TY - JOUR
AB - We investigate the complexity of finding an embedded non-orientable surface of Euler genus g in a triangulated 3-manifold. This problem occurs both as a natural question in low-dimensional topology, and as a first non-trivial instance of embeddability of complexes into 3-manifolds. We prove that the problem is NP-hard, thus adding to the relatively few hardness results that are currently known in 3-manifold topology. In addition, we show that the problem lies in NP when the Euler genus g is odd, and we give an explicit algorithm in this case.
AU - Burton, Benjamin
AU - De Mesmay, Arnaud N
AU - Wagner, Uli
ID - 534
IS - 4
JF - Discrete & Computational Geometry
SN - 01795376
TI - Finding non-orientable surfaces in 3-Manifolds
VL - 58
ER -
TY - JOUR
AB - Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren. Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität während der Embryonalentwicklung.
AU - Kainrath, Stephanie
AU - Stadler, Manuela
AU - Gschaider-Reichhart, Eva
AU - Distel, Martin
AU - Janovjak, Harald L
ID - 538
IS - 16
JF - Angewandte Chemie
TI - Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen
VL - 129
ER -
TY - JOUR
AB - RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics. A subsequent mass-spectrometric analysis of L protein pulldowns from infected human cells revealed a comprehensive network of interacting host proteins. The obtained LCMV L protein interactome was bioinformatically integrated with known host protein interactors of RdRps from other RNA viruses, emphasizing interconnected modules of human proteins. Functional characterization of selected interactors highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors. To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired virus control in chronic infection. These results provide insights into the complex interactions of the arenavirus LCMV and other viral RdRps with the host proteome and contribute to a better molecular understanding of how chronic viruses interact with their host.
AU - Khamina, Kseniya
AU - Lercher, Alexander
AU - Caldera, Michael
AU - Schliehe, Christopher
AU - Vilagos, Bojan
AU - Sahin, Mehmet
AU - Kosack, Lindsay
AU - Bhattacharya, Anannya
AU - Májek, Peter
AU - Stukalov, Alexey
AU - Sacco, Roberto
AU - James, Leo
AU - Pinschewer, Daniel
AU - Bennett, Keiryn
AU - Menche, Jörg
AU - Bergthaler, Andreas
ID - 540
IS - 12
JF - PLoS Pathogens
SN - 15537366
TI - Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein
VL - 13
ER -
TY - JOUR
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives. There exist two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector. We consider optimization with respect to both objectives at once, thus unifying the existing semantics. Precisely, the goal is to optimize the expectation while ensuring the satisfaction constraint. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensure certain probabilistic guarantee). Our main results are as follows: First, we present algorithms for the decision problems which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Second, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Křetínská, Zuzana
AU - Kretinsky, Jan
ID - 466
IS - 2
JF - Logical Methods in Computer Science
SN - 18605974
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
VL - 13
ER -
TY - JOUR
AB - Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata or in any other known decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata, which makes it possible to express important quantitative properties such as average response time. In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in runtime verification. We establish an almost-complete decidability picture for the basic decision problems about nested weighted automata and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 467
IS - 4
JF - ACM Transactions on Computational Logic (TOCL)
SN - 15293785
TI - Nested weighted automata
VL - 18
ER -
TY - JOUR
AB - The edit distance between two words w 1 , w 2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w 1 to w 2 . The edit distance generalizes to languages L 1 , L 2 , where the edit distance from L 1 to L 2 is the minimal number k such that for every word from L 1 there exists a word in L 2 with edit distance at most k . We study the edit distance computation problem between pushdown automata and their subclasses. The problem of computing edit distance to a pushdown automaton is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for the following problems: (1) deciding whether, for a given threshold k , the edit distance from a pushdown automaton to a finite automaton is at most k , and (2) deciding whether the edit distance from a pushdown automaton to a finite automaton is finite.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Ibsen-Jensen, Rasmus
AU - Otop, Jan
ID - 465
IS - 3
JF - Logical Methods in Computer Science
SN - 18605974
TI - Edit distance for pushdown automata
VL - 13
ER -
TY - CHAP
AB - Development of vascular tissue is a remarkable example of intercellular communication and coordinated development involving hormonal signaling and tissue polarity. Thus far, studies on vascular patterning and regeneration have been conducted mainly in trees—woody plants—with a well-developed layer of vascular cambium and secondary tissues. Trees are difficult to use as genetic models, i.e., due to long generation time, unstable environmental conditions, and lack of available mutants and transgenic lines. Therefore, the use of the main genetic model plant Arabidopsis thaliana (L.) Heynh., with a wealth of available marker and transgenic lines, provides a unique opportunity to address molecular mechanism of vascular tissue formation and regeneration. With specific treatments, the tiny weed Arabidopsis can serve as a model to understand the growth of mighty trees and interconnect a tree physiology with molecular genetics and cell biology of Arabidopsis.
AU - Mazur, Ewa
AU - Friml, Jirí
ED - Jurić, Snježana
ID - 545
T2 - Plant Engineering
TI - Vascular tissue development and regeneration in the model plant arabidopsis
ER -
TY - JOUR
AB - The fixation probability is the probability that a new mutant introduced in a homogeneous population eventually takes over the entire population. The fixation probability is a fundamental quantity of natural selection, and known to depend on the population structure. Amplifiers of natural selection are population structures which increase the fixation probability of advantageous mutants, as compared to the baseline case of well-mixed populations. In this work we focus on symmetric population structures represented as undirected graphs. In the regime of undirected graphs, the strongest amplifier known has been the Star graph, and the existence of undirected graphs with stronger amplification properties has remained open for over a decade. In this work we present the Comet and Comet-swarm families of undirected graphs. We show that for a range of fitness values of the mutants, the Comet and Cometswarm graphs have fixation probability strictly larger than the fixation probability of the Star graph, for fixed population size and at the limit of large populations, respectively.
AU - Pavlogiannis, Andreas
AU - Tkadlec, Josef
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 512
IS - 1
JF - Scientific Reports
SN - 20452322
TI - Amplification on undirected population structures: Comets beat stars
VL - 7
ER -
TY - JOUR
AB - A fundamental algorithmic problem at the heart of static analysis is Dyck reachability. The input is a graph where the edges are labeled with different types of opening and closing parentheses, and the reachability information is computed via paths whose parentheses are properly matched. We present new results for Dyck reachability problems with applications to alias analysis and data-dependence analysis. Our main contributions, that include improved upper bounds as well as lower bounds that establish optimality guarantees, are as follows: First, we consider Dyck reachability on bidirected graphs, which is the standard way of performing field-sensitive points-to analysis. Given a bidirected graph with n nodes and m edges, we present: (i) an algorithm with worst-case running time O(m + n · α(n)), where α(n) is the inverse Ackermann function, improving the previously known O(n2) time bound; (ii) a matching lower bound that shows that our algorithm is optimal wrt to worst-case complexity; and (iii) an optimal average-case upper bound of O(m) time, improving the previously known O(m · logn) bound. Second, we consider the problem of context-sensitive data-dependence analysis, where the task is to obtain analysis summaries of library code in the presence of callbacks. Our algorithm preprocesses libraries in almost linear time, after which the contribution of the library in the complexity of the client analysis is only linear, and only wrt the number of call sites. Third, we prove that combinatorial algorithms for Dyck reachability on general graphs with truly sub-cubic bounds cannot be obtained without obtaining sub-cubic combinatorial algorithms for Boolean Matrix Multiplication, which is a long-standing open problem. Thus we establish that the existing combinatorial algorithms for Dyck reachability are (conditionally) optimal for general graphs. We also show that the same hardness holds for graphs of constant treewidth. Finally, we provide a prototype implementation of our algorithms for both alias analysis and data-dependence analysis. Our experimental evaluation demonstrates that the new algorithms significantly outperform all existing methods on the two problems, over real-world benchmarks.
AU - Chatterjee, Krishnendu
AU - Choudhary, Bhavya
AU - Pavlogiannis, Andreas
ID - 10416
IS - POPL
JF - Proceedings of the ACM on Programming Languages
TI - Optimal Dyck reachability for data-dependence and Alias analysis
VL - 2
ER -
TY - GEN
AB - A fundamental algorithmic problem at the heart of static analysis is Dyck reachability. The input is a graphwhere the edges are labeled with different types of opening and closing parentheses, and the reachabilityinformation is computed via paths whose parentheses are properly matched. We present new results for Dyckreachability problems with applications to alias analysis and data-dependence analysis. Our main contributions,that include improved upper bounds as well as lower bounds that establish optimality guarantees, are asfollows:First, we consider Dyck reachability on bidirected graphs, which is the standard way of performing field-sensitive points-to analysis. Given a bidirected graph withnnodes andmedges, we present: (i) an algorithmwith worst-case running timeO(m+n·α(n)), whereα(n)is the inverse Ackermann function, improving thepreviously knownO(n2)time bound; (ii) a matching lower bound that shows that our algorithm is optimalwrt to worst-case complexity; and (iii) an optimal average-case upper bound ofO(m)time, improving thepreviously knownO(m·logn)bound.Second, we consider the problem of context-sensitive data-dependence analysis, where the task is to obtainanalysis summaries of library code in the presence of callbacks. Our algorithm preprocesses libraries in almostlinear time, after which the contribution of the library in the complexity of the client analysis is only linear,and only wrt the number of call sites.Third, we prove that combinatorial algorithms for Dyck reachability on general graphs with truly sub-cubic bounds cannot be obtained without obtaining sub-cubic combinatorial algorithms for Boolean MatrixMultiplication, which is a long-standing open problem. Thus we establish that the existing combinatorialalgorithms for Dyck reachability are (conditionally) optimal for general graphs. We also show that the samehardness holds for graphs of constant treewidth.Finally, we provide a prototype implementation of our algorithms for both alias analysis and data-dependenceanalysis. Our experimental evaluation demonstrates that the new algorithms significantly outperform allexisting methods on the two problems, over real-world benchmarks.
AU - Chatterjee, Krishnendu
AU - Choudhary, Bhavya
AU - Pavlogiannis, Andreas
ID - 5455
SN - 2664-1690
TI - Optimal Dyck reachability for data-dependence and alias analysis
ER -
TY - GEN
AB - In this report the implementation of the institutional data repository IST DataRep at IST Austria will be covered: Starting with the research phase when requirements for a repository were established, the procedure of choosing a repository-software and its customization based on the results of user-testings will be discussed. Followed by reflections on the marketing strategies in regard of impact, and at the end sharing some experiences of one year operating IST DataRep.
AU - Barbara Petritsch
ID - 5450
TI - Implementing the institutional data repository IST DataRep
ER -
TY - CONF
AB - Model checking is usually based on a comprehensive traversal of the state space. Causality-based model checking is a radically different approach that instead analyzes the cause-effect relationships in a program. We give an overview on a new class of model checking algorithms that capture the causal relationships in a special data structure called concurrent traces. Concurrent traces identify key events in an execution history and link them through their cause-effect relationships. The model checker builds a tableau of concurrent traces, where the case splits represent different causal explanations of a hypothetical error. Causality-based model checking has been implemented in the ARCTOR tool, and applied to previously intractable multi-threaded benchmarks.
AU - Finkbeiner, Bernd
AU - Kupriyanov, Andrey
ID - 549
SN - 20752180
T2 - Electronic Proceedings in Theoretical Computer Science
TI - Causality-based model checking
VL - 259
ER -
TY - JOUR
AB - We present a new dynamic partial-order reduction method for stateless model checking of concurrent programs. A common approach for exploring program behaviors relies on enumerating the traces of the program, without storing the visited states (aka stateless exploration). As the number of distinct traces grows exponentially, dynamic partial-order reduction (DPOR) techniques have been successfully used to partition the space of traces into equivalence classes (Mazurkiewicz partitioning), with the goal of exploring only few representative traces from each class.
We introduce a new equivalence on traces under sequential consistency semantics, which we call the observation equivalence. Two traces are observationally equivalent if every read event observes the same write event in both traces. While the traditional Mazurkiewicz equivalence is control-centric, our new definition is data-centric. We show that our observation equivalence is coarser than the Mazurkiewicz equivalence, and in many cases even exponentially coarser. We devise a DPOR exploration of the trace space, called data-centric DPOR, based on the observation equivalence.
AU - Chalupa, Marek
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Sinha, Nishant
AU - Vaidya, Kapil
ID - 10417
IS - POPL
JF - Proceedings of the ACM on Programming Languages
TI - Data-centric dynamic partial order reduction
VL - 2
ER -
TY - GEN
AB - We present a new dynamic partial-order reduction method for stateless model checking of concurrent programs. A common approach for exploring program behaviors relies on enumerating the traces of the program, without storing the visited states (aka stateless exploration). As the number of distinct traces grows exponentially, dynamic partial-order reduction (DPOR) techniques have been successfully used to partition the space of traces into equivalence classes (Mazurkiewicz partitioning), with the goal of exploring only few representative traces from each class.
We introduce a new equivalence on traces under sequential consistency semantics, which we call the observation equivalence. Two traces are observationally equivalent if every read event observes the same write event in both traces. While the traditional Mazurkiewicz equivalence is control-centric, our new definition is data-centric. We show that our observation equivalence is coarser than the Mazurkiewicz equivalence, and in many cases even exponentially coarser. We devise a DPOR exploration of the trace space, called data-centric DPOR, based on the observation equivalence.
1. For acyclic architectures, our algorithm is guaranteed to explore exactly one representative trace from each observation class, while spending polynomial time per class. Hence, our algorithm is optimal wrt the observation equivalence, and in several cases explores exponentially fewer traces than any enumerative method based on the Mazurkiewicz equivalence.
