@inproceedings{710, abstract = {We revisit the problem of estimating entropy of discrete distributions from independent samples, studied recently by Acharya, Orlitsky, Suresh and Tyagi (SODA 2015), improving their upper and lower bounds on the necessary sample size n. For estimating Renyi entropy of order alpha, up to constant accuracy and error probability, we show the following * Upper bounds n = O(1) 2^{(1-1/alpha)H_alpha} for integer alpha>1, as the worst case over distributions with Renyi entropy equal to H_alpha. * Lower bounds n = Omega(1) K^{1-1/alpha} for any real alpha>1, with the constant being an inverse polynomial of the accuracy, as the worst case over all distributions on K elements. Our upper bounds essentially replace the alphabet size by a factor exponential in the entropy, which offers improvements especially in low or medium entropy regimes (interesting for example in anomaly detection). As for the lower bounds, our proof explicitly shows how the complexity depends on both alphabet and accuracy, partially solving the open problem posted in previous works. The argument for upper bounds derives a clean identity for the variance of falling-power sum of a multinomial distribution. Our approach for lower bounds utilizes convex optimization to find a distribution with possibly worse estimation performance, and may be of independent interest as a tool to work with Le Cam’s two point method. }, author = {Obremski, Maciej and Skórski, Maciej}, issn = {18688969}, location = {Berkeley, USA}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Renyi entropy estimation revisited}}, doi = {10.4230/LIPIcs.APPROX-RANDOM.2017.20}, volume = {81}, year = {2017}, } @article{713, abstract = {To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta.}, author = {Andergassen, Daniel and Dotter, Christoph and Wenzel, Dyniel and Sigl, Verena and Bammer, Philipp and Muckenhuber, Markus and Mayer, Daniela and Kulinski, Tomasz and Theussl, Hans and Penninger, Josef and Bock, Christoph and Barlow, Denise and Pauler, Florian and Hudson, Quanah}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Mapping the mouse Allelome reveals tissue specific regulation of allelic expression}}, doi = {10.7554/eLife.25125}, volume = {6}, year = {2017}, } @inproceedings{711, abstract = {Nested weighted automata (NWA) present a robust and convenient automata-theoretic formalism for quantitative specifications. Previous works have considered NWA that processed input words only in the forward direction. It is natural to allow the automata to process input words backwards as well, for example, to measure the maximal or average time between a response and the preceding request. We therefore introduce and study bidirectional NWA that can process input words in both directions. First, we show that bidirectional NWA can express interesting quantitative properties that are not expressible by forward-only NWA. Second, for the fundamental decision problems of emptiness and universality, we establish decidability and complexity results for the new framework which match the best-known results for the special case of forward-only NWA. Thus, for NWA, the increased expressiveness of bidirectionality is achieved at no additional computational complexity. This is in stark contrast to the unweighted case, where bidirectional finite automata are no more expressive but exponentially more succinct than their forward-only counterparts.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, issn = {18688969}, location = {Berlin, Germany}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Bidirectional nested weighted automata}}, doi = {10.4230/LIPIcs.CONCUR.2017.5}, volume = {85}, year = {2017}, } @article{712, abstract = {We establish a weak–strong uniqueness principle for solutions to entropy-dissipating reaction–diffusion equations: As long as a strong solution to the reaction–diffusion equation exists, any weak solution and even any renormalized solution must coincide with this strong solution. Our assumptions on the reaction rates are just the entropy condition and local Lipschitz continuity; in particular, we do not impose any growth restrictions on the reaction rates. Therefore, our result applies to any single reversible reaction with mass-action kinetics as well as to systems of reversible reactions with mass-action kinetics satisfying the detailed balance condition. Renormalized solutions are known to exist globally in time for reaction–diffusion equations with entropy-dissipating reaction rates; in contrast, the global-in-time existence of weak solutions is in general still an open problem–even for smooth data–, thereby motivating the study of renormalized solutions. The key ingredient of our result is a careful adjustment of the usual relative entropy functional, whose evolution cannot be controlled properly for weak solutions or renormalized solutions.}, author = {Fischer, Julian L}, issn = {0362546X}, journal = {Nonlinear Analysis: Theory, Methods and Applications}, pages = {181 -- 207}, publisher = {Elsevier}, title = {{Weak–strong uniqueness of solutions to entropy dissipating reaction–diffusion equations}}, doi = {10.1016/j.na.2017.03.001}, volume = {159}, year = {2017}, } @article{714, abstract = {Background HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical channels. The influx of cations depolarizes the membrane promoting additional Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously found that cocaine targets NAcc neurons directly (independent of the inhibition of dopamine transporter) only when IP3-generating mechanisms are concomitantly initiated. When tested here, cocaine produced a dose-dependent potentiation of the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization and a potentiation of the effect of Tat by cocaine, which may be relevant for the reward axis in cocaine-abusing HIV-1-positive patients.}, author = {Brailoiu, Gabriela and Deliu, Elena and Barr, Jeffrey and Console Bram, Linda and Ciuciu, Alexandra and Abood, Mary and Unterwald, Ellen and Brǎiloiu, Eugen}, issn = {03768716}, journal = {Drug and Alcohol Dependence}, pages = {7 -- 14}, publisher = {Elsevier}, title = {{HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens}}, doi = {10.1016/j.drugalcdep.2017.04.015}, volume = {178}, year = {2017}, } @article{715, abstract = {D-cycloserine ameliorates breathing abnormalities and survival rate in a mouse model of Rett syndrome.}, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {405}, publisher = {American Association for the Advancement of Science}, title = {{More excitation for Rett syndrome}}, doi = {10.1126/scitranslmed.aao4218}, volume = {9}, year = {2017}, } @article{716, abstract = {Two-player games on graphs are central in many problems in formal verification and program analysis, such as synthesis and verification of open systems. In this work, we consider solving recursive game graphs (or pushdown game graphs) that model the control flow of sequential programs with recursion.While pushdown games have been studied before with qualitative objectives-such as reachability and ?-regular objectives- in this work, we study for the first time such games with the most well-studied quantitative objective, the mean-payoff objective. In pushdown games, two types of strategies are relevant: (1) global strategies, which depend on the entire global history; and (2) modular strategies, which have only local memory and thus do not depend on the context of invocation but rather only on the history of the current invocation of the module. Our main results are as follows: (1) One-player pushdown games with mean-payoff objectives under global strategies are decidable in polynomial time. (2) Two-player pushdown games with mean-payoff objectives under global strategies are undecidable. (3) One-player pushdown games with mean-payoff objectives under modular strategies are NP-hard. (4) Two-player pushdown games with mean-payoff objectives under modular strategies can be solved in NP (i.e., both one-player and two-player pushdown games with mean-payoff objectives under modular strategies are NP-complete). We also establish the optimal strategy complexity by showing that global strategies for mean-payoff objectives require infinite memory even in one-player pushdown games and memoryless modular strategies are sufficient in two-player pushdown games. Finally, we also show that all the problems have the same complexity if the stack boundedness condition is added, where along with the mean-payoff objective the player must also ensure that the stack height is bounded.}, author = {Chatterjee, Krishnendu and Velner, Yaron}, issn = {00045411}, journal = {Journal of the ACM}, number = {5}, pages = {34}, publisher = {ACM}, title = {{The complexity of mean-payoff pushdown games}}, doi = {10.1145/3121408}, volume = {64}, year = {2017}, } @article{717, abstract = {We consider finite-state and recursive game graphs with multidimensional mean-payoff objectives. In recursive games two types of strategies are relevant: global strategies and modular strategies. Our contributions are: (1) We show that finite-state multidimensional mean-payoff games can be solved in polynomial time if the number of dimensions and the maximal absolute value of weights are fixed; whereas for arbitrary dimensions the problem is coNP-complete. (2) We show that one-player recursive games with multidimensional mean-payoff objectives can be solved in polynomial time. Both above algorithms are based on hyperplane separation technique. (3) For recursive games we show that under modular strategies the multidimensional problem is undecidable. We show that if the number of modules, exits, and the maximal absolute value of the weights are fixed, then one-dimensional recursive mean-payoff games under modular strategies can be solved in polynomial time, whereas for unbounded number of exits or modules the problem is NP-hard.}, author = {Chatterjee, Krishnendu and Velner, Yaron}, journal = {Journal of Computer and System Sciences}, pages = {236 -- 259}, publisher = {Academic Press}, title = {{Hyperplane separation technique for multidimensional mean-payoff games}}, doi = {10.1016/j.jcss.2017.04.005}, volume = {88}, year = {2017}, } @article{719, abstract = {The ubiquity of computation in modern machines and devices imposes a need to assert the correctness of their behavior. Especially in the case of safety-critical systems, their designers need to take measures that enforce their safe operation. Formal methods has emerged as a research field that addresses this challenge: by rigorously proving that all system executions adhere to their specifications, the correctness of an implementation under concern can be assured. To achieve this goal, a plethora of techniques are nowadays available, all of which are optimized for different system types and application domains.}, author = {Chatterjee, Krishnendu and Ehlers, Rüdiger}, issn = {00015903}, journal = {Acta Informatica}, number = {6}, pages = {543 -- 544}, publisher = {Springer}, title = {{Special issue: Synthesis and SYNT 2014}}, doi = {10.1007/s00236-017-0299-0}, volume = {54}, year = {2017}, } @article{720, abstract = {Advances in multi-unit recordings pave the way for statistical modeling of activity patterns in large neural populations. Recent studies have shown that the summed activity of all neurons strongly shapes the population response. A separate recent finding has been that neural populations also exhibit criticality, an anomalously large dynamic range for the probabilities of different population activity patterns. Motivated by these two observations, we introduce a class of probabilistic models which takes into account the prior knowledge that the neural population could be globally coupled and close to critical. These models consist of an energy function which parametrizes interactions between small groups of neurons, and an arbitrary positive, strictly increasing, and twice differentiable function which maps the energy of a population pattern to its probability. We show that: 1) augmenting a pairwise Ising model with a nonlinearity yields an accurate description of the activity of retinal ganglion cells which outperforms previous models based on the summed activity of neurons; 2) prior knowledge that the population is critical translates to prior expectations about the shape of the nonlinearity; 3) the nonlinearity admits an interpretation in terms of a continuous latent variable globally coupling the system whose distribution we can infer from data. Our method is independent of the underlying system’s state space; hence, it can be applied to other systems such as natural scenes or amino acid sequences of proteins which are also known to exhibit criticality.}, author = {Humplik, Jan and Tkacik, Gasper}, issn = {1553734X}, journal = {PLoS Computational Biology}, number = {9}, publisher = {Public Library of Science}, title = {{Probabilistic models for neural populations that naturally capture global coupling and criticality}}, doi = {10.1371/journal.pcbi.1005763}, volume = {13}, year = {2017}, } @article{721, abstract = {Let S be a positivity-preserving symmetric linear operator acting on bounded functions. The nonlinear equation -1/m=z+Sm with a parameter z in the complex upper half-plane ℍ has a unique solution m with values in ℍ. We show that the z-dependence of this solution can be represented as the Stieltjes transforms of a family of probability measures v on ℝ. Under suitable conditions on S, we show that v has a real analytic density apart from finitely many algebraic singularities of degree at most 3. Our motivation comes from large random matrices. The solution m determines the density of eigenvalues of two prominent matrix ensembles: (i) matrices with centered independent entries whose variances are given by S and (ii) matrices with correlated entries with a translation-invariant correlation structure. Our analysis shows that the limiting eigenvalue density has only square root singularities or cubic root cusps; no other singularities occur.}, author = {Ajanki, Oskari H and Krüger, Torben H and Erdös, László}, issn = {00103640}, journal = {Communications on Pure and Applied Mathematics}, number = {9}, pages = {1672 -- 1705}, publisher = {Wiley-Blackwell}, title = {{Singularities of solutions to quadratic vector equations on the complex upper half plane}}, doi = {10.1002/cpa.21639}, volume = {70}, year = {2017}, } @article{722, abstract = {Plants are sessile organisms rooted in one place. The soil resources that plants require are often distributed in a highly heterogeneous pattern. To aid foraging, plants have evolved roots whose growth and development are highly responsive to soil signals. As a result, 3D root architecture is shaped by myriad environmental signals to ensure resource capture is optimised and unfavourable environments are avoided. The first signals sensed by newly germinating seeds — gravity and light — direct root growth into the soil to aid seedling establishment. Heterogeneous soil resources, such as water, nitrogen and phosphate, also act as signals that shape 3D root growth to optimise uptake. Root architecture is also modified through biotic interactions that include soil fungi and neighbouring plants. This developmental plasticity results in a ‘custom-made’ 3D root system that is best adapted to forage for resources in each soil environment that a plant colonises.}, author = {Morris, Emily and Griffiths, Marcus and Golebiowska, Agata and Mairhofer, Stefan and Burr Hersey, Jasmine and Goh, Tatsuaki and Von Wangenheim, Daniel and Atkinson, Brian and Sturrock, Craig and Lynch, Jonathan and Vissenberg, Kris and Ritz, Karl and Wells, Darren and Mooney, Sacha and Bennett, Malcolm}, issn = {09609822}, journal = {Current Biology}, number = {17}, pages = {R919 -- R930}, publisher = {Cell Press}, title = {{Shaping 3D root system architecture}}, doi = {10.1016/j.cub.2017.06.043}, volume = {27}, year = {2017}, } @article{725, abstract = {Individual computations and social interactions underlying collective behavior in groups of animals are of great ethological, behavioral, and theoretical interest. While complex individual behaviors have successfully been parsed into small dictionaries of stereotyped behavioral modes, studies of collective behavior largely ignored these findings; instead, their focus was on inferring single, mode-independent social interaction rules that reproduced macroscopic and often qualitative features of group behavior. Here, we bring these two approaches together to predict individual swimming patterns of adult zebrafish in a group. We show that fish alternate between an “active” mode, in which they are sensitive to the swimming patterns of conspecifics, and a “passive” mode, where they ignore them. Using a model that accounts for these two modes explicitly, we predict behaviors of individual fish with high accuracy, outperforming previous approaches that assumed a single continuous computation by individuals and simple metric or topological weighing of neighbors’ behavior. At the group level, switching between active and passive modes is uncorrelated among fish, but correlated directional swimming behavior still emerges. Our quantitative approach for studying complex, multi-modal individual behavior jointly with emergent group behavior is readily extensible to additional behavioral modes and their neural correlates as well as to other species.