TY - JOUR AB - Motivation Computational prediction of the effect of mutations on protein stability is used by researchers in many fields. The utility of the prediction methods is affected by their accuracy and bias. Bias, a systematic shift of the predicted change of stability, has been noted as an issue for several methods, but has not been investigated systematically. Presence of the bias may lead to misleading results especially when exploring the effects of combination of different mutations. Results Here we use a protocol to measure the bias as a function of the number of introduced mutations. It is based on a self-consistency test of the reciprocity the effect of a mutation. An advantage of the used approach is that it relies solely on crystal structures without experimentally measured stability values. We applied the protocol to four popular algorithms predicting change of protein stability upon mutation, FoldX, Eris, Rosetta and I-Mutant, and found an inherent bias. For one program, FoldX, we manage to substantially reduce the bias using additional relaxation by Modeller. Authors using algorithms for predicting effects of mutations should be aware of the bias described here. AU - Usmanova, Dinara R AU - Bogatyreva, Natalya S AU - Ariño Bernad, Joan AU - Eremina, Aleksandra A AU - Gorshkova, Anastasiya A AU - Kanevskiy, German M AU - Lonishin, Lyubov R AU - Meister, Alexander V AU - Yakupova, Alisa G AU - Kondrashov, Fyodor AU - Ivankov, Dmitry ID - 5995 IS - 21 JF - Bioinformatics SN - 1367-4803 TI - Self-consistency test reveals systematic bias in programs for prediction change of stability upon mutation VL - 34 ER - TY - JOUR AB - Lamellipodia are flat membrane protrusions formed during mesenchymal motion. Polymerization at the leading edge assembles the actin filament network and generates protrusion force. How this force is supported by the network and how the assembly rate is shared between protrusion and network retrograde flow determines the protrusion rate. We use mathematical modeling to understand experiments changing the F-actin density in lamellipodia of B16-F1 melanoma cells by modulation of Arp2/3 complex activity or knockout of the formins FMNL2 and FMNL3. Cells respond to a reduction of density with a decrease of protrusion velocity, an increase in the ratio of force to filament number, but constant network assembly rate. The relation between protrusion force and tension gradient in the F-actin network and the density dependency of friction, elasticity, and viscosity of the network explain the experimental observations. The formins act as filament nucleators and elongators with differential rates. Modulation of their activity suggests an effect on network assembly rate. Contrary to these expectations, the effect of changes in elongator composition is much weaker than the consequences of the density change. We conclude that the force acting on the leading edge membrane is the force required to drive F-actin network retrograde flow. AU - Dolati, Setareh AU - Kage, Frieda AU - Mueller, Jan AU - Müsken, Mathias AU - Kirchner, Marieluise AU - Dittmar, Gunnar AU - Sixt, Michael K AU - Rottner, Klemens AU - Falcke, Martin ID - 5992 IS - 22 JF - Molecular Biology of the Cell TI - On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility VL - 29 ER - TY - JOUR AB - The optic tectum (TeO), or superior colliculus, is a multisensory midbrain center that organizes spatially orienting responses to relevant stimuli. To define the stimulus with the highest priority at each moment, a network of reciprocal connections between the TeO and the isthmi promotes competition between concurrent tectal inputs. In the avian midbrain, the neurons mediating enhancement and suppression of tectal inputs are located in separate isthmic nuclei, facilitating the analysis of the neural processes that mediate competition. A specific subset of radial neurons in the intermediate tectal layers relay retinal inputs to the isthmi, but at present it is unclear whether separate neurons innervate individual nuclei or a single neural type sends a common input to several of them. In this study, we used in vitro neural tracing and cell-filling experiments in chickens to show that single neurons innervate, via axon collaterals, the three nuclei that comprise the isthmotectal network. This demonstrates that the input signals representing the strength of the incoming stimuli are simultaneously relayed to the mechanisms promoting both enhancement and suppression of the input signals. By performing in vivo recordings in anesthetized chicks, we also show that this common input generates synchrony between both antagonistic mechanisms, demonstrating that activity enhancement and suppression are closely coordinated. From a computational point of view, these results suggest that these tectal neurons constitute integrative nodes that combine inputs from different sources to drive in parallel several concurrent neural processes, each performing complementary functions within the network through different firing patterns and connectivity. AU - Garrido-Charad, Florencia AU - Vega Zuniga, Tomas A AU - Gutiérrez-Ibáñez, Cristián AU - Fernandez, Pedro AU - López-Jury, Luciana AU - González-Cabrera, Cristian AU - Karten, Harvey J. AU - Luksch, Harald AU - Marín, Gonzalo J. ID - 6010 IS - 32 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - “Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network VL - 115 ER - TY - JOUR AB - Digital fabrication devices are powerful tools for creating tangible reproductions of 3D digital models. Most available printing technologies aim at producing an accurate copy of a tridimensional shape. However, fabrication technologies can also be used to create a stylistic representation of a digital shape. We refer to this class of methods as ‘stylized fabrication methods’. These methods abstract geometric and physical features of a given shape to create an unconventional representation, to produce an optical illusion or to devise a particular interaction with the fabricated model. In this state‐of‐the‐art report, we classify and overview this broad and emerging class of approaches and also propose possible directions for future research. AU - Bickel, Bernd AU - Cignoni, Paolo AU - Malomo, Luigi AU - Pietroni, Nico ID - 6003 IS - 6 JF - Computer Graphics Forum SN - 0167-7055 TI - State of the art on stylized fabrication VL - 37 ER - TY - JOUR AB - The Bogoliubov free energy functional is analysed. The functional serves as a model of a translation-invariant Bose gas at positive temperature. We prove the existence of minimizers in the case of repulsive interactions given by a sufficiently regular two-body potential. Furthermore, we prove the existence of a phase transition in this model and provide its phase diagram. AU - Napiórkowski, Marcin M AU - Reuvers, Robin AU - Solovej, Jan Philip ID - 6002 IS - 3 JF - Archive for Rational Mechanics and Analysis SN - 0003-9527 TI - The Bogoliubov free energy functional I: Existence of minimizers and phase diagram VL - 229 ER - TY - JOUR AB - In pipes, turbulence sets in despite the linear stability of the laminar Hagen–Poiseuille flow. The Reynolds number ( ) for which turbulence first appears in a given experiment – the ‘natural transition point’ – depends on imperfections of the set-up, or, more precisely, on the magnitude of finite amplitude perturbations. At onset, turbulence typically only occupies a certain fraction of the flow, and this fraction equally is found to differ from experiment to experiment. Despite these findings, Reynolds proposed that after sufficiently long times, flows may settle to steady conditions: below a critical velocity, flows should (regardless of initial conditions) always return to laminar, while above this velocity, eddying motion should persist. As will be shown, even in pipes several thousand diameters long, the spatio-temporal intermittent flow patterns observed at the end of the pipe strongly depend on the initial conditions, and there is no indication that different flow patterns would eventually settle to a (statistical) steady state. Exploiting the fact that turbulent puffs do not age (i.e. they are memoryless), we continuously recreate the puff sequence exiting the pipe at the pipe entrance, and in doing so introduce periodic boundary conditions for the puff pattern. This procedure allows us to study the evolution of the flow patterns for arbitrary long times, and we find that after times in excess of advective time units, indeed a statistical steady state is reached. Although the resulting flows remain spatio-temporally intermittent, puff splitting and decay rates eventually reach a balance, so that the turbulent fraction fluctuates around a well-defined level which only depends on . In accordance with Reynolds’ proposition, we find that at lower (here 2020), flows eventually always resume to laminar, while for higher ( ), turbulence persists. The critical point for pipe flow hence falls in the interval of $2020 , which is in very good agreement with the recently proposed value of . The latter estimate was based on single-puff statistics and entirely neglected puff interactions. Unlike in typical contact processes where such interactions strongly affect the percolation threshold, in pipe flow, the critical point is only marginally influenced. Interactions, on the other hand, are responsible for the approach to the statistical steady state. As shown, they strongly affect the resulting flow patterns, where they cause ‘puff clustering’, and these regions of large