TY - CONF AB - For deterministic systems, a counterexample to a property can simply be an error trace, whereas counterexamples in probabilistic systems are necessarily more complex. For instance, a set of erroneous traces with a sufficient cumulative probability mass can be used. Since these are too large objects to understand and manipulate, compact representations such as subchains have been considered. In the case of probabilistic systems with non-determinism, the situation is even more complex. While a subchain for a given strategy (or scheduler, resolving non-determinism) is a straightforward choice, we take a different approach. Instead, we focus on the strategy itself, and extract the most important decisions it makes, and present its succinct representation. The key tools we employ to achieve this are (1) introducing a concept of importance of a state w.r.t. the strategy, and (2) learning using decision trees. There are three main consequent advantages of our approach. Firstly, it exploits the quantitative information on states, stressing the more important decisions. Secondly, it leads to a greater variability and degree of freedom in representing the strategies. Thirdly, the representation uses a self-explanatory data structure. In summary, our approach produces more succinct and more explainable strategies, as opposed to e.g. binary decision diagrams. Finally, our experimental results show that we can extract several rules describing the strategy even for very large systems that do not fit in memory, and based on the rules explain the erroneous behaviour. AU - Brázdil, Tomáš AU - Chatterjee, Krishnendu AU - Chmelik, Martin AU - Fellner, Andreas AU - Kretinsky, Jan ID - 1603 TI - Counterexample explanation by learning small strategies in Markov decision processes VL - 9206 ER - TY - DATA AB - This repository contains the experimental part of the CAV 2015 publication Counterexample Explanation by Learning Small Strategies in Markov Decision Processes. We extended the probabilistic model checker PRISM to represent strategies of Markov Decision Processes as Decision Trees. The archive contains a java executable version of the extended tool (prism_dectree.jar) together with a few examples of the PRISM benchmark library. To execute the program, please have a look at the README.txt, which provides instructions and further information on the archive. The archive contains scripts that (if run often enough) reproduces the data presented in the publication. AU - Fellner, Andreas ID - 5549 KW - Markov Decision Process KW - Decision Tree KW - Probabilistic Verification KW - Counterexample Explanation TI - Experimental part of CAV 2015 publication: Counterexample Explanation by Learning Small Strategies in Markov Decision Processes ER - TY - CONF AB - We show that very weak topological assumptions are enough to ensure the existence of a Helly-type theorem. More precisely, we show that for any non-negative integers b and d there exists an integer h(b,d) such that the following holds. If F is a finite family of subsets of R^d such that the ith reduced Betti number (with Z_2 coefficients in singular homology) of the intersection of any proper subfamily G of F is at most b for every non-negative integer i less or equal to (d-1)/2, then F has Helly number at most h(b,d). These topological conditions are sharp: not controlling any of these first Betti numbers allow for families with unbounded Helly number. Our proofs combine homological non-embeddability results with a Ramsey-based approach to build, given an arbitrary simplicial complex K, some well-behaved chain map from C_*(K) to C_*(R^d). Both techniques are of independent interest. AU - Goaoc, Xavier AU - Paták, Pavel AU - Patakova, Zuzana AU - Tancer, Martin AU - Wagner, Uli ID - 1512 TI - Bounding Helly numbers via Betti numbers VL - 34 ER - TY - JOUR AB - We show that a non-singular integral form of degree d is soluble non-trivially over the integers if and only if it is soluble non-trivially over the reals and the p-adic numbers, provided that the form has at least (d-\sqrt{d}/2)2^d variables. This improves on a longstanding result of Birch. AU - Browning, Timothy D AU - Prendiville, Sean ID - 271 IS - 731 JF - Journal fur die Reine und Angewandte Mathematik SN - 0075-4102 TI - Improvements in Birch's theorem on forms in many variables VL - 2017 ER - TY - CONF AB - Proofs of work (PoW) have been suggested by Dwork and Naor (Crypto’92) as protection to a shared resource. The basic idea is to ask the service requestor to dedicate some non-trivial amount of computational work to every request. The original applications included prevention of spam and protection against denial of service attacks. More recently, PoWs have been used to prevent double spending in the Bitcoin digital currency system. In this work, we put forward an alternative concept for PoWs - so-called proofs of space (PoS), where a service requestor must dedicate a significant amount of disk space as opposed to computation. We construct secure PoS schemes in the random oracle model (with one additional mild assumption required for the proof to go through), using graphs with high “pebbling complexity” and Merkle hash-trees. We discuss some applications, including follow-up work where a decentralized digital currency scheme called Spacecoin is constructed that uses PoS (instead of wasteful PoW like in Bitcoin) to prevent double spending. The main technical contribution of this work is the construction of (directed, loop-free) graphs on N vertices with in-degree O(log logN) such that even if one places Θ(N) pebbles on the nodes of the graph, there’s a constant fraction of nodes that needs Θ(N) steps to be pebbled (where in every step one can put a pebble on a node if all its parents have a pebble). AU - Dziembowski, Stefan AU - Faust, Sebastian AU - Kolmogorov, Vladimir AU - Pietrzak, Krzysztof Z ID - 1675 SN - 0302-9743 T2 - 35th Annual Cryptology Conference TI - Proofs of space VL - 9216 ER - TY - JOUR AB - The circadian clock orchestrates global changes in transcriptional regulation on a daily basis via the bHLH-PAS transcription factor CLOCK:BMAL1. Pathways driven by other bHLH-PAS transcription factors have a homologous repressor that modulates activity on a tissue-specific basis, but none have been identified for CLOCK:BMAL1. We show here that the cancer/testis antigen PASD1 fulfills this role to suppress circadian rhythms. PASD1 is evolutionarily related to CLOCK and interacts with the CLOCK:BMAL1 complex to repress transcriptional activation. Expression of PASD1 is restricted to germline tissues in healthy individuals but can be induced in cells of somatic origin upon oncogenic transformation. Reducing PASD1 in human cancer cells significantly increases the amplitude of transcriptional oscillations to generate more robust circadian rhythms. Our results describe a function for a germline-specific protein in regulation of the circadian clock and provide a molecular link from oncogenic transformation to suppression of circadian rhythms. AU - Michael, Alicia Kathleen AU - Harvey, Stacy L. AU - Sammons, Patrick J. AU - Anderson, Amanda P. AU - Kopalle, Hema M. AU - Banham, Alison H. AU - Partch, Carrie L. ID - 15160 IS - 5 JF - Molecular Cell KW - Cell Biology KW - Molecular Biology SN - 1097-2765 TI - Cancer/Testis antigen PASD1 silences the circadian clock VL - 58 ER - TY - JOUR AB - It is widely recognized that BMAL1 is an essential subunit of the primary transcription factor that drives rhythmic circadian transcription in the nucleus. In a surprising turn, Lipton et al. now show that BMAL1 rhythmically interacts with translational machinery in the cytosol to stimulate protein synthesis in response to mTOR signaling. AU - Michael, Alicia Kathleen AU - Asimgil, Hande AU - Partch, Carrie L. ID - 15159 IS - 9 JF - Trends in Biochemical Sciences KW - Molecular Biology KW - Biochemistry SN - 0968-0004 TI - Cytosolic BMAL1 moonlights as a translation factor VL - 40 ER - TY - JOUR AB - The emergence of drug resistant pathogens is a serious public health problem. It is a long-standing goal to predict rates of resistance evolution and design optimal treatment strategies accordingly. To this end, it is crucial to reveal the underlying causes of drug-specific differences in the evolutionary dynamics leading to resistance. However, it remains largely unknown why the rates of resistance evolution via spontaneous mutations and the diversity of mutational paths vary substantially between drugs. Here we comprehensively quantify the distribution of fitness effects (DFE) of mutations, a key determinant of evolutionary dynamics, in the presence of eight antibiotics representing the main modes of action. Using precise high-throughput fitness measurements for genome-wide Escherichia coli gene deletion strains, we find that the width of the DFE varies dramatically between antibiotics and, contrary to conventional wisdom, for some drugs the DFE width is lower than in the absence of stress. We show that this previously underappreciated divergence in DFE width among antibiotics is largely caused by their distinct drug-specific dose-response characteristics. Unlike the DFE, the magnitude of the changes in tolerated drug concentration resulting from genome-wide mutations is similar for most drugs but exceptionally small for the antibiotic nitrofurantoin, i.e., mutations generally have considerably smaller resistance effects for nitrofurantoin than for other drugs. A population genetics model predicts that resistance evolution for drugs with this property is severely limited and confined to reproducible mutational paths. We tested this prediction in laboratory evolution experiments using the “morbidostat”, a device for evolving bacteria in well-controlled drug environments. Nitrofurantoin resistance indeed evolved extremely slowly via reproducible mutations—an almost paradoxical behavior since this drug causes DNA damage and increases the mutation rate. Overall, we identified novel quantitative characteristics of the evolutionary landscape that provide the conceptual foundation for predicting the dynamics of drug resistance evolution. AU - Chevereau, Guillaume AU - Dravecka, Marta AU - Batur, Tugce AU - Guvenek, Aysegul AU - Ayhan, Dilay AU - Toprak, Erdal AU - Bollenbach, Mark Tobias ID - 1619 IS - 11 JF - PLoS Biology TI - Quantifying the determinants of evolutionary dynamics leading to drug resistance VL - 13 ER - TY - JOUR AB - Protein oligomers have been implicated as toxic agents in a wide range of amyloid-related diseases. However, it has remained unsolved whether the oligomers are a necessary step in the formation of amyloid fibrils or just a dangerous byproduct. Analogously, it has not been resolved if the amyloid nucleation process is a classical one-step nucleation process or a two-step process involving prenucleation clusters. We use coarse-grained computer simulations to study the effect of nonspecific attractions between peptides on the primary nucleation process underlying amyloid fibrillization. We find that, for peptides that do not attract, the classical one-step nucleation mechanism is possible but only at nonphysiologically high peptide concentrations. At low peptide concentrations, which mimic the physiologically relevant regime, attractive interpeptide interactions are essential for fibril formation. Nucleation then inevitably takes place through a two-step mechanism involving prefibrillar oligomers. We show that oligomers not only help peptides meet each other but also, create an environment that facilitates the conversion of monomers into the β-sheet–rich form characteristic of fibrils. Nucleation typically does not proceed through the most prevalent oligomers but through an oligomer size that is only observed in rare fluctuations, which is why such aggregates might be hard to capture experimentally. Finally, we find that the nucleation of amyloid fibrils cannot be described by classical nucleation theory: in the two-step mechanism, the critical nucleus size increases with increases in both concentration and interpeptide interactions, which is in direct contrast with predictions