 T2 - Proceedings of the International Joint Conference on Neural Networks TI - Response characterization for auditing cell dynamics in long short-term memory networks ER - TY - JOUR AB - 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. AU - Mondelli, Marco AU - Hassani, S. Hamed AU - Urbanke, RĂŒdiger ID - 7007 IS - 10 JF - Algorithms SN - 1999-4893 TI - A new coding paradigm for the primitive relay channel VL - 12 ER - TY - CONF AB - 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. AU - Geher, Gyorgy Pal AU - Titkos, Tamas AU - Virosztek, Daniel ID - 7035 T2 - Kyoto RIMS KĂŽkyĂ»roku TI - Dirac masses and isometric rigidity VL - 2125 ER - TY - JOUR AB - 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. AU - Shirer, Kent R. AU - Modic, Kimberly A AU - Zimmerling, Tino AU - Bachmann, Maja D. AU - König, Markus AU - Moll, Philip J. W. AU - Schoop, Leslie AU - Mackenzie, Andrew P. ID - 7055 IS - 10 JF - APL Materials SN - 2166-532X TI - Out-of-plane transport in ZrSiS and ZrSiSe microstructures VL - 7 ER - TY - JOUR AB - 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. AU - Modic, Kimberly A AU - Meng, Tobias AU - Ronning, Filip AU - Bauer, Eric D. AU - Moll, Philip J. W. AU - Ramshaw, B. J. ID - 7057 IS - 1 JF - Scientific Reports SN - 2045-2322 TI - Thermodynamic signatures of Weyl fermions in NbP VL - 9 ER - TY - JOUR AB - 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. AU - Martino, Edoardo AU - Bachmann, Maja D AU - Rossi, Lidia AU - Modic, Kimberly A AU - Zivkovic, Ivica AU - RĂžnnow, Henrik M AU - Moll, Philip J W AU - Akrap, Ana AU - ForrĂł, LĂĄszlĂł AU - Katrych, Sergiy ID - 7056 IS - 48 JF - Journal of Physics: Condensed Matter SN - 0953-8984 TI - Persistent antiferromagnetic order in heavily overdoped Ca1−x La x FeAs2 VL - 31 ER - TY - JOUR AB - 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 ÎČ-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. AU - Torrini, Consuelo AU - Cubero, Ryan J AU - Dirkx, Ellen AU - Braga, Luca AU - Ali, Hashim AU - Prosdocimo, Giulia AU - Gutierrez, Maria Ines AU - Collesi, Chiara AU - Licastro, Danilo AU - Zentilin, Lorena AU - Mano, Miguel AU - Zacchigna, Serena AU - Vendruscolo, Michele AU - Marsili, Matteo AU - Samal, Areejit AU - Giacca, Mauro ID - 7128 IS - 9 JF - Cell Reports KW - cardiomyocyte KW - cell cycle KW - Cofilin2 KW - cytoskeleton KW - Hippo KW - microRNA KW - regeneration KW - YAP SN - 2211-1247 TI - Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation VL - 27 ER - TY - JOUR AB - 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. AU - Cubero, Ryan J AU - Jo, Junghyo AU - Marsili, Matteo AU - Roudi, Yasser AU - Song, Juyong ID - 7130 IS - 6 JF - Journal of Statistical Mechanics: Theory and Experiment KW - optimization under uncertainty KW - source coding KW - large deviation SN - 1742-5468 TI - Statistical criticality arises in most informative representations VL - 2019 ER - TY - JOUR AB - 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. AU - Censor-Hillel, Keren AU - Kaski, Petteri AU - Korhonen, Janne AU - Lenzen, Christoph AU - Paz, Ami AU - Suomela, Jukka ID - 7150 IS - 6 JF - Distributed Computing SN - 0178-2770 TI - Algebraic methods in the congested clique VL - 32 ER - TY - JOUR AB - 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. AU - Mourad, ElĂ©onore AU - Petit, Yann K. AU - Spezia, Riccardo AU - Samojlov, Aleksej AU - Summa, Francesco F. AU - Prehal, Christian AU - Leypold, Christian AU - Mahne, Nika AU - Slugovc, Christian AU - Fontaine, Olivier AU - Brutti, Sergio AU - Freunberger, Stefan Alexander ID - 7275 IS - 8 JF - Energy & Environmental Science SN - 1754-5692 TI - Singlet oxygen from cation driven superoxide disproportionation and consequences for aprotic metal–O2 batteries VL - 12 ER - TY - JOUR AB - 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. AU - Kwak, Won-Jin AU - Kim, Hun AU - Petit, Yann K. AU - Leypold, Christian AU - Nguyen, Trung Thien AU - Mahne, Nika AU - Redfern, Paul AU - Curtiss, Larry A. AU - Jung, Hun-Gi AU - Borisov, Sergey M. AU - Freunberger, Stefan Alexander AU - Sun, Yang-Kook ID - 7280 JF - Nature Communications