puff densities are observed to travel across the puff pattern in a wave-like fashion. AU - Vasudevan, Mukund AU - Hof, Björn ID - 5996 JF - Journal of Fluid Mechanics SN - 0022-1120 TI - The critical point of the transition to turbulence in pipe flow VL - 839 ER - TY - JOUR AB - In this article, we consider the termination problem of probabilistic programs with real-valued variables. Thequestions concerned are: qualitative ones that ask (i) whether the program terminates with probability 1(almost-sure termination) and (ii) whether the expected termination time is finite (finite termination); andquantitative ones that ask (i) to approximate the expected termination time (expectation problem) and (ii) tocompute a boundBsuch that the probability not to terminate afterBsteps decreases exponentially (con-centration problem). To solve these questions, we utilize the notion of ranking supermartingales, which isa powerful approach for proving termination of probabilistic programs. In detail, we focus on algorithmicsynthesis of linear ranking-supermartingales over affine probabilistic programs (Apps) with both angelic anddemonic non-determinism. An important subclass of Apps is LRApp which is defined as the class of all Appsover which a linear ranking-supermartingale exists.Our main contributions are as follows. Firstly, we show that the membership problem of LRApp (i) canbe decided in polynomial time for Apps with at most demonic non-determinism, and (ii) isNP-hard and inPSPACEfor Apps with angelic non-determinism. Moreover, theNP-hardness result holds already for Appswithout probability and demonic non-determinism. Secondly, we show that the concentration problem overLRApp can be solved in the same complexity as for the membership problem of LRApp. Finally, we show thatthe expectation problem over LRApp can be solved in2EXPTIMEand isPSPACE-hard even for Apps withoutprobability and non-determinism (i.e., deterministic programs). Our experimental results demonstrate theeffectiveness of our approach to answer the qualitative and quantitative questions over Apps with at mostdemonic non-determinism. AU - Chatterjee, Krishnendu AU - Fu, Hongfei AU - Novotný, Petr AU - Hasheminezhad, Rouzbeh ID - 5993 IS - 2 JF - ACM Transactions on Programming Languages and Systems SN - 0164-0925 TI - Algorithmic analysis of qualitative and quantitative termination problems for affine probabilistic programs VL - 40 ER - TY - JOUR AB - We introduce for each quiver Q and each algebraic oriented cohomology theory A, the cohomological Hall algebra (CoHA) of Q, as the A-homology of the moduli of representations of the preprojective algebra of Q. This generalizes the K-theoretic Hall algebra of commuting varieties defined by Schiffmann-Vasserot. When A is the Morava K-theory, we show evidence that this algebra is a candidate for Lusztig's reformulated conjecture on modular representations of algebraic groups. We construct an action of the preprojective CoHA on the A-homology of Nakajima quiver varieties. We compare this with the action of the Borel subalgebra of Yangian when A is the intersection theory. We also give a shuffle algebra description of this CoHA in terms of the underlying formal group law of A. As applications, we obtain a shuffle description of the Yangian. AU - Yang, Yaping AU - Zhao, Gufang ID - 5999 IS - 5 JF - Proceedings of the London Mathematical Society SN - 0024-6115 TI - The cohomological Hall algebra of a preprojective algebra VL - 116 ER - TY - JOUR AB - Schistosomes are the causative agents of schistosomiasis, a neglected tropical disease affecting over 230 million people worldwide.Additionally to their major impact on human health, they are also models of choice in evolutionary biology. These parasitic flatwormsare unique among the common hermaphroditic trematodes as they have separate sexes. This so-called “evolutionary scandal”displays a female heterogametic genetic sex-determination system (ZZ males and ZW females), as well as a pronounced adult sexualdimorphism. These phenotypic differences are determined by a shared set of genes in both sexes, potentially leading to intralocussexual conflicts. To resolve these conflicts in sexually selected traits, molecular mechanisms such as sex-biased gene expression couldoccur, but parent-of-origin gene expression also provides an alternative. In this work we investigated the latter mechanism, that is,genes expressed preferentially from either the maternal or the paternal allele, inSchistosoma mansonispecies. To this end, tran-scriptomes from male and female hybrid adults obtained by strain crosses were sequenced. Strain-specific single nucleotide poly-morphism (SNP) markers allowed us to discriminate the parental origin, while reciprocal crosses helped to differentiate parentalexpression from strain-specific expression. We identified genes containing SNPs expressed in a parent-of-origin manner consistentwith paternal and maternal imprints. Although the majority of the SNPs was identified in mitochondrial and Z-specific loci, theremaining SNPs found in male and female transcriptomes were situated in genes that have the potential to explain sexual differencesin schistosome parasites. Furthermore, we identified and validated four new Z-specific scaffolds. AU - Kincaid-Smith, Julien AU - Picard, Marion A L AU - Cosseau, Céline AU - Boissier, Jérôme AU - Severac, Dany AU - Grunau, Christoph AU - Toulza, Eve ID - 5989 IS - 3 JF - Genome Biology and Evolution SN - 1759-6653 TI - Parent-of-Origin-Dependent Gene Expression in Male and Female Schistosome Parasites VL - 10 ER - TY - CONF AB - We introduce Clover, a new library for efficient computation using low-precision data, providing mathematical routines required by fundamental methods in optimization and sparse recovery. Our library faithfully implements variants of stochastic quantization that guarantee convergence at low precision, and supports data formats from 4-bit quantized to 32-bit IEEE-754 on current Intel processors. In particular, we show that 4-bit can be implemented efficiently using Intel AVX despite the lack of native support for this data format. Experimental results with dot product, matrix-vector multiplication (MVM), gradient descent (GD), and iterative hard thresholding (IHT) demonstrate that the attainable speedups are in many cases close to linear with respect to the reduction of precision due to reduced data movement. Finally, for GD and IHT, we show examples of absolute speedup achieved by 4-bit versus 32-bit, by iterating until a given target error is achieved. AU - Stojanov, Alen AU - Smith, Tyler Michael AU - Alistarh, Dan-Adrian AU - Puschel, Markus ID - 6031 T2 - 2018 IEEE International Workshop on Signal Processing Systems TI - Fast quantized arithmetic on x86: Trading compute for data movement VL - 2018-October ER - TY - CONF AB - Partially observable Markov decision processes (POMDPs) are the standard models for planning under uncertainty with both finite and infinite horizon. Besides the well-known discounted-sum objective, indefinite-horizon objective (aka Goal-POMDPs) is another classical objective for POMDPs. In this case, given a set of target states and a positive cost for each transition, the optimization objective is to minimize the expected total cost until a target state is reached. In the literature, RTDP-Bel or heuristic search value iteration (HSVI) have been used for solving Goal-POMDPs. Neither of these algorithms has theoretical convergence guarantees, and HSVI may even fail to terminate its trials. We give the following contributions: (1) We discuss the challenges introduced in Goal-POMDPs and illustrate how they prevent the original HSVI from converging. (2) We present a novel algorithm inspired by HSVI, termed Goal-HSVI, and show that our algorithm has convergence guarantees. (3) We show that Goal-HSVI outperforms RTDP-Bel on a set of well-known examples. AU - Horák, Karel AU - Bošanský, Branislav AU - Chatterjee, Krishnendu ID - 25 T2 - Proceedings of the Twenty-Seventh International Joint Conference on Artificial Intelligence TI - Goal-HSVI: Heuristic search value iteration for goal-POMDPs VL - 2018-July ER - TY - CONF AB - Partially-observable Markov decision processes (POMDPs) with discounted-sum payoff are a standard framework to model a wide range of problems related to decision making under uncertainty. Traditionally, the goal has been to obtain policies that optimize the expectation of the discounted-sum payoff. A key drawback of the expectation measure is that even low probability events with extreme payoff can significantly affect the expectation, and thus the obtained policies are not necessarily risk-averse. An alternate approach is to optimize the probability that the payoff is above a certain threshold, which allows obtaining risk-averse policies, but ignores optimization of the expectation. We consider the expectation optimization with probabilistic guarantee (EOPG) problem, where the goal is to optimize the expectation ensuring that the payoff is above a given threshold with at least a specified probability. We present several results on the EOPG problem, including the first algorithm to solve it. AU - Chatterjee, Krishnendu AU - Elgyütt, Adrian AU - Novotny, Petr AU - Rouillé, Owen ID - 24 TI - Expectation optimization with probabilistic guarantees in POMDPs with discounted-sum objectives VL - 2018 ER - TY - CONF AB - Partially observable Markov decision processes (POMDPs) are widely used in probabilistic planning problems in which an agent interacts with an environment using noisy and