2. For cyclic architectures, we consider an equivalence between traces which is finer than the observation equivalence; but coarser than the Mazurkiewicz equivalence, and in some cases is exponentially coarser. Our data-centric DPOR algorithm remains optimal under this trace equivalence.
Finally, we perform a basic experimental comparison between the existing Mazurkiewicz-based DPOR and our data-centric DPOR on a set of academic benchmarks. Our results show a significant reduction in both running time and the number of explored equivalence classes.
AU - Chalupa, Marek
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Sinha, Nishant
AU - Vaidya, Kapil
ID - 5456
SN - 2664-1690
TI - Data-centric dynamic partial order reduction
ER -
TY - JOUR
AB - In this work maximum entropy distributions in the space of steady states of metabolic networks are considered upon constraining the first and second moments of the growth rate. Coexistence of fast and slow phenotypes, with bimodal flux distributions, emerges upon considering control on the average growth (optimization) and its fluctuations (heterogeneity). This is applied to the carbon catabolic core of Escherichia coli where it quantifies the metabolic activity of slow growing phenotypes and it provides a quantitative map with metabolic fluxes, opening the possibility to detect coexistence from flux data. A preliminary analysis on data for E. coli cultures in standard conditions shows degeneracy for the inferred parameters that extend in the coexistence region.
AU - De Martino, Daniele
ID - 548
IS - 6
JF - Physical Review E
SN - 24700045
TI - Maximum entropy modeling of metabolic networks by constraining growth-rate moments predicts coexistence of phenotypes
VL - 96
ER -
TY - CONF
AB - Evolutionary graph theory studies the evolutionary dynamics in a population structure given as a connected graph. Each node of the graph represents an individual of the population, and edges determine how offspring are placed. We consider the classical birth-death Moran process where there are two types of individuals, namely, the residents with fitness 1 and mutants with fitness r. The fitness indicates the reproductive strength. The evolutionary dynamics happens as follows: in the initial step, in a population of all resident individuals a mutant is introduced, and then at each step, an individual is chosen proportional to the fitness of its type to reproduce, and the offspring replaces a neighbor uniformly at random. The process stops when all individuals are either residents or mutants. The probability that all individuals in the end are mutants is called the fixation probability, which is a key factor in the rate of evolution. We consider the problem of approximating the fixation probability. The class of algorithms that is extremely relevant for approximation of the fixation probabilities is the Monte-Carlo simulation of the process. Previous results present a polynomial-time Monte-Carlo algorithm for undirected graphs when r is given in unary. First, we present a simple modification: instead of simulating each step, we discard ineffective steps, where no node changes type (i.e., either residents replace residents, or mutants replace mutants). Using the above simple modification and our result that the number of effective steps is concentrated around the expected number of effective steps, we present faster polynomial-time Monte-Carlo algorithms for undirected graphs. Our algorithms are always at least a factor O(n2/ log n) faster as compared to the previous algorithms, where n is the number of nodes, and is polynomial even if r is given in binary. We also present lower bounds showing that the upper bound on the expected number of effective steps we present is asymptotically tight for undirected graphs.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Nowak, Martin
ID - 551
SN - 978-395977046-0
T2 - Leibniz International Proceedings in Informatics
TI - Faster Monte Carlo algorithms for fixation probability of the Moran process on undirected graphs
VL - 83
ER -
TY - CONF
AB - Graph games provide the foundation for modeling and synthesis of reactive processes. Such games are played over graphs where the vertices are controlled by two adversarial players. We consider graph games where the objective of the first player is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a meanpayoff condition). There are two variants of the problem, namely, the threshold problem where the quantitative goal is to ensure that the mean-payoff value is above a threshold, and the value problem where the quantitative goal is to ensure the optimal mean-payoff value; in both cases ensuring the qualitative parity objective. The previous best-known algorithms for game graphs with n vertices, m edges, parity objectives with d priorities, and maximal absolute reward value W for mean-payoff objectives, are as follows: O(nd+1 . m . w) for the threshold problem, and O(nd+2 · m · W) for the value problem. Our main contributions are faster algorithms, and the running times of our algorithms are as follows: O(nd-1 · m ·W) for the threshold problem, and O(nd · m · W · log(n · W)) for the value problem. For mean-payoff parity objectives with two priorities, our algorithms match the best-known bounds of the algorithms for mean-payoff games (without conjunction with parity objectives). Our results are relevant in synthesis of reactive systems with both functional requirement (given as a qualitative objective) and performance requirement (given as a quantitative objective).
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika H
AU - Svozil, Alexander
ID - 552
SN - 978-395977046-0
T2 - Leibniz International Proceedings in Informatics
TI - Faster algorithms for mean-payoff parity games
VL - 83
ER -
TY - CONF
AB - We consider two player, zero-sum, finite-state concurrent reachability games, played for an infinite number of rounds, where in every round, each player simultaneously and independently of the other players chooses an action, whereafter the successor state is determined by a probability distribution given by the current state and the chosen actions. Player 1 wins iff a designated goal state is eventually visited. We are interested in the complexity of stationary strategies measured by their patience, which is defined as the inverse of the smallest non-zero probability employed. Our main results are as follows: We show that: (i) the optimal bound on the patience of optimal and -optimal strategies, for both players is doubly exponential; and (ii) even in games with a single non-absorbing state exponential (in the number of actions) patience is necessary.
AU - Chatterjee, Krishnendu
AU - Hansen, Kristofer
AU - Ibsen-Jensen, Rasmus
ID - 553
SN - 978-395977046-0
T2 - Leibniz International Proceedings in Informatics
TI - Strategy complexity of concurrent safety games
VL - 83
ER -
TY - DATA
AB - This data was collected as part of the study [1]. It consists of preprocessed multi-electrode array recording from 160 salamander retinal ganglion cells responding to 297 repeats of a 19 s natural movie. The data is available in two formats: (1) a .mat file containing an array with dimensions “number of repeats” x “number of neurons” x “time in a repeat”; (2) a zipped .txt file containing the same data represented as an array with dimensions “number of neurons” x “number of samples”, where the number of samples is equal to the product of the number of repeats and timebins within a repeat. The time dimension is divided into 20 ms time windows, and the array is binary indicating whether a given cell elicited at least one spike in a given time window during a particular repeat. See the reference below for details regarding collection and preprocessing:
[1] Tkačik G, Marre O, Amodei D, Schneidman E, Bialek W, Berry MJ II. Searching for Collective Behavior in a Large Network of Sensory Neurons. PLoS Comput Biol. 2014;10(1):e1003408.
AU - Marre, Olivier
AU - Tkacik, Gasper
AU - Amodei, Dario
AU - Schneidman, Elad
AU - Bialek, William
AU - Berry, Michael
ID - 5562
KW - multi-electrode recording
KW - retinal ganglion cells
TI - Multi-electrode array recording from salamander retinal ganglion cells
ER -
TY - DATA
AB - Graph matching problems as described in "Active Graph Matching for Automatic Joint Segmentation and Annotation of C. Elegans." by Kainmueller, Dagmar and Jug, Florian and Rother, Carsten and Myers, Gene, MICCAI 2014. Problems are in OpenGM2 hdf5 format (see http://hciweb2.iwr.uni-heidelberg.de/opengm/) and a custom text format used by the feature matching solver described in "Feature Correspondence via Graph Matching: Models and Global Optimization." by Lorenzo Torresani, Vladimir Kolmogorov and Carsten Rother, ECCV 2008, code at http://pub.ist.ac.at/~vnk/software/GraphMatching-v1.02.src.zip.
AU - Kainmueller, Dagmar
AU - Jug, Florian
AU - Rother, Carsten
AU - Meyers, Gene
ID - 5561
KW - graph matching
KW - feature matching
KW - QAP
KW - MAP-inference
TI - Graph matching problems for annotating C. Elegans
ER -
TY - DATA
AB - MATLAB code and processed datasets available for reproducing the results in:
Lukačišin, M.*, Landon, M.*, Jajoo, R*. (2016) Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast.
*equal contributions
AU - Lukacisin, Martin
ID - 5563
TI - MATLAB analysis code for 'Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast'
ER -
TY - DATA
AB - Immunological synapse DC-Tcells
AU - Leithner, Alexander F
ID - 5567
KW - Immunological synapse
TI - Immunological synapse DC-Tcells
ER -
TY - JOUR
AB - PURPOSE. Gene therapy of retinal ganglion cells (RGCs) has promise as a powerful therapeutic for the rescue and regeneration of these cells after optic nerve damage. However, early after damage, RGCs undergo atrophic changes, including gene silencing. It is not known if these changes will deleteriously affect transduction and transgene expression, or if the therapeutic protein can influence reactivation of the endogenous genome. METHODS. Double-transgenic mice carrying a Rosa26-(LoxP)-tdTomato reporter, and a mutant allele for the proapoptotic Bax gene were reared. The Bax mutant blocks apoptosis, but RGCs still exhibit nuclear atrophy and gene silencing. At times ranging from 1 hour to 4 weeks after optic nerve crush (ONC), eyes received an intravitreal injection of AAV2 virus carrying the Cre recombinase. Successful transduction was monitored by expression of the tdTomato reporter. Immunostaining was used to localize tdTomato expression in select cell types. RESULTS. Successful transduction of RGCs was achieved at all time points after ONC using AAV2 expressing Cre from the phosphoglycerate kinase (Pgk) promoter, but not the CMV promoter. ONC promoted an increase in the transduction of cell types in the inner nuclear layer, including Müller cells and rod bipolar neurons. There was minimal evidence of transduction of amacrine cells and astrocytes in the inner retina or optic nerve. CONCLUSIONS. Damaged RGCs can be transduced and at least some endogenous genes can be subsequently activated. Optic nerve damage may change retinal architecture to allow greater penetration of an AAV2 virus to transduce several additional cell types in the inner nuclear layer.
AU - Nickells, Robert
AU - Schmitt, Heather
AU - Maes, Margaret E
AU - Schlamp, Cassandra
ID - 557
IS - 14
JF - Investigative Ophthalmology and Visual Science
SN - 01460404
TI - AAV2 mediated transduction of the mouse retina after optic nerve injury
VL - 58
ER -
TY - DATA
AB - Matlab script to calculate the forward migration indexes (/) from TrackMate spot-statistics files.
AU - Hauschild, Robert
ID - 5570
KW - Cell migration
KW - tracking
KW - forward migration index
KW - FMI
TI - Forward migration indexes
ER -
TY - JOUR
AB - Immune specificity is the degree to which a host’s immune system discriminates among various pathogens or antigenic variants. Vertebrate immune memory is highly specific due to antibody responses. On the other hand, some invertebrates show immune priming, i.e. improved survival after secondary exposure to a previously encountered pathogen. Until now, specificity of priming has only been demonstrated via the septic infection route or when live pathogens were used for priming. Therefore, we tested for specificity in the oral priming route in the red flour beetle, Tribolium castaneum. For priming, we used pathogen-free supernatants derived from three different strains of the entomopathogen, Bacillus thuringiensis, which express different Cry toxin variants known for their toxicity against this beetle. Subsequent exposure to the infective spores showed that oral priming was specific for two naturally occurring strains, while a third engineered strain did not induce any priming effect. Our data demonstrate that oral immune priming with a non-infectious bacterial agent can be specific, but the priming effect is not universal across all bacterial strains.
AU - Futo, Momir
AU - Sell, Marie
AU - Kutzer, Megan
AU - Kurtz, Joachim
ID - 558
IS - 12
JF - Biology Letters
SN - 17449561
TI - Specificity of oral immune priming in the red flour beetle Tribolium castaneum
VL - 13
ER -
TY - JOUR
AB - In a recent article (Jentzen et al. 2016 Commun. Math. Sci. 14, 1477–1500 (doi:10.4310/CMS.2016.v14. n6.a1)), it has been established that, for every arbitrarily slow convergence speed and every natural number d ? {4, 5, . . .}, there exist d-dimensional stochastic differential equations with infinitely often differentiable and globally bounded coefficients such that no approximation method based on finitely many observations of the driving Brownian motion can converge in absolute mean to the solution faster than the given speed of convergence. In this paper, we strengthen the above result by proving that this slow convergence phenomenon also arises in two (d = 2) and three (d = 3) space dimensions.
AU - Gerencser, Mate
AU - Jentzen, Arnulf
AU - Salimova, Diyora
ID - 560
IS - 2207
JF - Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences
SN - 13645021
TI - On stochastic differential equations with arbitrarily slow convergence rates for strong approximation in two space dimensions
VL - 473
ER -
TY - BOOK
AB - This book is a concise and self-contained introduction of recent techniques to prove local spectral universality for large random matrices. Random matrix theory is a fast expanding research area, and this book mainly focuses on the methods that the authors participated in developing over the past few years. Many other interesting topics are not included, and neither are several new developments within the framework of these methods. The authors have chosen instead to present key concepts that they believe are the core of these methods and should be relevant for future applications. They keep technicalities to a minimum to make the book accessible to graduate students. With this in mind, they include in this book the basic notions and tools for high-dimensional analysis, such as large deviation, entropy, Dirichlet form, and the logarithmic Sobolev inequality.