}, author = {Harpaz, Roy and Tkacik, Gasper and Schneidman, Elad}, issn = {00278424}, journal = {PNAS}, number = {38}, pages = {10149 -- 10154}, publisher = {National Academy of Sciences}, title = {{Discrete modes of social information processing predict individual behavior of fish in a group}}, doi = {10.1073/pnas.1703817114}, volume = {114}, year = {2017}, } @article{724, abstract = {We investigate the stationary and dynamical behavior of an Anderson localized chain coupled to a single central bound state. Although this coupling partially dilutes the Anderson localized peaks towards nearly resonant sites, the most weight of the original peaks remains unchanged. This leads to multifractal wave functions with a frozen spectrum of fractal dimensions, which is characteristic for localized phases in models with power-law hopping. Using a perturbative approach we identify two different dynamical regimes. At weak couplings to the central site, the transport of particles and information is logarithmic in time, a feature usually attributed to many-body localization. We connect such transport to the persistence of the Poisson statistics of level spacings in parts of the spectrum. In contrast, at stronger couplings the level repulsion is established in the entire spectrum, the problem can be mapped to the Fano resonance, and the transport is ballistic.}, author = {Hetterich, Daniel and Serbyn, Maksym and Domínguez, Fernando and Pollmann, Frank and Trauzettel, Björn}, issn = {24699950}, journal = {Physical Review B}, number = {10}, publisher = {American Physical Society}, title = {{Noninteracting central site model localization and logarithmic entanglement growth}}, doi = {10.1103/PhysRevB.96.104203}, volume = {96}, year = {2017}, } @article{731, abstract = {Genetic variations in the oxytocin receptor gene affect patients with ASD and ADHD differently.}, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {411}, publisher = {American Association for the Advancement of Science}, title = {{The science of love in ASD and ADHD}}, doi = {10.1126/scitranslmed.aap8168}, volume = {9}, year = {2017}, } @article{7360, abstract = {Inflammation, which is a highly regulated host response against danger signals, may be harmful if it is excessive and deregulated. Ideally, anti-inflammatory therapy should autonomously commence as soon as possible after the onset of inflammation, should be controllable by a physician, and should not systemically block beneficial immune response in the long term. We describe a genetically encoded anti-inflammatory mammalian cell device based on a modular engineered genetic circuit comprising a sensor, an amplifier, a “thresholder” to restrict activation of a positive-feedback loop, a combination of advanced clinically used biopharmaceutical proteins, and orthogonal regulatory elements that linked modules into the functional device. This genetic circuit was autonomously activated by inflammatory signals, including endogenous cecal ligation and puncture (CLP)-induced inflammation in mice and serum from a systemic juvenile idiopathic arthritis (sIJA) patient, and could be reset externally by a chemical signal. The microencapsulated anti-inflammatory device significantly reduced the pathology in dextran sodium sulfate (DSS)-induced acute murine colitis, demonstrating a synthetic immunological approach for autonomous anti-inflammatory therapy.}, author = {Smole, Anže and Lainšček, Duško and Bezeljak, Urban and Horvat, Simon and Jerala, Roman}, issn = {1525-0016}, journal = {Molecular Therapy}, number = {1}, pages = {102--119}, publisher = {Elsevier}, title = {{A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation}}, doi = {10.1016/j.ymthe.2016.10.005}, volume = {25}, year = {2017}, } @inproceedings{750, abstract = {Modern communication technologies allow first responders to contact thousands of potential volunteers simultaneously for support during a crisis or disaster event. However, such volunteer efforts must be well coordinated and monitored, in order to offer an effective relief to the professionals. In this paper we extend earlier work on optimally assigning volunteers to selected landmark locations. In particular, we emphasize the aspect that obtaining good assignments requires not only advanced computational tools, but also a realistic measure of distance between volunteers and landmarks. Specifically, we propose the use of the Open Street Map (OSM) driving distance instead of he previously used flight distance. We find the OSM driving distance to be better aligned with the interests of volunteers and first responders. Furthermore, we show that relying on the flying distance leads to a substantial underestimation of the number of required volunteers, causing negative side effects in case of an actual crisis situation.}, author = {Pielorz, Jasmin and Prandtstetter, Matthias and Straub, Markus and Lampert, Christoph}, booktitle = {2017 IEEE International Conference on Big Data}, isbn = {978-153862714-3}, location = {Boston, MA, United States}, pages = {3760 -- 3763}, publisher = {IEEE}, title = {{Optimal geospatial volunteer allocation needs realistic distances}}, doi = {10.1109/BigData.2017.8258375}, year = {2017}, } @article{795, abstract = {We introduce a common generalization of the strong Hanani–Tutte theorem and the weak Hanani–Tutte theorem: if a graph G has a drawing D in the plane where every pair of independent edges crosses an even number of times, then G has a planar drawing preserving the rotation of each vertex whose incident edges cross each other evenly in D. The theorem is implicit in the proof of the strong Hanani–Tutte theorem by Pelsmajer, Schaefer and Štefankovič. We give a new, somewhat simpler proof.}, author = {Fulek, Radoslav and Kynčl, Jan and Pálvölgyi, Dömötör}, issn = {10778926}, journal = {Electronic Journal of Combinatorics}, number = {3}, publisher = {International Press}, title = {{Unified Hanani Tutte theorem}}, doi = {10.37236/6663}, volume = {24}, year = {2017}, } @article{797, abstract = {Phasenübergänge helfen beim Verständnis von Vielteilchensystemen in der Festkörperphysik und Fluiddynamik bis hin zur Teilchenphysik. Unserer internationalen Kollaboration ist es gelungen, einen neuartigen Phasenübergang in einem Quantensystem zu beobachten [1]. In einem Mikrowellenresonator konnte erstmals die spontane Zustandsänderung von undurchsichtig zu transparent nachgewiesen werden.}, author = {Fink, Johannes M}, journal = {Physik in unserer Zeit}, number = {3}, pages = {111 -- 113}, publisher = {Wiley}, title = {{Photonenblockade aufgelöst}}, doi = {10.1002/piuz.201770305}, volume = {48}, year = {2017}, } @article{807, abstract = {On January the 1st, 2016 a new agreement between 32 Austrian scientific libraries and the publisher Springer took its effect: this deal covers accessing the licensed content on the one hand, and publishing open access on the other hand. More than 1000 papers by Austrian authors were published open access at Springer in the first year alone. The working group "Springer Compact Evaluierung" made the data for these articles available via the platform OpenAPC and would like to use this opportunity to give a short account of what this publishing agreement actually entails and the working group intends to do.}, author = {Andrae, Magdalena and Villányi, Márton}, issn = {10222588}, journal = {Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare}, number = {2}, pages = {274 -- 280}, publisher = {VÖB}, title = {{Der Springer Compact-Deal – Ein erster Einblick in die Evaluierung einer Offsetting-Vereinbarung}}, doi = {10.31263/voebm.v70i2.1898}, volume = {70}, year = {2017}, } @article{825, abstract = {What data is needed about data? Describing the process to answer this question for the institutional data repository IST DataRep.}, author = {Petritsch, Barbara}, issn = {10222588}, journal = {Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen & Bibliothekare}, number = {2}, pages = {200 -- 207}, publisher = {VÖB}, title = {{Metadata for research data in practice}}, doi = {10.31263/voebm.v70i2.1678}, volume = {70}, year = {2017}, } @inbook{957, abstract = {Small molecule biosensors based on Forster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors. Here, we show how these problems can be overcome using ancestral protein reconstruction and circular permutation. Ancestral protein reconstruction, used as a protein engineering strategy, leverages phylogenetic information to improve the thermostability of proteins, while circular permutation enables the termini of an SBP to be repositioned to maximize the dynamic range of the resulting FRET sensor. We also provide a protocol for cloning the engineered SBPs into FRET sensor constructs using Golden Gate assembly and discuss considerations for in situ characterization of the FRET sensors.}, author = {Clifton, Ben and Whitfield, Jason and Sanchez Romero, Inmaculada and Herde, Michel and Henneberger, Christian and Janovjak, Harald L and Jackson, Colin}, booktitle = {Synthetic Protein Switches}, editor = {Stein, Viktor}, issn = {10643745}, pages = {71 -- 87}, publisher = {Springer}, title = {{Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors}}, doi = {10.1007/978-1-4939-6940-1_5}, volume = {1596}, year = {2017}, } @inproceedings{963, abstract = {Network games are widely used as a model for selfish resource-allocation problems. In the classical model, each player selects a path connecting her source and target vertex. The cost of traversing an edge depends on the number of players that traverse it. Thus, it abstracts the fact that different users may use a resource at different times and for different durations, which plays an important role in defining the costs of the users in reality. For example, when transmitting packets in a communication network, routing traffic in a road network, or processing a task in a production system, the traversal of the network involves an inherent delay, and so sharing and congestion of resources crucially depends on time. We study timed network games , which add a time component to network games. Each vertex v in the network is associated with a cost function, mapping the load on v to the price that a player pays for staying in v for one time unit with this load. In addition, each edge has a guard, describing time intervals in which the edge can be traversed, forcing the players to spend time on vertices. Unlike earlier work that add a time component to network games, the time in our model is continuous and cannot be discretized. In particular, players have uncountably many strategies, and a game may have uncountably many pure Nash equilibria. We study properties of timed network games with cost-sharing or congestion cost functions: their stability, equilibrium inefficiency, and complexity. In particular, we show that the answer to the question whether we can restrict attention to boundary strategies, namely ones in which edges are traversed only at the boundaries of guards, is mixed. }, author = {Avni, Guy and Guha, Shibashis and Kupferman, Orna}, issn = {18688969}, location = {Aalborg, Denmark}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Timed network games with clocks}}, doi = {10.4230/LIPIcs.MFCS.2017.37}, volume = {83}, year = {2017}, } @misc{9709, abstract = {Across the nervous system, certain population spiking patterns are observed far more frequently than others. A hypothesis about this structure is that these collective activity patterns function as population codewords–collective modes–carrying information distinct from that of any single cell. We investigate this phenomenon in recordings of ∼150 retinal ganglion cells, the retina’s output. We develop a novel statistical model that decomposes the population response into modes; it predicts the distribution of spiking activity in the ganglion cell population with high accuracy. We found that the modes represent localized features of the visual stimulus that are distinct from the features represented by single neurons. Modes form clusters of activity states that are readily discriminated from one another. When we repeated the same visual stimulus, we found that the same mode was robustly elicited. These results suggest that retinal ganglion cells’ collective signaling is endowed with a form of error-correcting code–a principle that may hold in brain areas beyond retina.}, author = {Prentice, Jason and Marre, Olivier and Ioffe, Mark and Loback, Adrianna and Tkačik, Gašper and Berry, Michael}, publisher = {Dryad}, title = {{Data from: Error-robust modes of the retinal population code}}, doi = {10.5061/dryad.1f1rc}, year = {2017}, } @article{541, abstract = {While we have good understanding of bacterial metabolism at the population level, we know little about the metabolic behavior of individual cells: do single cells in clonal populations sometimes specialize on different metabolic pathways? Such metabolic specialization could be driven by stochastic gene expression and could provide individual cells with growth benefits of specialization. We measured the degree of phenotypic specialization in two parallel metabolic pathways, the assimilation of glucose and arabinose. We grew Escherichia coli in chemostats, and used isotope-labeled sugars in combination with nanometer-scale secondary ion mass spectrometry and mathematical modeling to quantify sugar assimilation at the single-cell level. We found large variation in metabolic activities between single cells, both in absolute assimilation and in the degree to which individual cells specialize in the assimilation of different sugars. Analysis of transcriptional reporters indicated that this variation was at least partially based on cell-to-cell variation in gene expression. Metabolic differences between cells in clonal populations could potentially reduce metabolic incompatibilities between different pathways, and increase the rate at which parallel reactions can be performed.}, author = {Nikolic, Nela and Schreiber, Frank and Dal Co, Alma and Kiviet, Daniel and Bergmiller, Tobias and Littmann, Sten and Kuypers, Marcel and Ackermann, Martin}, issn = {15537390}, journal = {PLoS Genetics}, number = {12}, publisher = {Public Library of Science}, title = {{Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations}}, doi = {10.1371/journal.pgen.1007122}, volume = {13}, year = {2017}, } @misc{9847, abstract = {information on culture conditions, phage mutagenesis, verification and lysate preparation; Raw data}, author = {Pleska, Maros and Guet, Calin C}, publisher = {The Royal Society}, title = {{Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification}}, doi = {10.6084/m9.figshare.5633917.v1}, year = {2017}, } @misc{9845, abstract = {Estimates of 13 C-arabinose and 2 H-glucose uptake from the fractions of heavy isotopes measured in single cells}, author = {Nikolic, Nela and Schreiber, Frank and Dal Co, Alma and Kiviet, Daniel and Bergmiller, Tobias and Littmann, Sten and Kuypers, Marcel and Ackermann, Martin}, publisher = {Public Library of Science}, title = {{Mathematical model}}, doi = {10.1371/journal.pgen.1007122.s017}, year = {2017}, } @misc{9849, abstract = {This text provides additional information about the model, a derivation of the analytic results in Eq (4), and details about simulations of an additional parameter set.}, author = {Lukacisinova, Marta and Novak, Sebastian and Paixao, Tiago}, publisher = {Public Library of Science}, title = {{Modelling and simulation details}}, doi = {10.1371/journal.pcbi.1005609.s001}, year = {2017}, } @misc{9850, abstract = {In this text, we discuss how a cost of resistance and the possibility of lethal mutations impact our model.}, author = {Lukacisinova, Marta and Novak, Sebastian and Paixao, Tiago}, publisher = {Public Library of Science}, title = {{Extensions of the model}}, doi = {10.1371/journal.pcbi.1005609.s002}, year = {2017}, } @misc{9846, author = {Nikolic, Nela and Schreiber, Frank and Dal Co, Alma and Kiviet, Daniel and Bergmiller, Tobias and Littmann, Sten and Kuypers, Marcel and Ackermann, Martin}, publisher = {Public Library of Science}, title = {{Supplementary methods}}, doi = {10.1371/journal.pgen.1007122.s016}, year = {2017}, } @article{680, abstract = {In order to respond reliably to specific features of their environment, sensory neurons need to integrate multiple incoming noisy signals. Crucially, they also need to compete for the interpretation of those signals with other neurons representing similar features. The form that this competition should take depends critically on the noise corrupting these signals. In this study we show that for the type of noise commonly observed in sensory systems, whose variance scales with the mean signal, sensory neurons should selectively divide their input signals by their predictions, suppressing ambiguous cues while amplifying others. Any change in the stimulus context alters which inputs are suppressed, leading to a deep dynamic reshaping of neural receptive fields going far beyond simple surround suppression. Paradoxically, these highly variable receptive fields go alongside and are in fact required for an invariant representation of external sensory features. In addition to offering a normative account of context-dependent changes in sensory responses, perceptual inference in the presence of signal-dependent noise accounts for ubiquitous features of sensory neurons such as divisive normalization, gain control and contrast dependent temporal dynamics.}, author = {Chalk, Matthew J and Masset, Paul and Gutkin, Boris and Denève, Sophie}, issn = {1553734X}, journal = {PLoS Computational Biology}, number = {6}, publisher = {Public Library of Science}, title = {{Sensory noise predicts divisive reshaping of receptive fields}}, doi = {10.1371/journal.pcbi.1005582}, volume = {13}, year = {2017}, } @misc{9851, abstract = {Based on the intuitive derivation of the dynamics of SIM allele frequency pM in the main text, we present a heuristic prediction for the long-term SIM allele frequencies with χ > 1 stresses and compare it to numerical simulations.