imprecise sensors. We study a setting in which the sensors are only partially defined and the goal is to synthesize “weakest” additional sensors, such that in the resulting POMDP, there is a small-memory policy for the agent that almost-surely (with probability 1) satisfies a reachability objective. We show that the problem is NP-complete, and present a symbolic algorithm by encoding the problem into SAT instances. We illustrate trade-offs between the amount of memory of the policy and the number of additional sensors on a simple example. We have implemented our approach and consider three classical POMDP examples from the literature, and show that in all the examples the number of sensors can be significantly decreased (as compared to the existing solutions in the literature) without increasing the complexity of the policies. AU - Chatterjee, Krishnendu AU - Chemlík, Martin AU - Topcu, Ufuk ID - 34 TI - Sensor synthesis for POMDPs with reachability objectives VL - 2018 ER - TY - JOUR AB - An N-superconcentrator is a directed, acyclic graph with N input nodes and N output nodes such that every subset of the inputs and every subset of the outputs of same cardinality can be connected by node-disjoint paths. It is known that linear-size and bounded-degree superconcentrators exist. We prove the existence of such superconcentrators with asymptotic density 25.3 (where the density is the number of edges divided by N). The previously best known densities were 28 [12] and 27.4136 [17]. AU - Kolmogorov, Vladimir AU - Rolinek, Michal ID - 18 IS - 10 JF - Ars Combinatoria SN - 0381-7032 TI - Superconcentrators of density 25.3 VL - 141 ER - TY - JOUR AB - We prove that any cyclic quadrilateral can be inscribed in any closed convex C1-curve. The smoothness condition is not required if the quadrilateral is a rectangle. AU - Akopyan, Arseniy AU - Avvakumov, Sergey ID - 6355 JF - Forum of Mathematics, Sigma SN - 2050-5094 TI - Any cyclic quadrilateral can be inscribed in any closed convex smooth curve VL - 6 ER - TY - CONF AB - In the context of robotic manipulation and grasping, the shift from a view that is static (force closure of a single posture) and contact-deprived (only contact for force closure is allowed, everything else is obstacle) towards a view that is dynamic and contact-rich (soft manipulation) has led to an increased interest in soft hands. These hands can easily exploit environmental constraints and object surfaces without risk, and safely interact with humans, but present also some challenges. Designing them is difficult, as well as predicting, modelling, and “programming” their interactions with the objects and the environment. This paper tackles the problem of simulating them in a fast and effective way, leveraging on novel and existing simulation technologies. We present a triple-layered simulation framework where dynamic properties such as stiffness are determined from slow but accurate FEM simulation data once, and then condensed into a lumped parameter model that can be used to fast simulate soft fingers and soft hands. We apply our approach to the simulation of soft pneumatic fingers. AU - Pozzi, Maria AU - Miguel Villalba, Eder AU - Deimel, Raphael AU - Malvezzi, Monica AU - Bickel, Bernd AU - Brock, Oliver AU - Prattichizzo, Domenico ID - 6195 SN - 9781538630815 TI - Efficient FEM-based simulation of soft robots modeled as kinematic chains ER - TY - CONF AB - Bitcoin has become the most successful cryptocurrency ever deployed, and its most distinctive feature is that it is decentralized. Its underlying protocol (Nakamoto consensus) achieves this by using proof of work, which has the drawback that it causes the consumption of vast amounts of energy to maintain the ledger. Moreover, Bitcoin mining dynamics have become less distributed over time. Towards addressing these issues, we propose SpaceMint, a cryptocurrency based on proofs of space instead of proofs of work. Miners in SpaceMint dedicate disk space rather than computation. We argue that SpaceMint’s design solves or alleviates several of Bitcoin’s issues: most notably, its large energy consumption. SpaceMint also rewards smaller miners fairly according to their contribution to the network, thus incentivizing more distributed participation. This paper adapts proof of space to enable its use in cryptocurrency, studies the attacks that can arise against a Bitcoin-like blockchain that uses proof of space, and proposes a new blockchain format and transaction types to address these attacks. Our prototype shows that initializing 1 TB for mining takes about a day (a one-off setup cost), and miners spend on average just a fraction of a second per block mined. Finally, we provide a game-theoretic analysis modeling SpaceMint as an extensive game (the canonical game-theoretic notion for games that take place over time) and show that this stylized game satisfies a strong equilibrium notion, thereby arguing for SpaceMint ’s stability and consensus. AU - Park, Sunoo AU - Kwon, Albert AU - Fuchsbauer, Georg AU - Gazi, Peter AU - Alwen, Joel F AU - Pietrzak, Krzysztof Z ID - 6941 SN - 0302-9743 T2 - 22nd International Conference on Financial Cryptography and Data Security TI - SpaceMint: A cryptocurrency based on proofs of space VL - 10957 ER - TY - JOUR AB - T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b−/− CD8+ T cells in lymphoid tissue and similar expansion and differentiation during immune responses. In contrast, accumulation of Myo9b−/− CD8+ T cells in NLTs was strongly impaired. Specifically, Myo9b was required for T cell crossing of basement membranes, such as those which are present between dermis and epidermis. As consequence, Myo9b−/− CD8+ T cells showed impaired control of skin infections. In sum, we show that Myo9b is critical for the CD8+ T cell adaptation from lymphoid to NLT surveillance and the establishment of protective tissue–resident T cell populations. AU - Moalli, Federica AU - Ficht, Xenia AU - Germann, Philipp AU - Vladymyrov, Mykhailo AU - Stolp, Bettina AU - de Vries, Ingrid AU - Lyck, Ruth AU - Balmer, Jasmin AU - Fiocchi, Amleto AU - Kreutzfeldt, Mario AU - Merkler, Doron AU - Iannacone, Matteo AU - Ariga, Akitaka AU - Stoffel, Michael H. AU - Sharpe, James AU - Bähler, Martin AU - Sixt, Michael K AU - Diz-Muñoz, Alba AU - Stein, Jens V. ID - 6497 IS - 7 JF - The Journal of Experimental Medicine SN - 0022-1007 TI - The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8+T cells VL - 2015 ER - TY - JOUR AB - Expansion microscopy is a recently introduced imaging technique that achieves super‐resolution through physically expanding the specimen by ~4×, after embedding into a swellable gel. The resolution attained is, correspondingly, approximately fourfold better than the diffraction limit, or ~70 nm. This is a major improvement over conventional microscopy, but still lags behind modern STED or STORM setups, whose resolution can reach 20–30 nm. We addressed this issue here by introducing an improved gel recipe that enables an expansion factor of ~10× in each dimension, which corresponds to an expansion of the sample volume by more than 1,000‐fold. Our protocol, which we termed X10 microscopy, achieves a resolution of 25–30 nm on conventional epifluorescence microscopes. X10 provides multi‐color images similar or even superior to those produced with more challenging methods, such as STED, STORM, and iterative expansion microscopy (iExM). X10 is therefore the cheapest and easiest option for high‐quality super‐resolution imaging currently available. X10 should be usable in any laboratory, irrespective of the machinery owned or of the technical knowledge. AU - Truckenbrodt, Sven M AU - Maidorn, Manuel AU - Crzan, Dagmar AU - Wildhagen, Hanna AU - Kabatas, Selda AU - Rizzoli, Silvio O ID - 6499 IS - 9 JF - EMBO reports SN - 1469-221X TI - X10 expansion microscopy enables 25‐nm resolution on conventional microscopes VL - 19 ER - TY - CONF AB - Population protocols are a popular model of distributed computing, in which n agents with limited local state interact randomly, and cooperate to collectively compute global predicates. Inspired by recent developments in DNA programming, an extensive series of papers, across different communities, has examined the computability and complexity characteristics of this model. Majority, or consensus, is a central task in this model, in which agents need to collectively reach a decision as to which one of two states A or B had a higher initial count. Two metrics are important: the time that a protocol requires to stabilize to an output decision, and the state space size that each agent requires to do so. It is known that majority requires Ω(log log n) states per agent to allow for fast (poly-logarithmic time) stabilization, and that O(log2 n) states are sufficient. Thus, there is an exponential gap between the space upper and lower bounds for this problem. This paper addresses this question. On the negative side, we provide a new lower bound of Ω(log n) states for any protocol which stabilizes in O(n1–c) expected time, for any constant c > 0. This result is conditional on monotonicity and output assumptions, satisfied by all known protocols. Technically, it represents a departure from previous lower bounds, in that it does not rely on the existence of dense configurations. Instead, we introduce a new generalized surgery technique to prove the existence of incorrect executions for any algorithm which would contradict the lower bound. Subsequently, our lower bound also applies to general initial configurations, including ones