AU - Erdös, László
AU - Yau, Horng
ID - 567
SN - 9-781-4704-3648-3
TI - A Dynamical Approach to Random Matrix Theory
VL - 28
ER -
TY - JOUR
AB - We study robust properties of zero sets of continuous maps f: X → ℝn. Formally, we analyze the family Z< r(f) := (g-1(0): ||g - f|| < r) of all zero sets of all continuous maps g closer to f than r in the max-norm. All of these sets are outside A := (x: |f(x)| ≥ r) and we claim that Z< r(f) is fully determined by A and an element of a certain cohomotopy group which (by a recent result) is computable whenever the dimension of X is at most 2n - 3. By considering all r > 0 simultaneously, the pointed cohomotopy groups form a persistence module-a structure leading to persistence diagrams as in the case of persistent homology or well groups. Eventually, we get a descriptor of persistent robust properties of zero sets that has better descriptive power (Theorem A) and better computability status (Theorem B) than the established well diagrams. Moreover, if we endow every point of each zero set with gradients of the perturbation, the robust description of the zero sets by elements of cohomotopy groups is in some sense the best possible (Theorem C).
AU - Franek, Peter
AU - Krcál, Marek
ID - 568
IS - 2
JF - Homology, Homotopy and Applications
SN - 15320073
TI - Persistence of zero sets
VL - 19
ER -
TY - JOUR
AB - Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution.
AU - Lagator, Mato
AU - Sarikas, Srdjan
AU - Acar, Hande
AU - Bollback, Jonathan P
AU - Guet, Calin C
ID - 570
JF - eLife
SN - 2050084X
TI - Regulatory network structure determines patterns of intermolecular epistasis
VL - 6
ER -
TY - JOUR
AB - The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. We quantified actin filament order in human cells using fluorescence polarization microscopy and found that cleavage furrow ingression initiates by contraction of an equatorial actin network with randomly oriented filaments. The network subsequently gradually reoriented actin filaments along the cell equator. This strictly depended on myosin II activity, suggesting local network reorganization by mechanical forces. Cortical laser microsurgery revealed that during cytokinesis progression, mechanical tension increased substantially along the direction of the cell equator, while the network contracted laterally along the pole-to-pole axis without a detectable increase in tension. Our data suggest that an asymmetric increase in cortical tension promotes filament reorientation along the cytokinetic cleavage furrow, which might have implications for diverse other biological processes involving actomyosin rings.
AU - Spira, Felix
AU - Cuylen Haering, Sara
AU - Mehta, Shalin
AU - Samwer, Matthias
AU - Reversat, Anne
AU - Verma, Amitabh
AU - Oldenbourg, Rudolf
AU - Sixt, Michael K
AU - Gerlich, Daniel
ID - 569
JF - eLife
SN - 2050084X
TI - Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments
VL - 6
ER -
TY - JOUR
AB - Blood platelets are critical for hemostasis and thrombosis and play diverse roles during immune responses. Despite these versatile tasks in mammalian biology, their skills on a cellular level are deemed limited, mainly consisting in rolling, adhesion, and aggregate formation. Here, we identify an unappreciated asset of platelets and show that adherent platelets use adhesion receptors to mechanically probe the adhesive substrate in their local microenvironment. When actomyosin-dependent traction forces overcome substrate resistance, platelets migrate and pile up the adhesive substrate together with any bound particulate material. They use this ability to act as cellular scavengers, scanning the vascular surface for potential invaders and collecting deposited bacteria. Microbe collection by migrating platelets boosts the activity of professional phagocytes, exacerbating inflammatory tissue injury in sepsis. This assigns platelets a central role in innate immune responses and identifies them as potential targets to dampen inflammatory tissue damage in clinical scenarios of severe systemic infection. In addition to their role in thrombosis and hemostasis, platelets can also migrate to sites of infection to help trap bacteria and clear the vascular surface.
AU - Gärtner, Florian R
AU - Ahmad, Zerkah
AU - Rosenberger, Gerhild
AU - Fan, Shuxia
AU - Nicolai, Leo
AU - Busch, Benjamin
AU - Yavuz, Gökce
AU - Luckner, Manja
AU - Ishikawa Ankerhold, Hellen
AU - Hennel, Roman
AU - Benechet, Alexandre
AU - Lorenz, Michael
AU - Chandraratne, Sue
AU - Schubert, Irene
AU - Helmer, Sebastian
AU - Striednig, Bianca
AU - Stark, Konstantin
AU - Janko, Marek
AU - Böttcher, Ralph
AU - Verschoor, Admar
AU - Leon, Catherine
AU - Gachet, Christian
AU - Gudermann, Thomas
AU - Mederos Y Schnitzler, Michael
AU - Pincus, Zachary
AU - Iannacone, Matteo
AU - Haas, Rainer
AU - Wanner, Gerhard
AU - Lauber, Kirsten
AU - Sixt, Michael K
AU - Massberg, Steffen
ID - 571
IS - 6
JF - Cell Press
SN - 00928674
TI - Migrating platelets are mechano scavengers that collect and bundle bacteria
VL - 171
ER -
TY - JOUR
AB - In this review, we summarize the different biosynthesis-related pathways that contribute to the regulation of endogenous auxin in plants. We demonstrate that all known genes involved in auxin biosynthesis also have a role in root formation, from the initiation of a root meristem during embryogenesis to the generation of a functional root system with a primary root, secondary lateral root branches and adventitious roots. Furthermore, the versatile adaptation of root development in response to environmental challenges is mediated by both local and distant control of auxin biosynthesis. In conclusion, auxin homeostasis mediated by spatial and temporal regulation of auxin biosynthesis plays a central role in determining root architecture.
AU - Olatunji, Damilola
AU - Geelen, Danny
AU - Verstraeten, Inge
ID - 572
IS - 12
JF - International Journal of Molecular Sciences
TI - Control of endogenous auxin levels in plant root development
VL - 18
ER -
TY - CHAP
AB - Different distance metrics produce Voronoi diagrams with different properties. It is a well-known that on the (real) 2D plane or even on any 3D plane, a Voronoi diagram (VD) based on the Euclidean distance metric produces convex Voronoi regions. In this paper, we first show that this metric produces a persistent VD on the 2D digital plane, as it comprises digitally convex Voronoi regions and hence correctly approximates the corresponding VD on the 2D real plane. Next, we show that on a 3D digital plane D, the Euclidean metric spanning over its voxel set does not guarantee a digital VD which is persistent with the real-space VD. As a solution, we introduce a novel concept of functional-plane-convexity, which is ensured by the Euclidean metric spanning over the pedal set of D. Necessary proofs and some visual result have been provided to adjudge the merit and usefulness of the proposed concept.
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5803
SN - 0302-9743
T2 - Combinatorial image analysis
TI - Construction of persistent Voronoi diagram on 3D digital plane
VL - 10256
ER -
TY - CONF
AB - Tunneling of a particle through a potential barrier remains one of the most remarkable quantum phenomena. Owing to advances in laser technology, electric fields comparable to those electrons experience in atoms are readily generated and open opportunities to dynamically investigate the process of electron tunneling through the potential barrier formed by the superposition of both laser and atomic fields. Attosecond-time and angstrom-space resolution of the strong laser-field technique allow to address fundamental questions related to tunneling, which are still open and debated: Which time is spent under the barrier and what momentum is picked up by the particle in the meantime? In this combined experimental and theoretical study we demonstrate that for strong-field ionization the leading quantum mechanical Wigner treatment for the time resolved description of tunneling is valid. We achieve a high sensitivity on the tunneling barrier and unambiguously isolate its effects by performing a differential study of two systems with almost identical tunneling geometry. Moreover, working with a low frequency laser, we essentially limit the non-adiabaticity of the process as a major source of uncertainty. The agreement between experiment and theory implies two substantial corrections with respect to the widely employed quasiclassical treatment: In addition to a non-vanishing longitudinal momentum along the laser field-direction we provide clear evidence for a non-zero tunneling time delay. This addresses also the fundamental question how the transition occurs from the tunnel barrier to free space classical evolution of the ejected electron.
AU - Camus, Nicolas
AU - Yakaboylu, Enderalp
AU - Fechner, Lutz
AU - Klaiber, Michael
AU - Laux, Martin
AU - Mi, Yonghao
AU - Hatsagortsyan, Karen
AU - Pfeifer, Thomas
AU - Keitel, Cristoph
AU - Moshammer, Robert
ID - 313
IS - 1
SN - 17426588
TI - Experimental evidence for Wigner's tunneling time
VL - 999
ER -
TY - JOUR
AB - The first hundred attoseconds of the electron dynamics during strong field tunneling ionization are investigated. We quantify theoretically how the electron’s classical trajectories in the continuum emerge from the tunneling process and test the results with those achieved in parallel from attoclock measurements. An especially high sensitivity on the tunneling barrier is accomplished here by comparing the momentum distributions of two atomic species of slightly deviating atomic potentials (argon and krypton) being ionized under absolutely identical conditions with near-infrared laser pulses (1300 nm). The agreement between experiment and theory provides clear evidence for a nonzero tunneling time delay and a nonvanishing longitudinal momentum of the electron at the “tunnel exit.”
AU - Camus, Nicolas
AU - Yakaboylu, Enderalp
AU - Fechner, Lutz
AU - Klaiber, Michael
AU - Laux, Martin
AU - Mi, Yonghao
AU - Hatsagortsyan, Karen Z.
AU - Pfeifer, Thomas
AU - Keitel, Christoph H.
AU - Moshammer, Robert
ID - 6013
IS - 2
JF - Physical Review Letters
SN - 0031-9007
TI - Experimental evidence for quantum tunneling time
VL - 119
ER -
TY - CONF
AB - Position based cryptography (PBC), proposed in the seminal work of Chandran, Goyal, Moriarty, and Ostrovsky (SIAM J. Computing, 2014), aims at constructing cryptographic schemes in which the identity of the user is his geographic position. Chandran et al. construct PBC schemes for secure positioning and position-based key agreement in the bounded-storage model (Maurer, J. Cryptology, 1992). Apart from bounded memory, their security proofs need a strong additional restriction on the power of the adversary: he cannot compute joint functions of his inputs. Removing this assumption is left as an open problem. We show that an answer to this question would resolve a long standing open problem in multiparty communication complexity: finding a function that is hard to compute with low communication complexity in the simultaneous message model, but easy to compute in the fully adaptive model. On a more positive side: we also show some implications in the other direction, i.e.: we prove that lower bounds on the communication complexity of certain multiparty problems imply existence of PBC primitives. Using this result we then show two attractive ways to “bypass” our hardness result: the first uses the random oracle model, the second weakens the locality requirement in the bounded-storage model to online computability. The random oracle construction is arguably one of the simplest proposed so far in this area. Our results indicate that constructing improved provably secure protocols for PBC requires a better understanding of multiparty communication complexity. This is yet another example where negative results in one area (in our case: lower bounds in multiparty communication complexity) can be used to construct secure cryptographic schemes.
AU - Brody, Joshua
AU - Dziembowski, Stefan
AU - Faust, Sebastian
AU - Pietrzak, Krzysztof Z
ED - Kalai, Yael
ED - Reyzin, Leonid
ID - 605
SN - 978-331970499-9
TI - Position based cryptography and multiparty communication complexity
VL - 10677
ER -
TY - CHAP
AB - In several settings of physics and chemistry one has to deal with molecules interacting with some kind of an external environment, be it a gas, a solution, or a crystal surface. Understanding molecular processes in the presence of such a many-particle bath is inherently challenging, and usually requires large-scale numerical computations. Here, we present an alternative approach to the problem, based on the notion of the angulon quasiparticle. We show that molecules rotating inside superfluid helium nanodroplets and Bose–Einstein condensates form angulons, and therefore can be described by straightforward solutions of a simple microscopic Hamiltonian. Casting the problem in the language of angulons allows us not only to greatly simplify it, but also to gain insights into the origins of the observed phenomena and to make predictions for future experimental studies.
AU - Lemeshko, Mikhail
AU - Schmidt, Richard
ED - Dulieu, Oliver
ED - Osterwalder, Andreas
ID - 604
SN - 20413181
T2 - Cold Chemistry: Molecular Scattering and Reactivity Near Absolute Zero
TI - Molecular impurities interacting with a many-particle environment: From ultracold gases to helium nanodroplets
VL - 11
ER -
TY - CONF
AB - Several cryptographic schemes and applications are based on functions that are both reasonably efficient to compute and moderately hard to invert, including client puzzles for Denial-of-Service protection, password protection via salted hashes, or recent proof-of-work blockchain systems. Despite their wide use, a definition of this concept has not yet been distilled and formalized explicitly. Instead, either the applications are proven directly based on the assumptions underlying the function, or some property of the function is proven, but the security of the application is argued only informally. The goal of this work is to provide a (universal) definition that decouples the efforts of designing new moderately hard functions and of building protocols based on them, serving as an interface between the two. On a technical level, beyond the mentioned definitions, we instantiate the model for four different notions of hardness. We extend the work of Alwen and Serbinenko (STOC 2015) by providing a general tool for proving security for the first notion of memory-hard functions that allows for provably secure applications. The tool allows us to recover all of the graph-theoretic techniques developed for proving security under the older, non-composable, notion of security used by Alwen and Serbinenko. As an application of our definition of moderately hard functions, we prove the security of two different schemes for proofs of effort (PoE). We also formalize and instantiate the concept of a non-interactive proof of effort (niPoE), in which the proof is not bound to a particular communication context but rather any bit-string chosen by the prover.