from classical nucleation theory. AU - Šarić, Anđela AU - Chebaro, Yassmine C. AU - Knowles, Tuomas P. J. AU - Frenkel, Daan ID - 10382 IS - 50 JF - Proceedings of the National Academy of Sciences KW - multidisciplinary SN - 0027-8424 TI - Crucial role of nonspecific interactions in amyloid nucleation VL - 111 ER - TY - JOUR AB - We use numerical simulations to compute the equation of state of a suspension of spherical self-propelled nanoparticles in two and three dimensions. We study in detail the effect of excluded volume interactions and confinement as a function of the system's temperature, concentration, and strength of the propulsion. We find a striking nonmonotonic dependence of the pressure on the temperature and provide simple scaling arguments to predict and explain the occurrence of such anomalous behavior. We explicitly show how our results have important implications for the effective forces on passive components suspended in a bath of active particles. AU - Mallory, S. A. AU - Šarić, Anđela AU - Valeriani, C. AU - Cacciuto, A. ID - 10383 IS - 5 JF - Physical Review E SN - 1539-3755 TI - Anomalous thermomechanical properties of a self-propelled colloidal fluid VL - 89 ER - TY - JOUR AB - Diffraction-unlimited far-field super-resolution fluorescence (nanoscopy) methods typically rely on transiently transferring fluorophores between two states, whereby this transfer is usually laid out as a switch. However, depending on whether this is induced in a spatially controlled manner using a pattern of light (coordinate-targeted) or stochastically on a single-molecule basis, specific requirements on the fluorophores are imposed. Therefore, the fluorophores are usually utilized just for one class of methods only. In this study we demonstrate that the reversibly switchable fluorescent protein Dreiklang enables live-cell recordings in both spatially controlled and stochastic modes. We show that the Dreiklang chromophore entails three different light-induced switching mechanisms, namely a reversible photochemical one, off-switching by stimulated emission, and a reversible transfer to a long-lived dark state from the S1 state, all of which can be utilized to overcome the diffraction barrier. We also find that for the single-molecule- based stochastic GSDIM approach (ground-state depletion followed by individual molecule return), Dreiklang provides a larger number of on-off localization events as compared to its progenitor Citrine. Altogether, Dreiklang is a versatile probe for essentially all popular forms of live-cell fluorescence nanoscopy. AU - Jensen, Nickels AU - Danzl, Johann G AU - Willig, Katrin AU - Lavoie Cardinal, Flavie AU - Brakemann, Tanja AU - Hell, Stefan AU - Jakobs, Stefan ID - 1058 IS - 4 JF - ChemPhysChem TI - Coordinate-targeted and coordinate-stochastic super-resolution microscopy with the reversibly switchable fluorescent protein dreiklang VL - 15 ER - TY - JOUR AB - In the last several decades, developmental biology has clarified the molecular mechanisms of embryogenesis and organogenesis. In particular, it has demonstrated that the “tool-kit genes” essential for regulating developmental processes are not only highly conserved among species, but are also used as systems at various times and places in an organism to control distinct developmental events. Therefore, mutations in many of these tool-kit genes may cause congenital diseases involving morphological abnormalities. This link between genes and abnormal morphological phenotypes underscores the importance of understanding how cells behave and contribute to morphogenesis as a result of gene function. Recent improvements in live imaging and in quantitative analyses of cellular dynamics will advance our understanding of the cellular pathogenesis of congenital diseases associated with aberrant morphologies. In these studies, it is critical to select an appropriate model organism for the particular phenomenon of interest. AU - Hashimoto, Masakazu AU - Morita, Hitoshi AU - Ueno, Naoto ID - 10815 IS - 1 JF - Congenital Anomalies KW - Developmental Biology KW - Embryology KW - General Medicine KW - Pediatrics KW - Perinatology KW - and Child Health SN - 0914-3505 TI - Molecular and cellular mechanisms of development underlying congenital diseases VL - 54 ER - TY - BOOK AB - Auxin is an important signaling compound in plants and vital for plant development and growth. The present book, Auxin and its Role in Plant Development, provides the reader with detailed and comprehensive insight into the functioning of the molecule on the whole and specifically in plant development. In the first part, the functioning, metabolism and signaling pathways of auxin in plants are explained, the second part depicts the specific role of auxin in plant development and the third part describes the interaction and functioning of the signaling compound upon stimuli of the environment. Each chapter is written by international experts in the respective field and designed for scientists and researchers in plant biology, plant development and cell biology to summarize the recent progress in understanding the role of auxin and suggest future perspectives for auxin research. ED - Zažímalová, Eva ED - Petrášek, Jan ED - Benková, Eva ID - 10811 SN - 9783709115251 TI - Auxin and Its Role in Plant Development ER - TY - CONF AB - We revisit the parameterized model checking problem for token-passing systems and specifications in indexed CTL  ∗ \X. Emerson and Namjoshi (1995, 2003) have shown that parameterized model checking of indexed CTL  ∗ \X in uni-directional token rings can be reduced to checking rings up to some cutoff size. Clarke et al. (2004) have shown a similar result for general topologies and indexed LTL \X, provided processes cannot choose the directions for sending or receiving the token. We unify and substantially extend these results by systematically exploring fragments of indexed CTL  ∗ \X with respect to general topologies. For each fragment we establish whether a cutoff exists, and for some concrete topologies, such as rings, cliques and stars, we infer small cutoffs. Finally, we show that the problem becomes undecidable, and thus no cutoffs exist, if processes are allowed to choose the directions in which they send or from which they receive the token. AU - Aminof, Benjamin AU - Jacobs, Swen AU - Khalimov, Ayrat AU - Rubin, Sasha ID - 10884 SN - 0302-9743 T2 - Verification, Model Checking, and Abstract Interpretation TI - Parameterized model checking of token-passing systems VL - 8318 ER - TY - CHAP AB - Saddle periodic orbits are an essential and stable part of the topological skeleton of a 3D vector field. Nevertheless, there is currently no efficient algorithm to robustly extract these features. In this chapter, we present a novel technique to extract saddle periodic orbits. Exploiting the analytic properties of such an orbit, we propose a scalar measure based on the finite-time Lyapunov exponent (FTLE) that indicates its presence. Using persistent homology, we can then extract the robust cycles of this field. These cycles thereby represent the saddle periodic orbits of the given vector field. We discuss the different existing FTLE approximation schemes regarding their applicability to this specific problem and propose an adapted version of FTLE called Normalized Velocity Separation. Finally, we evaluate our method using simple analytic vector field data. AU - Kasten, Jens AU - Reininghaus, Jan AU - Reich, Wieland AU - Scheuermann, Gerik ED - Bremer, Peer-Timo ED - Hotz, Ingrid ED - Pascucci, Valerio ED - Peikert, Ronald ID - 10893 SN - 1612-3786 T2 - Topological Methods in Data Analysis and Visualization III TI - Toward the extraction of saddle periodic orbits VL - 1 ER - TY - JOUR AB - The spindle assembly checkpoint prevents separation of sister chromatids until each kinetochore is attached to the mitotic spindle. Rodriguez-Bravo et al. report that the nuclear pore complex scaffolds spindle assembly checkpoint signaling in interphase, providing a store of inhibitory signals that limits the speed of the subsequent mitosis. AU - Buchwalter, Abigail AU - HETZER, Martin W ID - 11080 IS - 5 JF - Cell KW - General Biochemistry KW - Genetics and Molecular Biology SN - 0092-8674 TI - Nuclear pores set the speed limit for mitosis VL - 156 ER - TY - JOUR AB - The nuclear pore complex (NPC) plays a critical role in gene expression by mediating import of transcription regulators into the nucleus and export of RNA transcripts to the cytoplasm. Emerging evidence suggests that in addition to mediating transport, a subset of nucleoporins (Nups) engage in transcriptional activation and elongation at genomic loci that are not associated with NPCs. The underlying mechanism and regulation of Nup mobility on and off nuclear pores remain unclear. Here we show that Nup50 is a mobile Nup with a pronounced presence both at the NPC and in the nucleoplasm that can move between these different localizations. Strikingly, the dynamic behavior of Nup50 in both locations is dependent on active transcription by RNA polymerase II and requires the N-terminal half of the protein, which contains importin α– and Nup153-binding domains. However, Nup50 dynamics are independent of importin α, Nup153, and Nup98, even though the latter two proteins also exhibit transcription-dependent mobility. Of interest, depletion of Nup50 from C2C12 myoblasts does not affect cell proliferation but inhibits differentiation into myotubes. Taken together, our results suggest a transport-independent role for Nup50 in chromatin biology that occurs away from the NPC. AU - Buchwalter, Abigail L. AU - Liang, Yun AU - HETZER, Martin W ID - 11082 IS - 16 JF - Molecular Biology of the Cell KW - Cell Biology KW - Molecular Biology SN - 1059-1524 TI - Nup50 is required for cell differentiation and exhibits transcription-dependent dynamics VL - 25 ER - TY - JOUR AB - In eukaryotic cells the nuclear genome is enclosed by the nuclear envelope (NE). In metazoans, the NE breaks down in mitosis and it has been assumed that the physical barrier separating nucleoplasm and cytoplasm remains intact during the rest of the cell cycle and cell differentiation. However, recent studies suggest that nonmitotic NE remodeling plays a critical role in development, virus infection, laminopathies, and cancer. Although the mechanisms underlying these NE restructuring events are currently being defined, one common theme is activation of protein kinase C family members in the interphase nucleus to disrupt the nuclear lamina, demonstrating the importance of the lamina in maintaining nuclear integrity. AU - Hatch, Emily AU - HETZER, Martin W ID - 11081 IS - 2 JF - Journal of Cell Biology KW - Cell Biology SN - 1540-8140 TI - Breaching the nuclear envelope in development and disease VL - 205 ER - TY - JOUR AB - Candidate galaxies at redshifts of z ∼ 10 are now being found in extremely deep surveys, probing very small areas. As a consequence, candidates are very faint, making spectroscopic confirmation practically impossible. In order to overcome such limitations, we have undertaken the CF-HiZELS survey, which is a large-area, medium-depth near-infrared narrow-band survey targeted at z = 8.8 Lyman α (Lyα) emitters (LAEs) and covering 10 deg2 in part of the SSA22 field with the Canada–France–Hawaii Telescope (CFHT). We surveyed a comoving volume of 4.7 × 106 Mpc3 to a Lyα luminosity limit of 6.3 × 1043舁erg舁s−1. We look for Lyα candidates by applying the following criteria: (i) clear emission-line source, (ii) no optical detections (ugriz from CFHTLS), (iii) no visible detection in the optical stack (ugriz > 27), (iv) visually checked reliable NBJ and J detections and (v) J − K ≤ 0. We compute photometric redshifts and remove a significant amount of dusty lower redshift line-emitters at z ∼ 1.4 or 2.2. A total of 13 Lyα candidates were found, of which two are marked as strong candidates, but the majority have very weak constraints on their spectral energy distributions. Using follow-up observations with SINFONI/VLT, we are able to exclude the most robust candidates as LAEs. We put a strong constraint on the Lyα