with a leader. On the positive side, we give a new algorithm for majority which uses O(log n) states, and stabilizes in O(log2 n) expected time. Central to the algorithm is a new leaderless phase clock technique, which allows agents to synchronize in phases of Θ(n log n) consecutive interactions using O(log n) states per agent, exploiting a new connection between population protocols and power-of-two-choices load balancing mechanisms. We also employ our phase clock to build a leader election algorithm with a state space of size O(log n), which stabilizes in O(log2 n) expected time. AU - Alistarh, Dan-Adrian AU - Aspnes, James AU - Gelashvili, Rati ID - 7123 SN - 9781611975031 T2 - Proceedings of the 29th Annual ACM-SIAM Symposium on Discrete Algorithms TI - Space-optimal majority in population protocols ER - TY - JOUR AB - Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g., outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e., focuses on spatial patterns of allele frequency change) with system-specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome-wide SNP set from an ideally suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non-neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non-neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasizes that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems. AU - Westram, Anja M AU - Rafajlović, Marina AU - Chaube, Pragya AU - Faria, Rui AU - Larsson, Tomas AU - Panova, Marina AU - Ravinet, Mark AU - Blomberg, Anders AU - Mehlig, Bernhard AU - Johannesson, Kerstin AU - Butlin, Roger ID - 9917 IS - 4 JF - Evolution Letters SN - 2056-3744 TI - Clines on the seashore: The genomic architecture underlying rapid divergence in the face of gene flow VL - 2 ER - TY - JOUR AB - The evolution of assortative mating is a key part of the speciation process. Stronger assortment, or greater divergence in mating traits, between species pairs with overlapping ranges is commonly observed, but possible causes of this pattern of reproductive character displacement are difficult to distinguish. We use a multidisciplinary approach to provide a rare example where it is possible to distinguish among hypotheses concerning the evolution of reproductive character displacement. We build on an earlier comparative analysis that illustrated a strong pattern of greater divergence in penis form between pairs of sister species with overlapping ranges than between allopatric sister-species pairs, in a large clade of marine gastropods (Littorinidae). We investigate both assortative mating and divergence in male genitalia in one of the sister-species pairs, discriminating among three contrasting processes each of which can generate a pattern of reproductive character displacement: reinforcement, reproductive interference and the Templeton effect. We demonstrate reproductive character displacement in assortative mating, but not in genital form between this pair of sister species and use demographic models to distinguish among the different processes. Our results support a model with no gene flow since secondary contact and thus favor reproductive interference as the cause of reproductive character displacement for mate choice, rather than reinforcement. High gene flow within species argues against the Templeton effect. Secondary contact appears to have had little impact on genital divergence. AU - Hollander, Johan AU - Montaño-Rendón, Mauricio AU - Bianco, Giuseppe AU - Yang, Xi AU - Westram, Anja M AU - Duvaux, Ludovic AU - Reid, David G. AU - Butlin, Roger K. ID - 9915 IS - 6 JF - Evolution Letters SN - 2056-3744 TI - Are assortative mating and genital divergence driven by reinforcement? VL - 2 ER - TY - JOUR AB - The reversibly switchable fluorescent proteins (RSFPs) commonly used for RESOLFT nanoscopy have been developed from fluorescent proteins of the GFP superfamily. These proteins are bright, but exhibit several drawbacks such as relatively large size, oxygen-dependence, sensitivity to low pH, and limited switching speed. Therefore, RSFPs from other origins with improved properties need to be explored. Here, we report the development of two RSFPs based on the LOV domain of the photoreceptor protein YtvA from Bacillus subtilis. LOV domains obtain their fluorescence by association with the abundant cellular cofactor flavin mononucleotide (FMN). Under illumination with blue and ultraviolet light, they undergo a photocycle, making these proteins inherently photoswitchable. Our first improved variant, rsLOV1, can be used for RESOLFT imaging, whereas rsLOV2 proved useful for STED nanoscopy of living cells with a resolution of down to 50 nm. In addition to their smaller size compared to GFP-related proteins (17 kDa instead of 27 kDa) and their usability at low pH, rsLOV1 and rsLOV2 exhibit faster switching kinetics, switching on and off 3 times faster than rsEGFP2, the fastest-switching RSFP reported to date. Therefore, LOV-domain-based RSFPs have potential for applications where the switching speed of GFP-based proteins is limiting. AU - Gregor, Carola AU - Sidenstein, Sven C. AU - Andresen, Martin AU - Sahl, Steffen J. AU - Danzl, Johann G AU - Hell, Stefan W. ID - 8618 JF - Scientific Reports KW - Multidisciplinary SN - 2045-2322 TI - Novel reversibly switchable fluorescent proteins for RESOLFT and STED nanoscopy engineered from the bacterial photoreceptor YtvA VL - 8 ER - TY - JOUR AB - Strigolactones (SLs) are a relatively recent addition to the list of plant hormones that control different aspects of plant development. SL signalling is perceived by an α/β hydrolase, DWARF 14 (D14). A close homolog of D14, KARRIKIN INSENSTIVE2 (KAI2), is involved in perception of an uncharacterized molecule called karrikin (KAR). Recent studies in Arabidopsis identified the SUPPRESSOR OF MAX2 1 (SMAX1) and SMAX1-LIKE 7 (SMXL7) to be potential SCF–MAX2 complex-mediated proteasome targets of KAI2 and D14, respectively. Genetic studies on SMXL7 and SMAX1 demonstrated distinct developmental roles for each, but very little is known about these repressors in terms of their sequence features. In this study, we performed an extensive comparative analysis of SMXLs and determined their phylogenetic and evolutionary history in the plant lineage. Our results show that SMXL family members can be sub-divided into four distinct phylogenetic clades/classes, with an ancient SMAX1. Further, we identified the clade-specific motifs that have evolved and that might act as determinants of SL-KAR signalling specificity. These specificities resulted from functional diversities among the clades. Our results suggest that a gradual co-evolution of SMXL members with their upstream receptors D14/KAI2 provided an increased specificity to both the SL perception and response in land plants. AU - Moturu, Taraka Ramji AU - Thula, Sravankumar AU - Singh, Ravi Kumar AU - Nodzyński, Tomasz AU - Vařeková, Radka Svobodová AU - Friml, Jiří AU - Simon, Sibu ID - 10881 IS - 9 JF - Journal of Experimental Botany KW - Plant Science KW - Physiology SN - 0022-0957 TI - Molecular evolution and diversification of the SMXL gene family VL - 69 ER - TY - JOUR AB - Acquisition of evolutionary novelties is a fundamental process for adapting to the external environment and invading new niches and results in the diversification of life, which we can see in the world today. How such novel phenotypic traits are acquired in the course of evolution and are built up in developing embryos has been a central question in biology. Whole-genome duplication (WGD) is a process of genome doubling that supplies raw genetic materials and increases genome complexity. Recently, it has been gradually revealed that WGD and subsequent fate changes of duplicated genes can facilitate phenotypic evolution. Here, we review the current understanding of the relationship between WGD and the acquisition of evolutionary novelties. We show some examples of this link and discuss how WGD and subsequent duplicated genes can facilitate phenotypic evolution as well as when such genomic doubling can be advantageous for adaptation. AU - Yuuta, Moriyama AU - Koshiba-Takeuchi, Kazuko ID - 10880 IS - 5 JF - Briefings in Functional Genomics KW - Genetics KW - Molecular Biology KW - Biochemistry KW - General Medicine SN - 2041-2649 TI - Significance of whole-genome duplications on the emergence of evolutionary novelties VL - 17 ER - TY - GEN AB - Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g. outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e. focuses on spatial patterns of allele frequency change) with system-specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome-wide SNP set from an ideally-suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non-neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non-neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasises that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems. AU - Westram, Anja M AU - Rafajlović, Marina AU - Chaube, Pragya AU - Faria, Rui AU - Larsson, Tomas AU - Panova, Marina AU - Ravinet, Mark AU - Blomberg, Anders AU - Mehlig, Bernhard AU - Johannesson, Kerstin AU - Butlin, Roger ID - 9930 TI - Data from: Clines on the seashore: the genomic architecture underlying rapid divergence in the face of gene flow ER - TY - GEN AB - The evolution of assortative mating is a key part of the speciation process. Stronger assortment, or greater divergence in mating traits, between species pairs with overlapping ranges is commonly observed, but possible causes of this pattern of reproductive character displacement are difficult to