AU - Alwen, Joel F
AU - Tackmann, Björn
ED - Kalai, Yael
ED - Reyzin, Leonid
ID - 609
SN - 978-331970499-9
TI - Moderately hard functions: Definition, instantiations, and applications
VL - 10677
ER -
TY - JOUR
AB - The fact that the complete graph K5 does not embed in the plane has been generalized in two independent directions. On the one hand, the solution of the classical Heawood problem for graphs on surfaces established that the complete graph Kn embeds in a closed surface M (other than the Klein bottle) if and only if (n−3)(n−4) ≤ 6b1(M), where b1(M) is the first Z2-Betti number of M. On the other hand, van Kampen and Flores proved that the k-skeleton of the n-dimensional simplex (the higher-dimensional analogue of Kn+1) embeds in R2k if and only if n ≤ 2k + 1. Two decades ago, Kühnel conjectured that the k-skeleton of the n-simplex embeds in a compact, (k − 1)-connected 2k-manifold with kth Z2-Betti number bk only if the following generalized Heawood inequality holds: (k+1 n−k−1) ≤ (k+1 2k+1)bk. This is a common generalization of the case of graphs on surfaces as well as the van Kampen–Flores theorem. In the spirit of Kühnel’s conjecture, we prove that if the k-skeleton of the n-simplex embeds in a compact 2k-manifold with kth Z2-Betti number bk, then n ≤ 2bk(k 2k+2)+2k+4. This bound is weaker than the generalized Heawood inequality, but does not require the assumption that M is (k−1)-connected. Our results generalize to maps without q-covered points, in the spirit of Tverberg’s theorem, for q a prime power. Our proof uses a result of Volovikov about maps that satisfy a certain homological triviality condition.
AU - Goaoc, Xavier
AU - Mabillard, Isaac
AU - Paták, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ID - 610
IS - 2
JF - Israel Journal of Mathematics
TI - On generalized Heawood inequalities for manifolds: A van Kampen–Flores type nonembeddability result
VL - 222
ER -
TY - JOUR
AB - Small RNAs (sRNAs) regulate genes in plants and animals. Here, we show that population-wide differences in color patterns in snapdragon flowers are caused by an inverted duplication that generates sRNAs. The complexity and size of the transcripts indicate that the duplication represents an intermediate on the pathway to microRNA evolution. The sRNAs repress a pigment biosynthesis gene, creating a yellow highlight at the site of pollinator entry. The inverted duplication exhibits steep clines in allele frequency in a natural hybrid zone, showing that the allele is under selection. Thus, regulatory interactions of evolutionarily recent sRNAs can be acted upon by selection and contribute to the evolution of phenotypic diversity.
AU - Bradley, Desmond
AU - Xu, Ping
AU - Mohorianu, Irina
AU - Whibley, Annabel
AU - Field, David
AU - Tavares, Hugo
AU - Couchman, Matthew
AU - Copsey, Lucy
AU - Carpenter, Rosemary
AU - Li, Miaomiao
AU - Li, Qun
AU - Xue, Yongbiao
AU - Dalmay, Tamas
AU - Coen, Enrico
ID - 611
IS - 6365
JF - Science
SN - 00368075
TI - Evolution of flower color pattern through selection on regulatory small RNAs
VL - 358
ER -
TY - JOUR
AB - Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior.
AU - Chait, Remy P
AU - Ruess, Jakob
AU - Bergmiller, Tobias
AU - Tkacik, Gasper
AU - Guet, Calin C
ID - 613
IS - 1
JF - Nature Communications
SN - 20411723
TI - Shaping bacterial population behavior through computer interfaced control of individual cells
VL - 8
ER -
TY - JOUR
AB - We show that the Dyson Brownian Motion exhibits local universality after a very short time assuming that local rigidity and level repulsion of the eigenvalues hold. These conditions are verified, hence bulk spectral universality is proven, for a large class of Wigner-like matrices, including deformed Wigner ensembles and ensembles with non-stochastic variance matrices whose limiting densities differ from Wigner's semicircle law.
AU - Erdös, László
AU - Schnelli, Kevin
ID - 615
IS - 4
JF - Annales de l'institut Henri Poincare (B) Probability and Statistics
SN - 02460203
TI - Universality for random matrix flows with time dependent density
VL - 53
ER -
TY - JOUR
AB - The mammalian cerebral cortex is responsible for higher cognitive functions such as perception, consciousness, and acquiring and processing information. The neocortex is organized into six distinct laminae, each composed of a rich diversity of cell types which assemble into highly complex cortical circuits. Radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. Here, we discuss recent discoveries emerging from clonal lineage analysis at the single RGP cell level that provide us with an inaugural quantitative framework of RGP lineage progression. We further discuss the importance of the relative contribution of intrinsic gene functions and non-cell-autonomous or community effects in regulating RGP proliferation behavior and lineage progression.
AU - Beattie, Robert J
AU - Hippenmeyer, Simon
ID - 621
IS - 24
JF - FEBS letters
SN - 00145793
TI - Mechanisms of radial glia progenitor cell lineage progression
VL - 591
ER -
TY - CHAP
AB - Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research. Extracerebral influences on the physiology could begin in utero and contribute to changes in the brain and in the development of other body systems and further lead to epigenetic changes. Therefore, multiple recent studies have aimed at elucidating the role of gene-environment interactions in ASD. Here we provide an overview on the extracerebral systems that might play an important associative role in ASD and review evidence regarding the potential roles of inflammation, trace metals, metabolism, genetic susceptibility, enteric nervous system function and the microbiota of the gastrointestinal (GI) tract on the development of endophenotypes in animal models of ASD. By influencing environmental conditions, it might be possible to reduce or limit the severity of ASD pathology.
AU - Hill Yardin, Elisa
AU - Mckeown, Sonja
AU - Novarino, Gaia
AU - Grabrucker, Andreas
ED - Schmeisser, Michael
ED - Boekers, Tobias
ID - 623
SN - 03015556
T2 - Translational Anatomy and Cell Biology of Autism Spectrum Disorder
TI - Extracerebral dysfunction in animal models of autism spectrum disorder
VL - 224
ER -
TY - JOUR
AB - Our focus here is on the infinitesimal model. In this model, one or several quantitative traits are described as the sum of a genetic and a non-genetic component, the first being distributed within families as a normal random variable centred at the average of the parental genetic components, and with a variance independent of the parental traits. Thus, the variance that segregates within families is not perturbed by selection, and can be predicted from the variance components. This does not necessarily imply that the trait distribution across the whole population should be Gaussian, and indeed selection or population structure may have a substantial effect on the overall trait distribution. One of our main aims is to identify some general conditions on the allelic effects for the infinitesimal model to be accurate. We first review the long history of the infinitesimal model in quantitative genetics. Then we formulate the model at the phenotypic level in terms of individual trait values and relationships between individuals, but including different evolutionary processes: genetic drift, recombination, selection, mutation, population structure, …. We give a range of examples of its application to evolutionary questions related to stabilising selection, assortative mating, effective population size and response to selection, habitat preference and speciation. We provide a mathematical justification of the model as the limit as the number M of underlying loci tends to infinity of a model with Mendelian inheritance, mutation and environmental noise, when the genetic component of the trait is purely additive. We also show how the model generalises to include epistatic effects. We prove in particular that, within each family, the genetic components of the individual trait values in the current generation are indeed normally distributed with a variance independent of ancestral traits, up to an error of order 1∕M. Simulations suggest that in some cases the convergence may be as fast as 1∕M.
AU - Barton, Nicholas H
AU - Etheridge, Alison
AU - Véber, Amandine
ID - 626
JF - Theoretical Population Biology
SN - 00405809
TI - The infinitesimal model: Definition derivation and implications
VL - 118
ER -
TY - CHAP
AB - In the analysis of reactive systems a quantitative objective assigns a real value to every trace of the system. The value decision problem for a quantitative objective requires a trace whose value is at least a given threshold, and the exact value decision problem requires a trace whose value is exactly the threshold. We compare the computational complexity of the value and exact value decision problems for classical quantitative objectives, such as sum, discounted sum, energy, and mean-payoff for two standard models of reactive systems, namely, graphs and graph games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ED - Aceto, Luca
ED - Bacci, Giorgio
ED - Ingólfsdóttir, Anna
ED - Legay, Axel
ED - Mardare, Radu
ID - 625
SN - 0302-9743
T2 - Models, Algorithms, Logics and Tools
TI - The cost of exactness in quantitative reachability
VL - 10460
ER -
TY - JOUR
AB - Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allows Escherichia coli to alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin module mazEF that is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigate mazEF expression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest that mazEF transcription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in the grcA reporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein.
AU - Nikolic, Nela
AU - Didara, Zrinka
AU - Moll, Isabella
ID - 624
IS - 9
JF - PeerJ
SN - 21678359
TI - MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations
VL - 2017
ER -
TY - JOUR
AB - Beige adipocytes are a new type of recruitable brownish adipocytes, with highly mitochondrial membrane uncoupling protein 1 expression and thermogenesis. Beige adipocytes were found among white adipocytes, especially in subcutaneous white adipose tissue (sWAT). Therefore, beige adipocytes may be involved in the regulation of energy metabolism and fat deposition. Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the thermogenic function of brown adiposytes. However, the involvement of TRPM8 in the thermogenic function of WAT remains unexplored. Our data revealed that TRPM8 was expressed in mouse white adipocytes at mRNA, protein and functional levels. The mRNA expression of Trpm8 was significantly increased in the differentiated white adipocytes than pre-adipocytes. Moreover, activation of TRPM8 by menthol enhanced the expression of thermogenic genes in cultured white aidpocytes. And menthol-induced increases of the thermogenic genes in white adipocytes was inhibited by either KT5720 (a protein kinase A inhibitor) or BAPTA-AM. In addition, high fat diet (HFD)-induced obesity in mice was significantly recovered by co-treatment with menthol. Dietary menthol enhanced WAT "browning" and improved glucose metabolism in HFD-induced obesity mice as well. Therefore, we concluded that TRPM8 might be involved in WAT "browning" by increasing the expression levels of genes related to thermogenesis and energy metabolism. And dietary menthol could be a novel approach for combating human obesity and related metabolic diseases.
AU - Jiang, Changyu
AU - Zhai, Ming-Zhu
AU - Yan, Dong
AU - Li, Da
AU - Li, Chen
AU - Zhang, Yonghong
AU - Xiao, Lizu
AU - Xiong, Donglin
AU - Deng, Qiwen
AU - Sun, Wuping
ID - 627
IS - 43
JF - Oncotarget
SN - 19492553
TI - Dietary menthol-induced TRPM8 activation enhances WAT “browning” and ameliorates diet-induced obesity
VL - 8
ER -
TY - CONF
AB - We consider the problem of developing automated techniques for solving recurrence relations to aid the expected-runtime analysis of programs. The motivation is that several classical textbook algorithms have quite efficient expected-runtime complexity, whereas the corresponding worst-case bounds are either inefficient (e.g., Quick-Sort), or completely ineffective (e.g., Coupon-Collector). Since the main focus of expected-runtime analysis is to obtain efficient bounds, we consider bounds that are either logarithmic, linear or almost-linear (O(log n), O(n), O(n · log n), respectively, where n represents the input size). Our main contribution is an efficient (simple linear-time algorithm) sound approach for deriving such expected-runtime bounds for the analysis of recurrence relations induced by randomized algorithms. The experimental results show that our approach can efficiently derive asymptotically optimal expected-runtime bounds for recurrences of classical randomized algorithms, including Randomized-Search, Quick-Sort, Quick-Select, Coupon-Collector, where the worst-case bounds are either inefficient (such as linear as compared to logarithmic expected-runtime complexity, or quadratic as compared to linear or almost-linear expected-runtime complexity), or ineffective.
AU - Chatterjee, Krishnendu
AU - Fu, Hongfei
AU - Murhekar, Aniket
ED - Majumdar, Rupak
ED - Kunčak, Viktor
ID - 628
SN - 978-331963386-2
TI - Automated recurrence analysis for almost linear expected runtime bounds
VL - 10426
ER -
TY - CHAP
AB - Even simple cells like bacteria have precisely regulated cellular anatomies, which allow them to grow, divide and to respond to internal or external cues with high fidelity. How spatial and temporal intracellular organization in prokaryotic cells is achieved and maintained on the basis of locally interacting proteins still remains largely a mystery. Bulk biochemical assays with purified components and in vivo experiments help us to approach key cellular processes from two opposite ends, in terms of minimal and maximal complexity. However, to understand how cellular phenomena emerge, that are more than the sum of their parts, we have to assemble cellular subsystems step by step from the bottom up. Here, we review recent in vitro reconstitution experiments with proteins of the bacterial cell division machinery and illustrate how they help to shed light on fundamental cellular mechanisms that constitute spatiotemporal order and regulate cell division.
AU - Loose, Martin
AU - Zieske, Katja
AU - Schwille, Petra
ID - 629
T2 - Prokaryotic Cytoskeletons
TI - Reconstitution of protein dynamics involved in bacterial cell division
VL - 84
ER -
TY - CONF
AB - Background: Standards have become available to share semantically encoded vital parameters from medical devices, as required for example by personal healthcare records. Standardised sharing of biosignal data largely remains open. Objectives: The goal of this work is to explore available biosignal file format and data exchange standards and profiles, and to conceptualise end-To-end solutions. Methods: The authors reviewed and discussed available biosignal file format standards with other members of international standards development organisations (SDOs). Results: A raw concept for standards based acquisition, storage, archiving and sharing of biosignals was developed. The GDF format may serve for storing biosignals. Signals can then be shared using FHIR resources and may be stored on FHIR servers or in DICOM archives, with DICOM waveforms as one possible format. Conclusion: Currently a group of international SDOs (e.g. HL7, IHE, DICOM, IEEE) is engaged in intensive discussions. This discussion extends existing work that already was adopted by large implementer communities. The concept presented here only reports the current status of the discussion in Austria. The discussion will continue internationally, with results to be expected over the coming years.