}, author = {Lukacisinova, Marta and Novak, Sebastian and Paixao, Tiago}, publisher = {Public Library of Science}, title = {{Heuristic prediction for multiple stresses}}, doi = {10.1371/journal.pcbi.1005609.s003}, year = {2017}, } @misc{9852, abstract = {We show how different combination strategies affect the fraction of individuals that are multi-resistant.}, author = {Lukacisinova, Marta and Novak, Sebastian and Paixao, Tiago}, publisher = {Public Library of Science}, title = {{Resistance frequencies for different combination strategies}}, doi = {10.1371/journal.pcbi.1005609.s004}, year = {2017}, } @misc{9855, abstract = {Includes derivation of optimal estimation algorithm, generalisation to non-poisson noise statistics, correlated input noise, and implementation of in a multi-layer neural network.}, author = {Chalk, Matthew J and Masset, Paul and Gutkin, Boris and Denève, Sophie}, publisher = {Public Library of Science}, title = {{Supplementary appendix}}, doi = {10.1371/journal.pcbi.1005582.s001}, year = {2017}, } @inproceedings{941, abstract = {Recently there has been a proliferation of automated program repair (APR) techniques, targeting various programming languages. Such techniques can be generally classified into two families: syntactic- and semantics-based. Semantics-based APR, on which we focus, typically uses symbolic execution to infer semantic constraints and then program synthesis to construct repairs conforming to them. While syntactic-based APR techniques have been shown successful on bugs in real-world programs written in both C and Java, semantics-based APR techniques mostly target C programs. This leaves empirical comparisons of the APR families not fully explored, and developers without a Java-based semantics APR technique. We present JFix, a semantics-based APR framework that targets Java, and an associated Eclipse plugin. JFix is implemented atop Symbolic PathFinder, a well-known symbolic execution engine for Java programs. It extends one particular APR technique (Angelix), and is designed to be sufficiently generic to support a variety of such techniques. We demonstrate that semantics-based APR can indeed efficiently and effectively repair a variety of classes of bugs in large real-world Java programs. This supports our claim that the framework can both support developers seeking semantics-based repair of bugs in Java programs, as well as enable larger scale empirical studies comparing syntactic- and semantics-based APR targeting Java. The demonstration of our tool is available via the project website at: https://xuanbachle.github.io/semanticsrepair/ }, author = {Le, Xuan and Chu, Duc Hiep and Lo, David and Le Goues, Claire and Visser, Willem}, booktitle = {Proceedings of the 26th ACM SIGSOFT International Symposium on Software Testing and Analysis}, location = {Santa Barbara, CA, United States}, pages = {376 -- 379 }, publisher = {ACM}, title = {{JFIX: Semantics-based repair of Java programs via symbolic PathFinder}}, doi = {10.1145/3092703.3098225}, year = {2017}, } @inbook{958, abstract = {Biosensors that exploit Forster resonance energy transfer (FRET) can be used to visualize biological and physiological processes and are capable of providing detailed information in both spatial and temporal dimensions. In a FRET-based biosensor, substrate binding is associated with a change in the relative positions of two fluorophores, leading to a change in FRET efficiency that may be observed in the fluorescence spectrum. As a result, their design requires a ligand-binding protein that exhibits a conformational change upon binding. However, not all ligand-binding proteins produce responsive sensors upon conjugation to fluorescent proteins or dyes, and identifying the optimum locations for the fluorophores often involves labor-intensive iterative design or high-throughput screening. Combining the genetic fusion of a fluorescent protein to the ligand-binding protein with site-specific covalent attachment of a fluorescent dye can allow fine control over the positions of the two fluorophores, allowing the construction of very sensitive sensors. This relies upon the accurate prediction of the locations of the two fluorophores in bound and unbound states. In this chapter, we describe a method for computational identification of dye-attachment sites that allows the use of cysteine modification to attach synthetic dyes that can be paired with a fluorescent protein for the purposes of creating FRET sensors.}, author = {Mitchell, Joshua and Zhang, William and Herde, Michel and Henneberger, Christian and Janovjak, Harald L and O'Mara, Megan and Jackson, Colin}, booktitle = {Synthetic Protein Switches}, editor = {Stein, Viktor}, issn = {10643745}, pages = {89 -- 99}, publisher = {Springer}, title = {{Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment}}, doi = {10.1007/978-1-4939-6940-1_6}, volume = {1596}, year = {2017}, } @misc{9707, abstract = {Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM), combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret−/− or Etv4−/− sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret/Etv4 signaling promotes directed cell movements in the ureteric bud tips, and suggest a model in which these cell movements mediate branching morphogenesis.}, author = {Riccio, Paul and Cebrián, Christina and Zong, Hui and Hippenmeyer, Simon and Costantini, Frank}, publisher = {Dryad}, title = {{Data from: Ret and Etv4 promote directed movements of progenitor cells during renal branching morphogenesis}}, doi = {10.5061/dryad.pk16b}, year = {2017}, } @misc{9844, author = {Nikolic, Nela and Schreiber, Frank and Dal Co, Alma and Kiviet, Daniel and Bergmiller, Tobias and Littmann, Sten and Kuypers, Marcel and Ackermann, Martin}, publisher = {Public Library of Science}, title = {{Source data for figures and tables}}, doi = {10.1371/journal.pgen.1007122.s018}, year = {2017}, } @inproceedings{12905, author = {Schlögl, Alois and Kiss, Janos}, booktitle = {AHPC17 – Austrian HPC Meeting 2017}, location = {Grundlsee, Austria}, pages = {28}, publisher = {FSP Scientific Computing}, title = {{Scientific Computing at IST Austria}}, year = {2017}, } @inproceedings{13160, abstract = {Transforming deterministic ω -automata into deterministic parity automata is traditionally done using variants of appearance records. We present a more efficient variant of this approach, tailored to Rabin automata, and several optimizations applicable to all appearance records. We compare the methods experimentally and find out that our method produces smaller automata than previous approaches. Moreover, the experiments demonstrate the potential of our method for LTL synthesis, using LTL-to-Rabin translators. It leads to significantly smaller parity automata when compared to state-of-the-art approaches on complex formulae.}, author = {Kretinsky, Jan and Meggendorfer, Tobias and Waldmann, Clara and Weininger, Maximilian}, booktitle = {Tools and Algorithms for the Construction and Analysis of Systems}, isbn = {9783662545768}, issn = {1611-3349}, location = {Uppsala, Sweden}, pages = {443--460}, publisher = {Springer}, title = {{Index appearance record for transforming Rabin automata into parity automata}}, doi = {10.1007/978-3-662-54577-5_26}, volume = {10205}, year = {2017}, } @inproceedings{950, abstract = {Two-player games on graphs are widely studied in formal methods as they model the interaction between a system and its environment. The game is played by moving a token throughout a graph to produce an infinite path. There are several common modes to determine how the players move the token through the graph; e.g., in turn-based games the players alternate turns in moving the token. We study the bidding mode of moving the token, which, to the best of our knowledge, has never been studied in infinite-duration games. Both players have separate budgets, which sum up to $1$. In each turn, a bidding takes place. Both players submit bids simultaneously, and a bid is legal if it does not exceed the available budget. The winner of the bidding pays his bid to the other player and moves the token. For reachability objectives, repeated bidding games have been studied and are called Richman games. There, a central question is the existence and computation of threshold budgets; namely, a value t\in [0,1] such that if\PO's budget exceeds $t$, he can win the game, and if\PT's budget exceeds 1-t, he can win the game. We focus on parity games and mean-payoff games. We show the existence of threshold budgets in these games, and reduce the problem of finding them to Richman games. We also determine the strategy-complexity of an optimal strategy. Our most interesting result shows that memoryless strategies suffice for mean-payoff bidding games. }, author = {Avni, Guy and Henzinger, Thomas A and Chonev, Ventsislav K}, issn = {1868-8969}, location = {Berlin, Germany}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Infinite-duration bidding games}}, doi = {10.4230/LIPIcs.CONCUR.2017.21}, volume = {85}, year = {2017}, } @inproceedings{683, abstract = {Given a triangulation of a point set in the plane, a flip deletes an edge e whose removal leaves a convex quadrilateral, and replaces e by the opposite diagonal of the quadrilateral. It is well known that any triangulation of a point set can be reconfigured to any other triangulation by some sequence of flips. We explore this question in the setting where each edge of a triangulation has a label, and a flip transfers the label of the removed edge to the new edge. It is not true that every labelled triangulation of a point set can be reconfigured to every other labelled triangulation via a sequence of flips, but we characterize when this is possible. There is an obvious necessary condition: for each label l, if edge e has label l in the first triangulation and edge f has label l in the second triangulation, then there must be some sequence of flips that moves label l from e to f, ignoring all other labels. Bose, Lubiw, Pathak and Verdonschot formulated the Orbit Conjecture, which states that this necessary condition is also sufficient, i.e. that all labels can be simultaneously mapped to their destination if and only if each label individually can be mapped to its destination. We prove this conjecture. Furthermore, we give a polynomial-time algorithm to find a sequence of flips to reconfigure one labelled triangulation to another, if such a sequence exists, and we prove an upper bound of O(n7) on the length of the flip sequence. Our proof uses the topological result that the sets of pairwise non-crossing edges on a planar point set form a simplicial complex that is homeomorphic to a high-dimensional ball (this follows from a result of Orden and Santos; we give a different proof based on a shelling argument). The dual cell complex of this simplicial ball, called the flip complex, has the usual flip graph as its 1-skeleton. We use properties of the 2-skeleton of the flip complex to prove the Orbit Conjecture.}, author = {Lubiw, Anna and Masárová, Zuzana and Wagner, Uli}, location = {Brisbane, Australia}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{A proof of the orbit conjecture for flipping edge labelled triangulations}}, doi = {10.4230/LIPIcs.SoCG.2017.49}, volume = {77}, year = {2017}, } @phdthesis{1155, abstract = {This dissertation concerns the automatic verification of probabilistic systems and programs with arrays by statistical and logical methods. Although statistical and logical methods are different in nature, we show that they can be successfully combined for system analysis. In the first part of the dissertation we present a new statistical algorithm for the verification of probabilistic systems with respect to unbounded properties, including linear temporal logic. Our algorithm often performs faster than the previous approaches, and at the same time requires less information about the system. In addition, our method can be generalized to unbounded quantitative properties such as mean-payoff bounds. In the second part, we introduce two techniques for comparing probabilistic systems. Probabilistic systems are typically compared using the notion of equivalence, which requires the systems to have the equal probability of all behaviors. However, this notion is often too strict, since probabilities are typically only empirically estimated, and any imprecision may break the relation between processes. On the one hand, we propose to replace the Boolean notion of equivalence by a quantitative distance of similarity. For this purpose, we introduce a statistical framework for estimating distances between Markov chains based on their simulation runs, and we investigate which distances can be approximated in our framework. On the other hand, we propose to compare systems with respect to a new qualitative logic, which expresses that behaviors occur with probability one or a positive probability. This qualitative analysis is robust with respect to modeling errors and applicable to many domains. In the last part, we present a new quantifier-free logic for integer arrays, which allows us to express counting. Counting properties are prevalent in array-manipulating programs, however they cannot be expressed in the quantified fragments of the theory of arrays. We present a decision procedure for our logic, and provide several complexity results.}, author = {Daca, Przemyslaw}, issn = {2663-337X}, pages = {163}, publisher = {Institute of Science and Technology Austria}, title = {{Statistical and logical methods for property checking}}, doi = {10.15479/AT:ISTA:TH_730}, year = {2017}, } @phdthesis{6291, abstract = {Bacteria and their pathogens – phages – are the most abundant living entities on Earth. Throughout their coevolution, bacteria have evolved multiple immune systems to overcome the ubiquitous threat from the phages. Although the molecu- lar details of these immune systems’ functions are relatively well understood, their epidemiological consequences for the phage-bacterial communities have been largely neglected. In this thesis we employed both experimental and theoretical methods to explore whether herd and social immunity may arise in bacterial popu- lations. Using our experimental system consisting of Escherichia coli strains with a CRISPR based immunity to the T7 phage we show that herd immunity arises in phage-bacterial communities and that it is accentuated when the populations are spatially structured. By fitting a mathematical model, we inferred expressions for the herd immunity threshold and the velocity of spread of a phage epidemic in partially resistant bacterial populations, which both depend on the bacterial growth rate, phage burst size and phage latent period. We also investigated the poten- tial for social immunity in Streptococcus thermophilus and its phage 2972 using a bioinformatic analysis of potentially coding short open reading frames with a signalling signature, encoded within the CRISPR associated genes. Subsequently, we tested one identified potentially signalling peptide and found that its addition to a phage-challenged culture increases probability of survival of bacteria two fold, although the results were only marginally significant. Together, these results demonstrate that the ubiquitous arms races between bacteria and phages have further consequences at the level of the population.}, author = {Payne, Pavel}, issn = {2663-337X}, pages = {83}, publisher = {Institute of Science and Technology Austria}, title = {{Bacterial herd and social immunity to phages}}, year = {2017}, } @article{561, abstract = {Restriction–modification systems are widespread genetic elements that protect bacteria from bacteriophage infections by recognizing and cleaving heterologous DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence shows that restriction sites are significantly underrepresented in bacteriophage genomes, presumably because bacteriophages with fewer restriction sites are more likely to escape cleavage by restriction–modification systems. However, how mutations in restriction sites affect the likelihood of bacteriophage escape is unknown. Using the bacteriophage l and the restriction–modification system EcoRI, we show that while mutation effects at different restriction sites are unequal, they are independent. As a result, the probability of bacteriophage escape increases with each mutated restriction site. Our results experimentally support the role of restriction site avoidance as a response to selection imposed by restriction–modification systems and offer an insight into the events underlying the process of bacteriophage escape.