luminosity function at z ∼ 9 and make realistic predictions for ongoing and future surveys. Our results show that surveys for the highest redshift LAEs are susceptible of multiple contaminations and that spectroscopic follow-up is absolutely necessary. AU - Matthee, Jorryt J AU - Sobral, David AU - Swinbank, A. M. AU - Smail, Ian AU - Best, P. N. AU - Kim, Jae-Woo AU - Franx, Marijn AU - Milvang-Jensen, Bo AU - Fynbo, Johan ID - 11583 IS - 3 JF - Monthly Notices of the Royal Astronomical Society KW - Space and Planetary Science KW - Astronomy and Astrophysics KW - galaxies: evolution KW - galaxies: high-redshift KW - cosmology: observations KW - dark ages KW - reionization KW - first stars SN - 0035-8711 TI - A 10 deg2 Lyman α survey at z=8.8 with spectroscopic follow-up: Strong constraints on the luminosity function and implications for other surveys VL - 440 ER - TY - JOUR AB - We have observed a sample of typical z ∼ 1 star-forming galaxies, selected from the HiZELS survey, with the new K-band Multi-Object Spectrograph (KMOS) near-infrared, multi-integral field unit instrument on the Very Large Telescope (VLT), in order to obtain their dynamics and metallicity gradients. The majority of our galaxies have a metallicity gradient consistent with being flat or negative (i.e. higher metallicity cores than outskirts). Intriguingly, we find a trend between metallicity gradient and specific star formation rate (sSFR), such that galaxies with a high sSFR tend to have relatively metal poor centres, a result which is strengthened when combined with data sets from the literature. This result appears to explain the discrepancies reported between different high-redshift studies and varying claims for evolution. From a galaxy evolution perspective, the trend we see would mean that a galaxy's sSFR is governed by the amount of metal-poor gas that can be funnelled into its core, triggered either by merging or through efficient accretion. In fact, merging may play a significant role as it is the starburst galaxies at all epochs, which have the more positive metallicity gradients. Our results may help to explain the origin of the fundamental metallicity relation, in which galaxies at a fixed mass are observed to have lower metallicities at higher star formation rates, especially if the metallicity is measured in an aperture encompassing only the central regions of the galaxy. Finally, we note that this study demonstrates the power of KMOS as an efficient instrument for large-scale resolved galaxy surveys. AU - Stott, John P. AU - Sobral, David AU - Swinbank, A. M. AU - Smail, Ian AU - Bower, Richard AU - Best, Philip N. AU - Sharples, Ray M. AU - Geach, James E. AU - Matthee, Jorryt J ID - 11582 IS - 3 JF - Monthly Notices of the Royal Astronomical Society KW - Space and Planetary Science KW - Astronomy and Astrophysics KW - galaxies: abundances KW - galaxies: evolution KW - galaxies: kinematics and dynamics SN - 0035-8711 TI - A relationship between specific star formation rate and metallicity gradient within z ∼ 1 galaxies from KMOS-HiZELS VL - 443 ER - TY - JOUR AB - We report on the magnetic properties of a hot-pressed FeSb 2 sample. We find a significant increase in the magnetic susceptibility in our sample when compared with the values previously reported for the polycrystalline sample. The pronounced Curie tail at low temperature corresponds to 0.2% of Fe 2+ impurities per mole. In the intrinsic conductivity region, the susceptibility due to free carriers shows thermally activated behavior and is consistent with the data reported for single crystal FeSb 2 . Based on our data and analysis, while the enhanced magnetic susceptibility in our sample comes mainly from a small amount of unreacted Fe, the contribution from the enhanced carrier density due to lattice and strain defects arising from the ball milling process is also significant. Existence of an unreacted Fe phase is evidenced by small coercivity values of ~100 observed at 50 and 300 K. AU - Pokharel, Mani AU - Zhao, Huaizhou AU - Modic, Kimberly A AU - Ren, Zhifeng AU - Opeil, Cyril ID - 11750 IS - 5 JF - IEEE Transactions on Magnetics SN - 0018-9464 TI - Magnetic properties of hot-pressed FeSb2 VL - 50 ER - TY - CONF AB - We study a weighted online bipartite matching problem: G(V 1, V 2, E) is a weighted bipartite graph where V 1 is known beforehand and the vertices of V 2 arrive online. The goal is to match vertices of V 2 as they arrive to vertices in V 1, so as to maximize the sum of weights of edges in the matching. If assignments to V 1 cannot be changed, no bounded competitive ratio is achievable. We study the weighted online matching problem with free disposal, where vertices in V 1 can be assigned multiple times, but only get credit for the maximum weight edge assigned to them over the course of the algorithm. For this problem, the greedy algorithm is 0.5-competitive and determining whether a better competitive ratio is achievable is a well known open problem. We identify an interesting special case where the edge weights are decomposable as the product of two factors, one corresponding to each end point of the edge. This is analogous to the well studied related machines model in the scheduling literature, although the objective functions are different. For this case of decomposable edge weights, we design a 0.5664 competitive randomized algorithm in complete bipartite graphs. We show that such instances with decomposable weights are non-trivial by establishing upper bounds of 0.618 for deterministic and 0.8 for randomized algorithms. A tight competitive ratio of 1 − 1/e ≈ 0.632 was known previously for both the 0-1 case as well as the case where edge weights depend on the offline vertices only, but for these cases, reassignments cannot change the quality of the solution. Beating 0.5 for weighted matching where reassignments are necessary has been a significant challenge. We thus give the first online algorithm with competitive ratio strictly better than 0.5 for a non-trivial case of weighted matching with free disposal. AU - Charikar, Moses AU - Henzinger, Monika H AU - Nguyễn, Huy L. ID - 11789 SN - 0302-9743 T2 - 22nd Annual European Symposium on Algorithms TI - Online bipartite matching with decomposable weights VL - 8737 ER - TY - CONF AB - Assume a seller wants to sell a digital product in a social network where a buyer’s valuation of the item has positive network externalities from her neighbors that already have the item. The goal of the seller is to maximize his revenue. Previous work on this problem [7] studies the case where clients are offered the item in sequence and have to pay personalized prices. This is highly infeasible in large scale networks such as the Facebook graph: (1) Offering items to the clients one after the other consumes a large amount of time, and (2) price-discrimination of clients could appear unfair to them and result in negative client reaction or could conflict with legal requirements. We study a setting dealing with these issues. Specifically, the item is offered in parallel to multiple clients at the same time and at the same price. This is called a round. We show that with O(logn) rounds, where n is the number of clients, a constant factor of the revenue with price discrimination can be achieved and that this is not possible with o(logn) rounds. Moreover we show that it is APX-hard to maximize the revenue and we give constant factor approximation algorithms for various further settings of limited price discrimination. AU - Cigler, Luděk AU - Dvořák, Wolfgang AU - Henzinger, Monika H AU - Starnberger, Martin ID - 11790 SN - 0302-9743 T2 - 10th International Conference of Web and Internet Economics TI - Limiting price discrimination when selling products with positive network externalities VL - 8877 ER - TY - JOUR AB - While the penetration of objects into granular media is well-studied, there is little understanding of how objects settle in gravities, geff, different from that of Earth - a scenario potentially relevant to the geomorphology of planets and asteroids and also to their exploration using man-made devices. By conducting experiments in an accelerating frame, we explore geff ranging from 0.4 g to 1.2 g. Surprisingly, we find that the rest depth is independent of geff and also that the time required for the object to come to rest scales like geff-1/2. With discrete element modeling simulations, we reproduce the experimental results and extend the range of geff to objects as small as asteroids and as large as Jupiter. Our results shed light on the initial stage of sedimentation into dry granular media across a range of celestial bodies and also have implications for the design of man-made, extraterrestrial vehicles and structures. Key Points The settling depth in granular media is independent of gravity The settling time scales like g-1/2 Layering driven by granular sedimentation should be similar. AU - Altshuler, Ernesto AU - Torres, H AU - González_Pita, A AU - Sánchez, Colina G AU - Pérez Penichet, Carlos AU - Waitukaitis, Scott R AU - Hidalgo, Rauól ID - 118 IS - 9 JF - Geophysical Research Letters TI - Settling into dry granular media in different gravities VL - 41 ER - TY - CONF AB - The decremental single-source shortest paths (SSSP) problem concerns maintaining the distances between a given source node s to every node in an n-node m-edge graph G undergoing edge deletions. While its static counterpart can be easily solved in near-linear time, this decremental problem is much more challenging even in the undirected unweighted case. In this case, the classic O(mn) total update time of Even and Shiloach (JACM 1981) has been the fastest known algorithm for three decades. With the loss of a (1 + ε)-approximation factor, the running time was recently improved to O(n 2+o(1) ) by Bernstein and Roditty (SODA 2011), and more recently to O(n 1.8+o(1) + m 1+o(1) ) by Henzinger, Krinninger, and Nanongkai (SODA 2014). In this paper, we finally bring the running time of this case down to near-linear: We give a (1 + ε)-approximation algorithm with O(m 1+o(1) ) total update time, thus obtaining near-linear time. Moreover, we obtain O(m 1+o(1) log W) time for the weighted case, where the edge weights are integers from 1 to W. The only prior work on weighted graphs in o(mn log W) time is the O(mn 0.986 log W)-time algorithm by Henzinger, Krinninger, and Nanongkai (STOC 2014) which works for the general weighted directed case. In contrast to the previous results which rely on maintaining a sparse emulator, our algorithm relies on maintaining a so-called sparse (d, ε)-hop set introduced by Cohen (JACM 2000) in the PRAM literature. A (d, ε)-hop set of a graph G = (V, E) is a set E' of weighted edges such that the distance between any pair of nodes in G can be (1 + ε)-approximated by their d-hop distance (given by a path containing at most d edges) on G'=(V, E∪E'). Our algorithm can maintain an (n o(1) , ε)-hop set of near-linear size in near-linear time under edge deletions. It is the first of its kind to the best of our knowledge. To maintain the distances on this hop set, we develop a monotone bounded-hop Even-Shiloach tree. It results from extending and combining the monotone Even-Shiloach tree of Henzinger, Krinninger, and Nanongkai (FOCS 2013) with the bounded-hop SSSP technique of Bernstein (STOC 2013). These two new tools might be of independent interest. AU - Henzinger, Monika H AU - Krinninger, Sebastian AU - Nanongkai, Danupon ID - 11855 SN - 0272-5428 T2 - 55th Annual Symposium on Foundations of Computer Science TI - Decremental single-source shortest paths on undirected graphs in near-linear total update time ER - TY - CONF AB - We consider dynamic algorithms for maintaining Single-Source Reachability (SSR) and approximate Single-Source Shortest Paths (SSSP) on n-node m-edge directed graphs under edge deletions (decremental algorithms). The previous fastest algorithm for SSR and SSSP goes back three decades to Even and Shiloach (JACM 1981); it has O(1) query time and O(mn) total update time (i.e., linear amortized update time if all edges are deleted). This algorithm serves as a building block