AU - Sauermann, Stefan
AU - David, Veronika
AU - Schlögl, Alois
AU - Egelkraut, Reinhard
AU - Frohner, Matthias
AU - Pohn, Birgit
AU - Urbauer, Philipp
AU - Mense, Alexander
ID - 630
SN - 978-161499758-0
TI - Biosignals standards and FHIR: The way to go
VL - 236
ER -
TY - JOUR
AB - We consider a 2D quantum system of N bosons in a trapping potential |x|s, interacting via a pair potential of the form N2β−1 w(Nβ x). We show that for all 0 < β < (s + 1)/(s + 2), the leading order behavior of ground states of the many-body system is described in the large N limit by the corresponding cubic nonlinear Schrödinger energy functional. Our result covers the focusing case (w < 0) where even the stability of the many-body system is not obvious. This answers an open question mentioned by X. Chen and J. Holmer for harmonic traps (s = 2). Together with the BBGKY hierarchy approach used by these authors, our result implies the convergence of the many-body quantum dynamics to the focusing NLS equation with harmonic trap for all 0 < β < 3/4.
AU - Lewin, Mathieu
AU - Nam, Phan
AU - Rougerie, Nicolas
ID - 632
IS - 6
JF - Proceedings of the American Mathematical Society
TI - A note on 2D focusing many boson systems
VL - 145
ER -
TY - CHAP
AB - As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental condition, long-time consensus was that its hallmark features are irreversible. However, several studies from recent years using defined mouse models of ASD have provided clear evidence that in mice neurobiological and behavioural alterations can be ameliorated or even reversed by genetic restoration or pharmacological treatment either before or after symptom onset. Here, we review findings on genetic and pharmacological reversibility of phenotypes in mouse models of ASD. Our review should give a comprehensive overview on both aspects and encourage future studies to better understand the underlying molecular mechanisms that might be translatable from animals to humans.
AU - Schroeder, Jan
AU - Deliu, Elena
AU - Novarino, Gaia
AU - Schmeisser, Michael
ED - Schmeisser, Michael
ED - Boekers, Tobias
ID - 634
T2 - Translational Anatomy and Cell Biology of Autism Spectrum Disorder
TI - Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder
VL - 224
ER -
TY - CONF
AB - A Rapidly-exploring Random Tree (RRT) is an algorithm which can search a non-convex region of space by incrementally building a space-filling tree. The tree is constructed from random points drawn from system’s state space and is biased to grow towards large unexplored areas in the system. RRT can provide better coverage of a system’s possible behaviors compared with random simulations, but is more lightweight than full reachability analysis. In this paper, we explore some of the design decisions encountered while implementing a hybrid extension of the RRT algorithm, which have not been elaborated on before. In particular, we focus on handling non-determinism, which arises due to discrete transitions. We introduce the notion of important points to account for this phenomena. We showcase our ideas using heater and navigation benchmarks.
AU - Bak, Stanley
AU - Bogomolov, Sergiy
AU - Henzinger, Thomas A
AU - Kumar, Aviral
ED - Abate, Alessandro
ED - Bodo, Sylvie
ID - 633
SN - 978-331963500-2
TI - Challenges and tool implementation of hybrid rapidly exploring random trees
VL - 10381
ER -
TY - CONF
AB - Memory-hard functions (MHFs) are hash algorithms whose evaluation cost is dominated by memory cost. As memory, unlike computation, costs about the same across different platforms, MHFs cannot be evaluated at significantly lower cost on dedicated hardware like ASICs. MHFs have found widespread applications including password hashing, key derivation, and proofs-of-work. This paper focuses on scrypt, a simple candidate MHF designed by Percival, and described in RFC 7914. It has been used within a number of cryptocurrencies (e.g., Litecoin and Dogecoin) and has been an inspiration for Argon2d, one of the winners of the recent password-hashing competition. Despite its popularity, no rigorous lower bounds on its memory complexity are known. We prove that scrypt is optimally memory-hard, i.e., its cumulative memory complexity (cmc) in the parallel random oracle model is Ω(n2w), where w and n are the output length and number of invocations of the underlying hash function, respectively. High cmc is a strong security target for MHFs introduced by Alwen and Serbinenko (STOC’15) which implies high memory cost even for adversaries who can amortize the cost over many evaluations and evaluate the underlying hash functions many times in parallel. Our proof is the first showing optimal memory-hardness for any MHF. Our result improves both quantitatively and qualitatively upon the recent work by Alwen et al. (EUROCRYPT’16) who proved a weaker lower bound of Ω(n2w/ log2 n) for a restricted class of adversaries.
AU - Alwen, Joel F
AU - Chen, Binchi
AU - Pietrzak, Krzysztof Z
AU - Reyzin, Leonid
AU - Tessaro, Stefano
ED - Coron, Jean-Sébastien
ED - Buus Nielsen, Jesper
ID - 635
SN - 978-331956616-0
TI - Scrypt is maximally memory hard
VL - 10212
ER -
TY - CONF
AB - Signal regular expressions can specify sequential properties of real-valued signals based on threshold conditions, regular operations, and duration constraints. In this paper we endow them with a quantitative semantics which indicates how robustly a signal matches or does not match a given expression. First, we show that this semantics is a safe approximation of a distance between the signal and the language defined by the expression. Then, we consider the robust matching problem, that is, computing the quantitative semantics of every segment of a given signal relative to an expression. We present an algorithm that solves this problem for piecewise-constant and piecewise-linear signals and show that for such signals the robustness map is a piecewise-linear function. The availability of an indicator describing how robustly a signal segment matches some regular pattern provides a general framework for quantitative monitoring of cyber-physical systems.
AU - Bakhirkin, Alexey
AU - Ferrere, Thomas
AU - Maler, Oded
AU - Ulus, Dogan
ED - Abate, Alessandro
ED - Geeraerts, Gilles
ID - 636
SN - 978-331965764-6
TI - On the quantitative semantics of regular expressions over real-valued signals
VL - 10419
ER -
TY - GEN
AB - This book constitutes the refereed proceedings of the 9th InternationalWorkshop on Numerical Software Verification, NSV 2016, held in Toronto, ON, Canada in July 2011 - colocated with CAV 2016, the 28th International Conference on Computer Aided Verification.
The NSV workshop is dedicated to the development of logical and mathematical techniques for the reasoning about programmability and reliability.
ED - Bogomolov, Sergiy
ED - Martel, Matthieu
ED - Prabhakar, Pavithra
ID - 638
SN - 0302-9743
TI - Numerical Software Verification
VL - 10152
ER -
TY - CONF
AB - Data-independent Memory Hard Functions (iMHFS) are finding a growing number of applications in security; especially in the domain of password hashing. An important property of a concrete iMHF is specified by fixing a directed acyclic graph (DAG) Gn on n nodes. The quality of that iMHF is then captured by the following two pebbling complexities of Gn: – The parallel cumulative pebbling complexity Π∥cc(Gn) must be as high as possible (to ensure that the amortized cost of computing the function on dedicated hardware is dominated by the cost of memory). – The sequential space-time pebbling complexity Πst(Gn) should be as close as possible to Π∥cc(Gn) (to ensure that using many cores in parallel and amortizing over many instances does not give much of an advantage). In this paper we construct a family of DAGs with best possible parameters in an asymptotic sense, i.e., where Π∥cc(Gn) = Ω(n2/ log(n)) (which matches a known upper bound) and Πst(Gn) is within a constant factor of Π∥cc(Gn). Our analysis relies on a new connection between the pebbling complexity of a DAG and its depth-robustness (DR) – a well studied combinatorial property. We show that high DR is sufficient for high Π∥cc. Alwen and Blocki (CRYPTO’16) showed that high DR is necessary and so, together, these results fully characterize DAGs with high Π∥cc in terms of DR. Complementing these results, we provide new upper and lower bounds on the Π∥cc of several important candidate iMHFs from the literature. We give the first lower bounds on the memory hardness of the Catena and Balloon Hashing functions in a parallel model of computation and we give the first lower bounds of any kind for (a version) of Argon2i. Finally we describe a new class of pebbling attacks improving on those of Alwen and Blocki (CRYPTO’16). By instantiating these attacks we upperbound the Π∥cc of the Password Hashing Competition winner Argon2i and one of the Balloon Hashing functions by O (n1.71). We also show an upper bound of O(n1.625) for the Catena functions and the two remaining Balloon Hashing functions.
AU - Alwen, Joel F
AU - Blocki, Jeremiah
AU - Pietrzak, Krzysztof Z
ED - Coron, Jean-Sébastien
ED - Buus Nielsen, Jesper
ID - 640
SN - 978-331956616-0
TI - Depth-robust graphs and their cumulative memory complexity
VL - 10212
ER -
TY - CONF
AB - We introduce two novel methods for learning parameters of graphical models for image labelling. The following two tasks underline both methods: (i) perturb model parameters based on given features and ground truth labelings, so as to exactly reproduce these labelings as optima of the local polytope relaxation of the labelling problem; (ii) train a predictor for the perturbed model parameters so that improved model parameters can be applied to the labelling of novel data. Our first method implements task (i) by inverse linear programming and task (ii) using a regressor e.g. a Gaussian process. Our second approach simultaneously solves tasks (i) and (ii) in a joint manner, while being restricted to linearly parameterised predictors. Experiments demonstrate the merits of both approaches.
AU - Trajkovska, Vera
AU - Swoboda, Paul
AU - Åström, Freddie
AU - Petra, Stefanie
ED - Lauze, François
ED - Dong, Yiqiu
ED - Bjorholm Dahl, Anders
ID - 641
SN - 978-331958770-7
TI - Graphical model parameter learning by inverse linear programming
VL - 10302
ER -
TY - GEN
AB - Synchronous programs are easy to specify because the side effects of an operation are finished by the time the invocation of the operation returns to the caller. Asynchronous programs, on the other hand, are difficult to specify because there are side effects due to pending computation scheduled as a result of the invocation of an operation. They are also difficult to verify because of the large number of possible interleavings of concurrent asynchronous computation threads. We show that specifications and correctness proofs for asynchronous programs can be structured by introducing the fiction, for proof purposes, that intermediate, non-quiescent states of asynchronous operations can be ignored. Then, the task of specification becomes relatively simple and the task of verification can be naturally decomposed into smaller sub-tasks. The sub-tasks iteratively summarize, guided by the structure of an asynchronous program, the atomic effect of non-atomic operations and the synchronous effect of asynchronous operations. This structuring of specifications and proofs corresponds to the introduction of multiple layers of stepwise refinement for asynchronous programs. We present the first proof rule, called synchronization, to reduce asynchronous invocations on a lower layer to synchronous invocations on a higher layer. We implemented our proof method in CIVL and evaluated it on a collection of benchmark programs.
AU - Henzinger, Thomas A
AU - Kragl, Bernhard
AU - Qadeer, Shaz
ID - 6426
SN - 2664-1690
TI - Synchronizing the asynchronous
ER -
TY - JOUR
AB - It has been reported that nicotinamide-overload induces oxidative stress associated with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance tests (GTT) were carried out in adult Sprague-Dawley rats treated with or without cumulative doses of B vitamins. More specifically, insulin tolerance tests (ITT) were also carried out in adult Sprague-Dawley rats treated with or without cumulative doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration significantly increased the plasma H2O2 levels associated with high insulin levels. Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration of nicotinic acid, another form of Vitamin B3, also significantly increased plasma insulin level and H2O2 generation. Moreover, cumulative administration of nicotinic acid or nicotinamide impaired glucose metabolism. This study suggested that excess Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance.
AU - Sun, Wuping
AU - Zhai, Ming-Zhu
AU - Zhou, Qian
AU - Qian, Chengrui
AU - Jiang, Changyu
ID - 643
IS - 4
JF - Chinese Journal of Physiology
SN - 03044920
TI - Effects of B vitamins overload on plasma insulin level and hydrogen peroxide generation in rats
VL - 60
ER -
TY - JOUR
AB - Cauchy problems with SPDEs on the whole space are localized to Cauchy problems on a ball of radius R. This localization reduces various kinds of spatial approximation schemes to finite dimensional problems. The error is shown to be exponentially small. As an application, a numerical scheme is presented which combines the localization and the space and time discretization, and thus is fully implementable.
AU - Gerencser, Mate
AU - Gyöngy, István
ID - 642
IS - 307
JF - Mathematics of Computation
SN - 00255718
TI - Localization errors in solving stochastic partial differential equations in the whole space
VL - 86
ER -
TY - CONF
AB - Markov decision processes (MDPs) are standard models for probabilistic systems with non-deterministic behaviours. Long-run average rewards provide a mathematically elegant formalism for expressing long term performance. Value iteration (VI) is one of the simplest and most efficient algorithmic approaches to MDPs with other properties, such as reachability objectives. Unfortunately, a naive extension of VI does not work for MDPs with long-run average rewards, as there is no known stopping criterion. In this work our contributions are threefold. (1) We refute a conjecture related to stopping criteria for MDPs with long-run average rewards. (2) We present two practical algorithms for MDPs with long-run average rewards based on VI. First, we show that a combination of applying VI locally for each maximal end-component (MEC) and VI for reachability objectives can provide approximation guarantees. Second, extending the above approach with a simulation-guided on-demand variant of VI, we present an anytime algorithm that is able to deal with very large models. (3) Finally, we present experimental results showing that our methods significantly outperform the standard approaches on several benchmarks.