}, author = {Pleska, Maros and Guet, Calin C}, issn = {1744-9561}, journal = {Biology Letters}, number = {12}, publisher = {The Royal Society}, title = {{Effects of mutations in phage restriction sites during escape from restriction–modification}}, doi = {10.1098/rsbl.2017.0646}, volume = {13}, year = {2017}, } @phdthesis{818, abstract = {Antibiotics have diverse effects on bacteria, including massive changes in bacterial gene expression. Whereas the gene expression changes under many antibiotics have been measured, the temporal organization of these responses and their dependence on the bacterial growth rate are unclear. As described in Chapter 1, we quantified the temporal gene expression changes in the bacterium Escherichia coli in response to the sudden exposure to antibiotics using a fluorescent reporter library and a robotic system. Our data show temporally structured gene expression responses, with response times for individual genes ranging from tens of minutes to several hours. We observed that many stress response genes were activated in response to antibiotics. As certain stress responses cross-protect bacteria from other stressors, we then asked whether cellular responses to antibiotics have a similar protective role in Chapter 2. Indeed, we found that the trimethoprim-induced acid stress response protects bacteria from subsequent acid stress. We combined microfluidics with time-lapse imaging to monitor survival, intracellular pH, and acid stress response in single cells. This approach revealed that the variable expression of the acid resistance operon gadBC strongly correlates with single-cell survival time. Cells with higher gadBC expression following trimethoprim maintain higher intracellular pH and survive the acid stress longer. Overall, we provide a way to identify single-cell cross-protection between antibiotics and environmental stressors from temporal gene expression data, and show how antibiotics can increase bacterial fitness in changing environments. While gene expression changes to antibiotics show a clear temporal structure at the population-level, it is unclear whether this clear temporal order is followed by every single cell. Using dual-reporter strains described in Chapter 3, we measured gene expression dynamics of promoter pairs in the same cells using microfluidics and microscopy. Chapter 4 shows that the oxidative stress response and the DNA stress response showed little timing variability and a clear temporal order under the antibiotic nitrofurantoin. In contrast, the acid stress response under trimethoprim ran independently from all other activated response programs including the DNA stress response, which showed particularly high timing variability in this stress condition. In summary, this approach provides insight into the temporal organization of gene expression programs at the single-cell level and suggests dependencies between response programs and the underlying variability-introducing mechanisms. Altogether, this work advances our understanding of the diverse effects that antibiotics have on bacteria. These results were obtained by taking into account gene expression dynamics, which allowed us to identify general principles, molecular mechanisms, and dependencies between genes. Our findings may have implications for infectious disease treatments, and microbial communities in the human body and in nature. }, author = {Mitosch, Karin}, issn = {2663-337X}, pages = {113}, publisher = {Institute of Science and Technology Austria}, title = {{Timing, variability and cross-protection in bacteria – insights from dynamic gene expression responses to antibiotics}}, doi = {10.15479/AT:ISTA:th_862}, year = {2017}, } @article{666, abstract = {Antibiotics elicit drastic changes in microbial gene expression, including the induction of stress response genes. While certain stress responses are known to “cross-protect” bacteria from other stressors, it is unclear whether cellular responses to antibiotics have a similar protective role. By measuring the genome-wide transcriptional response dynamics of Escherichia coli to four antibiotics, we found that trimethoprim induces a rapid acid stress response that protects bacteria from subsequent exposure to acid. Combining microfluidics with time-lapse imaging to monitor survival and acid stress response in single cells revealed that the noisy expression of the acid resistance operon gadBC correlates with single-cell survival. Cells with higher gadBC expression following trimethoprim maintain higher intracellular pH and survive the acid stress longer. The seemingly random single-cell survival under acid stress can therefore be predicted from gadBC expression and rationalized in terms of GadB/C molecular function. Overall, we provide a roadmap for identifying the molecular mechanisms of single-cell cross-protection between antibiotics and other stressors.}, author = {Mitosch, Karin and Rieckh, Georg and Bollenbach, Tobias}, issn = {24054712}, journal = {Cell Systems}, number = {4}, pages = {393 -- 403}, publisher = {Cell Press}, title = {{Noisy response to antibiotic stress predicts subsequent single cell survival in an acidic environment}}, doi = {10.1016/j.cels.2017.03.001}, volume = {4}, year = {2017}, } @phdthesis{821, abstract = {This dissertation focuses on algorithmic aspects of program verification, and presents modeling and complexity advances on several problems related to the static analysis of programs, the stateless model checking of concurrent programs, and the competitive analysis of real-time scheduling algorithms. Our contributions can be broadly grouped into five categories. Our first contribution is a set of new algorithms and data structures for the quantitative and data-flow analysis of programs, based on the graph-theoretic notion of treewidth. It has been observed that the control-flow graphs of typical programs have special structure, and are characterized as graphs of small treewidth. We utilize this structural property to provide faster algorithms for the quantitative and data-flow analysis of recursive and concurrent programs. In most cases we make an algebraic treatment of the considered problem, where several interesting analyses, such as the reachability, shortest path, and certain kind of data-flow analysis problems follow as special cases. We exploit the constant-treewidth property to obtain algorithmic improvements for on-demand versions of the problems, and provide data structures with various tradeoffs between the resources spent in the preprocessing and querying phase. We also improve on the algorithmic complexity of quantitative problems outside the algebraic path framework, namely of the minimum mean-payoff, minimum ratio, and minimum initial credit for energy problems. Our second contribution is a set of algorithms for Dyck reachability with applications to data-dependence analysis and alias analysis. In particular, we develop an optimal algorithm for Dyck reachability on bidirected graphs, which are ubiquitous in context-insensitive, field-sensitive points-to analysis. Additionally, we develop an efficient algorithm for context-sensitive data-dependence analysis via Dyck reachability, 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 (i)~linear in the number of call sites and (ii)~only logarithmic in the size of the whole library, as opposed to linear in the size of the whole library. Finally, we prove that Dyck reachability is Boolean Matrix Multiplication-hard in general, and the hardness also holds for graphs of constant treewidth. This hardness result strongly indicates that there exist no combinatorial algorithms for Dyck reachability with truly subcubic complexity. Our third contribution is the formalization and algorithmic treatment of the Quantitative Interprocedural Analysis framework. In this framework, the transitions of a recursive program are annotated as good, bad or neutral, and receive a weight which measures the magnitude of their respective effect. The Quantitative Interprocedural Analysis problem asks to determine whether there exists an infinite run of the program where the long-run ratio of the bad weights over the good weights is above a given threshold. We illustrate how several quantitative problems related to static analysis of recursive programs can be instantiated in this framework, and present some case studies to this direction. Our fourth contribution is a new dynamic partial-order reduction for the stateless model checking of concurrent programs. Traditional approaches rely on the standard Mazurkiewicz equivalence between traces, by means of partitioning the trace space into equivalence classes, and attempting to explore a few representatives from each class. We present a new dynamic partial-order reduction method called the Data-centric Partial Order Reduction (DC-DPOR). Our algorithm is based on a new equivalence between traces, called the observation equivalence. DC-DPOR explores a coarser partitioning of the trace space than any exploration method based on the standard Mazurkiewicz equivalence. Depending on the program, the new partitioning can be even exponentially coarser. Additionally, DC-DPOR spends only polynomial time in each explored class. Our fifth contribution is the use of automata and game-theoretic verification techniques in the competitive analysis and synthesis of real-time scheduling algorithms for firm-deadline tasks. On the analysis side, we leverage automata on infinite words to compute the competitive ratio of real-time schedulers subject to various environmental constraints. On the synthesis side, we introduce a new instance of two-player mean-payoff partial-information games, and show how the synthesis of an optimal real-time scheduler can be reduced to computing winning strategies in this new type of games.}, author = {Pavlogiannis, Andreas}, issn = {2663-337X}, pages = {418}, publisher = {Institute of Science and Technology Austria}, title = {{Algorithmic advances in program analysis and their applications}}, doi = {10.15479/AT:ISTA:th_854}, year = {2017}, } @phdthesis{820, abstract = {The lac operon is a classic model system for bacterial gene regulation, and has been studied extensively in E. coli, a classic model organism. However, not much is known about E. coli’s ecology and life outside the laboratory, in particular in soil and water environments. The natural diversity of the lac operon outside the laboratory, its role in the ecology of E. coli and the selection pressures it is exposed to, are similarly unknown. In Chapter Two of this thesis, I explore the genetic diversity, phylogenetic history and signatures of selection of the lac operon across 20 natural isolates of E. coli and divergent clades of Escherichia. I found that complete lac operons were present in all isolates examined, which in all but one case were functional. The lac operon phylogeny conformed to the whole-genome phylogeny of the divergent Escherichia clades, which excludes horizontal gene transfer as an explanation for the presence of functional lac operons in these clades. All lac operon genes showed a signature of purifying selection; this signature was strongest for the lacY gene. Lac operon genes of human and environmental isolates showed similar signatures of selection, except the lacZ gene, which showed a stronger signature of selection in environmental isolates. In Chapter Three, I try to identify the natural genetic variation relevant for phenotype and fitness in the lac operon, comparing growth rate on lactose and LacZ activity of the lac operons of these wild isolates in a common genetic background. Sequence variation in the lac promoter region, upstream of the -10 and -35 RNA polymerase binding motif, predicted variation in LacZ activity at full induction, using a thermodynamic model of polymerase binding (Tugrul, 2016). However, neither variation in LacZ activity, nor RNA polymerase binding predicted by the model correlated with variation in growth rate. Lac operons of human and environmental isolates did not differ systematically in either growth rate on lactose or LacZ protein activity, suggesting that these lac operons have been exposed to similar selection pressures. We thus have no evidence that the phenotypic variation we measured is relevant for fitness. To start assessing the effect of genomic background on the growth phenotype conferred by the lac operon, I compared growth on minimal medium with lactose between lac operon constructs and the corresponding original isolates, I found that maximal growth rate was determined by genomic background, with almost all backgrounds conferring higher growth rates than lab strain K12 MG1655. However, I found no evidence that the lactose concentration at which growth was half maximal depended on genomic background.}, author = {Jesse, Fabienne}, issn = {2663-337X}, pages = {87}, publisher = {Institute of Science and Technology Austria}, title = {{The lac operon in the wild}}, doi = {10.15479/AT:ISTA:th_857}, year = {2017}, } @phdthesis{838, abstract = {In this thesis we discuss the exact security of message authentications codes HMAC , NMAC , and PMAC . NMAC is a mode of operation which turns a fixed input-length keyed hash function f into a variable input-length function. A practical single-key variant of NMAC called HMAC is a very popular and widely deployed message authentication code (MAC). PMAC is a block-cipher based mode of operation, which also happens to be the most famous fully parallel MAC. NMAC was introduced by Bellare, Canetti and Krawczyk Crypto’96, who proved it to be a secure pseudorandom function (PRF), and thus also a MAC, under two assumptions. Unfortunately, for many instantiations of HMAC one of them has been found to be wrong. To restore the provable guarantees for NMAC , Bellare [Crypto’06] showed its security without this assumption. PMAC was introduced by Black and Rogaway at Eurocrypt 2002. If instantiated with a pseudorandom permutation over n -bit strings, PMAC constitutes a provably secure variable input-length PRF. For adversaries making q queries, each of length at most ` (in n -bit blocks), and of total length σ ≤ q` , the original paper proves an upper bound on the distinguishing advantage of O ( σ 2 / 2 n ), while the currently best bound is O ( qσ/ 2 n ). In this work we show that this bound is tight by giving an attack with advantage Ω( q 2 `/ 2 n ). In the PMAC construction one initially XORs a mask to every message block, where the mask for the i th block is computed as τ i := γ i · L , where L is a (secret) random value, and γ i is the i -th codeword of the Gray code. Our attack applies more generally to any sequence of γ i ’s which contains a large coset of a subgroup of GF (2 n ). As for NMAC , our first contribution is a simpler and uniform proof: If f is an ε -secure PRF (against q queries) and a δ - non-adaptively secure PRF (against q queries), then NMAC f is an ( ε + `qδ )-secure PRF against q queries of length at most ` blocks each. We also show that this ε + `qδ bound is basically tight by constructing an f for which an attack with advantage `qδ exists. Moreover, we analyze the PRF-security of a modification of NMAC called NI by An and Bellare that avoids the constant rekeying on multi-block messages in NMAC and allows for an information-theoretic analysis. We carry out such an analysis, obtaining a tight `q 2 / 2 c bound for this step, improving over the trivial bound of ` 2 q 2 / 2 c . Finally, we investigate, if the security of PMAC can be further improved by using τ i ’s that are k -wise independent, for k > 1 (the original has k = 1). We observe that the security of PMAC will not increase in general if k = 2, and then prove that the security increases to O ( q 2 / 2 n ), if the k = 4. Due to simple extension attacks, this is the best bound one can hope for, using any distribution on the masks. Whether k = 3 is already sufficient to get this level of security is left as an open problem. Keywords: Message authentication codes, Pseudorandom functions, HMAC, PMAC. }, author = {Rybar, Michal}, issn = {2663-337X}, pages = {86}, publisher = {Institute of Science and Technology Austria}, title = {{(The exact security of) Message authentication codes}}, doi = {10.15479/AT:ISTA:th_828}, year = {2017}, } @article{6196, abstract = {PMAC is a simple and parallel block-cipher mode of operation, which was introduced by Black and Rogaway at Eurocrypt 2002. If instantiated with a (pseudo)random permutation over n-bit strings, PMAC constitutes a provably secure variable input-length (pseudo)random function. For adversaries making q queries, each of length at most l (in n-bit blocks), and of total length σ ≤ ql, the original paper proves an upper bound on the distinguishing advantage of Ο(σ2/2n), while the currently best bound is Ο (qσ/2n).In this work we show that this bound is tight by giving an attack with advantage Ω (q2l/2n). In the PMAC construction one initially XORs a mask to every message block, where the mask for the ith block is computed as τi := γi·L, where L is a (secret) random value, and γi is the i-th codeword of the Gray code. Our attack applies more generally to any sequence of γi’s which contains a large coset of a subgroup of GF(2n). We then investigate if the security of PMAC can be further improved by using τi’s that are k-wise independent, for k > 1 (the original distribution is only 1-wise independent). We observe that the security of PMAC will not increase in general, even if the masks are chosen from a 2-wise independent distribution, and then prove that the security increases to O(q<2/2n), if the τi are 4-wise independent. Due to simple extension attacks, this is the best bound one can hope for, using any distribution on the masks. Whether 3-wise independence is already sufficient to get this level of security is left as an open problem.