for several other dynamic algorithms. The question whether its total update time can be improved is a major, long standing, open problem. In this paper, we answer this question affirmatively. We obtain a randomized algorithm which, in a simplified form, achieves an Õ(mn0.984) expected total update time for SSR and (1 + ε)-approximate SSSP, where Õ(·) hides poly log n. We also extend our algorithm to achieve roughly the same running time for Strongly Connected Components (SCC), improving the algorithm of Roditty and Zwick (FOCS 2002), and an algorithm that improves the Õ (mn log W)-time algorithm of Bernstein (STOC 2013) for approximating SSSP on weighted directed graphs, where the edge weights are integers from 1 to W. All our algorithms have constant query time in the worst case. AU - Henzinger, Monika H AU - Krinninger, Sebastian AU - Nanongkai, Danupon ID - 11870 SN - 0737-8017 T2 - 46th Annual ACM Symposium on Theory of Computing TI - Sublinear-time decremental algorithms for single-source reachability and shortest paths on directed graphs ER - TY - CONF AB - We study dynamic (1 + ∊)-approximation algorithms for the single-source shortest paths problem in an unweighted undirected n-node m-edge graph under edge deletions. The fastest algorithm for this problem is an algorithm with O(n2+o(1)) total update time and constant query time by Bernstein and Roditty (SODA 2011). In this paper, we improve the total update time to O(n1.8+o(1) + m1+o(1)) while keeping the query time constant. This running time is essentially tight when m = Ω(n1.8) since we need Ω(m) time even in the static setting. For smaller values of m, the running time of our algorithm is subquadratic, and is the first that breaks through the quadratic time barrier. In obtaining this result, we develop a fast algorithm for what we call center cover data structure. We also make non-trivial extensions to our previous techniques called lazy-update and monotone Even-Shiloach trees (ICALP 2013 and FOCS 2013). As by-products of our new techniques, we obtain two new results for the decremental all-pairs shortest-paths problem. Our first result is the first approximation algorithm whose total update time is faster than Õ(mn) for all values of m. Our second result is a new trade-off between the total update time and the additive approximation guarantee. AU - Henzinger, Monika H AU - Krinninger, Sebastian AU - Nanongkai, Danupon ID - 11876 SN - 978-1-61197-338-9 T2 - 25th Annual ACM-SIAM Symposium on Discrete Algorithms TI - A subquadratic-time algorithm for decremental single-source shortest paths ER - TY - CONF AB - We present the first deterministic data structures for maintaining approximate minimum vertex cover and maximum matching in a fully dynamic graph in time per update. In particular, for minimum vertex cover we provide deterministic data structures for maintaining a (2 + ε) approximation in O(log n/ε2) amortized time per update. For maximum matching, we show how to maintain a (3 + e) approximation in O(m1/3/ε2) amortized time per update, and a (4 + ε) approximation in O(m1/3/ε2) worst-case time per update. Our data structure for fully dynamic minimum vertex cover is essentially near-optimal and settles an open problem by Onak and Rubinfeld [13]. AU - Bhattacharya, Sayan AU - Henzinger, Monika H AU - Italiano, Giuseppe F. ID - 11875 SN - 978-1-61197-374-7 T2 - 26th Annual ACM-SIAM Symposium on Discrete Algorithms TI - Deterministic fully dynamic data structures for vertex cover and matching ER - TY - JOUR AB - Observations of flowing granular matter have suggested that same-material tribocharging depends on particle size, typically rendering large grains positive and small ones negative. Models assuming the transfer of trapped electrons can account for this trend, but have not been validated. Tracking individual grains in an electric field, we show quantitatively that charge is transferred based on size between materially identical grains. However, the surface density of trapped electrons, measured independently by thermoluminescence techniques, is orders of magnitude too small to account for the scale of charge transferred. This reveals that trapped electrons are not a necessary ingredient for same-material tribocharging. AU - Waitukaitis, Scott R AU - Lee, Victor AU - Pierson, James AU - Forman, Steven AU - Jaeger, Heinrich ID - 119 IS - 21 JF - APS Physics, Physical Review Letters TI - Size-dependent same-material tribocharging in insulating grains VL - 112 ER - TY - JOUR AB - Membrane phospholipids typically contain fatty acids (FAs) of 16 and 18 carbon atoms. This particular chain length is evolutionarily highly conserved and presumably provides maximum stability and dynamic properties to biological membranes in response to nutritional or environmental cues. Here, we show that the relative proportion of C16 versus C18 FAs is regulated by the activity of acetyl-CoA carboxylase (Acc1), the first and rate-limiting enzyme of FA de novo synthesis. Acc1 activity is attenuated by AMPK/Snf1-dependent phosphorylation, which is required to maintain an appropriate acyl-chain length distribution. Moreover, we find that the transcriptional repressor Opi1 preferentially binds to C16 over C18 phosphatidic acid (PA) species: thus, C16-chain containing PA sequesters Opi1 more effectively to the ER, enabling AMPK/Snf1 control of PA acyl-chain length to determine the degree of derepression of Opi1 target genes. These findings reveal an unexpected regulatory link between the major energy-sensing kinase, membrane lipid composition, and transcription. AU - Hofbauer, Harald F. AU - Schopf, Florian H. AU - Schleifer, Hannes AU - Knittelfelder, Oskar L. AU - Pieber, Bartholomäus AU - Rechberger, Gerald N. AU - Wolinski, Heimo AU - Gaspar, Maria L. AU - Kappe, C. Oliver AU - Stadlmann, Johannes AU - Mechtler, Karl AU - Zenz, Alexandra AU - Lohner, Karl AU - Tehlivets, Oksana AU - Henry, Susan A. AU - Kohlwein, Sepp D. ID - 11968 IS - 6 JF - Developmental Cell SN - 1534-5807 TI - Regulation of gene expression through a transcriptional repressor that senses acyl-chain length in membrane phospholipids VL - 29 ER - TY - JOUR AB - An experimentally easy to perform method for the generation of alumina-supported Fe3O4 nanoparticles [(6±1) nm size, 0.67 wt %]and the use of this material in hydrazine-mediated heterogeneously catalyzed reductions of nitroarenes to anilines under batch and continuous-flow conditions is presented. The bench-stable, reusable nano-Fe3O4@Al2O3 catalyst can selectively reduce functionalized nitroarenes at 1 mol % catalyst loading by using a 20 mol % excess of hydrazine hydrate in an elevated temperature regime (150 °C, reaction time 2–6 min in batch). For continuous-flow processing, the catalyst material is packed into dedicated cartridges and used in a commercially available high-temperature/-pressure flow device. In continuous mode, reaction times can be reduced to less than 1 min at 150 °C (30 bar back pressure) in a highly intensified process. The nano-Fe3O4@Al2O3 catalyst demonstrated stable reduction of nitrobenzene (0.5 M in MeOH) for more than 10 h on stream at a productivity of 30 mmol h−1 (0.72 mol per day). Importantly, virtually no leaching of the catalytically active material could be observed by inductively coupled plasma MS monitoring. AU - Moghaddam, Mojtaba Mirhosseini AU - Pieber, Bartholomäus AU - Glasnov, Toma AU - Kappe, C. Oliver ID - 11967 IS - 11 JF - ChemSusChem SN - 1864-5631 TI - Immobilized iron oxide nanoparticles as stable and reusable catalysts for hydrazine-mediated nitro reductions in continuous flow VL - 7 ER - TY - JOUR AB - A method for the direct lithiation of terminal alkynes and heterocycles with subsequent carboxylation in a continuous flow format was developed. This method provides carboxylic acids at ambient conditions within less than five seconds with only little excess of the organometallic base and CO2. AU - Pieber, Bartholomäus AU - Glasnov, Toma AU - Kappe, C. O. ID - 11987 IS - 26 JF - RSC Advances TI - Flash carboxylation: Fast lithiation–carboxylation sequence at room temperature in continuous flow VL - 4 ER - TY - JOUR AB - We show that weak solutions of the Derrida-Lebowitz-Speer-Spohn (DLSS) equation display infinite speed of support propagation. We apply our method to the case of the quantum drift-diffusion equation which augments the DLSS equation with a drift term and possibly a second-order diffusion term. The proof is accomplished using weighted entropy estimates, Hardy's inequality and a family of singular weight functions to derive a differential inequality; the differential inequality shows exponential growth of the weighted entropy, with the growth constant blowing up very fast as the singularity of the weight becomes sharper. To the best of our knowledge, this is the first example of a nonnegativity-preserving higher-order parabolic equation displaying infinite speed of support propagation. AU - Julian Fischer ID - 1309 IS - 1 JF - Nonlinear Differential Equations and Applications TI - Infinite speed of support propagation for the Derrida-Lebowitz-Speer-Spohn equation and quantum drift-diffusion models VL - 21 ER - TY - JOUR AB - We derive upper bounds on the waiting time of solutions to the thin-film equation in the regime of weak slippage n ∈ [2, 32\11). In particular, we give sufficient conditions on the initial data for instantaneous forward motion of the free boundary. For n ∈ (2, 32\11), our estimates are sharp, for n = 2, they are sharp up to a logarithmic correction term. Note that the case n = 2 corresponds-with a grain of salt-to the assumption of the Navier slip condition at the fluid-solid interface. We also obtain results in the regime of strong slippage n ∈ (1,2); however, in this regime we expect them not to be optimal. Our method is based on weighted backward entropy estimates, Hardy's inequality and singular weight functions; we deduce a differential inequality which would enforce blowup of the weighted entropy if the contact line were to remain stationary for too long. AU - Julian Fischer ID - 1312 IS - 3 JF - Archive for Rational Mechanics and Analysis TI - Upper bounds on waiting times for the Thin-film equation: The case of weak slippage VL - 211 ER - TY - JOUR AB - We consider directed graphs where each edge is labeled with an integer weight and study the fundamental algorithmic question of computing the value of a cycle with minimum mean weight. Our contributions are twofold: (1) First we show that the algorithmic question is reducible to the problem of a logarithmic number of min-plus matrix multiplications of n×n-matrices, where n is the number of vertices of the graph. (2) Second, when the weights are nonnegative, we present the first (1+ε)-approximation algorithm for the problem and the running time of our algorithm is Õ(nωlog3(nW/ε)/ε),1 where O(nω) is the time required for the classic n×n-matrix multiplication and W is the maximum value of the weights. With an additional O(log(nW/ε)) factor in space a cycle with approximately optimal weight can be computed within the same time bound. AU - Chatterjee, Krishnendu AU - Henzinger, Monika H AU - Krinninger, Sebastian AU - Loitzenbauer, Veronika AU - Raskin, Michael ID - 1375 IS - C JF - Theoretical Computer Science TI - Approximating the minimum cycle mean VL - 547 ER - TY - CONF AB - Fault-tolerant distributed algorithms play an important role in ensuring the reliability of many software applications. In this paper we consider distributed algorithms whose computations are organized in rounds. To verify the correctness of such algorithms, we reason about (i) properties (such as invariants) of the state, (ii) the transitions controlled by the algorithm, and (iii) the communication graph. We introduce a logic that addresses these points, and contains set comprehensions with cardinality constraints, function symbols to describe the local states of each process, and a limited form of quantifier alternation to express the verification conditions. We show its use in automating the verification of consensus algorithms. In particular, we give a semi-decision procedure for the unsatisfiability