AU - Ashok, Pranav
AU - Chatterjee, Krishnendu
AU - Daca, Przemyslaw
AU - Kretinsky, Jan
AU - Meggendorfer, Tobias
ED - Majumdar, Rupak
ED - Kunčak, Viktor
ID - 645
SN - 978-331963386-2
TI - Value iteration for long run average reward in markov decision processes
VL - 10426
ER -
TY - JOUR
AB - An instance of the valued constraint satisfaction problem (VCSP) is given by a finite set of variables, a finite domain of labels, and a sum of functions, each function depending on a subset of the variables. Each function can take finite values specifying costs of assignments of labels to its variables or the infinite value, which indicates an infeasible assignment. The goal is to find an assignment of labels to the variables that minimizes the sum. We study, assuming that P 6= NP, how the complexity of this very general problem depends on the set of functions allowed in the instances, the so-called constraint language. The case when all allowed functions take values in f0;1g corresponds to ordinary CSPs, where one deals only with the feasibility issue, and there is no optimization. This case is the subject of the algebraic CSP dichotomy conjecture predicting for which constraint languages CSPs are tractable (i.e., solvable in polynomial time) and for which they are NP-hard. The case when all allowed functions take only finite values corresponds to a finitevalued CSP, where the feasibility aspect is trivial and one deals only with the optimization issue. The complexity of finite-valued CSPs was fully classified by Thapper and Živný. An algebraic necessary condition for tractability of a general-valued CSP with a fixed constraint language was recently given by Kozik and Ochremiak. As our main result, we prove that if a constraint language satisfies this algebraic necessary condition, and the feasibility CSP (i.e., the problem of deciding whether a given instance has a feasible solution) corresponding to the VCSP with this language is tractable, then the VCSP is tractable. The algorithm is a simple combination of the assumed algorithm for the feasibility CSP and the standard LP relaxation. As a corollary, we obtain that a dichotomy for ordinary CSPs would imply a dichotomy for general-valued CSPs.
AU - Kolmogorov, Vladimir
AU - Krokhin, Andrei
AU - Rolinek, Michal
ID - 644
IS - 3
JF - SIAM Journal on Computing
TI - The complexity of general-valued CSPs
VL - 46
ER -
TY - CONF
AB - We present a novel convex relaxation and a corresponding inference algorithm for the non-binary discrete tomography problem, that is, reconstructing discrete-valued images from few linear measurements. In contrast to state of the art approaches that split the problem into a continuous reconstruction problem for the linear measurement constraints and a discrete labeling problem to enforce discrete-valued reconstructions, we propose a joint formulation that addresses both problems simultaneously, resulting in a tighter convex relaxation. For this purpose a constrained graphical model is set up and evaluated using a novel relaxation optimized by dual decomposition. We evaluate our approach experimentally and show superior solutions both mathematically (tighter relaxation) and experimentally in comparison to previously proposed relaxations.
AU - Kuske, Jan
AU - Swoboda, Paul
AU - Petra, Stefanie
ED - Lauze, François
ED - Dong, Yiqiu
ED - Bjorholm Dahl, Anders
ID - 646
SN - 978-331958770-7
TI - A novel convex relaxation for non binary discrete tomography
VL - 10302
ER -
TY - CONF
AB - Pseudoentropy has found a lot of important applications to cryptography and complexity theory. In this paper we focus on the foundational problem that has not been investigated so far, namely by how much pseudoentropy (the amount seen by computationally bounded attackers) diﬀers from its information-theoretic counterpart (seen by unbounded observers), given certain limits on attacker’s computational power? We provide the following answer for HILL pseudoentropy, which exhibits a threshold behavior around the size exponential in the entropy amount:– If the attacker size (s) and advantage () satisfy s (formula presented) where k is the claimed amount of pseudoentropy, then the pseudoentropy boils down to the information-theoretic smooth entropy. – If s (formula presented) then pseudoentropy could be arbitrarily bigger than the information-theoretic smooth entropy. Besides answering the posted question, we show an elegant application of our result to the complexity theory, namely that it implies the clas-sical result on the existence of functions hard to approximate (due to Pippenger). In our approach we utilize non-constructive techniques: the duality of linear programming and the probabilistic method.
AU - Skórski, Maciej
ED - Jäger, Gerhard
ED - Steila, Silvia
ID - 648
SN - 978-331955910-0
TI - On the complexity of breaking pseudoentropy
VL - 10185
ER -
TY - CHAP
AB - We give a short overview on a recently developed notion of Ricci curvature for discrete spaces. This notion relies on geodesic convexity properties of the relative entropy along geodesics in the space of probability densities, for a metric which is similar to (but different from) the 2-Wasserstein metric. The theory can be considered as a discrete counterpart to the theory of Ricci curvature for geodesic measure spaces developed by Lott–Sturm–Villani.
AU - Maas, Jan
ED - Najman, Laurent
ED - Romon, Pascal
ID - 649
SN - 978-3-319-58001-2
T2 - Modern Approaches to Discrete Curvature
TI - Entropic Ricci curvature for discrete spaces
VL - 2184
ER -
TY - CONF
AB - In this work we present a short and unified proof for the Strong and Weak Regularity Lemma, based on the cryptographic tech-nique called low-complexity approximations. In short, both problems reduce to a task of finding constructively an approximation for a certain target function under a class of distinguishers (test functions), where dis-tinguishers are combinations of simple rectangle-indicators. In our case these approximations can be learned by a simple iterative procedure, which yields a unified and simple proof, achieving for any graph with density d and any approximation parameter the partition size. The novelty in our proof is: (a) a simple approach which yields both strong and weaker variant, and (b) improvements when d = o(1). At an abstract level, our proof can be seen a refinement and simplification of the “analytic” proof given by Lovasz and Szegedy.
AU - Skórski, Maciej
ED - Jäger, Gerhard
ED - Steila, Silvia
ID - 650
SN - 03029743
TI - A cryptographic view of regularity lemmas: Simpler unified proofs and refined bounds
VL - 10185
ER -
TY - CONF
AB - Graph games with omega-regular winning conditions provide a mathematical framework to analyze a wide range of problems in the analysis of reactive systems and programs (such as the synthesis of reactive systems, program repair, and the verification of branching time properties). Parity conditions are canonical forms to specify omega-regular winning conditions. Graph games with parity conditions are equivalent to mu-calculus model checking, and thus a very important algorithmic problem. Symbolic algorithms are of great significance because they provide scalable algorithms for the analysis of large finite-state systems, as well as algorithms for the analysis of infinite-state systems with finite quotient. A set-based symbolic algorithm uses the basic set operations and the one-step predecessor operators. We consider graph games with n vertices and parity conditions with c priorities (equivalently, a mu-calculus formula with c alternations of least and greatest fixed points). While many explicit algorithms exist for graph games with parity conditions, for set-based symbolic algorithms there are only two algorithms (notice that we use space to refer to the number of sets stored by a symbolic algorithm): (a) the basic algorithm that requires O(n^c) symbolic operations and linear space; and (b) an improved algorithm that requires O(n^{c/2+1}) symbolic operations but also O(n^{c/2+1}) space (i.e., exponential space). In this work we present two set-based symbolic algorithms for parity games: (a) our first algorithm requires O(n^{c/2+1}) symbolic operations and only requires linear space; and (b) developing on our first algorithm, we present an algorithm that requires O(n^{c/3+1}) symbolic operations and only linear space. We also present the first linear space set-based symbolic algorithm for parity games that requires at most a sub-exponential number of symbolic operations.
AU - Chatterjee, Krishnendu
AU - Dvorák, Wolfgang
AU - Henzinger, Monika H
AU - Loitzenbauer, Veronika
ID - 6519
TI - Improved set-based symbolic algorithms for parity games
VL - 82
ER -
TY - CONF
AB - A (possibly degenerate) drawing of a graph G in the plane is approximable by an embedding if it can be turned into an embedding by an arbitrarily small perturbation. We show that testing, whether a drawing of a planar graph G in the plane is approximable by an embedding, can be carried out in polynomial time, if a desired embedding of G belongs to a fixed isotopy class, i.e., the rotation system (or equivalently the faces) of the embedding of G and the choice of outer face are fixed. In other words, we show that c-planarity with embedded pipes is tractable for graphs with fixed embeddings. To the best of our knowledge an analogous result was previously known essentially only when G is a cycle.
AU - Fulek, Radoslav
ID - 6517
TI - Embedding graphs into embedded graphs
VL - 92
ER -
TY - CONF
AB - We present an approach that enables robots to self-organize their sensorimotor behavior from scratch without providing specific information about neither the robot nor its environment. This is achieved by a simple neural control law that increases the consistency between external sensor dynamics and internal neural dynamics of the utterly simple controller. In this way, the embodiment and the agent-environment coupling are the only source of individual development. We show how an anthropomorphic tendon driven arm-shoulder system develops different behaviors depending on that coupling. For instance: Given a bottle half-filled with water, the arm starts to shake it, driven by the physical response of the water. When attaching a brush, the arm can be manipulated into wiping a table, and when connected to a revolvable wheel it finds out how to rotate it. Thus, the robot may be said to discover the affordances of the world. When allowing two (simulated) humanoid robots to interact physically, they engage into a joint behavior development leading to, for instance, spontaneous cooperation. More social effects are observed if the robots can visually perceive each other. Although, as an observer, it is tempting to attribute an apparent intentionality, there is nothing of the kind put in. As a conclusion, we argue that emergent behavior may be much less rooted in explicit intentions, internal motivations, or specific reward systems than is commonly believed.
AU - Der, Ralf
AU - Martius, Georg S
ID - 652
SN - 978-150905069-7
TI - Dynamical self consistency leads to behavioral development and emergent social interactions in robots
ER -
TY - JOUR
AB - Superhydrophobic surfaces reduce the frictional drag between water and solid materials, but this effect is often temporary. The realization of sustained drag reduction has applications for water vehicles and pipeline flows.
AU - Hof, Björn
ID - 651
IS - 7636
JF - Nature
SN - 00280836
TI - Fluid dynamics: Water flows out of touch
VL - 541
ER -
TY - JOUR
AB - The extent of heterogeneity among driver gene mutations present in naturally occurring metastases - that is, treatment-naive metastatic disease - is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity. Even with respect to these passenger mutations, our analysis suggests that the genetic similarity among the founding cells of metastases was higher than that expected for any two cells randomly taken from a normal tissue. The uniformity of known driver gene mutations among metastases in the same patient has critical and encouraging implications for the success of future targeted therapies in advanced-stage disease.
AU - Makohon Moore, Alvin
AU - Zhang, Ming
AU - Reiter, Johannes
AU - Božić, Ivana
AU - Allen, Benjamin
AU - Kundu, Deepanjan
AU - Chatterjee, Krishnendu
AU - Wong, Fay
AU - Jiao, Yuchen
AU - Kohutek, Zachary
AU - Hong, Jungeui
AU - Attiyeh, Marc
AU - Javier, Breanna
AU - Wood, Laura
AU - Hruban, Ralph
AU - Nowak, Martin
AU - Papadopoulos, Nickolas
AU - Kinzler, Kenneth
AU - Vogelstein, Bert
AU - Iacobuzio Donahue, Christine
ID - 653
IS - 3
JF - Nature Genetics
SN - 10614036
TI - Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer
VL - 49
ER -
TY - CONF
AB - A memory-hard function (MHF) ƒn with parameter n can be computed in sequential time and space n. Simultaneously, a high amortized parallel area-time complexity (aAT) is incurred per evaluation. In practice, MHFs are used to limit the rate at which an adversary (using a custom computational device) can evaluate a security sensitive function that still occasionally needs to be evaluated by honest users (using an off-the-shelf general purpose device). The most prevalent examples of such sensitive functions are Key Derivation Functions (KDFs) and password hashing algorithms where rate limits help mitigate off-line dictionary attacks. As the honest users' inputs to these functions are often (low-entropy) passwords special attention is given to a class of side-channel resistant MHFs called iMHFs.
Essentially all iMHFs can be viewed as some mode of operation (making n calls to some round function) given by a directed acyclic graph (DAG) with very low indegree. Recently, a combinatorial property of a DAG has been identified (called "depth-robustness") which results in good provable security for an iMHF based on that DAG. Depth-robust DAGs have also proven useful in other cryptographic applications. Unfortunately, up till now, all known very depth-robust DAGs are impractically complicated and little is known about their exact (i.e. non-asymptotic) depth-robustness both in theory and in practice.
In this work we build and analyze (both formally and empirically) several exceedingly simple and efficient to navigate practical DAGs for use in iMHFs and other applications. For each DAG we:
*Prove that their depth-robustness is asymptotically maximal.
*Prove bounds of at least 3 orders of magnitude better on their exact depth-robustness compared to known bounds for other practical iMHF.
*Implement and empirically evaluate their depth-robustness and aAT against a variety of state-of-the art (and several new) depth-reduction and low aAT attacks.
We find that, against all attacks, the new DAGs perform significantly better in practice than Argon2i, the most widely deployed iMHF in practice.
Along the way we also improve the best known empirical attacks on the aAT of Argon2i by implementing and testing several heuristic versions of a (hitherto purely theoretical) depth-reduction attack. Finally, we demonstrate practicality of our constructions by modifying the Argon2i code base to use one of the new high aAT DAGs. Experimental benchmarks on a standard off-the-shelf CPU show that the new modifications do not adversely affect the impressive throughput of Argon2i (despite seemingly enjoying significantly higher aAT).