distinguish. We use a multidisciplinary approach to provide a rare example where it is possible to distinguish among hypotheses concerning the evolution of reproductive character displacement. We build on an earlier comparative analysis that illustrated a strong pattern of greater divergence in penis form between pairs of sister species with overlapping ranges than between allopatric sister-species pairs, in a large clade of marine gastropods (Littorinidae). We investigate both assortative mating and divergence in male genitalia in one of the sister-species pairs, discriminating among three contrasting processes each of which can generate a pattern of reproductive character displacement: reinforcement, reproductive interference and the Templeton effect. We demonstrate reproductive character displacement in assortative mating, but not in genital form between this pair of sister species and use demographic models to distinguish among the different processes. Our results support a model with no gene flow since secondary contact and thus favour reproductive interference as the cause of reproductive character displacement for mate choice, rather than reinforcement. High gene flow within species argues against the Templeton effect. Secondary contact appears to have had little impact on genital divergence. AU - Hollander, Johan AU - Montaño-Rendón, Mauricio AU - Bianco, Giuseppe AU - Yang, Xi AU - Westram, Anja M AU - Duvaux, Ludovic AU - Reid, David G. AU - Butlin, Roger K. ID - 9929 TI - Data from: Are assortative mating and genital divergence driven by reinforcement? ER - TY - CONF AB - We introduce Intelligent Annotation Dialogs for bounding box annotation. We train an agent to automatically choose a sequence of actions for a human annotator to produce a bounding box in a minimal amount of time. Specifically, we consider two actions: box verification [34], where the annotator verifies a box generated by an object detector, and manual box drawing. We explore two kinds of agents, one based on predicting the probability that a box will be positively verified, and the other based on reinforcement learning. We demonstrate that (1) our agents are able to learn efficient annotation strategies in several scenarios, automatically adapting to the image difficulty, the desired quality of the boxes, and the detector strength; (2) in all scenarios the resulting annotation dialogs speed up annotation compared to manual box drawing alone and box verification alone, while also outperforming any fixed combination of verification and drawing in most scenarios; (3) in a realistic scenario where the detector is iteratively re-trained, our agents evolve a series of strategies that reflect the shifting trade-off between verification and drawing as the detector grows stronger. AU - Uijlings, Jasper AU - Konyushkova, Ksenia AU - Lampert, Christoph AU - Ferrari, Vittorio ID - 10882 SN - 9781538664209 T2 - 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition TI - Learning intelligent dialogs for bounding box annotation ER - TY - CONF AB - This paper studies the problem of distributed stochastic optimization in an adversarial setting where, out of m machines which allegedly compute stochastic gradients every iteration, an α-fraction are Byzantine, and may behave adversarially. Our main result is a variant of stochastic gradient descent (SGD) which finds ε-approximate minimizers of convex functions in T=O~(1/ε²m+α²/ε²) iterations. In contrast, traditional mini-batch SGD needs T=O(1/ε²m) iterations, but cannot tolerate Byzantine failures. Further, we provide a lower bound showing that, up to logarithmic factors, our algorithm is information-theoretically optimal both in terms of sample complexity and time complexity. AU - Alistarh, Dan-Adrian AU - Allen-Zhu, Zeyuan AU - Li, Jerry ID - 6558 T2 - Advances in Neural Information Processing Systems TI - Byzantine stochastic gradient descent VL - 2018 ER - TY - JOUR AB - The main result of this article 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. Using a reduction to even Δ-matroids, we then extend the tractability result to larger classes of Δ-matroids that we call efficiently coverable. It properly includes classes that were known to be tractable before, namely, co-independent, compact, local, linear, and binary, with the following caveat:We represent Δ-matroids by lists of tuples, while the last two use a representation by matrices. Since an n ×n matrix can represent exponentially many tuples, our tractability result is not strictly stronger than the known algorithm for linear and binary Δ-matroids. AU - Kazda, Alexandr AU - Kolmogorov, Vladimir AU - Rolinek, Michal ID - 6032 IS - 2 JF - ACM Transactions on Algorithms TI - Even delta-matroids and the complexity of planar boolean CSPs VL - 15 ER - TY - THES AB - This thesis is concerned with the inference of current population structure based on geo-referenced genetic data. The underlying idea is that population structure affects its spatial genetic structure. Therefore, genotype information can be utilized to estimate important demographic parameters such as migration rates. These indirect estimates of population structure have become very attractive, as genotype data is now widely available. However, there also has been much concern about these approaches. Importantly, genetic structure can be influenced by many complex patterns, which often cannot be disentangled. Moreover, many methods merely fit heuristic patterns of genetic structure, and do not build upon population genetics theory. Here, I describe two novel inference methods that address these shortcomings. In Chapter 2, I introduce an inference scheme based on a new type of signal, identity by descent (IBD) blocks. Recently, it has become feasible to detect such long blocks of genome shared between pairs of samples. These blocks are direct traces of recent coalescence events. As such, they contain ample signal for inferring recent demography. I examine sharing of IBD blocks in two-dimensional populations with local migration. Using a diffusion approximation, I derive formulas for an isolation by distance pattern of long IBD blocks and show that sharing of long IBD blocks approaches rapid exponential decay for growing sample distance. I describe an inference scheme based on these results. It can robustly estimate the dispersal rate and population density, which is demonstrated on simulated data. I also show an application to estimate mean migration and the rate of recent population growth within Eastern Europe. Chapter 3 is about a novel method to estimate barriers to gene flow in a two dimensional population. This inference scheme utilizes geographically localized allele frequency fluctuations - a classical isolation by distance signal. The strength of these local fluctuations increases on average next to a barrier, and there is less correlation across it. I again use a framework of diffusion of ancestral lineages to model this effect, and provide an efficient numerical implementation to fit the results to geo-referenced biallelic SNP data. This inference scheme is able to robustly estimate strong barriers to gene flow, as tests on simulated data confirm. AU - Ringbauer, Harald ID - 200 SN - 2663-337X TI - Inferring recent demography from spatial genetic structure ER - TY - JOUR AB - In 1945, A.W. Goodman and R.E. Goodman proved the following conjecture by P. Erdős: Given a family of (round) disks of radii r1, … , rn in the plane, it is always possible to cover them by a disk of radius R= ∑ ri, provided they cannot be separated into two subfamilies by a straight line disjoint from the disks. In this note we show that essentially the same idea may work for different analogues and generalizations of their result. In particular, we prove the following: Given a family of positive homothetic copies of a fixed convex body K⊂ Rd with homothety coefficients τ1, … , τn> 0 , it is always possible to cover them by a translate of d+12(∑τi)K, provided they cannot be separated into two subfamilies by a hyperplane disjoint from the homothets. AU - Akopyan, Arseniy AU - Balitskiy, Alexey AU - Grigorev, Mikhail ID - 1064 IS - 4 JF - Discrete & Computational Geometry SN - 01795376 TI - On the circle covering theorem by A.W. Goodman and R.E. Goodman VL - 59 ER - TY - THES AB - The aim of this thesis was the development of new strategies for optical and optogenetic control of proliferative and pro-survival signaling, and characterizing them from the molecular mechanism up to cellular effects. These new light-based methods have unique features, such as red light as an activator, or the avoidance of gene delivery, which enable to overcome current limitations, such as light delivery to target tissues and feasibility as therapeutic approach. A special focus was placed on implementing these new light-based approaches in pancreatic β-cells, as β-cells are the key players in diabetes and especially their loss in number negatively affects disease progression. Currently no treatment options are available to compensate the lack of functional β-cells in diabetic patients. In a first approach, red-light-activated growth factor receptors, in particular receptor tyrosine kinases were engineered and characterized. Receptor activation with light allows spatio-temporal control compared to ligand-based activation, and especially red light exhibits deeper tissue penetration than other wavelengths of the visible spectrum. Red-light-activated receptor tyrosine kinases robustly activated major growth factor related signaling pathways with