}, author = {Gazi, Peter and Pietrzak, Krzysztof Z and Rybar, Michal}, issn = {2519-173X}, journal = {IACR Transactions on Symmetric Cryptology}, number = {2}, pages = {145--161}, publisher = {Ruhr University Bochum}, title = {{The exact security of PMAC}}, doi = {10.13154/TOSC.V2016.I2.145-161}, volume = {2016}, year = {2017}, } @phdthesis{837, abstract = {The hippocampus is a key brain region for memory and notably for spatial memory, and is needed for both spatial working and reference memories. Hippocampal place cells selectively discharge in specific locations of the environment to form mnemonic represen tations of space. Several behavioral protocols have been designed to test spatial memory which requires the experimental subject to utilize working memory and reference memory. However, less is known about how these memory traces are presented in the hippo campus, especially considering tasks that require both spatial working and long -term reference memory demand. The aim of my thesis was to elucidate how spatial working memory, reference memory, and the combination of both are represented in the hippocampus. In this thesis, using a radial eight -arm maze, I examined how the combined demand on these memories influenced place cell assemblies while reference memories were partially updated by changing some of the reward- arms. This was contrasted with task varian ts requiring working or reference memories only. Reference memory update led to gradual place field shifts towards the rewards on the switched arms. Cells developed enhanced firing in passes between newly -rewarded arms as compared to those containing an unchanged reward. The working memory task did not show such gradual changes. Place assemblies on occasions replayed trajectories of the maze; at decision points the next arm choice was preferentially replayed in tasks needing reference memory while in the pure working memory task the previously visited arm was replayed. Hence trajectory replay only reflected the decision of the animal in tasks needing reference memory update. At the reward locations, in all three tasks outbound trajectories of the current arm were preferentially replayed, showing the animals’ next path to the center. At reward locations trajectories were replayed preferentially in reverse temporal order. Moreover, in the center reverse replay was seen in the working memory task but in the other tasks forward replay was seen. Hence, the direction of reactivation was determined by the goal locations so that part of the trajectory which was closer to the goal was reactivated later in an HSE while places further away from the goal were reactivated earlier. Altogether my work demonstrated that reference memory update triggers several levels of reorganization of the hippocampal cognitive map which are not seen in simpler working memory demand s. Moreover, hippocampus is likely to be involved in spatial decisions through reactivating planned trajectories when reference memory recall is required for such a decision. }, author = {Xu, Haibing}, issn = {2663-337X}, pages = {93}, publisher = {Institute of Science and Technology Austria}, title = {{Reactivation of the hippocampal cognitive map in goal-directed spatial tasks}}, doi = {10.15479/AT:ISTA:th_858}, year = {2017}, } @phdthesis{938, abstract = {The thesis encompasses several topics of plant cell biology which were studied in the model plant Arabidopsis thaliana. Chapter 1 concerns the plant hormone auxin and its polar transport through cells and tissues. The highly controlled, directional transport of auxin is facilitated by plasma membrane-localized transporters. Transporters from the PIN family direct auxin transport due to their polarized localizations at cell membranes. Substantial effort has been put into research on cellular trafficking of PIN proteins, which is thought to underlie their polar distribution. I participated in a forward genetic screen aimed at identifying novel regulators of PIN polarity. The screen yielded several genes which may be involved in PIN polarity regulation or participate in polar auxin transport by other means. Chapter 2 focuses on the endomembrane system, with particular attention to clathrin-mediated endocytosis. The project started with identification of several proteins that interact with clathrin light chains. Among them, I focused on two putative homologues of auxilin, which in non-plant systems is an endocytotic factor known for uncoating clathrin-coated vesicles in the final step of endocytosis. The body of my work consisted of an in-depth characterization of transgenic A. thaliana lines overexpressing these putative auxilins in an inducible manner. Overexpression of these proteins leads to an inhibition of endocytosis, as documented by imaging of cargoes and clathrin-related endocytic machinery. An extension of this work is an investigation into a concept of homeostatic regulation acting between distinct transport processes in the endomembrane system. With auxilin overexpressing lines, where endocytosis is blocked specifically, I made observations on the mutual relationship between two opposite trafficking processes of secretion and endocytosis. In Chapter 3, I analyze cortical microtubule arrays and their relationship to auxin signaling and polarized growth in elongating cells. In plants, microtubules are organized into arrays just below the plasma membrane, and it is thought that their function is to guide membrane-docked cellulose synthase complexes. These, in turn, influence cell wall structure and cell shape by directed deposition of cellulose fibres. In elongating cells, cortical microtubule arrays are able to reorient in relation to long cell axis, and these reorientations have been linked to cell growth and to signaling of growth-regulating factors such as auxin or light. In this chapter, I am addressing the causal relationship between microtubule array reorientation, growth, and auxin signaling. I arrive at a model where array reorientation is not guided by auxin directly, but instead is only controlled by growth, which, in turn, is regulated by auxin.}, author = {Adamowski, Maciek}, issn = {2663-337X}, pages = {117}, publisher = {Institute of Science and Technology Austria}, title = {{Investigations into cell polarity and trafficking in the plant model Arabidopsis thaliana }}, doi = {10.15479/AT:ISTA:th_842}, year = {2017}, } @phdthesis{992, abstract = {An instance of the Constraint Satisfaction Problem (CSP) is given by a finite set of variables, a finite domain of labels, and a set of constraints, each constraint acting on a subset of the variables. The goal is to find an assignment of labels to its variables that satisfies all constraints (or decide whether one exists). If we allow more general “soft” constraints, which come with (possibly infinite) costs of particular assignments, we obtain instances from a richer class called Valued Constraint Satisfaction Problem (VCSP). There the goal is to find an assignment with minimum total cost. In this thesis, we focus (assuming that P 6 = NP) on classifying computational com- plexity of CSPs and VCSPs under certain restricting conditions. Two results are the core content of the work. In one of them, we consider VCSPs parametrized by a constraint language, that is the set of “soft” constraints allowed to form the instances, and finish the complexity classification modulo (missing pieces of) complexity classification for analogously parametrized CSP. The other result is a generalization of Edmonds’ perfect matching algorithm. This generalization contributes to complexity classfications in two ways. First, it gives a new (largest known) polynomial-time solvable class of Boolean CSPs in which every variable may appear in at most two constraints and second, it settles full classification of Boolean CSPs with planar drawing (again parametrized by a constraint language).}, author = {Rolinek, Michal}, issn = {2663-337X}, pages = {97}, publisher = {Institute of Science and Technology Austria}, title = {{Complexity of constraint satisfaction}}, doi = {10.15479/AT:ISTA:th_815}, year = {2017}, } @article{718, abstract = {Mapping every simplex in the Delaunay mosaic of a discrete point set to the radius of the smallest empty circumsphere gives a generalized discrete Morse function. Choosing the points from a Poisson point process in ℝ n , we study the expected number of simplices in the Delaunay mosaic as well as the expected number of critical simplices and nonsingular intervals in the corresponding generalized discrete gradient. Observing connections with other probabilistic models, we obtain precise expressions for the expected numbers in low dimensions. In particular, we obtain the expected numbers of simplices in the Poisson–Delaunay mosaic in dimensions n ≤ 4.}, author = {Edelsbrunner, Herbert and Nikitenko, Anton and Reitzner, Matthias}, issn = {00018678}, journal = {Advances in Applied Probability}, number = {3}, pages = {745 -- 767}, publisher = {Cambridge University Press}, title = {{Expected sizes of poisson Delaunay mosaics and their discrete Morse functions}}, doi = {10.1017/apr.2017.20}, volume = {49}, year = {2017}, } @inproceedings{559, abstract = {Proofs of space (PoS) were suggested as more ecological and economical alternative to proofs of work, which are currently used in blockchain designs like Bitcoin. The existing PoS are based on rather sophisticated graph pebbling lower bounds. Much simpler and in several aspects more efficient schemes based on inverting random functions have been suggested, but they don’t give meaningful security guarantees due to existing time-memory trade-offs. In particular, Hellman showed that any permutation over a domain of size N can be inverted in time T by an algorithm that is given S bits of auxiliary information whenever (Formula presented). For functions Hellman gives a weaker attack with S2· T≈ N2 (e.g., S= T≈ N2/3). To prove lower bounds, one considers an adversary who has access to an oracle f: [ N] → [N] and can make T oracle queries. The best known lower bound is S· T∈ Ω(N) and holds for random functions and permutations. We construct functions that provably require more time and/or space to invert. Specifically, for any constant k we construct a function [N] → [N] that cannot be inverted unless Sk· T∈ Ω(Nk) (in particular, S= T≈ (Formula presented). Our construction does not contradict Hellman’s time-memory trade-off, because it cannot be efficiently evaluated in forward direction. However, its entire function table can be computed in time quasilinear in N, which is sufficient for the PoS application. Our simplest construction is built from a random function oracle g: [N] × [N] → [ N] and a random permutation oracle f: [N] → N] and is defined as h(x) = g(x, x′) where f(x) = π(f(x′)) with π being any involution without a fixed point, e.g. flipping all the bits. For this function we prove that any adversary who gets S bits of auxiliary information, makes at most T oracle queries, and inverts h on an ϵ fraction of outputs must satisfy S2· T∈ Ω(ϵ2N2).}, author = {Abusalah, Hamza M and Alwen, Joel F and Cohen, Bram and Khilko, Danylo and Pietrzak, Krzysztof Z and Reyzin, Leonid}, isbn = {978-331970696-2}, location = {Hong Kong, China}, pages = {357 -- 379}, publisher = {Springer}, title = {{Beyond Hellman’s time-memory trade-offs with applications to proofs of space}}, doi = {10.1007/978-3-319-70697-9_13}, volume = {10625}, year = {2017}, } @article{550, abstract = {For large random matrices X with independent, centered entries but not necessarily identical variances, the eigenvalue density of XX* is well-approximated by a deterministic measure on ℝ. We show that the density of this measure has only square and cubic-root singularities away from zero. We also extend the bulk local law in [5] to the vicinity of these singularities.}, author = {Alt, Johannes}, issn = {1083589X}, journal = {Electronic Communications in Probability}, publisher = {Institute of Mathematical Statistics}, title = {{Singularities of the density of states of random Gram matrices}}, doi = {10.1214/17-ECP97}, volume = {22}, year = {2017}, } @inproceedings{647, abstract = {Despite researchers’ efforts in the last couple of decades, reachability analysis is still a challenging problem even for linear hybrid systems. Among the existing approaches, the most practical ones are mainly based on bounded-time reachable set over-approximations. For the purpose of unbounded-time analysis, one important strategy is to abstract the original system and find an invariant for the abstraction. In this paper, we propose an approach to constructing a new kind of abstraction called conic abstraction for affine hybrid systems, and to computing reachable sets based on this abstraction. The essential feature of a conic abstraction is that it partitions the state space of a system into a set of convex polyhedral cones which is derived from a uniform conic partition of the derivative space. Such a set of polyhedral cones is able to cut all trajectories of the system into almost straight segments so that every segment of a reach pipe in a polyhedral cone tends to be straight as well, and hence can be over-approximated tightly by polyhedra using similar techniques as HyTech or PHAVer. In particular, for diagonalizable affine systems, our approach can guarantee to find an invariant for unbounded reachable sets, which is beyond the capability of bounded-time reachability analysis tools. We implemented the approach in a tool and experiments on benchmarks show that our approach is more powerful than SpaceEx and PHAVer in dealing with diagonalizable systems.}, author = {Bogomolov, Sergiy and Giacobbe, Mirco and Henzinger, Thomas A and Kong, Hui}, isbn = {978-331965764-6}, location = {Berlin, Germany}, pages = {116 -- 132}, publisher = {Springer}, title = {{Conic abstractions for hybrid systems}}, doi = {10.1007/978-3-319-65765-3_7}, volume = {10419 }, year = {2017}, } @inproceedings{631, abstract = {Template polyhedra generalize intervals and octagons to polyhedra whose facets are orthogonal to a given set of arbitrary directions. They have been employed in the abstract interpretation of programs and, with particular success, in the reachability analysis of hybrid automata. While previously, the choice of directions has been left to the user or a heuristic, we present a method for the automatic discovery of directions that generalize and eliminate spurious counterexamples. We show that for the class of convex hybrid automata, i.e., hybrid automata with (possibly nonlinear) convex constraints on derivatives, such directions always exist and can be found using convex optimization. We embed our method inside a CEGAR loop, thus enabling the time-unbounded reachability analysis of an important and richer class of hybrid automata than was previously possible. We evaluate our method on several benchmarks, demonstrating also its superior efficiency for the special case of linear hybrid automata.}, author = {Bogomolov, Sergiy and Frehse, Goran and Giacobbe, Mirco and Henzinger, Thomas A}, isbn = {978-366254576-8}, location = {Uppsala, Sweden}, pages = {589 -- 606}, publisher = {Springer}, title = {{Counterexample guided refinement of template polyhedra}}, doi = {10.1007/978-3-662-54577-5_34}, volume = {10205}, year = {2017}, } @article{1144, abstract = {We show that matrix elements of functions of N × N Wigner matrices fluctuate on a scale of order N−1/2 and we identify the limiting fluctuation. Our result holds for any function f of the matrix that has bounded variation thus considerably relaxing the regularity requirement imposed in [7, 11].}, author = {Erdös, László and Schröder, Dominik J}, journal = {Electronic Communications in Probability}, publisher = {Institute of Mathematical Statistics}, title = {{Fluctuations of functions of Wigner matrices}}, doi = {10.1214/16-ECP38}, volume = {21}, year = {2017}, } @article{486, abstract = {Color texture reproduction in 3D printing commonly ignores volumetric light transport (cross-talk) between surface points on a 3D print. Such light diffusion leads to significant blur of details and color bleeding, and is particularly severe for highly translucent resin-based print materials. Given their widely varying scattering properties, this cross-talk between surface points strongly depends on the internal structure of the volume surrounding each surface point. Existing scattering-aware methods use simplified models for light diffusion, and often accept the visual blur as an immutable property of the print medium. In contrast, our work counteracts heterogeneous scattering to obtain the impression of a crisp albedo texture on top of the 3D print, by optimizing for a fully volumetric material distribution that preserves the target appearance. Our method employs an efficient numerical optimizer on top of a general Monte-Carlo simulation of heterogeneous scattering, supported by a practical calibration procedure to obtain scattering parameters from a given set of printer materials. Despite the inherent translucency of the medium, we reproduce detailed surface textures on 3D prints. We evaluate our system using a commercial, five-tone 3D print process and compare against the printer’s native color texturing mode, demonstrating that our method preserves high-frequency features well without having to compromise on color gamut.}, author = {Elek, Oskar and Sumin, Denis and Zhang, Ran and Weyrich, Tim and Myszkowski, Karol and Bickel, Bernd and Wilkie, Alexander and Krivanek, Jaroslav}, issn = {07300301}, journal = {ACM Transactions on Graphics}, number = {6}, publisher = {ACM}, title = {{Scattering-aware texture reproduction for 3D printing}}, doi = {10.1145/3130800.3130890}, volume = {36}, year = {2017}, } @inproceedings{637, abstract = {For many cryptographic primitives, it is relatively easy to achieve selective security (where the adversary commits a-priori to some of the choices to be made later in the attack) but appears difficult to achieve the more natural notion of adaptive security (where the adversary can make all choices on the go as the attack progresses). A series of several recent works shows how to cleverly achieve adaptive security in several such scenarios including generalized selective decryption (Panjwani, TCC ’07 and Fuchsbauer et al., CRYPTO ’15), constrained PRFs (Fuchsbauer et al., ASIACRYPT ’14), and Yao garbled circuits (Jafargholi and Wichs, TCC ’16b). Although the above works expressed vague intuition that they share a common technique, the connection was never made precise. In this work we present a new framework that connects all of these works and allows us to present them in a unified and simplified fashion. Moreover, we use the framework to derive a new result for adaptively secure secret sharing over access structures defined via monotone circuits. We envision that further applications will follow in the future. Underlying our framework is the following simple idea. It is well known that selective security, where the adversary commits to n-bits of information about his future choices, automatically implies adaptive security at the cost of amplifying the adversary’s advantage by a factor of up to 2n. However, in some cases the proof of selective security proceeds via a sequence of hybrids, where each pair of adjacent hybrids locally only requires some smaller partial information consisting of m ≪ n bits. The partial information needed might be completely different between different pairs of hybrids, and if we look across all the hybrids we might rely on the entire n-bit commitment. Nevertheless, the above is sufficient to prove adaptive security, at the cost of amplifying the adversary’s advantage by a factor of only 2m ≪ 2n. In all of our examples using the above framework, the different hybrids are captured by some sort of a graph pebbling game and the amount of information that the adversary needs to commit to in each pair of hybrids is bounded by the maximum number of pebbles in play at any point in time. Therefore, coming up with better strategies for proving adaptive security translates to various pebbling strategies for different types of graphs.