AU - Alwen, Joel F
AU - Blocki, Jeremiah
AU - Harsha, Ben
ID - 6527
SN - 9781450349468
T2 - Proceedings of the 2017 ACM SIGSAC Conference on Computer and Communications Security
TI - Practical graphs for optimal side-channel resistant memory-hard functions
ER -
TY - JOUR
AB - In November 2016, developmental biologists, synthetic biologists and engineers gathered in Paris for a meeting called ‘Engineering the embryo’. The participants shared an interest in exploring how synthetic systems can reveal new principles of embryonic development, and how the in vitro manipulation and modeling of development using stem cells can be used to integrate ideas and expertise from physics, developmental biology and tissue engineering. As we review here, the conference pinpointed some of the challenges arising at the intersection of these fields, along with great enthusiasm for finding new approaches and collaborations.
AU - Kicheva, Anna
AU - Rivron, Nicolas
ID - 654
IS - 5
JF - Development
SN - 09501991
TI - Creating to understand – developmental biology meets engineering in Paris
VL - 144
ER -
TY - CONF
AB - This paper studies the complexity of estimating Rényi divergences of discrete distributions: p observed from samples and the baseline distribution q known a priori. Extending the results of Acharya et al. (SODA'15) on estimating Rényi entropy, we present improved estimation techniques together with upper and lower bounds on the sample complexity. We show that, contrarily to estimating Rényi entropy where a sublinear (in the alphabet size) number of samples suffices, the sample complexity is heavily dependent on events occurring unlikely in q, and is unbounded in general (no matter what an estimation technique is used). For any divergence of integer order bigger than 1, we provide upper and lower bounds on the number of samples dependent on probabilities of p and q (the lower bounds hold for non-integer orders as well). We conclude that the worst-case sample complexity is polynomial in the alphabet size if and only if the probabilities of q are non-negligible. This gives theoretical insights into heuristics used in the applied literature to handle numerical instability, which occurs for small probabilities of q. Our result shows that they should be handled with care not only because of numerical issues, but also because of a blow up in the sample complexity.
AU - Skórski, Maciej
ID - 6526
SN - 9781509040964
T2 - 2017 IEEE International Symposium on Information Theory (ISIT)
TI - On the complexity of estimating Rènyi divergences
ER -
TY - JOUR
AB - The bacterial flagellum is a self-assembling nanomachine. The external flagellar filament, several times longer than a bacterial cell body, is made of a few tens of thousands subunits of a single protein: flagellin. A fundamental problem concerns the molecular mechanism of how the flagellum grows outside the cell, where no discernible energy source is available. Here, we monitored the dynamic assembly of individual flagella using in situ labelling and real-time immunostaining of elongating flagellar filaments. We report that the rate of flagellum growth, initially ~1,700 amino acids per second, decreases with length and that the previously proposed chain mechanism does not contribute to the filament elongation dynamics. Inhibition of the proton motive force-dependent export apparatus revealed a major contribution of substrate injection in driving filament elongation. The combination of experimental and mathematical evidence demonstrates that a simple, injection-diffusion mechanism controls bacterial flagella growth outside the cell.
AU - Renault, Thibaud
AU - Abraham, Anthony
AU - Bergmiller, Tobias
AU - Paradis, Guillaume
AU - Rainville, Simon
AU - Charpentier, Emmanuelle
AU - Guet, Calin C
AU - Tu, Yuhai
AU - Namba, Keiichi
AU - Keener, James
AU - Minamino, Tohru
AU - Erhardt, Marc
ID - 655
JF - eLife
SN - 2050084X
TI - Bacterial flagella grow through an injection diffusion mechanism
VL - 6
ER -
TY - JOUR
AB - Plant organs are typically organized into three main tissue layers. The middle ground tissue layer comprises the majority of the plant body and serves a wide range of functions, including photosynthesis, selective nutrient uptake and storage, and gravity sensing. Ground tissue patterning and maintenance in Arabidopsis are controlled by a well-established gene network revolving around the key regulator SHORT-ROOT (SHR). In contrast, it is completely unknown how ground tissue identity is first specified from totipotent precursor cells in the embryo. The plant signaling molecule auxin, acting through AUXIN RESPONSE FACTOR (ARF) transcription factors, is critical for embryo patterning. The auxin effector ARF5/MONOPTEROS (MP) acts both cell-autonomously and noncell-autonomously to control embryonic vascular tissue formation and root initiation, respectively. Here we show that auxin response and ARF activity cell-autonomously control the asymmetric division of the first ground tissue cells. By identifying embryonic target genes, we show that MP transcriptionally initiates the ground tissue lineage and acts upstream of the regulatory network that controls ground tissue patterning and maintenance. Strikingly, whereas the SHR network depends on MP, this MP function is, at least in part, SHR independent. Our study therefore identifies auxin response as a regulator of ground tissue specification in the embryonic root, and reveals that ground tissue initiation and maintenance use different regulators and mechanisms. Moreover, our data provide a framework for the simultaneous formation of multiple cell types by the same transcriptional regulator.
AU - Möller, Barbara
AU - Ten Hove, Colette
AU - Xiang, Daoquan
AU - Williams, Nerys
AU - López, Lorena
AU - Yoshida, Saiko
AU - Smit, Margot
AU - Datla, Raju
AU - Weijers, Dolf
ID - 657
IS - 12
JF - PNAS
SN - 00278424
TI - Auxin response cell autonomously controls ground tissue initiation in the early arabidopsis embryo
VL - 114
ER -
TY - JOUR
AB - Human neurons transplanted into a mouse model for Alzheimer’s disease show human-specific vulnerability to β-amyloid plaques and may help to identify new therapeutic targets.
AU - Novarino, Gaia
ID - 656
IS - 381
JF - Science Translational Medicine
SN - 19466234
TI - Modeling Alzheimer's disease in mice with human neurons
VL - 9
ER -
TY - JOUR
AB - With the accelerated development of robot technologies, control becomes one of the central themes of research. In traditional approaches, the controller, by its internal functionality, finds appropriate actions on the basis of specific objectives for the task at hand. While very successful in many applications, self-organized control schemes seem to be favored in large complex systems with unknown dynamics or which are difficult to model. Reasons are the expected scalability, robustness, and resilience of self-organizing systems. The paper presents a self-learning neurocontroller based on extrinsic differential plasticity introduced recently, applying it to an anthropomorphic musculoskeletal robot arm with attached objects of unknown physical dynamics. The central finding of the paper is the following effect: by the mere feedback through the internal dynamics of the object, the robot is learning to relate each of the objects with a very specific sensorimotor pattern. Specifically, an attached pendulum pilots the arm into a circular motion, a half-filled bottle produces axis oriented shaking behavior, a wheel is getting rotated, and wiping patterns emerge automatically in a table-plus-brush setting. By these object-specific dynamical patterns, the robot may be said to recognize the object's identity, or in other words, it discovers dynamical affordances of objects. Furthermore, when including hand coordinates obtained from a camera, a dedicated hand-eye coordination self-organizes spontaneously. These phenomena are discussed from a specific dynamical system perspective. Central is the dedicated working regime at the border to instability with its potentially infinite reservoir of (limit cycle) attractors "waiting" to be excited. Besides converging toward one of these attractors, variate behavior is also arising from a self-induced attractor morphing driven by the learning rule. We claim that experimental investigations with this anthropomorphic, self-learning robot not only generate interesting and potentially useful behaviors, but may also help to better understand what subjective human muscle feelings are, how they can be rooted in sensorimotor patterns, and how these concepts may feed back on robotics.
AU - Der, Ralf
AU - Martius, Georg S
ID - 658
IS - MAR
JF - Frontiers in Neurorobotics
SN - 16625218
TI - Self organized behavior generation for musculoskeletal robots
VL - 11
ER -
TY - JOUR
AB - Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.
AU - Kage, Frieda
AU - Winterhoff, Moritz
AU - Dimchev, Vanessa
AU - Müller, Jan
AU - Thalheim, Tobias
AU - Freise, Anika
AU - Brühmann, Stefan
AU - Kollasser, Jana
AU - Block, Jennifer
AU - Dimchev, Georgi A
AU - Geyer, Matthias
AU - Schnittler, Hams
AU - Brakebusch, Cord
AU - Stradal, Theresia
AU - Carlier, Marie
AU - Sixt, Michael K
AU - Käs, Josef
AU - Faix, Jan
AU - Rottner, Klemens
ID - 659
JF - Nature Communications
SN - 20411723
TI - FMNL formins boost lamellipodial force generation
VL - 8
ER -
TY - JOUR
AB - Growing microtubules are protected from depolymerization by the presence of a GTP or GDP/Pi cap. End-binding proteins of the EB1 family bind to the stabilizing cap, allowing monitoring of its size in real time. The cap size has been shown to correlate with instantaneous microtubule stability. Here we have quantitatively characterized the properties of cap size fluctuations during steadystate growth and have developed a theory predicting their timescale and amplitude from the kinetics of microtubule growth and cap maturation. In contrast to growth speed fluctuations, cap size fluctuations show a characteristic timescale, which is defined by the lifetime of the cap sites. Growth fluctuations affect the amplitude of cap size fluctuations; however, cap size does not affect growth speed, indicating that microtubules are far from instability during most of their time of growth. Our theory provides the basis for a quantitative understanding of microtubule stability fluctuations during steady-state growth.
AU - Rickman, Jamie
AU - Düllberg, Christian F
AU - Cade, Nicholas
AU - Griffin, Lewis
AU - Surrey, Thomas
ID - 660
IS - 13
JF - PNAS
SN - 00278424
TI - Steady state EB cap size fluctuations are determined by stochastic microtubule growth and maturation
VL - 114
ER -
TY - JOUR
AB - We report a direct-numerical-simulation study of the Taylor-Couette flow in the quasi-Keplerian regime at shear Reynolds numbers up to (105). Quasi-Keplerian rotating flow has been investigated for decades as a simplified model system to study the origin of turbulence in accretion disks that is not fully understood. The flow in this study is axially periodic and thus the experimental end-wall effects on the stability of the flow are avoided. Using optimal linear perturbations as initial conditions, our simulations find no sustained turbulence: the strong initial perturbations distort the velocity profile and trigger turbulence that eventually decays.
AU - Shi, Liang
AU - Hof, Björn
AU - Rampp, Markus
AU - Avila, Marc
ID - 662
IS - 4
JF - Physics of Fluids
SN - 10706631
TI - Hydrodynamic turbulence in quasi Keplerian rotating flows
VL - 29
ER -
TY - CONF
AB - In this paper, we propose an approach to automatically compute invariant clusters for nonlinear semialgebraic hybrid systems. An invariant cluster for an ordinary differential equation (ODE) is a multivariate polynomial invariant g(u→, x→) = 0, parametric in u→, which can yield an infinite number of concrete invariants by assigning different values to u→ so that every trajectory of the system can be overapproximated precisely by the intersection of a group of concrete invariants. For semialgebraic systems, which involve ODEs with multivariate polynomial right-hand sides, given a template multivariate polynomial g(u→, x→), an invariant cluster can be obtained by first computing the remainder of the Lie derivative of g(u→, x→) divided by g(u→, x→) and then solving the system of polynomial equations obtained from the coefficients of the remainder. Based on invariant clusters and sum-of-squares (SOS) programming, we present a new method for the safety verification of hybrid systems. Experiments on nonlinear benchmark systems from biology and control theory show that our approach is efficient.
AU - Kong, Hui
AU - Bogomolov, Sergiy
AU - Schilling, Christian
AU - Jiang, Yu
AU - Henzinger, Thomas A
ID - 663
SN - 978-145034590-3
T2 - Proceedings of the 20th International Conference on Hybrid Systems
TI - Safety verification of nonlinear hybrid systems based on invariant clusters
ER -
TY - JOUR
AB - Perinatal exposure to penicillin may result in longlasting gut and behavioral changes.
AU - Novarino, Gaia
ID - 667
IS - 387
JF - Science Translational Medicine
SN - 19466234
TI - The antisocial side of antibiotics
VL - 9
ER -
TY - JOUR
AB - Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading.
AU - Horsthemke, Markus
AU - Bachg, Anne
AU - Groll, Katharina
AU - Moyzio, Sven
AU - Müther, Barbara
AU - Hemkemeyer, Sandra
AU - Wedlich Söldner, Roland
AU - Sixt, Michael K
AU - Tacke, Sebastian
AU - Bähler, Martin
AU - Hanley, Peter
ID - 668
IS - 17
JF - Journal of Biological Chemistry
SN - 00219258
TI - Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion
VL - 292
ER -
TY - JOUR
AB - The exocyst, a eukaryotic tethering complex, coregulates targeted exocytosis as an effector of small GTPases in polarized cell growth. In land plants, several exocyst subunits are encoded by double or triple paralogs, culminating in tens of EXO70 paralogs. Out of 23 Arabidopsis thaliana EXO70 isoforms, we analyzed seven isoforms expressed in pollen. Genetic and microscopic analyses of single mutants in EXO70A2, EXO70C1, EXO70C2, EXO70F1, EXO70H3, EXO70H5, and EXO70H6 genes revealed that only a loss-of-function EXO70C2 allele resulted in a significant male-specific transmission defect (segregation 40%:51%:9%) due to aberrant pollen tube growth. Mutant pollen tubes grown in vitro exhibited an enhanced growth rate and a decreased thickness of the tip cell wall, causing tip bursts. However, exo70C2 pollen tubes could frequently recover and restart their speedy elongation, resulting in a repetitive stop-and-go growth dynamics. A pollenspecific depletion of the closest paralog, EXO70C1, using artificial microRNA in the exo70C2 mutant background, resulted in a complete pollen-specific transmission defect, suggesting redundant functions of EXO70C1 and EXO70C2. Both EXO70C1 and EXO70C2, GFP tagged and expressed under the control of their native promoters, localized in the cytoplasm of pollen grains, pollen tubes, and also root trichoblast cells. The expression of EXO70C2-GFP complemented the aberrant growth of exo70C2 pollen tubes. The absent EXO70C2 interactions with core exocyst subunits in the yeast two-hybrid assay, cytoplasmic localization, and genetic effect suggest an unconventional EXO70 function possibly as a regulator of exocytosis outside the exocyst complex. In conclusion, EXO70C2 is a novel factor contributing to the regulation of optimal tip growth of Arabidopsis pollen tubes.