problem of the logic and identify a decidable fragment. We successfully applied our framework to verify the correctness of a variety of consensus algorithms tolerant to both benign faults (message loss, process crashes) and value faults (message corruption). AU - Dragoi, Cezara AU - Henzinger, Thomas A AU - Veith, Helmut AU - Widder, Josef AU - Zufferey, Damien ID - 1392 TI - A logic-based framework for verifying consensus algorithms VL - 8318 ER - TY - CONF AB - Probabilistic programs are usual functional or imperative programs with two added constructs: (1) the ability to draw values at random from distributions, and (2) the ability to condition values of variables in a program via observations. Models from diverse application areas such as computer vision, coding theory, cryptographic protocols, biology and reliability analysis can be written as probabilistic programs. Probabilistic inference is the problem of computing an explicit representation of the probability distribution implicitly specified by a probabilistic program. Depending on the application, the desired output from inference may vary-we may want to estimate the expected value of some function f with respect to the distribution, or the mode of the distribution, or simply a set of samples drawn from the distribution. In this paper, we describe connections this research area called \Probabilistic Programming" has with programming languages and software engineering, and this includes language design, and the static and dynamic analysis of programs. We survey current state of the art and speculate on promising directions for future research. AU - Gordon, Andrew AU - Henzinger, Thomas A AU - Nori, Aditya AU - Rajamani, Sriram ID - 1393 T2 - Proceedings of the on Future of Software Engineering TI - Probabilistic programming ER - TY - THES AB - The co-evolution of hosts and pathogens is characterized by continuous adaptations of both parties. Pathogens of social insects need to adapt towards disease defences at two levels: 1) individual immunity of each colony member consisting of behavioural defence strategies as well as humoral and cellular immune responses and 2) social immunity that is collectively performed by all group members comprising behavioural, physiological and organisational defence strategies. To disentangle the selection pressure on pathogens by the collective versus individual level of disease defence in social insects, we performed an evolution experiment using the Argentine Ant, Linepithema humile, as a host and a mixture of the general insect pathogenic fungus Metarhizium spp. (6 strains) as a pathogen. We allowed pathogen evolution over 10 serial host passages to two different evolution host treatments: (1) only individual host immunity in a single host treatment, and (2) simultaneously acting individual and social immunity in a social host treatment, in which an exposed ant was accompanied by two untreated nestmates. Before starting the pathogen evolution experiment, the 6 Metarhizium spp. strains were characterised concerning conidiospore size killing rates in singly and socially reared ants, their competitiveness under coinfecting conditions and their influence on ant behaviour. We analysed how the ancestral atrain mixture changed in conidiospere size, killing rate and strain composition dependent on host treatment (single or social hosts) during 10 passages and found that killing rate and conidiospere size of the pathogen increased under both evolution regimes, but different depending on host treatment. Testing the evolved strain mixtures that evolved under either the single or social host treatment under both single and social current rearing conditions in a full factorial design experiment revealed that the additional collective defences in insect societies add new selection pressure for their coevolving pathogens that compromise their ability to adapt to its host at the group level. To our knowledge, this is the first study directly measuring the influence of social immunity on pathogen evolution. AU - Stock, Miriam ID - 1404 TI - Evolution of a fungal pathogen towards individual versus social immunity in ants ER - TY - CONF AB - We present a rigorous derivation of the BCS gap equation for superfluid fermionic gases with point interactions. Our starting point is the BCS energy functional, whose minimizer we investigate in the limit when the range of the interaction potential goes to zero. AU - Bräunlich, Gerhard AU - Hainzl, Christian AU - Seiringer, Robert ID - 1516 T2 - Proceedings of the QMath12 Conference TI - On the BCS gap equation for superfluid fermionic gases ER - TY - JOUR AB - We propose a method for propagating edit operations in 2D vector graphics, based on geometric relationship functions. These functions quantify the geometric relationship of a point to a polygon, such as the distance to the boundary or the direction to the closest corner vertex. The level sets of the relationship functions describe points with the same relationship to a polygon. For a given query point, we first determine a set of relationships to local features, construct all level sets for these relationships, and accumulate them. The maxima of the resulting distribution are points with similar geometric relationships. We show extensions to handle mirror symmetries, and discuss the use of relationship functions as local coordinate systems. Our method can be applied, for example, to interactive floorplan editing, and it is especially useful for large layouts, where individual edits would be cumbersome. We demonstrate populating 2D layouts with tens to hundreds of objects by propagating relatively few edit operations. AU - Guerrero, Paul AU - Jeschke, Stefan AU - Wimmer, Michael AU - Wonka, Peter ID - 1629 IS - 2 JF - ACM Transactions on Graphics TI - Edit propagation using geometric relationship functions VL - 33 ER - TY - CONF AB - The Hanani–Tutte theorem is a classical result proved for the first time in the 1930s that characterizes planar graphs as graphs that admit a drawing in the plane in which every pair of edges not sharing a vertex cross an even number of times. We generalize this classical result to clustered graphs with two disjoint clusters, and show that a straightforward extension of our result to flat clustered graphs with three or more disjoint clusters is not possible. We also give a new and short proof for a related result by Di Battista and Frati based on the matroid intersection algorithm. AU - Fulek, Radoslav AU - Kynčl, Jan AU - Malinović, Igor AU - Pálvölgyi, Dömötör ID - 10793 SN - 0302-9743 T2 - International Symposium on Graph Drawing TI - Clustered planarity testing revisited VL - 8871 ER - TY - CONF AB - We extend the notion of verifiable random functions (VRF) to constrained VRFs, which generalize the concept of constrained pseudorandom functions, put forward by Boneh and Waters (Asiacrypt’13), and independently by Kiayias et al. (CCS’13) and Boyle et al. (PKC’14), who call them delegatable PRFs and functional PRFs, respectively. In a standard VRF the secret key sk allows one to evaluate a pseudorandom function at any point of its domain; in addition, it enables computation of a non-interactive proof that the function value was computed correctly. In a constrained VRF from the key sk one can derive constrained keys skS for subsets S of the domain, which allow computation of function values and proofs only at points in S. After formally defining constrained VRFs, we derive instantiations from the multilinear-maps-based constrained PRFs by Boneh and Waters, yielding a VRF with constrained keys for any set that can be decided by a polynomial-size circuit. Our VRFs have the same function values as the Boneh-Waters PRFs and are proved secure under the same hardness assumption, showing that verifiability comes at no cost. Constrained (functional) VRFs were stated as an open problem by Boyle et al. AU - Fuchsbauer, Georg ED - Abdalla, Michel ED - De Prisco, Roberto ID - 1643 T2 - SCN 2014 TI - Constrained Verifiable Random Functions VL - 8642 ER - TY - CONF AB - In this paper we present INTERHORN, a solver for recursion-free Horn clauses. The main application domain of INTERHORN lies in solving interpolation problems arising in software verification. We show how a range of interpolation problems, including path, transition, nested, state/transition and well-founded interpolation can be handled directly by INTERHORN. By detailing these interpolation problems and their Horn clause representations, we hope to encourage the emergence of a common back-end interpolation interface useful for diverse verification tools. AU - Gupta, Ashutosh AU - Popeea, Corneliu AU - Rybalchenko, Andrey ID - 1702 T2 - Electronic Proceedings in Theoretical Computer Science, EPTCS TI - Generalised interpolation by solving recursion free-horn clauses VL - 169 ER - TY - CONF AB - It has been long argued that, because of inherent ambiguity and noise, the brain needs to represent uncertainty in the form of probability distributions. The neural encoding of such distributions remains however highly controversial. Here we present a novel circuit model for representing multidimensional real-valued distributions using a spike based spatio-temporal code. Our model combines the computational advantages of the currently competing models for probabilistic codes and exhibits realistic neural responses along a variety of classic measures. Furthermore, the model highlights the challenges associated with interpreting neural activity in relation to behavioral uncertainty and points to alternative population-level approaches for the experimental validation of distributed representations. AU - Savin, Cristina AU - Denève, Sophie ID - 1708 IS - January TI - Spatio-temporal representations of uncertainty in spiking neural networks VL - 3 ER - TY - JOUR AB - Metal silicides formed by means of thermal annealing processes are employed as contact materials in microelectronics. Control of the structure of silicide/silicon interfaces becomes a critical issue when the characteristic size of the device is reduced below a few tens of nanometers. Here, we report on silicide clustering occurring within the channel of PtSi/Si/PtSi Schottky-barrier transistors. This phenomenon is investigated through atomistic simulations and low-temperature resonant-tunneling spectroscopy. Our results provide evidence for the segregation of a PtSi cluster with a diameter of a few nanometers from the silicide contact. The cluster acts as a metallic quantum dot giving rise to distinct signatures of quantum transport through its discrete energy states. AU - Mongillo, Massimo AU - Spathis, Panayotis N AU - Georgios Katsaros AU - De Franceschi, Silvano AU - Gentile, Pascal AU - Rurali, Riccardo AU - Cartoixà, Xavier ID - 1761 IS - 4 JF - Physical Review X TI - PtSi clustering in silicon probed by transport spectroscopy VL - 3 ER - TY - JOUR AB - Acute gene inactivation using short hairpin RNA (shRNA, knockdown) in developing brain is a powerful technique to study genetic function; however, discrepancies between knockdown and knockout murine phenotypes have left unanswered questions. For example, doublecortin (Dcx) knockdown but not knockout shows a neocortical neuronal migration phenotype. Here we report that in utero electroporation of shRNA, but not siRNA or miRNA, to Dcx demonstrates a migration phenotype in Dcx knockouts akin to the effect in wild-type mice, suggestingshRNA-mediated off-target toxicity. This effect wasnot limited to Dcx, as it was observed in Dclk1 knockouts, as well as with a fraction of scrambled shRNAs, suggesting a sequence-dependent but not sequence-specific effect. Profiling RNAs from electroporated cells showed a defect in endogenous let7 miRNA levels, and disruption of let7 or Dicer recapitulated the migration defect. The results suggest that shRNA-mediated knockdown can produce untoward migration effects by altering endogenous miRNA pathways. AU - Baek, SeungTae AU - Kerjan, Géraldine AU - Bielas, Stephanie L AU - Lee, Jieun AU - Fenstermaker, Ali G AU - Gaia Novarino AU - Gleeson, Joseph G ID - 1791 IS - 6 JF - Neuron TI - Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous MicroRNA dysregulation VL - 82 ER - TY - CHAP AB - The generation of asymmetry, at both cellular and tissue level, is one of the most essential capabilities of all eukaryotic organisms. It mediates basically all multicellular development ranging from embryogenesis and de novo organ formation till responses to various environmental stimuli. In plants, the awe-inspiring number of such processes is regulated by phytohormone auxin and its directional, cell-to-cell transport. The mediators of this transport, PIN auxin transporters, are asymmetrically localized at the plasma membrane, and this polar localization determines the directionality of intercellular auxin flow. Thus, auxin transport contributes crucially to the generation of local auxin gradients or maxima, which instruct given cell to change its developmental program. Here, we introduce and discuss the molecular components and cellular mechanisms regulating the generation and maintenance of cellular PIN polarity, as the general hallmarks of cell polarity in plants. AU - Baster, Pawel AU - Friml, Jiří ED - Zažímalová, Eva ED - Petrášek, Jan ED - Benková, Eva ID - 1806 T2 - Auxin and Its Role in Plant Development TI - Auxin on the road navigated by cellular PIN polarity ER - TY - JOUR AB - Watermarking techniques for vector graphics dislocate vertices in order to embed imperceptible, yet detectable, statistical features into the input data. The embedding process may result in a change of the topology of the input data, e.g., by introducing self-intersections, which is undesirable or even disastrous for many applications. In this paper we present a watermarking framework for two-dimensional vector graphics that employs conventional watermarking techniques but still provides the guarantee that the topology of the input data is preserved. The geometric part of this framework computes so-called maximum perturbation regions (MPR) of vertices. We propose two efficient algorithms to compute MPRs based on Voronoi diagrams and constrained triangulations. Furthermore, we present two algorithms to conditionally correct the watermarked data in order to increase the watermark embedding capacity and still guarantee topological correctness. While we focus on the watermarking of input formed by straight-line segments, one of our approaches can also be extended to circular arcs. We conclude the paper by demonstrating and analyzing the applicability of our framework in conjunction with two well-known watermarking techniques. AU - Huber, Stefan AU - Held, Martin AU - Meerwald, Peter AU - Kwitt, Roland ID - 1816 IS - 1 JF - International Journal of Computational Geometry and Applications TI - Topology-preserving watermarking of vector graphics VL - 24 ER - TY - JOUR AB - We review recent progress towards a rigorous understanding of the Bogoliubov approximation for bosonic quantum many-body systems. We focus, in particular, on the excitation spectrum of a Bose gas in the mean-field (Hartree) limit. A list of open problems will be discussed at the end. AU - Seiringer, Robert ID - 1821 IS - 7 JF - Journal of Mathematical Physics TI - Bose gases, Bose-Einstein condensation, and the Bogoliubov approximation VL - 55 ER - TY - JOUR AU - Jakšić, Vojkan AU - Pillet, Claude AU - Seiringer, Robert ID - 1822 IS - 7 JF - Journal of Mathematical Physics TI - Introduction VL - 55 ER - TY - CHAP AB - Hitting and batting tasks, such as tennis forehands, ping-pong strokes, or baseball batting, depend on predictions where the ball can be intercepted and how it can properly be returned to the opponent. These predictions get more accurate over time, hence the behaviors need to be continuously modified. As a result, movement templates with a learned global shape need to be adapted during the execution so that the racket reaches a target position and velocity that will return the ball over to the other side of the net or court. It requires altering learned movements to hit a varying target with the necessary velocity at a specific instant in time. Such a task cannot be incorporated straightforwardly in most movement representations suitable for learning. For example, the standard formulation of the dynamical system based motor primitives (introduced by Ijspeert et al (2002b)) does not satisfy this property despite their flexibility which has allowed learning tasks ranging from locomotion to kendama. In order to fulfill this requirement, we reformulate the Ijspeert framework to incorporate the possibility of specifying a desired hitting point and a desired hitting velocity while maintaining all advantages of the original formulation.We show that the proposed movement template formulation works well in two scenarios, i.e., for hitting a ball on a string with a table tennis racket at a specified velocity and for returning balls launched by a ball gun successfully over the net using forehand movements. AU - Muelling, Katharina AU - Kroemer, Oliver AU - Lampert, Christoph AU - Schölkopf, Bernhard ED - Kober, Jens ED - Peters, Jan ID - 1829 T2 - Learning Motor Skills TI - Movement templates for learning of hitting and batting VL - 97 ER - TY - JOUR AB - Local protein interactions ("molecular context" effects) dictate amino acid replacements and can be described in terms of site-specific, energetic preferences for any different amino acid. It has been recently debated whether these preferences remain approximately constant during evolution or whether, due to coevolution of sites, they change strongly. Such research highlights an unresolved and fundamental issue with far-reaching implications for phylogenetic analysis and molecular evolution modeling. Here, we take advantage of the recent availability of phenotypically supported laboratory resurrections of Precambrian thioredoxins and β-lactamases to experimentally address the change of site-specific amino acid preferences over long geological timescales. Extensive mutational analyses support the notion that evolutionary adjustment to a new amino acid may occur, but to a large extent this is insufficient to erase the primitive preference for amino acid replacements. Generally, site-specific amino acid preferences appear to remain conserved throughout evolutionary history despite local sequence divergence. We show such preference conservation to be readily understandable in molecular terms and we provide crystallographic evidence for an intriguing structural-switch mechanism: Energetic preference for an ancestral amino acid in a modern protein can be linked to reorganization upon mutation to the ancestral local structure around the mutated site. Finally, we point out that site-specific preference conservation naturally leads to one plausible evolutionary explanation for the existence of intragenic global suppressor mutations. AU - Risso, Valeria AU - Manssour Triedo, Fadia AU - Delgado Delgado, Asuncion AU - Arco, Rocio AU - Barroso Deljesús, Alicia AU - Inglés Prieto, Álvaro AU - Godoy Ruiz, Raquel AU - Gavira, Josè AU - Gaucher, Eric AU - Ibarra Molero, Beatriz AU - Sánchez Ruiz, Jose ID - 1844 IS - 2 JF - Molecular Biology and Evolution TI - Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history VL - 32 ER - TY - JOUR AB - We prove polynomial upper bounds of geometric Ramsey numbers of pathwidth-2 outerplanar triangulations in both convex and general cases. We also prove that the geometric Ramsey numbers of the ladder graph on 2n vertices are bounded by O(n3) and O(n10), in the convex and general case, respectively. We then apply similar methods to prove an (Formula presented.) upper bound on the Ramsey number of a path with n ordered vertices. AU - Cibulka, Josef AU - Gao, Pu AU - Krcál, Marek AU - Valla, Tomáš AU - Valtr, Pavel ID - 1842 IS - 1 JF - Discrete & Computational Geometry TI - On the geometric ramsey number of outerplanar graphs VL - 53 ER - TY - JOUR AB - In this paper, we present a method for non-rigid, partial shape matching in vector graphics. Given a user-specified query region in a 2D shape, similar regions are found, even if they are non-linearly distorted. Furthermore, a non-linear mapping is established between the query regions and these matches, which allows the automatic transfer of editing operations such as texturing. This is achieved by a two-step approach. First, pointwise correspondences between the query region and the whole shape are established. The transformation parameters of these correspondences are registered in an appropriate transformation space. For transformations between similar regions, these parameters form surfaces in transformation space, which are extracted in the second step of our method. The extracted regions may be related to the query region by a non-rigid transform, enabling non-rigid shape matching. In this paper, we present a method for non-rigid, partial shape matching in vector graphics. Given a user-specified query region in a 2D shape, similar regions are found, even if they are non-linearly distorted. Furthermore, a non-linear mapping is established between the query regions and these matches, which allows the automatic transfer of editing operations such as texturing. This is achieved by a two-step approach. First, pointwise correspondences between the query region and the whole shape are established. The transformation parameters of these correspondences are registered in an appropriate transformation space. For transformations between similar regions, these parameters form surfaces in transformation space, which are extracted in the second step of our method. The extracted regions may be related to the query region by a non-rigid transform, enabling non-rigid shape matching. AU - Guerrero, Paul AU - Auzinger, Thomas AU - Wimmer, Michael AU - Jeschke, Stefan ID - 1854 IS - 1 JF - Computer Graphics Forum TI - Partial shape matching using transformation parameter similarity VL - 34 ER - TY - JOUR AB - To control morphogenesis, molecular regulatory networks have to interfere with the mechanical properties of the individual cells of developing organs and tissues, but how this is achieved is not well known. We study this issue here in the shoot meristem of higher plants, a group of undifferentiated cells where complex changes in growth rates and directions lead to the continuous formation of new organs [1, 2]. Here, we show that the plant hormone auxin plays an important role in this process via a dual, local effect on the extracellular matrix, the cell wall, which determines cell shape. Our study reveals that auxin not only causes a limited reduction in wall stiffness but also directly interferes with wall anisotropy via the regulation of cortical microtubule dynamics. We further show that to induce growth isotropy and organ outgrowth, auxin somehow interferes with the cortical microtubule-ordering activity of a network of proteins, including AUXIN BINDING PROTEIN 1 and KATANIN 1. Numerical simulations further indicate that the induced isotropy is sufficient to amplify the effects of the relatively minor changes in wall stiffness to promote organogenesis and the establishment of new growth axes in a robust manner. AU - Sassi, Massimiliano AU - Ali, Olivier AU - Boudon, Frédéric AU - Cloarec, Gladys AU - Abad, Ursula AU - Cellier, Coralie AU - Chen, Xu AU - Gilles, Benjamin AU - Milani, Pascale AU - Friml, Jirí AU - Vernoux, Teva AU - Godin, Christophe AU - Hamant, Olivier AU - Traas, Jan ID - 1852 IS - 19 JF - Current Biology TI - An auxin-mediated shift toward growth isotropy promotes organ formation at the shoot meristem in Arabidopsis VL - 24 ER - TY - CONF AB - Wireless sensor networks (WSNs) composed of low-power, low-cost sensor nodes are expected to form the backbone of future intelligent networks for a broad range of civil, industrial and military applications. These sensor nodes are often deployed through random spreading, and function in dynamic environments. Many applications of WSNs such as pollution tracking, forest fire detection, and military surveillance require knowledge of the location of constituent nodes. But the use of technologies such as GPS on all nodes is prohibitive due to power and cost constraints. So, the