a high temporal resolution. Moreover, the remote activation of the proliferative MAPK/Erk pathway by red-light-activated receptor tyrosine kinases in a pancreatic β-cell line was also achieved, through one centimeter thick mouse tissue. Although red-light-activated receptor tyrosine kinases are particularly attractive for applications in animal models due to the deep tissue penetration of red light, a drawback, especially with regard to translation into humans, is the requirement of gene therapy. In a second approach an endogenous light-sensitive mechanism was identified and its potential to promote proliferative and pro-survival signals was explored, towards light-based tissue regeneration without the need for gene transfer. Blue-green light illumination was found to be sufficient for the activation of proliferation and survival promoting signaling pathways in primary pancreatic murine and human islets. Blue-green light also led to an increase in proliferation of primary islet cells, an effect which was shown to be mostly β-cell specific in human islets. Moreover, it was demonstrated that this approach of pancreatic β-cell expansion did not have any negative effect on the β-cell function, in particular on their insulin secretion capacity. In contrast, a trend for enhanced insulin secretion under high glucose conditions after illumination was detected. In order to unravel the detailed characteristics of this endogenous light-sensitive mechanism, the precise light requirements were determined. In addition, the expression of light sensing proteins, OPN3 and rhodopsin, was detected. The observed effects were found to be independent of handling effects such as temperature differences and cytochrome c oxidase dependent ATP increase, but they were found to be enhanced through the knockout of OPN3. The exact mechanism of how islets cells sense light and the identity of the photoreceptor remains unknown. Summarized two new light-based systems with unique features were established that enable the activation of proliferative and pro-survival signaling pathways. While red-light-activated receptor tyrosine kinases open a new avenue for optogenetics research, by allowing non-invasive control of signaling in vivo, the identified endogenous light-sensitive mechanism has the potential to be the basis of a gene therapy-free therapeutical approach for light-based β-cell expansion. AU - Gschaider-Reichhart, Eva ID - 418 SN - 2663-337X TI - Optical and optogenetic control of proliferation and survival ER - TY - JOUR AB - We prove a new central limit theorem (CLT) for the difference of linear eigenvalue statistics of a Wigner random matrix H and its minor H and find that the fluctuation is much smaller than the fluctuations of the individual linear statistics, as a consequence of the strong correlation between the eigenvalues of H and H. In particular, our theorem identifies the fluctuation of Kerov's rectangular Young diagrams, defined by the interlacing eigenvalues ofH and H, around their asymptotic shape, the Vershik'Kerov'Logan'Shepp curve. Young diagrams equipped with the Plancherel measure follow the same limiting shape. For this, algebraically motivated, ensemble a CLT has been obtained in Ivanov and Olshanski [20] which is structurally similar to our result but the variance is different, indicating that the analogy between the two models has its limitations. Moreover, our theorem shows that Borodin's result [7] on the convergence of the spectral distribution of Wigner matrices to a Gaussian free field also holds in derivative sense. AU - Erdös, László AU - Schröder, Dominik J ID - 1012 IS - 10 JF - International Mathematics Research Notices SN - 10737928 TI - Fluctuations of rectangular young diagrams of interlacing wigner eigenvalues VL - 2018 ER - TY - JOUR AB - Network games (NGs) are played on directed graphs and are extensively used in network design and analysis. Search problems for NGs include finding special strategy profiles such as a Nash equilibrium and a globally-optimal solution. The networks modeled by NGs may be huge. In formal verification, abstraction has proven to be an extremely effective technique for reasoning about systems with big and even infinite state spaces. We describe an abstraction-refinement methodology for reasoning about NGs. Our methodology is based on an abstraction function that maps the state space of an NG to a much smaller state space. We search for a global optimum and a Nash equilibrium by reasoning on an under- and an over-approximation defined on top of this smaller state space. When the approximations are too coarse to find such profiles, we refine the abstraction function. We extend the abstraction-refinement methodology to labeled networks, where the objectives of the players are regular languages. Our experimental results demonstrate the effectiveness of the methodology. AU - Avni, Guy AU - Guha, Shibashis AU - Kupferman, Orna ID - 6006 IS - 3 JF - Games SN - 2073-4336 TI - An abstraction-refinement methodology for reasoning about network games VL - 9 ER - TY - CONF AB - We consider planning problems for graphs, Markov decision processes (MDPs), and games on graphs. While graphs represent the most basic planning model, MDPs represent interaction with nature and games on graphs represent interaction with an adversarial environment. We consider two planning problems where there are k different target sets, and the problems are as follows: (a) the coverage problem asks whether there is a plan for each individual target set; and (b) the sequential target reachability problem asks whether the targets can be reached in sequence. For the coverage problem, we present a linear-time algorithm for graphs, and quadratic conditional lower bound for MDPs and games on graphs. For the sequential target problem, we present a linear-time algorithm for graphs, a sub-quadratic algorithm for MDPs, and a quadratic conditional lower bound for games on graphs. Our results with conditional lower bounds establish (i) model-separation results showing that for the coverage problem MDPs and games on graphs are harder than graphs and for the sequential reachability problem games on graphs are harder than MDPs and graphs; and (ii) objective-separation results showing that for MDPs the coverage problem is harder than the sequential target problem. AU - Chatterjee, Krishnendu AU - Dvorák, Wolfgang AU - Henzinger, Monika H AU - Svozil, Alexander ID - 35 T2 - 28th International Conference on Automated Planning and Scheduling TI - Algorithms and conditional lower bounds for planning problems ER - TY - JOUR AB - This paper is devoted to automatic competitive analysis of real-time scheduling algorithms for firm-deadline tasksets, where only completed tasks con- tribute some utility to the system. Given such a taskset T , the competitive ratio of an on-line scheduling algorithm A for T is the worst-case utility ratio of A over the utility achieved by a clairvoyant algorithm. We leverage the theory of quantitative graph games to address the competitive analysis and competitive synthesis problems. For the competitive analysis case, given any taskset T and any finite-memory on- line scheduling algorithm A , we show that the competitive ratio of A in T can be computed in polynomial time in the size of the state space of A . Our approach is flexible as it also provides ways to model meaningful constraints on the released task sequences that determine the competitive ratio. We provide an experimental study of many well-known on-line scheduling algorithms, which demonstrates the feasibility of our competitive analysis approach that effectively replaces human ingenuity (required Preliminary versions of this paper have appeared in Chatterjee et al. ( 2013 , 2014 ). B Andreas Pavlogiannis pavlogiannis@ist.ac.at Krishnendu Chatterjee krish.chat@ist.ac.at Alexander Kößler koe@ecs.tuwien.ac.at Ulrich Schmid s@ecs.tuwien.ac.at 1 IST Austria (Institute of Science and Technology Austria), Am Campus 1, 3400 Klosterneuburg, Austria 2 Embedded Computing Systems Group, Vienna University of Technology, Treitlstrasse 3, 1040 Vienna, Austria 123 Real-Time Syst for finding worst-case scenarios) by computing power. For the competitive synthesis case, we are just given a taskset T , and the goal is to automatically synthesize an opti- mal on-line scheduling algorithm A , i.e., one that guarantees the largest competitive ratio possible for T . We show how the competitive synthesis problem can be reduced to a two-player graph game with partial information, and establish that the compu- tational complexity of solving this game is Np -complete. The competitive synthesis problem is hence in Np in the size of the state space of the non-deterministic labeled transition system encoding the taskset. Overall, the proposed framework assists in the selection of suitable scheduling algorithms for a given taskset, which is in fact the most common situation in real-time systems design. AU - Chatterjee, Krishnendu AU - Pavlogiannis, Andreas AU - Kößler, Alexander AU - Schmid, Ulrich ID - 738 IS - 1 JF - Real-Time Systems TI - Automated competitive analysis of real time scheduling with graph games VL - 54 ER - TY - THES AB - In this thesis we will discuss systems of point interacting fermions, their stability and other spectral properties. Whereas for bosons a point interacting system is always unstable this ques- tion is more subtle for a gas of two species of fermions. In particular the answer depends on the mass ratio between these two species. Most of this work will be focused on