}, author = {Jafargholi, Zahra and Kamath Hosdurg, Chethan and Klein, Karen and Komargodski, Ilan and Pietrzak, Krzysztof Z and Wichs, Daniel}, editor = {Katz, Jonathan and Shacham, Hovav}, isbn = {978-331963687-0}, location = {Santa Barbara, CA, United States}, pages = {133 -- 163}, publisher = {Springer}, title = {{Be adaptive avoid overcommitting}}, doi = {10.1007/978-3-319-63688-7_5}, volume = {10401}, year = {2017}, } @misc{9842, abstract = {Mathematica notebooks used to generate figures.}, author = {Etheridge, Alison and Barton, Nicholas H}, publisher = {Mendeley Data}, title = {{Data for: Establishment in a new habitat by polygenic adaptation}}, doi = {10.17632/nw68fxzjpm.1}, year = {2017}, } @phdthesis{202, abstract = {Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.}, author = {Pleska, Maros}, issn = {2663-337X}, pages = {126}, publisher = {Institute of Science and Technology Austria}, title = {{Biology of restriction-modification systems at the single-cell and population level}}, doi = {10.15479/AT:ISTA:th_916}, year = {2017}, } @phdthesis{6287, abstract = {The main objects considered in the present work are simplicial and CW-complexes with vertices forming a random point cloud. In particular, we consider a Poisson point process in R^n and study Delaunay and Voronoi complexes of the first and higher orders and weighted Delaunay complexes obtained as sections of Delaunay complexes, as well as the Čech complex. Further, we examine theDelaunay complex of a Poisson point process on the sphere S^n, as well as of a uniform point cloud, which is equivalent to the convex hull, providing a connection to the theory of random polytopes. Each of the complexes in question can be endowed with a radius function, which maps its cells to the radii of appropriately chosen circumspheres, called the radius of the cell. Applying and developing discrete Morse theory for these functions, joining it together with probabilistic and sometimes analytic machinery, and developing several integral geometric tools, we aim at getting the distributions of circumradii of typical cells. For all considered complexes, we are able to generalize and obtain up to constants the distribution of radii of typical intervals of all types. In low dimensions the constants can be computed explicitly, thus providing the explicit expressions for the expected numbers of cells. In particular, it allows to find the expected density of simplices of every dimension for a Poisson point process in R^4, whereas the result for R^3 was known already in 1970's.}, author = {Nikitenko, Anton}, issn = {2663-337X}, pages = {86}, publisher = {Institute of Science and Technology Austria}, title = {{Discrete Morse theory for random complexes }}, doi = {10.15479/AT:ISTA:th_873}, year = {2017}, } @phdthesis{1127, abstract = {Plant hormone auxin and its transport between cells belong to the most important mechanisms controlling plant development. Auxin itself could change localization of PINs and thereby control direction of its own flow. We performed an expression profiling experiment in Arabidopsis roots to identify potential regulators of PIN polarity which are transcriptionally regulated by auxin signalling. We identified several novel regulators and performed a detailed characterization of the transcription factor WRKY23 (At2g47260) and its role in auxin feedback on PIN polarity. Gain-of-function and dominant-negative mutants revealed that WRKY23 plays a crucial role in mediating the auxin effect on PIN polarity. In concordance, typical polar auxin transport processes such as gravitropism and leaf vascular pattern formation were disturbed by interfering with WRKY23 function. In order to identify direct targets of WRKY23, we performed consequential expression profiling experiments using a WRKY23 inducible gain-of-function line and dominant-negative WRKY23 line that is defunct in PIN re-arrangement. Among several genes mostly related to the groups of cell wall and defense process regulators, we identified LYSINE-HISTIDINE TRANSPORTER 1 (LHT1; At5g40780), a small amino acid permease gene from the amino acid/auxin permease family (AAAP), we present its detailed characterisation in auxin feedback on PIN repolarization, identified its transcriptional regulation, we propose a potential mechanism of its action. Moreover, we identified also a member of receptor-like protein kinase LRR-RLK (LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN KINASE PROTEIN 1; LRRK1; At1g05700), which also affects auxin-dependent PIN re-arrangement. We described its transcriptional behaviour, subcellular localization. Based on global expression data, we tried to identify ligand responsible for mechanism of signalling and suggest signalling partner and interactors. Additionally, we described role of novel phytohormone group, strigolactone, in auxin-dependent PIN re-arrangement, that could be a fundament for future studies in this field. Our results provide first insights into an auxin transcriptional network targeting PIN localization and thus regulating plant development. We highlighted WRKY23 transcriptional network and characterised its mediatory role in plant development. We identified direct effectors of this network, LHT1 and LRRK1, and describe their roles in PIN re-arrangement and PIN-dependent auxin transport processes.}, author = {Prat, Tomas}, issn = {2663-337X}, pages = {131}, publisher = {Institute of Science and Technology Austria}, title = {{Identification of novel regulators of PIN polarity and development of novel auxin sensor}}, year = {2017}, } @article{2016, abstract = {The Ising model is one of the simplest and most famous models of interacting systems. It was originally proposed to model ferromagnetic interactions in statistical physics and is now widely used to model spatial processes in many areas such as ecology, sociology, and genetics, usually without testing its goodness-of-fit. Here, we propose an exact goodness-of-fit test for the finite-lattice Ising model. The theory of Markov bases has been developed in algebraic statistics for exact goodness-of-fit testing using a Monte Carlo approach. However, this beautiful theory has fallen short of its promise for applications, because finding a Markov basis is usually computationally intractable. We develop a Monte Carlo method for exact goodness-of-fit testing for the Ising model which avoids computing a Markov basis and also leads to a better connectivity of the Markov chain and hence to a faster convergence. We show how this method can be applied to analyze the spatial organization of receptors on the cell membrane.}, author = {Martin Del Campo Sanchez, Abraham and Cepeda Humerez, Sarah A and Uhler, Caroline}, issn = {03036898}, journal = {Scandinavian Journal of Statistics}, number = {2}, pages = {285 -- 306}, publisher = {Wiley-Blackwell}, title = {{Exact goodness-of-fit testing for the Ising model}}, doi = {10.1111/sjos.12251}, volume = {44}, year = {2017}, } @article{1528, abstract = {We consider N×N Hermitian random matrices H consisting of blocks of size M≥N6/7. The matrix elements are i.i.d. within the blocks, close to a Gaussian in the four moment matching sense, but their distribution varies from block to block to form a block-band structure, with an essential band width M. We show that the entries of the Green’s function G(z)=(H−z)−1 satisfy the local semicircle law with spectral parameter z=E+iη down to the real axis for any η≫N−1, using a combination of the supersymmetry method inspired by Shcherbina (J Stat Phys 155(3): 466–499, 2014) and the Green’s function comparison strategy. Previous estimates were valid only for η≫M−1. The new estimate also implies that the eigenvectors in the middle of the spectrum are fully delocalized.}, author = {Bao, Zhigang and Erdös, László}, issn = {01788051}, journal = {Probability Theory and Related Fields}, number = {3-4}, pages = {673 -- 776}, publisher = {Springer}, title = {{Delocalization for a class of random block band matrices}}, doi = {10.1007/s00440-015-0692-y}, volume = {167}, year = {2017}, } @article{1433, abstract = {Phat is an open-source C. ++ library for the computation of persistent homology by matrix reduction, targeted towards developers of software for topological data analysis. We aim for a simple generic design that decouples algorithms from data structures without sacrificing efficiency or user-friendliness. We provide numerous different reduction strategies as well as data types to store and manipulate the boundary matrix. We compare the different combinations through extensive experimental evaluation and identify optimization techniques that work well in practical situations. We also compare our software with various other publicly available libraries for persistent homology.}, author = {Bauer, Ulrich and Kerber, Michael and Reininghaus, Jan and Wagner, Hubert}, issn = { 07477171}, journal = {Journal of Symbolic Computation}, pages = {76 -- 90}, publisher = {Academic Press}, title = {{Phat - Persistent homology algorithms toolbox}}, doi = {10.1016/j.jsc.2016.03.008}, volume = {78}, year = {2017}, } @article{1407, abstract = {We consider the problem of computing the set of initial states of a dynamical system such that there exists a control strategy to ensure that the trajectories satisfy a temporal logic specification with probability 1 (almost-surely). We focus on discrete-time, stochastic linear dynamics and specifications given as formulas of the Generalized Reactivity(1) fragment of Linear Temporal Logic over linear predicates in the states of the system. We propose a solution based on iterative abstraction-refinement, and turn-based 2-player probabilistic games. While the theoretical guarantee of our algorithm after any finite number of iterations is only a partial solution, we show that if our algorithm terminates, then the result is the set of all satisfying initial states. Moreover, for any (partial) solution our algorithm synthesizes witness control strategies to ensure almost-sure satisfaction of the temporal logic specification. While the proposed algorithm guarantees progress and soundness in every iteration, it is computationally demanding. We offer an alternative, more efficient solution for the reachability properties that decomposes the problem into a series of smaller problems of the same type. All algorithms are demonstrated on an illustrative case study.}, author = {Svoreňová, Mária and Kretinsky, Jan and Chmelik, Martin and Chatterjee, Krishnendu and Cěrná, Ivana and Belta, Cǎlin}, journal = {Nonlinear Analysis: Hybrid Systems}, number = {2}, pages = {230 -- 253}, publisher = {Elsevier}, title = {{Temporal logic control for stochastic linear systems using abstraction refinement of probabilistic games}}, doi = {10.1016/j.nahs.2016.04.006}, volume = {23}, year = {2017}, } @article{1367, abstract = {One of the major challenges in physically based modelling is making simulations efficient. Adaptive models provide an essential solution to these efficiency goals. These models are able to self-adapt in space and time, attempting to provide the best possible compromise between accuracy and speed. This survey reviews the adaptive solutions proposed so far in computer graphics. Models are classified according to the strategy they use for adaptation, from time-stepping and freezing techniques to geometric adaptivity in the form of structured grids, meshes and particles. Applications range from fluids, through deformable bodies, to articulated solids.}, author = {Manteaux, Pierre and Wojtan, Christopher J and Narain, Rahul and Redon, Stéphane and Faure, François and Cani, Marie}, issn = {01677055}, journal = {Computer Graphics Forum}, number = {6}, pages = {312 -- 337}, publisher = {Wiley-Blackwell}, title = {{Adaptive physically based models in computer graphics}}, doi = {10.1111/cgf.12941}, volume = {36}, year = {2017}, } @article{1338, abstract = {We present a computer-aided programming approach to concurrency. The approach allows programmers to program assuming a friendly, non-preemptive scheduler, and our synthesis procedure inserts synchronization to ensure that the final program works even with a preemptive scheduler. The correctness specification is implicit, inferred from the non-preemptive behavior. Let us consider sequences of calls that the program makes to an external interface. The specification requires that any such sequence produced under a preemptive scheduler should be included in the set of sequences produced under a non-preemptive scheduler. We guarantee that our synthesis does not introduce deadlocks and that the synchronization inserted is optimal w.r.t. a given objective function. The solution is based on a finitary abstraction, an algorithm for bounded language inclusion modulo an independence relation, and generation of a set of global constraints over synchronization placements. Each model of the global constraints set corresponds to a correctness-ensuring synchronization placement. The placement that is optimal w.r.t. the given objective function is chosen as the synchronization solution. We apply the approach to device-driver programming, where the driver threads call the software interface of the device and the API provided by the operating system. Our experiments demonstrate that our synthesis method is precise and efficient. The implicit specification helped us find one concurrency bug previously missed when model-checking using an explicit, user-provided specification. We implemented objective functions for coarse-grained and fine-grained locking and observed that different synchronization placements are produced for our experiments, favoring a minimal number of synchronization operations or maximum concurrency, respectively.}, author = {Cerny, Pavol and Clarke, Edmund and Henzinger, Thomas A and Radhakrishna, Arjun and Ryzhyk, Leonid and Samanta, Roopsha and Tarrach, Thorsten}, journal = {Formal Methods in System Design}, number = {2-3}, pages = {97 -- 139}, publisher = {Springer}, title = {{From non-preemptive to preemptive scheduling using synchronization synthesis}}, doi = {10.1007/s10703-016-0256-5}, volume = {50}, year = {2017}, } @article{1351, abstract = {The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.}, author = {Giacobbe, Mirco and Guet, Calin C and Gupta, Ashutosh and Henzinger, Thomas A and Paixao, Tiago and Petrov, Tatjana}, issn = {00015903}, journal = {Acta Informatica}, number = {8}, pages = {765 -- 787}, publisher = {Springer}, title = {{Model checking the evolution of gene regulatory networks}}, doi = {10.1007/s00236-016-0278-x}, volume = {54}, year = {2017}, } @article{1336, abstract = {Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse the runtimes of EAs on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrences of new mutations is much longer than the time it takes for a mutated genotype to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a stochastic process evolving one genotype by means of mutation and selection between the resident and the mutated genotype. The probability of accepting the mutated genotype then depends on the change in fitness. We study this process, SSWM, from an algorithmic perspective, quantifying its expected optimisation time for various parameters and investigating differences to a similar evolutionary algorithm, the well-known (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.}, author = {Paixao, Tiago and Pérez Heredia, Jorge and Sudholt, Dirk and Trubenova, Barbora}, issn = {01784617}, journal = {Algorithmica}, number = {2}, pages = {681 -- 713}, publisher = {Springer}, title = {{Towards a runtime comparison of natural and artificial evolution}}, doi = {10.1007/s00453-016-0212-1}, volume = {78}, year = {2017}, } @article{1337, abstract = {We consider the local eigenvalue distribution of large self-adjoint N×N random matrices H=H∗ with centered independent entries. In contrast to previous works the matrix of variances sij=\mathbbmE|hij|2 is not assumed to be stochastic. Hence the density of states is not the Wigner semicircle law. Its possible shapes are described in the companion paper (Ajanki et al. in Quadratic Vector Equations on the Complex Upper Half Plane. arXiv:1506.05095). We show that as N grows, the resolvent, G(z)=(H−z)−1, converges to a diagonal matrix, diag(m(z)), where m(z)=(m1(z),…,mN(z)) solves the vector equation −1/mi(z)=z+∑jsijmj(z) that has been analyzed in Ajanki et al. (Quadratic Vector Equations on the Complex Upper Half Plane. arXiv:1506.05095). We prove a local law down to the smallest spectral resolution scale, and bulk universality for both real symmetric and complex hermitian symmetry classes.