sensor nodes need to autonomously determine their locations. Most localization techniques use anchor nodes with known locations to determine the position of remaining nodes. Localization techniques have two conflicting requirements. On one hand, an ideal localization technique should be computationally simple and on the other hand, it must be resistant to attacks that compromise anchor nodes. In this paper, we propose a computationally light-weight game theoretic secure localization technique and demonstrate its effectiveness in comparison to existing techniques. AU - Jha, Susmit AU - Tripakis, Stavros AU - Seshia, Sanjit AU - Chatterjee, Krishnendu ID - 1853 TI - Game theoretic secure localization in wireless sensor networks ER - TY - JOUR AB - The prominent and evolutionarily ancient role of the plant hormone auxin is the regulation of cell expansion. Cell expansion requires ordered arrangement of the cytoskeleton but molecular mechanisms underlying its regulation by signalling molecules including auxin are unknown. Here we show in the model plant Arabidopsis thaliana that in elongating cells exogenous application of auxin or redistribution of endogenous auxin induces very rapid microtubule re-orientation from transverse to longitudinal, coherent with the inhibition of cell expansion. This fast auxin effect requires auxin binding protein 1 (ABP1) and involves a contribution of downstream signalling components such as ROP6 GTPase, ROP-interactive protein RIC1 and the microtubule-severing protein katanin. These components are required for rapid auxin-and ABP1-mediated re-orientation of microtubules to regulate cell elongation in roots and dark-grown hypocotyls as well as asymmetric growth during gravitropic responses. AU - Chen, Xu AU - Grandont, Laurie AU - Li, Hongjiang AU - Hauschild, Robert AU - Paque, Sébastien AU - Abuzeineh, Anas AU - Rakusova, Hana AU - Benková, Eva AU - Perrot Rechenmann, Catherine AU - Friml, Jirí ID - 1862 IS - 729 JF - Nature SN - 0028-0836 TI - Inhibition of cell expansion by rapid ABP1-mediated auxin effect on microtubules VL - 516 ER - TY - CONF AB - Boolean controllers for systems with complex datapaths are often very difficult to implement correctly, in particular when concurrency is involved. Yet, in many instances it is easy to formally specify correctness. For example, the specification for the controller of a pipelined processor only has to state that the pipelined processor gives the same results as a non-pipelined reference design. This makes such controllers a good target for automated synthesis. However, an efficient abstraction for the complex datapath elements is needed, as a bit-precise description is often infeasible. We present Suraq, the first controller synthesis tool which uses uninterpreted functions for the abstraction. Quantified firstorder formulas (with specific quantifier structure) serve as the specification language from which Suraq synthesizes Boolean controllers. Suraq transforms the specification into an unsatisfiable SMT formula, and uses Craig interpolation to compute its results. Using Suraq, we were able to synthesize a controller (consisting of two Boolean signals) for a five-stage pipelined DLX processor in roughly one hour and 15 minutes. AU - Hofferek, Georg AU - Gupta, Ashutosh ED - Yahav, Eran ID - 1869 T2 - HVC 2014 TI - Suraq - a controller synthesis tool using uninterpreted functions VL - 8855 ER - TY - CONF AB - Extensionality axioms are common when reasoning about data collections, such as arrays and functions in program analysis, or sets in mathematics. An extensionality axiom asserts that two collections are equal if they consist of the same elements at the same indices. Using extensionality is often required to show that two collections are equal. A typical example is the set theory theorem (∀x)(∀y)x∪y = y ∪x. Interestingly, while humans have no problem with proving such set identities using extensionality, they are very hard for superposition theorem provers because of the calculi they use. In this paper we show how addition of a new inference rule, called extensionality resolution, allows first-order theorem provers to easily solve problems no modern first-order theorem prover can solve. We illustrate this by running the VAMPIRE theorem prover with extensionality resolution on a number of set theory and array problems. Extensionality resolution helps VAMPIRE to solve problems from the TPTP library of first-order problems that were never solved before by any prover. AU - Gupta, Ashutosh AU - Kovács, Laura AU - Kragl, Bernhard AU - Voronkov, Andrei ED - Cassez, Franck ED - Raskin, Jean-François ID - 1872 T2 - ATVA 2014 TI - Extensional crisis and proving identity VL - 8837 ER - TY - CONF AB - We investigate the problem of checking if a finite-state transducer is robust to uncertainty in its input. Our notion of robustness is based on the analytic notion of Lipschitz continuity - a transducer is K-(Lipschitz) robust if the perturbation in its output is at most K times the perturbation in its input. We quantify input and output perturbation using similarity functions. We show that K-robustness is undecidable even for deterministic transducers. We identify a class of functional transducers, which admits a polynomial time automata-theoretic decision procedure for K-robustness. This class includes Mealy machines and functional letter-to-letter transducers. We also study K-robustness of nondeterministic transducers. Since a nondeterministic transducer generates a set of output words for each input word, we quantify output perturbation using setsimilarity functions. We show that K-robustness of nondeterministic transducers is undecidable, even for letter-to-letter transducers. We identify a class of set-similarity functions which admit decidable K-robustness of letter-to-letter transducers. AU - Henzinger, Thomas A AU - Otop, Jan AU - Samanta, Roopsha ID - 1870 T2 - Leibniz International Proceedings in Informatics, LIPIcs TI - Lipschitz robustness of finite-state transducers VL - 29 ER - TY - CONF AB - We present a formal framework for repairing infinite-state, imperative, sequential programs, with (possibly recursive) procedures and multiple assertions; the framework can generate repaired programs by modifying the original erroneous program in multiple program locations, and can ensure the readability of the repaired program using user-defined expression templates; the framework also generates a set of inductive assertions that serve as a proof of correctness of the repaired program. As a step toward integrating programmer intent and intuition in automated program repair, we present a cost-aware formulation - given a cost function associated with permissible statement modifications, the goal is to ensure that the total program modification cost does not exceed a given repair budget. As part of our predicate abstractionbased solution framework, we present a sound and complete algorithm for repair of Boolean programs. We have developed a prototype tool based on SMT solving and used it successfully to repair diverse errors in benchmark C programs. AU - Samanta, Roopsha AU - Olivo, Oswaldo AU - Allen, Emerson ED - Müller-Olm, Markus ED - Seidl, Helmut ID - 1875 TI - Cost-aware automatic program repair VL - 8723 ER - TY - JOUR AB - We study densities of functionals over uniformly bounded triangulations of a Delaunay set of vertices, and prove that the minimum is attained for the Delaunay triangulation if this is the case for finite sets. AU - Dolbilin, Nikolai AU - Edelsbrunner, Herbert AU - Glazyrin, Alexey AU - Musin, Oleg ID - 1876 IS - 3 JF - Moscow Mathematical Journal SN - 16093321 TI - Functionals on triangulations of delaunay sets VL - 14 ER - TY - JOUR AB - During inflammation, lymph nodes swell with an influx of immune cells. New findings identify a signalling pathway that induces relaxation in the contractile cells that give structure to these organs. AU - Sixt, Michael K AU - Vaahtomeri, Kari ID - 1877 IS - 7523 JF - Nature TI - Physiology: Relax and come in VL - 514 ER - TY - JOUR AB - Information processing in the sensory periphery is shaped by natural stimulus statistics. In the periphery, a transmission bottleneck constrains performance; thus efficient coding implies that natural signal components with a predictably wider range should be compressed. In a different regime—when sampling limitations constrain performance—efficient coding implies that more resources should be allocated to informative features that are more variable. We propose that this regime is relevant for sensory cortex when it extracts complex features from limited numbers of sensory samples. To test this prediction, we use central visual processing as a model: we show that visual sensitivity for local multi-point spatial correlations, described by dozens of independently-measured parameters, can be quantitatively predicted from the structure of natural images. This suggests that efficient coding applies centrally, where it extends to higher-order sensory features and operates in a regime in which sensitivity increases with feature variability. AU - Hermundstad, Ann AU - Briguglio, John AU - Conte, Mary AU - Victor, Jonathan AU - Balasubramanian, Vijay AU - Tkacik, Gasper ID - 1886 IS - November JF - eLife TI - Variance predicts salience in central sensory processing ER - TY - JOUR AB - To search for a target in a complex environment is an everyday behavior that ends with finding the target. When we search for two identical targets, however, we must continue the search after finding the first target and memorize its location. We used fixation-related potentials to investigate the neural correlates of different stages of the search, that is, before and after finding the first target. Having found the first target influenced subsequent distractor processing. Compared to distractor fixations before the first target fixation, a negative shift was observed for three subsequent distractor fixations. These results suggest that processing a target in continued search modulates the brain's response, either transiently by reflecting temporary working memory processes or permanently by reflecting working memory retention. AU - Körner, Christof AU - Braunstein, Verena AU - Stangl, Matthias AU - Schlögl, Alois AU - Neuper, Christa AU - Ischebeck, Anja ID - 1890 IS - 4 JF - Psychophysiology TI - Sequential effects in continued visual search: Using fixation-related potentials to compare distractor processing before and after target detection VL - 51 ER - TY - JOUR AB - Behavioural variation among conspecifics is typically contingent on individual state or environmental conditions. Sex-specific genetic polymorphisms are enigmatic because they lack conditionality, and genes causing adaptive trait variation in one sex may reduce Darwinian fitness in the other. One way to avoid such genetic antagonism is to control sex-specific traits by inheritance via sex chromosomes. Here, controlled laboratory crossings suggest that in snail-brooding cichlid fish a single locus, two-allele polymorphism located on a sex-linked chromosome of heterogametic males generates an extreme reproductive dimorphism. Both natural and sexual selection are responsible for exceptionally large body size of bourgeois males, creating a niche for a miniature male phenotype to evolve. This extreme intrasexual dimorphism results from selection on opposite size thresholds caused by a single ecological factor, empty snail shells used as breeding substrate. Paternity analyses reveal that in the field parasitic dwarf males sire the majority of offspring in direct sperm competition with large nest owners exceeding their size more than 40 times. Apparently, use of empty snail shells as breeding substrate and single locus sex-linked inheritance of growth are the major ecological and genetic mechanisms responsible for the extreme intrasexual diversity observed in Lamprologus callipterus. AU - Ocana, Sabine AU - Meidl, Patrick AU - Bonfils, Danielle AU - Taborsky, Michael ID - 1892 IS - 1794 JF - Proceedings of the Royal Society of London Series B Biological Sciences TI - Y-linked Mendelian inheritance