AU - Synek, Lukáš
AU - Vukašinović, Nemanja
AU - Kulich, Ivan
AU - Hála, Michal
AU - Aldorfová, Klára
AU - Fendrych, Matyas
AU - Žárský, Viktor
ID - 669
IS - 1
JF - Plant Physiology
SN - 00320889
TI - EXO70C2 is a key regulatory factor for optimal tip growth of pollen
VL - 174
ER -
TY - JOUR
AB - Humans routinely use conditionally cooperative strategies when interacting in repeated social dilemmas. They are more likely to cooperate if others cooperated before, and are ready to retaliate if others defected. To capture the emergence of reciprocity, most previous models consider subjects who can only choose from a restricted set of representative strategies, or who react to the outcome of the very last round only. As players memorize more rounds, the dimension of the strategy space increases exponentially. This increasing computational complexity renders simulations for individuals with higher cognitive abilities infeasible, especially if multiplayer interactions are taken into account. Here, we take an axiomatic approach instead. We propose several properties that a robust cooperative strategy for a repeated multiplayer dilemma should have. These properties naturally lead to a unique class of cooperative strategies, which contains the classical Win-Stay Lose-Shift rule as a special case. A comprehensive numerical analysis for the prisoner's dilemma and for the public goods game suggests that strategies of this class readily evolve across various memory-n spaces. Our results reveal that successful strategies depend not only on how cooperative others were in the past but also on the respective context of cooperation.
AU - Hilbe, Christian
AU - Martinez, Vaquero
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 671
IS - 18
JF - PNAS
SN - 00278424
TI - Memory-n strategies of direct reciprocity
VL - 114
ER -
TY - JOUR
AB - We propose an efficient method to model paper tearing in the context of interactive modeling. The method uses geometrical information to automatically detect potential starting points of tears. We further introduce a new hybrid geometrical and physical-based method to compute the trajectory of tears while procedurally synthesizing high resolution details of the tearing path using a texture based approach. The results obtained are compared with real paper and with previous studies on the expected geometric paths of paper that tears.
AU - Schreck, Camille
AU - Rohmer, Damien
AU - Hahmann, Stefanie
ID - 670
IS - 2
JF - Computer Graphics Forum
SN - 01677055
TI - Interactive paper tearing
VL - 36
ER -
TY - JOUR
AB - Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration.
AU - Vaahtomeri, Kari
AU - Brown, Markus
AU - Hauschild, Robert
AU - De Vries, Ingrid
AU - Leithner, Alexander F
AU - Mehling, Matthias
AU - Kaufmann, Walter
AU - Sixt, Michael K
ID - 672
IS - 5
JF - Cell Reports
SN - 22111247
TI - Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia
VL - 19
ER -
TY - JOUR
AB - We present a numerical study of wavy supercritical cylindrical Couette flow between counter-rotating cylinders in which the wavy pattern propagates either prograde with the inner cylinder or retrograde opposite the rotation of the inner cylinder. The wave propagation reversals from prograde to retrograde and vice versa occur at distinct values of the inner cylinder Reynolds number when the associated frequency of the wavy instability vanishes. The reversal occurs for both twofold and threefold symmetric wavy vortices. Moreover, the wave propagation reversal only occurs for sufficiently strong counter-rotation. The flow pattern reversal appears to be intrinsic in the system as either periodic boundary conditions or fixed end wall boundary conditions for different system sizes always result in the wave propagation reversal. We present a detailed bifurcation sequence and parameter space diagram with respect to retrograde behavior of wavy flows. The retrograde propagation of the instability occurs when the inner Reynolds number is about two times the outer Reynolds number. The mechanism for the retrograde propagation is associated with the inviscidly unstable region near the inner cylinder and the direction of the global average azimuthal velocity. Flow dynamics, spatio-temporal behavior, global mean angular velocity, and torque of the flow with the wavy pattern are explored.
AU - Altmeyer, Sebastian
AU - Lueptow, Richard
ID - 673
IS - 5
JF - Physical Review E - Statistical, Nonlinear, and Soft Matter Physics
SN - 24700045
TI - Wave propagation reversal for wavy vortices in wide gap counter rotating cylindrical Couette flow
VL - 95
ER -
TY - JOUR
AB - Navigation of cells along gradients of guidance cues is a determining step in many developmental and immunological processes. Gradients can either be soluble or immobilized to tissues as demonstrated for the haptotactic migration of dendritic cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate how gradient characteristics govern cellular response patterns, we here introduce an in vitro system allowing to track migratory responses of DCs to precisely controlled immobilized gradients of CCL21. We find that haptotactic sensing depends on the absolute CCL21 concentration and local steepness of the gradient, consistent with a scenario where DC directionality is governed by the signal-to-noise ratio of CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore, we find that CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. These findings suggest that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal guidance in vivo.
AU - Schwarz, Jan
AU - Bierbaum, Veronika
AU - Vaahtomeri, Kari
AU - Hauschild, Robert
AU - Brown, Markus
AU - De Vries, Ingrid
AU - Leithner, Alexander F
AU - Reversat, Anne
AU - Merrin, Jack
AU - Tarrant, Teresa
AU - Bollenbach, Tobias
AU - Sixt, Michael K
ID - 674
IS - 9
JF - Current Biology
SN - 09609822
TI - Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6
VL - 27
ER -
TY - JOUR
AB - We report the enhancement of infrared absorption of chemisorbed carbon monoxide on platinum in the gap of plasmonic nanoantennas. Our method is based on the self-assembled formation of platinum nanoislands on nanoscopic dipole antenna arrays manufactured via electron beam lithography. We employ systematic variations of the plasmonic antenna resonance to precisely couple to the molecular stretch vibration of carbon monoxide adsorbed on the platinum nanoislands. Ultimately, we reach more than 1500-fold infrared absorption enhancements, allowing for an ultrasensitive detection of a monolayer of chemisorbed carbon monoxide. The developed procedure can be adapted to other metal adsorbents and molecular species and could be utilized for coverage sensing in surface catalytic reactions.
AU - Haase, Johannes
AU - Bagiante, Salvatore
AU - Sigg, Hans
AU - Van Bokhoven, Jeroen
ID - 675
IS - 10
JF - Optics Letters
TI - Surface enhanced infrared absorption of chemisorbed carbon monoxide using plasmonic nanoantennas
VL - 42
ER -
TY - JOUR
AB - The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR—DNA end resection and presynaptic filament formation. Importantly, the second function is linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic filament formation and HR are restored in INO80-C-deficient mutants, suggesting that presynaptic filament formation is the crucial INO80-C function during HR.
AU - Lademann, Claudio
AU - Renkawitz, Jörg
AU - Pfander, Boris
AU - Jentsch, Stefan
ID - 677
IS - 7
JF - Cell Reports
SN - 22111247
TI - The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination
VL - 19
ER -
TY - JOUR
AB - Protective responses against pathogens require a rapid mobilization of resting neutrophils and the timely removal of activated ones. Neutrophils are exceptionally short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged neutrophils is regulated differently from that in the circulating steady-state pool. Here, we have found that under homeostatic conditions, the mRNA-destabilizing protein tristetraprolin (TTP) regulates apoptosis and the numbers of activated infiltrating murine neutrophils but not neutrophil cellularity. Activated TTP-deficient neutrophils exhibited decreased apoptosis and enhanced accumulation at the infection site. In the context of myeloid-specific deletion of Ttp, the potentiation of neutrophil deployment protected mice against lethal soft tissue infection with Streptococcus pyogenes and prevented bacterial dissemination. Neutrophil transcriptome analysis revealed that decreased apoptosis of TTP-deficient neutrophils was specifically associated with elevated expression of myeloid cell leukemia 1 (Mcl1) but not other antiapoptotic B cell leukemia/ lymphoma 2 (Bcl2) family members. Higher Mcl1 expression resulted from stabilization of Mcl1 mRNA in the absence of TTP. The low apoptosis rate of infiltrating TTP-deficient neutrophils was comparable to that of transgenic Mcl1-overexpressing neutrophils. Our study demonstrates that posttranscriptional gene regulation by TTP schedules the termination of the antimicrobial engagement of neutrophils. The balancing role of TTP comes at the cost of an increased risk of bacterial infections.
AU - Ebner, Florian
AU - Sedlyarov, Vitaly
AU - Tasciyan, Saren
AU - Ivin, Masa
AU - Kratochvill, Franz
AU - Gratz, Nina
AU - Kenner, Lukas
AU - Villunger, Andreas
AU - Sixt, Michael K
AU - Kovarik, Pavel
ID - 679
IS - 6
JF - The Journal of Clinical Investigation
SN - 00219738
TI - The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection
VL - 127
ER -
TY - JOUR
AB - The seminal observation that mechanical signals can elicit changes in biochemical signalling within cells, a process commonly termed mechanosensation and mechanotransduction, has revolutionized our understanding of the role of cell mechanics in various fundamental biological processes, such as cell motility, adhesion, proliferation and differentiation. In this Review, we will discuss how the interplay and feedback between mechanical and biochemical signals control tissue morphogenesis and cell fate specification in embryonic development.
AU - Petridou, Nicoletta
AU - Spiro, Zoltan P
AU - Heisenberg, Carl-Philipp J
ID - 678
IS - 6
JF - Nature Cell Biology
SN - 14657392
TI - Multiscale force sensing in development
VL - 19
ER -
TY - JOUR
AB - Two-player games on graphs provide the theoretical framework for many important problems such as reactive synthesis. While the traditional study of two-player zero-sum games has been extended to multi-player games with several notions of equilibria, they are decidable only for perfect-information games, whereas several applications require imperfect-information. In this paper we propose a new notion of equilibria, called doomsday equilibria, which is a strategy profile where all players satisfy their own objective, and if any coalition of players deviates and violates even one of the players' objective, then the objective of every player is violated. We present algorithms and complexity results for deciding the existence of doomsday equilibria for various classes of ω-regular objectives, both for imperfect-information games, and for perfect-information games. We provide optimal complexity bounds for imperfect-information games, and in most cases for perfect-information games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Filiot, Emmanuel
AU - Raskin, Jean
ID - 681
JF - Information and Computation
SN - 08905401
TI - Doomsday equilibria for omega-regular games
VL - 254
ER -
TY - CONF
AB - In classical machine learning, regression is treated as a black box process of identifying a suitable function from a hypothesis set without attempting to gain insight into the mechanism connecting inputs and outputs. In the natural sciences, however, finding an interpretable function for a phenomenon is the prime goal as it allows to understand and generalize results. This paper proposes a novel type of function learning network, called equation learner (EQL), that can learn analytical expressions and is able to extrapolate to unseen domains. It is implemented as an end-to-end differentiable feed-forward network and allows for efficient gradient based training. Due to sparsity regularization concise interpretable expressions can be obtained. Often the true underlying source expression is identified.
AU - Martius, Georg S
AU - Lampert, Christoph
ID - 6841
T2 - 5th International Conference on Learning Representations, ICLR 2017 - Workshop Track Proceedings
TI - Extrapolation and learning equations
ER -
TY - JOUR
AB - We generalize winning conditions in two-player games by adding a structural acceptance condition called obligations. Obligations are orthogonal to the linear winning conditions that define whether a play is winning. Obligations are a declaration that player 0 can achieve a certain value from a configuration. If the obligation is met, the value of that configuration for player 0 is 1. We define the value in such games and show that obligation games are determined. For Markov chains with Borel objectives and obligations, and finite turn-based stochastic parity games with obligations we give an alternative and simpler characterization of the value function. Based on this simpler definition we show that the decision problem of winning finite turn-based stochastic parity games with obligations is in NP∩co-NP. We also show that obligation games provide a game framework for reasoning about p-automata. © 2017 The Association for Symbolic Logic.
AU - Chatterjee, Krishnendu
AU - Piterman, Nir
ID - 684
IS - 2
JF - Journal of Symbolic Logic
SN - 0022-4812
TI - Obligation blackwell games and p-automata
VL - 82
ER -
TY - JOUR
AB - By applying methods and principles from the physical sciences to biological problems, D'Arcy Thompson's On Growth and Form demonstrated how mathematical reasoning reveals elegant, simple explanations for seemingly complex processes. This has had a profound influence on subsequent generations of developmental biologists. We discuss how this influence can be traced through twentieth century morphologists, embryologists and theoreticians to current research that explores the molecular and cellular mechanisms of tissue growth and patterning, including our own studies of the vertebrate neural tube.
AU - Briscoe, James
AU - Kicheva, Anna
ID - 685
JF - Mechanisms of Development
SN - 09254773
TI - The physics of development 100 years after D'Arcy Thompson's “on growth and form”
VL - 145
ER -