}, author = {Ajanki, Oskari H and Erdös, László and Krüger, Torben H}, issn = {01788051}, journal = {Probability Theory and Related Fields}, number = {3-4}, pages = {667 -- 727}, publisher = {Springer}, title = {{Universality for general Wigner-type matrices}}, doi = {10.1007/s00440-016-0740-2}, volume = {169}, year = {2017}, } @article{1294, abstract = {We study controller synthesis problems for finite-state Markov decision processes, where the objective is to optimize the expected mean-payoff performance and stability (also known as variability in the literature). We argue that the basic notion of expressing the stability using the statistical variance of the mean payoff is sometimes insufficient, and propose an alternative definition. We show that a strategy ensuring both the expected mean payoff and the variance below given bounds requires randomization and memory, under both the above definitions. We then show that the problem of finding such a strategy can be expressed as a set of constraints.}, author = {Brázdil, Tomáš and Chatterjee, Krishnendu and Forejt, Vojtěch and Kučera, Antonín}, journal = {Journal of Computer and System Sciences}, pages = {144 -- 170}, publisher = {Elsevier}, title = {{Trading performance for stability in Markov decision processes}}, doi = {10.1016/j.jcss.2016.09.009}, volume = {84}, year = {2017}, } @article{1228, abstract = {Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.}, author = {Sauerzopf, Ulrich and Sacco, Roberto and Novarino, Gaia and Niello, Marco and Weidenauer, Ana and Praschak Rieder, Nicole and Sitte, Harald and Willeit, Matthaeus}, journal = {European Journal of Neuroscience}, number = {1}, pages = {45 -- 57}, publisher = {Wiley-Blackwell}, title = {{Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence}}, doi = {10.1111/ejn.13418}, volume = {45}, year = {2017}, } @inbook{1213, abstract = {Bacterial cytokinesis is commonly initiated by the Z-ring, a dynamic cytoskeletal structure that assembles at the site of division. Its primary component is FtsZ, a tubulin-like GTPase, that like its eukaryotic relative forms protein filaments in the presence of GTP. Since the discovery of the Z-ring 25 years ago, various models for the role of FtsZ have been suggested. However, important information about the architecture and dynamics of FtsZ filaments during cytokinesis is still missing. One reason for this lack of knowledge has been the small size of bacteria, which has made it difficult to resolve the orientation and dynamics of individual FtsZ filaments in the Z-ring. While superresolution microscopy experiments have helped to gain more information about the organization of the Z-ring in the dividing cell, they were not yet able to elucidate a mechanism of how FtsZ filaments reorganize during assembly and disassembly of the Z-ring. In this chapter, we explain how to use an in vitro reconstitution approach to investigate the self-organization of FtsZ filaments recruited to a biomimetic lipid bilayer by its membrane anchor FtsA. We show how to perform single-molecule experiments to study the behavior of individual FtsZ monomers during the constant reorganization of the FtsZ-FtsA filament network. We describe how to analyze the dynamics of single molecules and explain why this information can help to shed light onto possible mechanism of Z-ring constriction. We believe that similar experimental approaches will be useful to study the mechanism of membrane-based polymerization of other cytoskeletal systems, not only from prokaryotic but also eukaryotic origin.}, author = {Baranova, Natalia and Loose, Martin}, booktitle = {Cytokinesis}, editor = {Echard, Arnaud }, issn = {0091679X}, pages = {355 -- 370}, publisher = {Academic Press}, title = {{Single-molecule measurements to study polymerization dynamics of FtsZ-FtsA copolymers}}, doi = {10.1016/bs.mcb.2016.03.036}, volume = {137}, year = {2017}, } @article{1198, abstract = {We consider a model of fermions interacting via point interactions, defined via a certain weighted Dirichlet form. While for two particles the interaction corresponds to infinite scattering length, the presence of further particles effectively decreases the interaction strength. We show that the model becomes trivial in the thermodynamic limit, in the sense that the free energy density at any given particle density and temperature agrees with the corresponding expression for non-interacting particles.}, author = {Moser, Thomas and Seiringer, Robert}, issn = {03779017}, journal = {Letters in Mathematical Physics}, number = {3}, pages = { 533 -- 552}, publisher = {Springer}, title = {{Triviality of a model of particles with point interactions in the thermodynamic limit}}, doi = {10.1007/s11005-016-0915-x}, volume = {107}, year = {2017}, } @article{1207, abstract = {The eigenvalue distribution of the sum of two large Hermitian matrices, when one of them is conjugated by a Haar distributed unitary matrix, is asymptotically given by the free convolution of their spectral distributions. We prove that this convergence also holds locally in the bulk of the spectrum, down to the optimal scales larger than the eigenvalue spacing. The corresponding eigenvectors are fully delocalized. Similar results hold for the sum of two real symmetric matrices, when one is conjugated by Haar orthogonal matrix.}, author = {Bao, Zhigang and Erdös, László and Schnelli, Kevin}, issn = {00103616}, journal = {Communications in Mathematical Physics}, number = {3}, pages = {947 -- 990}, publisher = {Springer}, title = {{Local law of addition of random matrices on optimal scale}}, doi = {10.1007/s00220-016-2805-6}, volume = {349}, year = {2017}, } @article{1196, abstract = {We define the . model-measuring problem: given a model . M and specification . ϕ, what is the maximal distance . ρ such that all models . M' within distance . ρ from . M satisfy (or violate) . ϕ. The model-measuring problem presupposes a distance function on models. We concentrate on . automatic distance functions, which are defined by weighted automata. The model-measuring problem subsumes several generalizations of the classical model-checking problem, in particular, quantitative model-checking problems that measure the degree of satisfaction of a specification; robustness problems that measure how much a model can be perturbed without violating the specification; and parameter synthesis for hybrid systems. We show that for automatic distance functions, and (a) . ω-regular linear-time, (b) . ω-regular branching-time, and (c) hybrid specifications, the model-measuring problem can be solved.We use automata-theoretic model-checking methods for model measuring, replacing the emptiness question for word, tree, and hybrid automata by the . optimal-value question for the weighted versions of these automata. For automata over words and trees, we consider weighted automata that accumulate weights by maximizing, summing, discounting, and limit averaging. For hybrid automata, we consider monotonic (parametric) hybrid automata, a hybrid counterpart of (discrete) weighted automata.We give several examples of using the model-measuring problem to compute various notions of robustness and quantitative satisfaction for temporal specifications. Further, we propose the modeling framework for model measuring to ease the specification and reduce the likelihood of errors in modeling.Finally, we present a variant of the model-measuring problem, called the . model-repair problem. The model-repair problem applies to models that do not satisfy the specification; it can be used to derive restrictions, under which the model satisfies the specification, i.e., to repair the model.}, author = {Henzinger, Thomas A and Otop, Jan}, journal = {Nonlinear Analysis: Hybrid Systems}, pages = {166 -- 190}, publisher = {Elsevier}, title = {{Model measuring for discrete and hybrid systems}}, doi = {10.1016/j.nahs.2016.09.001}, volume = {23}, year = {2017}, } @article{1199, abstract = {Much of quantitative genetics is based on the ‘infinitesimal model’, under which selection has a negligible effect on the genetic variance. This is typically justified by assuming a very large number of loci with additive effects. However, it applies even when genes interact, provided that the number of loci is large enough that selection on each of them is weak relative to random drift. In the long term, directional selection will change allele frequencies, but even then, the effects of epistasis on the ultimate change in trait mean due to selection may be modest. Stabilising selection can maintain many traits close to their optima, even when the underlying alleles are weakly selected. However, the number of traits that can be optimised is apparently limited to ~4Ne by the ‘drift load’, and this is hard to reconcile with the apparent complexity of many organisms. Just as for the mutation load, this limit can be evaded by a particular form of negative epistasis. A more robust limit is set by the variance in reproductive success. This suggests that selection accumulates information most efficiently in the infinitesimal regime, when selection on individual alleles is weak, and comparable with random drift. A review of evidence on selection strength suggests that although most variance in fitness may be because of alleles with large Nes, substantial amounts of adaptation may be because of alleles in the infinitesimal regime, in which epistasis has modest effects.}, author = {Barton, Nicholas H}, journal = {Heredity}, pages = {96 -- 109}, publisher = {Nature Publishing Group}, title = {{How does epistasis influence the response to selection?}}, doi = {10.1038/hdy.2016.109}, volume = {118}, year = {2017}, } @article{1208, abstract = {We study parameter estimation in linear Gaussian covariance models, which are p-dimensional Gaussian models with linear constraints on the covariance matrix. Maximum likelihood estimation for this class of models leads to a non-convex optimization problem which typically has many local maxima. Using recent results on the asymptotic distribution of extreme eigenvalues of the Wishart distribution, we provide sufficient conditions for any hill climbing method to converge to the global maximum. Although we are primarily interested in the case in which n≫p, the proofs of our results utilize large sample asymptotic theory under the scheme n/p→γ>1. Remarkably, our numerical simulations indicate that our results remain valid for p as small as 2. An important consequence of this analysis is that, for sample sizes n≃14p, maximum likelihood estimation for linear Gaussian covariance models behaves as if it were a convex optimization problem. © 2016 The Royal Statistical Society and Blackwell Publishing Ltd.}, author = {Zwiernik, Piotr and Uhler, Caroline and Richards, Donald}, issn = {13697412}, journal = {Journal of the Royal Statistical Society. Series B: Statistical Methodology}, number = {4}, pages = {1269 -- 1292}, publisher = {Wiley-Blackwell}, title = {{Maximum likelihood estimation for linear Gaussian covariance models}}, doi = {10.1111/rssb.12217}, volume = {79}, year = {2017}, } @inproceedings{1174, abstract = {Security of cryptographic applications is typically defined by security games. The adversary, within certain resources, cannot win with probability much better than 0 (for unpredictability applications, like one-way functions) or much better than 1/2 (indistinguishability applications for instance encryption schemes). In so called squared-friendly applications the winning probability of the adversary, for different values of the application secret randomness, is not only close to 0 or 1/2 on average, but also concentrated in the sense that its second central moment is small. The class of squared-friendly applications, which contains all unpredictability applications and many indistinguishability applications, is particularly important for key derivation. Barak et al. observed that for square-friendly applications one can beat the "RT-bound", extracting secure keys with significantly smaller entropy loss. In turn Dodis and Yu showed that in squared-friendly applications one can directly use a "weak" key, which has only high entropy, as a secure key. In this paper we give sharp lower bounds on square security assuming security for "weak" keys. We show that any application which is either (a) secure with weak keys or (b) allows for entropy savings for keys derived by universal hashing, must be square-friendly. Quantitatively, our lower bounds match the positive results of Dodis and Yu and Barak et al. (TCC\'13, CRYPTO\'11) Hence, they can be understood as a general characterization of squared-friendly applications. While the positive results on squared-friendly applications where derived by one clever application of the Cauchy-Schwarz Inequality, for tight lower bounds we need more machinery. In our approach we use convex optimization techniques and some theory of circular matrices.}, author = {Skórski, Maciej}, issn = {18688969}, location = {Hannover, Germany}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Lower bounds on key derivation for square-friendly applications}}, doi = {10.4230/LIPIcs.STACS.2017.57}, volume = {66}, year = {2017}, } @inproceedings{1176, abstract = {The algorithm Argon2i-B of Biryukov, Dinu and Khovratovich is currently being considered by the IRTF (Internet Research Task Force) as a new de-facto standard for password hashing. An older version (Argon2i-A) of the same algorithm was chosen as the winner of the recent Password Hashing Competition. An important competitor to Argon2i-B is the recently introduced Balloon Hashing (BH) algorithm of Corrigan-Gibs, Boneh and Schechter. A key security desiderata for any such algorithm is that evaluating it (even using a custom device) requires a large amount of memory amortized across multiple instances. Alwen and Blocki (CRYPTO 2016) introduced a class of theoretical attacks against Argon2i-A and BH. While these attacks yield large asymptotic reductions in the amount of memory, it was not, a priori, clear if (1) they can be extended to the newer Argon2i-B, (2) the attacks are effective on any algorithm for practical parameter ranges (e.g., 1GB of memory) and (3) if they can be effectively instantiated against any algorithm under realistic hardware constrains. In this work we answer all three of these questions in the affirmative for all three algorithms. This is also the first work to analyze the security of Argon2i-B. In more detail, we extend the theoretical attacks of Alwen and Blocki (CRYPTO 2016) to the recent Argon2i-B proposal demonstrating severe asymptotic deficiencies in its security. Next we introduce several novel heuristics for improving the attack's concrete memory efficiency even when on-chip memory bandwidth is bounded. We then simulate our attacks on randomly sampled Argon2i-A, Argon2i-B and BH instances and measure the resulting memory consumption for various practical parameter ranges and for a variety of upperbounds on the amount of parallelism available to the attacker. Finally we describe, implement, and test a new heuristic for applying the Alwen-Blocki attack to functions employing a technique developed by Corrigan-Gibs et al. for improving concrete security of memory-hard functions. We analyze the collected data and show the effects various parameters have on the memory consumption of the attack. In particular, we can draw several interesting conclusions about the level of security provided by these functions. · For the Alwen-Blocki attack to fail against practical memory parameters, Argon2i-B must be instantiated with more than 10 passes on memory - beyond the "paranoid" parameter setting in the current IRTF proposal. · The technique of Corrigan-Gibs for improving security can also be overcome by the Alwen-Blocki attack under realistic hardware constraints. · On a positive note, both the asymptotic and concrete security of Argon2i-B seem to improve on that of Argon2i-A.}, author = {Alwen, Joel F and Blocki, Jeremiah}, isbn = {978-150905761-0}, location = {Paris, France}, publisher = {IEEE}, title = {{Towards practical attacks on Argon2i and balloon hashing}}, doi = {10.1109/EuroSP.2017.47}, year = {2017}, } @article{1187, abstract = {We construct efficient authentication protocols and message authentication codes (MACs) whose security can be reduced to the learning parity with noise (LPN) problem. Despite a large body of work—starting with the (Formula presented.) protocol of Hopper and Blum in 2001—until now it was not even known how to construct an efficient authentication protocol from LPN which is secure against man-in-the-middle attacks. A MAC implies such a (two-round) protocol.}, author = {Kiltz, Eike and Pietrzak, Krzysztof Z and Venturi, Daniele and Cash, David and Jain, Abhishek}, journal = {Journal of Cryptology}, number = {4}, pages = {1238 -- 1275}, publisher = {Springer}, title = {{Efficient authentication from hard learning problems}}, doi = {10.1007/s00145-016-9247-3}, volume = {30}, year = {2017}, } @inproceedings{1192, abstract = {The main result of this paper is a generalization of the classical blossom algorithm for finding perfect matchings. Our algorithm can efficiently solve Boolean CSPs where each variable appears in exactly two constraints (we call it edge CSP) and all constraints are even Δ-matroid relations (represented by lists of tuples). As a consequence of this, we settle the complexity classification of planar Boolean CSPs started by Dvorak and Kupec. Knowing that edge CSP is tractable for even Δ-matroid constraints allows us to extend the tractability result to a larger class of Δ-matroids that includes many classes that were known to be tractable before, namely co-independent, compact, local and binary.