SN - 2041-1723 TI - Deactivation of redox mediators in lithium-oxygen batteries by singlet oxygen VL - 10 ER - TY - JOUR AB - 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. AU - Petit, Yann K. AU - Leypold, Christian AU - Mahne, Nika AU - Mourad, ElĂ©onore AU - Schafzahl, Lukas AU - Slugovc, Christian AU - Borisov, Sergey M. AU - Freunberger, Stefan Alexander ID - 7276 IS - 20 JF - Angewandte Chemie International Edition SN - 1433-7851 TI - DABCOnium: An efficient and high-voltage stable singlet oxygen quencher for metal-O2 cells VL - 58 ER - TY - JOUR AB - 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. AU - Kwak, Won-Jin AU - Freunberger, Stefan Alexander AU - Kim, Hun AU - Park, Jiwon AU - Nguyen, Trung Thien AU - Jung, Hun-Gi AU - Byon, Hye Ryung AU - Sun, Yang-Kook ID - 7281 IS - 11 JF - ACS Catalysis SN - 2155-5435 TI - Mutual conservation of redox mediator and singlet oxygen quencher in Lithium–Oxygen batteries VL - 9 ER - TY - JOUR AB - 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. AU - Freunberger, Stefan Alexander ID - 7282 IS - 9 JF - Nature Chemistry SN - 1755-4330 TI - Interphase identity crisis VL - 11 ER - TY - JOUR AB - 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. AU - Petit, Yann K. AU - Freunberger, Stefan Alexander ID - 7283 IS - 4 JF - Nature Materials SN - 1476-1122 TI - Thousands of cycles VL - 18 ER - TY - JOUR AB - 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. AU - Prehal, Christian AU - Freunberger, Stefan Alexander ID - 7284 IS - 2 JF - Joule SN - 2542-4351 TI - Li-O2 cell-scale energy densities VL - 3 ER - TY - GEN AB - 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 TGFÎČ superfamily signaling pathways and increased expression of genes associated with naĂŻve pluripotency. We further identify combinations of TGFÎČ-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. AU - Watanabe, Momoko AU - Haney, Jillian R. AU - Vishlaghi, Neda AU - Turcios, Felix AU - Buth, Jessie E. AU - Gu, Wen AU - Collier, Amanda J. AU - Miranda, Osvaldo AU - Chen, Di AU - Sabri, Shan AU - Clark, Amander T. AU - Plath, Kathrin AU - Christofk, Heather R. AU - Gandal, Michael J. AU - Novitch, Bennett G. ID - 7358 T2 - bioRxiv TI - TGFÎČ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids ER - TY - CONF AB - 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. AU - Fulek, Radoslav AU - Kyncl, Jan ID - 7401 SN - 1868-8969 T2 - 35th International Symposium on Computational Geometry (SoCG 2019) TI - Z_2-Genus of graphs and minimum rank of partial symmetric matrices VL - 129 ER - TY - CHAP AB - 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. AU - Alur, Rajeev AU - Giacobbe, Mirco AU - Henzinger, Thomas A AU - Larsen, Kim G. AU - Mikučionis, Marius ED - Steffen, Bernhard ED - Woeginger, Gerhard ID - 7453 SN - 1611-3349 T2 - Computing and Software Science TI - Continuous-time models for system design and analysis VL - 10000 ER - TY - JOUR AB - 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. AU - Andersen, Marianne Stemann AU - Hannezo, Edouard B AU - Ulyanchenko, Svetlana AU - Estrach, Soline AU - Antoku, Yasuko AU - Pisano, Sabrina AU - Boonekamp, Kim E. AU - Sendrup, Sarah AU - Maimets, Martti AU - Pedersen, Marianne Terndrup AU - Johansen, Jens V. AU - Clement, Ditte L. AU - Feral, Chloe C. AU - Simons, Benjamin D. AU - Jensen, Kim B. ID - 7476 IS - 8 JF - Nature Cell Biology SN - 1465-7392 TI - Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states VL - 21 ER - TY - JOUR AB - 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. AU - Portinale, Lorenzo AU - Stefanelli, Ulisse ID - 7550 IS - 2 JF - Advances in Mathematical Sciences and Applications SN - 1343-4373 TI - Penalization via global functionals of optimal-control problems for dissipative evolution VL - 28 ER - TY - GEN AB - 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. AU - Bialek, William AU - Gregor, Thomas AU - Tkačik, GaĆĄper ID - 7552 T2 - arXiv:1912.08579 TI - Action at a distance in transcriptional regulation ER - TY - CONF AB - 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. AU - Immler, Fabian AU - Althoff, Matthias AU - Benet, Luis AU - Chapoutot, Alexandre AU - Chen, Xin AU - Forets, Marcelo AU - Geretti, Luca AU - Kochdumper, Niklas AU - Sanders, David P. AU - Schilling, Christian ID - 7576 T2 - EPiC Series in Computing TI - ARCH-COMP19 Category Report: Continuous and hybrid systems with nonlinear dynamics VL - 61 ER - TY - GEN AB - 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. AU - Prehal, Christian AU - Samojlov, Aleksej AU - Nachtnebel, Manfred AU - Kriechbaum, Manfred AU - Amenitsch, Heinz AU - Freunberger, Stefan Alexander ID - 7627 TI - A revised O2 reduction model in Li-O2 batteries as revealed by in situ small angle X-ray scattering ER - TY - JOUR AB - 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. AU - Delaneau, Olivier AU - Zagury, Jean-François AU - Robinson, Matthew Richard AU - Marchini, Jonathan L. AU - Dermitzakis, Emmanouil T. ID - 7710 JF - Nature Communications SN - 2041-1723 TI - Accurate, scalable and integrative haplotype estimation VL - 10 ER - TY - GEN AB - 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. AU - Sulc, Jonathan AU - Mounier, Ninon AU - GĂŒnther, Felix AU - Winkler, Thomas AU - Wood, Andrew R. AU - Frayling, Timothy M. AU - Heid, Iris M. AU - Robinson, Matthew Richard AU - Kutalik, ZoltĂĄn ID - 7782 T2 - bioRxiv TI - Maximum likelihood method quantifies the overall contribution of gene-environment interaction to continuous traits: An application to complex traits in the UK Biobank ER - TY - JOUR AU - Currin, Christopher B. AU - Khoza, Phumlani N. AU - Antrobus, Alexander D. AU - Latham, Peter E. AU - Vogels, Tim P AU - Raimondo, Joseph V. ID - 8013 IS - 7 JF - PLOS Computational Biology SN - 1553-7358 TI - Think: Theory for Africa VL - 15 ER - TY - JOUR AB - 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. AU - Manohar, Sanjay G. AU - Zokaei, Nahid AU - Fallon, Sean J. AU - Vogels, Tim P AU - Husain, Masud ID - 8014 JF - Neuroscience and Biobehavioral Reviews SN - 0149-7634 TI - Neural mechanisms of attending to items in working memory VL - 101 ER - TY - CONF AB - 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. AU - Betea, Dan AU - Bouttier, JĂ©rĂ©mie AU - Nejjar, Peter AU - VuletĂ­c, Mirjana ID - 8175 T2 - Proceedings on the 31st International Conference on Formal Power Series and Algebraic Combinatorics TI - New edge asymptotics of skew Young diagrams via free boundaries ER - TY - JOUR AB - 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. AU - Singer, Josef AU - Achatz-Straussberger, Gertrude AU - Bentley-Lukschal, Anna AU - Fazekas-Singer, Judit AU - Achatz, Gernot AU - Karagiannis, Sophia N. AU - Jensen-Jarolim, Erika ID - 8228 IS - 7 JF - World Allergy Organization Journal SN - 1939-4551 TI - AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice VL - 12 ER - TY - JOUR AB - 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-Îł 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. AU - Ondracek, Anna S. AU - Heiden, Denise AU - Oostingh, Gertie J. AU - Fuerst, Elisabeth AU - Fazekas-Singer, Judit AU - Bergmayr, Cornelia AU - Rohrhofer, Johanna AU - Jensen-Jarolim, Erika AU - Duschl, Albert AU - Untersmayr, Eva ID - 8229 IS - 10 JF - Nutrients SN - 2072-6643 TI - Immune effects of the nitrated food allergen beta-lactoglobulin in an experimental food allergy model VL - 11 ER - TY - JOUR AU - Ilieva, Kristina M. AU - Fazekas-Singer, Judit AU - Bax, Heather J. AU - Crescioli, Silvia AU - Montero‐Morales, Laura AU - Mele, Silvia AU - Sow, Heng Sheng AU - Stavraka, Chara AU - Josephs, Debra H. AU - Spicer, James F. AU - Steinkellner, Herta AU - Jensen‐Jarolim, Erika AU - Tutt, Andrew N. J. AU - Karagiannis, Sophia N. ID - 8227 IS - 10 JF - Allergy SN - 0105-4538 TI - AllergoOncology: Expression platform development and functional profiling of an anti‐HER2 IgE antibody VL - 74 ER - TY - JOUR AB - 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. AU - Shelyakin, Pavel V. AU - Bochkareva, Olga AU - Karan, Anna A. AU - Gelfand, Mikhail S. ID - 8263 JF - BMC Evolutionary Biology SN - 1471-2148 TI - Micro-evolution of three Streptococcus species: Selection, antigenic variation, and horizontal gene inflow VL - 19 ER -