the N + M model which consists of two species of fermions with N, M particles respectively which interact via point interactions. We will introduce this model using a formal limit and discuss the N + 1 system in more detail. In particular, we will show that for mass ratios above a critical one, which does not depend on the particle number, the N + 1 system is stable. In the context of this model we will prove rigorous versions of Tan relations which relate various quantities of the point-interacting model. By restricting the N + 1 system to a box we define a finite density model with point in- teractions. In the context of this system we will discuss the energy change when introducing a point-interacting impurity into a system of non-interacting fermions. We will see that this change in energy is bounded independently of the particle number and in particular the bound only depends on the density and the scattering length. As another special case of the N + M model we will show stability of the 2 + 2 model for mass ratios in an interval around one. Further we will investigate a different model of point interactions which was discussed before in the literature and which is, contrary to the N + M model, not given by a limiting procedure but is based on a Dirichlet form. We will show that this system behaves trivially in the thermodynamic limit, i.e. the free energy per particle is the same as the one of the non-interacting system. AU - Moser, Thomas ID - 52 SN - 2663-337X TI - Point interactions in systems of fermions ER - TY - JOUR AB - Coordinated cell polarization in developing tissues is a recurrent theme in multicellular organisms. In plants, a directional distribution of the plant hormone auxin is at the core of many developmental programs. A feedback regulation of auxin on the polarized localization of PIN auxin transporters in individual cells has been proposed as a self-organizing mechanism for coordinated tissue polarization, but the molecular mechanisms linking auxin signalling to PIN-dependent auxin transport remain unknown. We performed a microarray-based approach to find regulators of the auxin-induced PIN relocation in the Arabidopsis thaliana root. We identified a subset of a family of phosphatidylinositol transfer proteins (PITP), the PATELLINs (PATL). Here, we show that PATLs are expressed in partially overlapping cells types in different tissues going through mitosis or initiating differentiation programs. PATLs are plasma membrane-associated proteins accumulated in Arabidopsis embryos, primary roots, lateral root primordia, and developing stomata. Higher order patl mutants display reduced PIN1 repolarization in response to auxin, shorter root apical meristem, and drastic defects in embryo and seedling development. This suggests PATLs redundantly play a crucial role in polarity and patterning in Arabidopsis. AU - Tejos, Ricardo AU - Rodríguez Furlán, Cecilia AU - Adamowski, Maciek AU - Sauer, Michael AU - Norambuena, Lorena AU - Friml, Jirí ID - 913 IS - 2 JF - Journal of Cell Science SN - 00219533 TI - PATELLINS are regulators of auxin mediated PIN1 relocation and plant development in Arabidopsis thaliana VL - 131 ER - TY - THES AB - A qubit, a unit of quantum information, is essentially any quantum mechanical two-level system which can be coherently controlled. Still, to be used for computation, it has to fulfill criteria. Qubits, regardless of the system in which they are realized, suffer from decoherence. This leads to loss of the information stored in the qubit. The upper bound of the time scale on which decoherence happens is set by the spin relaxation time. In this thesis I studied a two-level system consisting of a Zeeman-split hole spin confined in a quantum dot formed in a Ge hut wire. Such Ge hut wires have emerged as a promising material system for the realization of spin qubits, due to the combination of two significant properties: long spin coherence time as expected for group IV semiconductors due to the low hyperfine interaction and a strong valence band spin-orbit coupling. Here, I present how to fabricate quantum dot devices suitable for electrical transport measurements. Coupled quantum dot devices allowed the realization of a charge sensor, which is electrostatically and tunnel coupled to a quantum dot. By integrating the charge sensor into a radio-frequency reflectometry setup, I performed for the first time single-shot readout measurements of hole spins and extracted the hole spin relaxation times in Ge hut wires. AU - Vukušić, Lada ID - 69 SN - 2663-337X TI - Charge sensing and spin relaxation times of holes in Ge hut wires ER - TY - THES AB - Neuronal networks in the brain consist of two main types of neuron, glutamatergic principal neurons and GABAergic interneurons. Although these interneurons only represent 10–20% of the whole population, they mediate feedback and feedforward inhibition and are involved in the generation of high-frequency network oscillations. A hallmark functional property of GABAergic interneurons, especially of the parvalbumin‑expressing (PV+) subtypes, is the speed of signaling at their output synapse across species and brain regions. Several molecular and subcellular factors may underlie the submillisecond signaling at GABAergic synapses. Such as the selective use of P/Q type Ca2+ channels and the tight coupling between Ca2+ channels and Ca2+ sensors of exocytosis. However, whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Besides, these interneurons are mainly show depression in response to train of stimuli. How could they keep sufficient release to control the activity of postsynaptic principal neurons during high network activity, is largely elusive. For my Ph.D. work, we firstly examined the Ca2+ sensor of exocytosis at the GABAergic basket cell (BC) to Purkinje cell (PC) synapse in the 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% compared to the wild-type control, identifying Syt2 as the major Ca2+ sensor at BC‑PC synapses. Differential adenovirus-mediated rescue revealed 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 the release sensor at BC–PC synapse ensures fast feedforward inhibition in cerebellar microcircuits. Additionally, we tested the function of another synaptotagmin member, Syt7, for inhibitory synaptic transmission at the BC–PC synapse. Syt7 is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, it is strongly expressed in fast-spiking, PV+ GABAergic interneurons and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. How could Syt7, a facilitation sensor, contribute to the depressed inhibitory synaptic transmission needs to be further investigated and understood. Our results indicated that at the BC–PC synapse, Syt7 contributes to asynchronous release, pool replenishment and facilitation. In combination, these three effects ensure efficient transmitter release during high‑frequency activity and guarantee frequency independence of inhibition. Taken together, our results confirmed that Syt2, which has the fastest kinetic properties among all synaptotagmin members, is mainly used by the inhibitory BC‑PC synapse for synaptic transmission, contributing to the speed and temporal precision of transmitter release. Furthermore, we showed that Syt7, another highly expressed synaptotagmin member in the output synapses of cerebellar BCs, is used for ensuring efficient inhibitor synaptic transmission during high activity. AU - Chen, Chong ID - 324 SN - 2663-337X TI - Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release ER - TY - JOUR AB - We give a detailed and easily accessible proof of Gromov’s Topological Overlap Theorem. Let X be a finite simplicial complex or, more generally, a finite polyhedral cell complex of dimension d. Informally, the theorem states that if X has sufficiently strong higher-dimensional expansion properties (which generalize edge expansion of graphs and are defined in terms of cellular cochains of X) then X has the following topological overlap property: for every continuous map (Formula presented.) there exists a point (Formula presented.) that is contained in the images of a positive fraction (Formula presented.) of the d-cells of X. More generally, the conclusion holds if (Formula presented.) is replaced by any d-dimensional piecewise-linear manifold M, with a constant (Formula presented.) that depends only on d and on the expansion properties of X, but not on M. AU - Dotterrer, Dominic AU - Kaufman, Tali AU - Wagner, Uli ID - 742 IS - 1 JF - Geometriae Dedicata TI - On expansion and topological overlap VL - 195 ER - TY - JOUR AB - We consider the totally asymmetric simple exclusion process in a critical scaling parametrized by a≥0, which creates a shock in the particle density of order aT−1/3, T the observation time. When starting from step initial data, we provide bounds on the limiting law which in particular imply that in the double limit lima→∞limT→∞ one recovers the product limit law and the degeneration of the correlation length observed at shocks of order 1. This result is shown to apply to a general last-passage percolation model. We also obtain bounds on the two-point functions of several airy processes. AU - Nejjar, Peter ID - 70 IS - 2 JF - Latin American Journal of Probability and Mathematical Statistics SN - 1980-0436 TI - Transition to shocks in TASEP and decoupling of last passage times VL - 15 ER - TY - JOUR AB - Recent realization of a kinetically constrained chain of Rydberg atoms by Bernien et al., [Nature (London) 551, 579 (2017)] resulted in the observation of unusual revivals in the