}, author = {Kazda, Alexandr and Kolmogorov, Vladimir and Rolinek, Michal}, isbn = {978-161197478-2}, location = {Barcelona, Spain}, pages = {307 -- 326}, publisher = {SIAM}, title = {{Even delta-matroids and the complexity of planar Boolean CSPs}}, doi = {10.1137/1.9781611974782.20}, year = {2017}, } @article{1180, abstract = {In this article we define an algebraic vertex of a generalized polyhedron and show that the set of algebraic vertices is the smallest set of points needed to define the polyhedron. We prove that the indicator function of a generalized polytope P is a linear combination of indicator functions of simplices whose vertices are algebraic vertices of P. We also show that the indicator function of any generalized polyhedron is a linear combination, with integer coefficients, of indicator functions of cones with apices at algebraic vertices and line-cones. The concept of an algebraic vertex is closely related to the Fourier–Laplace transform. We show that a point v is an algebraic vertex of a generalized polyhedron P if and only if the tangent cone of P, at v, has non-zero Fourier–Laplace transform.}, author = {Akopyan, Arseniy and Bárány, Imre and Robins, Sinai}, issn = {00018708}, journal = {Advances in Mathematics}, pages = {627 -- 644}, publisher = {Academic Press}, title = {{Algebraic vertices of non-convex polyhedra}}, doi = {10.1016/j.aim.2016.12.026}, volume = {308}, year = {2017}, } @article{1159, abstract = {Auxin steers numerous physiological processes in plants, making the tight control of its endogenous levels and spatiotemporal distribution a necessity. This regulation is achieved by different mechanisms, including auxin biosynthesis, metabolic conversions, degradation, and transport. Here, we introduce cis-cinnamic acid (c-CA) as a novel and unique addition to a small group of endogenous molecules affecting in planta auxin concentrations. c-CA is the photo-isomerization product of the phenylpropanoid pathway intermediate trans-CA (t-CA). When grown on c-CA-containing medium, an evolutionary diverse set of plant species were shown to exhibit phenotypes characteristic for high auxin levels, including inhibition of primary root growth, induction of root hairs, and promotion of adventitious and lateral rooting. By molecular docking and receptor binding assays, we showed that c-CA itself is neither an auxin nor an anti-auxin, and auxin profiling data revealed that c-CA does not significantly interfere with auxin biosynthesis. Single cell-based auxin accumulation assays showed that c-CA, and not t-CA, is a potent inhibitor of auxin efflux. Auxin signaling reporters detected changes in spatiotemporal distribution of the auxin response along the root of c-CA-treated plants, and long-distance auxin transport assays showed no inhibition of rootward auxin transport. Overall, these results suggest that the phenotypes of c-CA-treated plants are the consequence of a local change in auxin accumulation, induced by the inhibition of auxin efflux. This work reveals a novel mechanism how plants may regulate auxin levels and adds a novel, naturally occurring molecule to the chemical toolbox for the studies of auxin homeostasis.}, author = {Steenackers, Ward and Klíma, Petr and Quareshy, Mussa and Cesarino, Igor and Kumpf, Robert and Corneillie, Sander and Araújo, Pedro and Viaene, Tom and Goeminne, Geert and Nowack, Moritz and Ljung, Karin and Friml, Jirí and Blakeslee, Joshua and Novák, Ondřej and Zažímalová, Eva and Napier, Richard and Boerjan, Wout and Vanholme, Bartel}, issn = {0032-0889}, journal = {Plant Physiology}, number = {1}, pages = {552 -- 565}, publisher = {American Society of Plant Biologists}, title = {{Cis-cinnamic acid is a novel natural auxin efflux inhibitor that promotes lateral root formation}}, doi = {10.1104/pp.16.00943}, volume = {173}, year = {2017}, } @article{1169, abstract = {Dispersal is a crucial factor in natural evolution, since it determines the habitat experienced by any population and defines the spatial scale of interactions between individuals. There is compelling evidence for systematic differences in dispersal characteristics within the same population, i.e., genotype-dependent dispersal. The consequences of genotype-dependent dispersal on other evolutionary phenomena, however, are poorly understood. In this article we investigate the effect of genotype-dependent dispersal on spatial gene frequency patterns, using a generalization of the classical diffusion model of selection and dispersal. Dispersal is characterized by the variance of dispersal (diffusion coefficient) and the mean displacement (directional advection term). We demonstrate that genotype-dependent dispersal may change the qualitative behavior of Fisher waves, which change from being “pulled” to being “pushed” wave fronts as the discrepancy in dispersal between genotypes increases. The speed of any wave is partitioned into components due to selection, genotype-dependent variance of dispersal, and genotype-dependent mean displacement. We apply our findings to wave fronts maintained by selection against heterozygotes. Furthermore, we identify a benefit of increased variance of dispersal, quantify its effect on the speed of the wave, and discuss the implications for the evolution of dispersal strategies.}, author = {Novak, Sebastian and Kollár, Richard}, issn = {00166731}, journal = {Genetics}, number = {1}, pages = {367 -- 374}, publisher = {Genetics Society of America}, title = {{Spatial gene frequency waves under genotype dependent dispersal}}, doi = {10.1534/genetics.116.193946}, volume = {205}, year = {2017}, } @article{1160, abstract = {We investigate fundamental nonlinear dynamics of ferrofluidic Taylor-Couette flow - flow confined be-tween two concentric independently rotating cylinders - consider small aspect ratio by solving the ferro-hydrodynamical equations, carrying out systematic bifurcation analysis. Without magnetic field, we find steady flow patterns, previously observed with a simple fluid, such as those containing normal one- or two vortex cells, as well as anomalous one-cell and twin-cell flow states. However, when a symmetry-breaking transverse magnetic field is present, all flow states exhibit stimulated, finite two-fold mode. Various bifurcations between steady and unsteady states can occur, corresponding to the transitions between the two-cell and one-cell states. While unsteady, axially oscillating flow states can arise, we also detect the emergence of new unsteady flow states. In particular, we uncover two new states: one contains only the azimuthally oscillating solution in the configuration of the twin-cell flow state, and an-other a rotating flow state. Topologically, these flow states are a limit cycle and a quasiperiodic solution on a two-torus, respectively. Emergence of new flow states in addition to observed ones with classical fluid, indicates that richer but potentially more controllable dynamics in ferrofluidic flows, as such flow states depend on the external magnetic field.}, author = {Altmeyer, Sebastian and Do, Younghae and Lai, Ying}, issn = {20452322}, journal = {Scientific Reports}, publisher = {Nature Publishing Group}, title = {{Dynamics of ferrofluidic flow in the Taylor-Couette system with a small aspect ratio}}, doi = {10.1038/srep40012}, volume = {7}, year = {2017}, } @article{1162, abstract = {Selected universal experimental properties of high-temperature superconducting (HTS) cuprates have been singled out in the last decade. One of the pivotal challenges in this field is the designation of a consistent interpretation framework within which we can describe quantitatively the universal features of those systems. Here we analyze in a detailed manner the principal experimental data and compare them quantitatively with the approach based on a single-band model of strongly correlated electrons supplemented with strong antiferromagnetic (super)exchange interaction (the so-called t−J−U model). The model rationale is provided by estimating its microscopic parameters on the basis of the three-band approach for the Cu-O plane. We use our original full Gutzwiller wave-function solution by going beyond the renormalized mean-field theory (RMFT) in a systematic manner. Our approach reproduces very well the observed hole doping (δ) dependence of the kinetic-energy gain in the superconducting phase, one of the principal non-Bardeen-Cooper-Schrieffer features of the cuprates. The calculated Fermi velocity in the nodal direction is practically δ-independent and its universal value agrees very well with that determined experimentally. Also, a weak doping dependence of the Fermi wave vector leads to an almost constant value of the effective mass in a pure superconducting phase which is both observed in experiment and reproduced within our approach. An assessment of the currently used models (t−J, Hubbard) is carried out and the results of the canonical RMFT as a zeroth-order solution are provided for comparison to illustrate the necessity of the introduced higher-order contributions.}, author = {Spałek, Jozef and Zegrodnik, Michał and Kaczmarczyk, Jan}, issn = {24699950}, journal = {Physical Review B - Condensed Matter and Materials Physics}, number = {2}, publisher = {American Physical Society}, title = {{Universal properties of high temperature superconductors from real space pairing t-J-U model and its quantitative comparison with experiment}}, doi = {10.1103/PhysRevB.95.024506}, volume = {95}, year = {2017}, } @article{1152, abstract = {We propose a new memetic strategy that can solve the multi-physics, complex inverse problems, formulated as the multi-objective optimization ones, in which objectives are misfits between the measured and simulated states of various governing processes. The multi-deme structure of the strategy allows for both, intensive, relatively cheap exploration with a moderate accuracy and more accurate search many regions of Pareto set in parallel. The special type of selection operator prefers the coherent alternative solutions, eliminating artifacts appearing in the particular processes. The additional accuracy increment is obtained by the parallel convex searches applied to the local scalarizations of the misfit vector. The strategy is dedicated for solving ill-conditioned problems, for which inverting the single physical process can lead to the ambiguous results. The skill of the selection in artifact elimination is shown on the benchmark problem, while the whole strategy was applied for identification of oil deposits, where the misfits are related to various frequencies of the magnetic and electric waves of the magnetotelluric measurements. 2016 Elsevier B.V.}, author = {Gajda-Zagorska, Ewa P and Schaefer, Robert and Smołka, Maciej and Pardo, David and Alvarez Aramberri, Julen}, issn = {18777503}, journal = {Journal of Computational Science}, pages = {85 -- 94}, publisher = {Elsevier}, title = {{A multi objective memetic inverse solver reinforced by local optimization methods}}, doi = {10.1016/j.jocs.2016.06.007}, volume = {18}, year = {2017}, } @article{1168, abstract = {Optimum experimental design theory has recently been extended for parameter estimation in copula models. The use of these models allows one to gain in flexibility by considering the model parameter set split into marginal and dependence parameters. However, this separation also leads to the natural issue of estimating only a subset of all model parameters. In this work, we treat this problem with the application of the (Formula presented.)-optimality to copula models. First, we provide an extension of the corresponding equivalence theory. Then, we analyze a wide range of flexible copula models to highlight the usefulness of (Formula presented.)-optimality in many possible scenarios. Finally, we discuss how the usage of the introduced design criterion also relates to the more general issue of copula selection and optimal design for model discrimination.}, author = {Perrone, Elisa and Rappold, Andreas and Müller, Werner}, journal = {Statistical Methods and Applications}, number = {3}, pages = {403 -- 418}, publisher = {Springer}, title = {{D inf s optimality in copula models}}, doi = {10.1007/s10260-016-0375-6}, volume = {26}, year = {2017}, } @article{1163, abstract = {We investigate the effect of the electron-hole (e-h) symmetry breaking on d-wave superconductivity induced by non-local effects of correlations in the generalized Hubbard model. The symmetry breaking is introduced in a two-fold manner: by the next-to-nearest neighbor hopping of electrons and by the charge-bond interaction - the off-diagonal term of the Coulomb potential. Both terms lead to a pronounced asymmetry of the superconducting order parameter. The next-to-nearest neighbor hopping enhances superconductivity for h-doping, while diminishes it for e-doping. The charge-bond interaction alone leads to the opposite effect and, additionally, to the kinetic-energy gain upon condensation in the underdoped regime. With both terms included, with similar amplitudes, the height of the superconducting dome and the critical doping remain in favor of h-doping. The influence of the charge-bond interaction on deviations from symmetry of the shape of the gap at the Fermi surface in the momentum space is briefly discussed.}, author = {Wysokiński, Marcin and Kaczmarczyk, Jan}, issn = {09538984}, journal = {Journal of Physics: Condensed Matter}, number = {8}, publisher = {IOP Publishing Ltd.}, title = {{Unconventional superconductivity in generalized Hubbard model role of electron–hole symmetry breaking terms}}, doi = {10.1088/1361-648X/aa532f}, volume = {29}, year = {2017}, } @article{1173, abstract = {We introduce the Voronoi functional of a triangulation of a finite set of points in the Euclidean plane and prove that among all geometric triangulations of the point set, the Delaunay triangulation maximizes the functional. This result neither extends to topological triangulations in the plane nor to geometric triangulations in three and higher dimensions.}, author = {Edelsbrunner, Herbert and Glazyrin, Alexey and Musin, Oleg and Nikitenko, Anton}, issn = {02099683}, journal = {Combinatorica}, number = {5}, pages = {887 -- 910}, publisher = {Springer}, title = {{The Voronoi functional is maximized by the Delaunay triangulation in the plane}}, doi = {10.1007/s00493-016-3308-y}, volume = {37}, year = {2017}, } @article{1161, abstract = {Coordinated changes of cell shape are often the result of the excitable, wave-like dynamics of the actin cytoskeleton. New work shows that, in migrating cells, protrusion waves arise from mechanochemical crosstalk between adhesion sites, membrane tension and the actin protrusive machinery.}, author = {Müller, Jan and Sixt, Michael K}, issn = {09609822}, journal = {Current Biology}, number = {1}, pages = {R24 -- R25}, publisher = {Cell Press}, title = {{Cell migration: Making the waves}}, doi = {10.1016/j.cub.2016.11.035}, volume = {27}, year = {2017}, } @inproceedings{1116, abstract = {Time-triggered switched networks are a deterministic communication infrastructure used by real-time distributed embedded systems. Due to the criticality of the applications running over them, developers need to ensure that end-to-end communication is dependable and predictable. Traditional approaches assume static networks that are not flexible to changes caused by reconfigurations or, more importantly, faults, which are dealt with in the application using redundancy. We adopt the concept of handling faults in the switches from non-real-time networks while maintaining the required predictability. We study a class of forwarding schemes that can handle various types of failures. We consider probabilistic failures. We study a class of forwarding schemes that can handle various types of failures. We consider probabilistic failures. For a given network with a forwarding scheme and a constant ℓ, we compute the {\em score} of the scheme, namely the probability (induced by faults) that at least ℓ messages arrive on time. We reduce the scoring problem to a reachability problem on a Markov chain with a "product-like" structure. Its special structure allows us to reason about it symbolically, and reduce the scoring problem to #SAT. Our solution is generic and can be adapted to different networks and other contexts. Also, we show the computational complexity of the scoring problem is #P-complete, and we study methods to estimate the score. We evaluate the effectiveness of our techniques with an implementation. }, author = {Avni, Guy and Goel, Shubham and Henzinger, Thomas A and Rodríguez Navas, Guillermo}, issn = {03029743}, location = {Uppsala, Sweden}, pages = {169 -- 187}, publisher = {Springer}, title = {{Computing scores of forwarding schemes in switched networks with probabilistic faults}}, doi = {10.1007/978-3-662-54580-5_10}, volume = {10206}, year = {2017}, } @article{1118, abstract = {Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV+ interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo.}, author = {Gan, Jian and Weng, Shih-Ming and Pernia-Andrade, Alejandro and Csicsvari, Jozsef L and Jonas, Peter M}, journal = {Neuron}, number = {2}, pages = {308 -- 314}, publisher = {Elsevier}, title = {{Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo}}, doi = {10.1016/j.neuron.2016.12.018}, volume = {93}, year = {2017}, } @article{1117, abstract = {GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-author}, author = {Chen, Chong and Arai, Itaru and Satterield, Rachel and Young, Samuel and Jonas, Peter M}, issn = {22111247}, journal = {Cell Reports}, number = {3}, pages = {723 -- 736}, publisher = {Cell Press}, title = {{Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse}}, doi = {10.1016/j.celrep.2016.12.067}, volume = {18}, year = {2017}, }