many-body quantum dynamics. In our previous work [C. J. Turner et al., Nat. Phys. 14, 745 (2018)], such dynamics was attributed to the existence of “quantum scarred” eigenstates in the many-body spectrum of the experimentally realized model. Here, we present a detailed study of the eigenstate properties of the same model. We find that the majority of the eigenstates exhibit anomalous thermalization: the observable expectation values converge to their Gibbs ensemble values, but parametrically slower compared to the predictions of the eigenstate thermalization hypothesis (ETH). Amidst the thermalizing spectrum, we identify nonergodic eigenstates that strongly violate the ETH, whose number grows polynomially with system size. Previously, the same eigenstates were identified via large overlaps with certain product states, and were used to explain the revivals observed in experiment. Here, we find that these eigenstates, in addition to highly atypical expectation values of local observables, also exhibit subthermal entanglement entropy that scales logarithmically with the system size. Moreover, we identify an additional class of quantum scarred eigenstates, and discuss their manifestations in the dynamics starting from initial product states. We use forward scattering approximation to describe the structure and physical properties of quantum scarred eigenstates. Finally, we discuss the stability of quantum scars to various perturbations. We observe that quantum scars remain robust when the introduced perturbation is compatible with the forward scattering approximation. In contrast, the perturbations which most efficiently destroy quantum scars also lead to the restoration of “canonical” thermalization. AU - Turner, C J AU - Michailidis, Alexios AU - Abanin, D A AU - Serbyn, Maksym AU - Papić, Z ID - 44 IS - 15 JF - Physical Review B TI - Quantum scarred eigenstates in a Rydberg atom chain: Entanglement, breakdown of thermalization, and stability to perturbations VL - 98 ER - TY - JOUR AB - The drag of turbulent flows can be drastically decreased by adding small amounts of high molecular weight polymers. While drag reduction initially increases with polymer concentration, it eventually saturates to what is known as the maximum drag reduction (MDR) asymptote; this asymptote is generally attributed to the dynamics being reduced to a marginal yet persistent state of subdued turbulent motion. Contrary to this accepted view, we show that, for an appropriate choice of parameters, polymers can reduce the drag beyond the suggested asymptotic limit, eliminating turbulence and giving way to laminar flow. At higher polymer concentrations, however, the laminar state becomes unstable, resulting in a fluctuating flow with the characteristic drag of the MDR asymptote. Our findings indicate that the asymptotic state is hence dynamically disconnected from ordinary turbulence. © 2018 American Physical Society. AU - Choueiri, George H AU - Lopez Alonso, Jose M AU - Hof, Björn ID - 328 IS - 12 JF - Physical Review Letters TI - Exceeding the asymptotic limit of polymer drag reduction VL - 120 ER - TY - JOUR AB - Recent studies suggest that unstable, nonchaotic solutions of the Navier-Stokes equation may provide deep insights into fluid turbulence. In this article, we present a combined experimental and numerical study exploring the dynamical role of unstable equilibrium solutions and their invariant manifolds in a weakly turbulent, electromagnetically driven, shallow fluid layer. Identifying instants when turbulent evolution slows down, we compute 31 unstable equilibria of a realistic two-dimensional model of the flow. We establish the dynamical relevance of these unstable equilibria by showing that they are closely visited by the turbulent flow. We also establish the dynamical relevance of unstable manifolds by verifying that they are shadowed by turbulent trajectories departing from the neighborhoods of unstable equilibria over large distances in state space. AU - Suri, Balachandra AU - Tithof, Jeffrey AU - Grigoriev, Roman AU - Schatz, Michael ID - 136 IS - 2 JF - Physical Review E TI - Unstable equilibria and invariant manifolds in quasi-two-dimensional Kolmogorov-like flow VL - 98 ER - TY - JOUR AB - Background: Transport protein particle (TRAPP) is a multisubunit complex that regulates membrane trafficking through the Golgi apparatus. The clinical phenotype associated with mutations in various TRAPP subunits has allowed elucidation of their functions in specific tissues. The role of some subunits in human disease, however, has not been fully established, and their functions remain uncertain. Objective: We aimed to expand the range of neurodevelopmental disorders associated with mutations in TRAPP subunits by exome sequencing of consanguineous families. Methods: Linkage and homozygosity mapping and candidate gene analysis were used to identify homozygous mutations in families. Patient fibroblasts were used to study splicing defect and zebrafish to model the disease. Results: We identified six individuals from three unrelated families with a founder homozygous splice mutation in TRAPPC6B, encoding a core subunit of the complex TRAPP I. Patients manifested a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features, and showed splicing defect. Zebrafish trappc6b morphants replicated the human phenotype, displaying decreased head size and neuronal hyperexcitability, leading to a lower seizure threshold. Conclusion: This study provides clinical and functional evidence of the role of TRAPPC6B in brain development and function. AU - Marin Valencia, Isaac AU - Novarino, Gaia AU - Johansen, Anide AU - Rosti, Başak AU - Issa, Mahmoud AU - Musaev, Damir AU - Bhat, Gifty AU - Scott, Eric AU - Silhavy, Jennifer AU - Stanley, Valentina AU - Rosti, Rasim AU - Gleeson, Jeremy AU - Imam, Farhad AU - Zaki, Maha AU - Gleeson, Joseph ID - 691 IS - 1 JF - Journal of Medical Genetics SN - 0022-2593 TI - A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features VL - 55 ER - TY - JOUR AB - Borel probability measures living on metric spaces are fundamental mathematical objects. There are several meaningful distance functions that make the collection of the probability measures living on a certain space a metric space. We are interested in the description of the structure of the isometries of such metric spaces. We overview some of the recent results of the topic and we also provide some new ones concerning the Wasserstein distance. More specifically, we consider the space of all Borel probability measures on the unit sphere of a Euclidean space endowed with the Wasserstein metric W_p for arbitrary p >= 1, and we show that the action of a Wasserstein isometry on the set of Dirac measures is induced by an isometry of the underlying unit sphere. AU - Virosztek, Daniel ID - 284 IS - 1-2 JF - Acta Scientiarum Mathematicarum SN - 0001-6969 TI - Maps on probability measures preserving certain distances - a survey and some new results VL - 84 ER - TY - JOUR AB - In this paper we define and study the classical Uniform Electron Gas (UEG), a system of infinitely many electrons whose density is constant everywhere in space. The UEG is defined differently from Jellium, which has a positive constant background but no constraint on the density. We prove that the UEG arises in Density Functional Theory in the limit of a slowly varying density, minimizing the indirect Coulomb energy. We also construct the quantum UEG and compare it to the classical UEG at low density. AU - Lewi, Mathieu AU - Lieb, Élliott AU - Seiringer, Robert ID - 180 JF - Journal de l'Ecole Polytechnique - Mathematiques SN - 2429-7100 TI - Statistical mechanics of the uniform electron gas VL - 5 ER - TY - JOUR AB - For ultrafast fixation of biological samples to avoid artifacts, high-pressure freezing (HPF) followed by freeze substitution (FS) is preferred over chemical fixation at room temperature. After HPF, samples are maintained at low temperature during dehydration and fixation, while avoiding damaging recrystallization. This is a notoriously slow process. McDonald and Webb demonstrated, in 2011, that sample agitation during FS dramatically reduces the necessary time. Then, in 2015, we (H.G. and S.R.) introduced an agitation module into the cryochamber of an automated FS unit and demonstrated that the preparation of algae could be shortened from days to a couple of hours. We argued that variability in the processing, reproducibility, and safety issues are better addressed using automated FS units. For dissemination, we started low-cost manufacturing of agitation modules for two of the most widely used FS units, the Automatic Freeze Substitution Systems, AFS(1) and AFS2, from Leica Microsystems, using three dimensional (3D)-printing of the major components. To test them, several labs independently used the modules on a wide variety of specimens that had previously been processed by manual agitation, or without agitation. We demonstrate that automated processing with sample agitation saves time, increases flexibility with respect to sample requirements and protocols, and produces data of at least as good quality as other approaches. AU - Reipert, Siegfried AU - Goldammer, Helmuth AU - Richardson, Christine AU - Goldberg, Martin AU - Hawkins, Timothy AU - Hollergschwandtner, Elena AU - Kaufmann, Walter AU - Antreich, Sebastian AU - Stierhof, York ID - 163 IS - 12 JF - Journal of Histochemistry and Cytochemistry SN - 0022-1554 TI - Agitation modules: Flexible means to accelerate automated freeze substitution VL - 66 ER -