of giant and dwarf male morphs in shell-brooding cichlids VL - 281 ER - TY - JOUR AB - We provide theoretical tests of a novel experimental technique to determine mechanostability of proteins based on stretching a mechanically protected protein by single-molecule force spectroscopy. This technique involves stretching a homogeneous or heterogeneous chain of reference proteins (single-molecule markers) in which one of them acts as host to the guest protein under study. The guest protein is grafted into the host through genetic engineering. It is expected that unraveling of the host precedes the unraveling of the guest removing ambiguities in the reading of the force-extension patterns of the guest protein. We study examples of such systems within a coarse-grained structure-based model. We consider systems with various ratios of mechanostability for the host and guest molecules and compare them to experimental results involving cohesin I as the guest molecule. For a comparison, we also study the force-displacement patterns in proteins that are linked in a serial fashion. We find that the mechanostability of the guest is similar to that of the isolated or serially linked protein. We also demonstrate that the ideal configuration of this strategy would be one in which the host is much more mechanostable than the single-molecule markers. We finally show that it is troublesome to use the highly stable cystine knot proteins as a host to graft a guest in stretching studies because this would involve a cleaving procedure. AU - Chwastyk, Mateusz AU - Galera Prat, Albert AU - Sikora, Mateusz K AU - Gómez Sicilia, Àngel AU - Carrión Vázquez, Mariano AU - Cieplak, Marek ID - 1891 IS - 5 JF - Proteins: Structure, Function and Bioinformatics TI - Theoretical tests of the mechanical protection strategy in protein nanomechanics VL - 82 ER - TY - JOUR AB - Unbiased high-throughput massively parallel sequencing methods have transformed the process of discovery of novel putative driver gene mutations in cancer. In chronic lymphocytic leukemia (CLL), these methods have yielded several unexpected findings, including the driver genes SF3B1, NOTCH1 and POT1. Recent analysis, utilizing down-sampling of existing datasets, has shown that the discovery process of putative drivers is far from complete across cancer. In CLL, while driver gene mutations affecting >10% of patients were efficiently discovered with previously published CLL cohorts of up to 160 samples subjected to whole exome sequencing (WES), this sample size has only 0.78 power to detect drivers affecting 5% of patients, and only 0.12 power for drivers affecting 2% of patients. These calculations emphasize the need to apply unbiased WES to larger patient cohorts. AU - Landau, Dan AU - Stewart, Chip AU - Reiter, Johannes AU - Lawrence, Michael AU - Sougnez, Carrie AU - Brown, Jennifer AU - Lopez Guillermo, Armando AU - Gabriel, Stacey AU - Lander, Eric AU - Neuberg, Donna AU - López Otín, Carlos AU - Campo, Elias AU - Getz, Gad AU - Wu, Catherine ID - 1884 IS - 21 JF - Blood TI - Novel putative driver gene mutations in chronic lymphocytic leukemia (CLL): results from a combined analysis of whole exome sequencing of 262 primary CLL aamples VL - 124 ER - TY - JOUR AB - We study translation-invariant quasi-free states for a system of fermions with two-particle interactions. The associated energy functional is similar to the BCS functional but also includes direct and exchange energies. We show that for suitable short-range interactions, these latter terms only lead to a renormalization of the chemical potential, with the usual properties of the BCS functional left unchanged. Our analysis thus represents a rigorous justification of part of the BCS approximation. We give bounds on the critical temperature below which the system displays superfluidity. AU - Bräunlich, Gerhard AU - Hainzl, Christian AU - Seiringer, Robert ID - 1889 IS - 7 JF - Reviews in Mathematical Physics TI - Translation-invariant quasi-free states for fermionic systems and the BCS approximation VL - 26 ER - TY - JOUR AB - Background: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. Methods and Results: Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. Conclusions: Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute the considerable insight to the Epsilonproteobacterial Dsb systems, which have been poorly understood so far. AU - Grabowska, Anna AU - Wywiał, Ewa AU - Dunin Horkawicz, Stanislaw AU - Łasica, Anna AU - Wösten, Marc AU - Nagy-Staron, Anna A AU - Godlewska, Renata AU - Bocian Ostrzycka, Katarzyna AU - Pieńkowska, Katarzyna AU - Łaniewski, Paweł AU - Bujnicki, Janusz AU - Van Putten, Jos AU - Jagusztyn Krynicka, Elzbieta ID - 1894 IS - 9 JF - PLoS One TI - Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA VL - 9 ER - TY - JOUR AB - Major histocompatibility complex class I (MHCI) molecules were recently identified as novel regulators of synaptic plasticity. These molecules are expressed in various brain areas, especially in regions undergoing activity-dependent synaptic plasticity, but their role in the nucleus accumbens (NAc) is unknown. In this study, we investigated the effects of genetic disruption of MHCI function, through deletion of β2-microblobulin, which causes lack of cell surface expression of MHCI. First, we confirmed that MHCI molecules are expressed in the NAc core in wild-type mice. Second, we performed electrophysiological recordings with NAc core slices from wild-type and β2-microglobulin knock-out mice lacking cell surface expression of MHCI. We found that low frequency stimulation induced long-term depression in wild-type but not knock-out mice, whereas high frequency stimulation induced long-term potentiation in both genotypes, with a larger magnitude in knock-out mice. Furthermore, we demonstrated that knock-out mice showed more persistent behavioral sensitization to cocaine, which is a NAc-related behavior. Using this model, we analyzed the density of total AMPA receptors and their subunits GluR1 and GluR2 in the NAc core, by SDS-digested freeze-fracture replica labeling. After repeated cocaine exposure, the density of GluR1 was increased, but there was no change in total AMPA receptors and GluR2 levels in wildtype mice. In contrast, following repeated cocaine exposure, increased densities of total AMPA receptors, GluR1 and GluR2 were observed in knock-out mice. These results indicate that functional deficiency of MHCI enhances synaptic potentiation, induced by electrical and pharmacological stimulation. AU - Edamura, Mitsuhiro AU - Murakami, Gen AU - Meng, Hongrui AU - Itakura, Makoto AU - Shigemoto, Ryuichi AU - Fukuda, Atsuo AU - Nakahara, Daiichiro ID - 1895 IS - 9 JF - PLoS One TI - Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice VL - 9 ER - TY - JOUR AB - Phosphatidylinositol (PtdIns) is a structural phospholipid that can be phosphorylated into various lipid signaling molecules, designated polyphosphoinositides (PPIs). The reversible phosphorylation of PPIs on the 3, 4, or 5 position of inositol is performed by a set of organelle-specific kinases and phosphatases, and the characteristic head groups make these molecules ideal for regulating biological processes in time and space. In yeast and mammals, PtdIns3P and PtdIns(3,5)P2 play crucial roles in trafficking toward the lytic compartments, whereas the role in plants is not yet fully understood. Here we identified the role of a land plant-specific subgroup of PPI phosphatases, the suppressor of actin 2 (SAC2) to SAC5, during vacuolar trafficking and morphogenesis in Arabidopsis thaliana. SAC2-SAC5 localize to the tonoplast along with PtdIns3P, the presumable product of their activity. In SAC gain- and loss-of-function mutants, the levels of PtdIns monophosphates and bisphosphates were changed, with opposite effects on the morphology of storage and lytic vacuoles, and the trafficking toward the vacuoles was defective. Moreover, multiple sac knockout mutants had an increased number of smaller storage and lytic vacuoles, whereas extralarge vacuoles were observed in the overexpression lines, correlating with various growth and developmental defects. The fragmented vacuolar phenotype of sac mutants could be mimicked by treating wild-type seedlings with PtdIns(3,5)P2, corroborating that this PPI is important for vacuole morphology. Taken together, these results provide evidence that PPIs, together with their metabolic enzymes SAC2-SAC5, are crucial for vacuolar trafficking and for vacuolar morphology and function in plants. AU - Nováková, Petra AU - Hirsch, Sibylle AU - Feraru, Elena AU - Tejos, Ricardo AU - Van Wijk, Ringo AU - Viaene, Tom AU - Heilmann, Mareike AU - Lerche, Jennifer AU - De Rycke, Riet AU - Feraru, Mugurel AU - Grones, Peter AU - Van Montagu, Marc AU - Heilmann, Ingo AU - Munnik, Teun AU - Friml, Jirí ID - 1893 IS - 7 JF - PNAS TI - SAC phosphoinositide phosphatases at the tonoplast mediate vacuolar function in Arabidopsis VL - 111 ER - TY - JOUR AB - Biopolymer length regulation is a complex process that involves a large number of biological, chemical, and physical subprocesses acting simultaneously across multiple spatial and temporal scales. An illustrative example important for genomic stability is the length regulation of telomeres - nucleoprotein structures at the ends of linear chromosomes consisting of tandemly repeated DNA sequences and a specialized set of proteins. Maintenance of telomeres is often facilitated by the enzyme telomerase but, particularly in telomerase-free systems, the maintenance of chromosomal termini depends on alternative lengthening of telomeres (ALT) mechanisms mediated by recombination. Various linear and circular DNA structures were identified to participate in ALT, however, dynamics of the whole process is still poorly understood. We propose a chemical kinetics model of ALT with kinetic rates systematically derived from the biophysics of DNA diffusion and looping. The reaction system is reduced to a coagulation-fragmentation system by quasi-steady-state approximation. The detailed treatment of kinetic rates yields explicit formulas for expected size distributions of telomeres that demonstrate the key role played by the J factor, a quantitative measure of bending of polymers. The results are in agreement with experimental data and point out interesting phenomena: an appearance of very long telomeric circles if the total telomere density exceeds a critical value (excess mass) and a nonlinear response of the telomere size distributions to the amount of telomeric DNA in the system. The results can be of general importance for understanding dynamics of telomeres in telomerase-independent systems as this mode of telomere maintenance is similar to the situation in tumor cells lacking telomerase activity. Furthermore, due to its universality, the model may also serve as a prototype of an interaction between linear and circular DNA structures in various settings. AU - Kollár, Richard AU - Bod'ová, Katarína AU - Nosek, Jozef AU - Tomáška, Ľubomír ID - 1896 IS - 3 JF - Physical Review E Statistical Nonlinear and Soft Matter Physics TI - Mathematical model of alternative mechanism of telomere length maintenance VL - 89 ER - TY - JOUR AB - GNOM is one of the most characterized membrane trafficking regulators in plants, with crucial roles in development. GNOM encodes an ARF-guanine nucleotide exchange factor (ARF-GEF) that activates small GTPases of the ARF (ADP ribosylation factor) class to mediate vesicle budding at endomembranes. The crucial role of GNOM in recycling of PIN auxin transporters and other proteins to the plasma membrane was identified in studies using the ARF-GEF inhibitor brefeldin A (BFA). GNOM, the most prominent regulator of recycling in plants, has been proposed to act and localize at so far elusive recycling endosomes. Here, we report the GNOM localization in context of its cellular function in Arabidopsis thaliana. State-of-the-art imaging, pharmacological interference, and ultrastructure analysis show that GNOM predominantly localizes to Golgi apparatus. Super-resolution confocal live imaging microscopy identified GNOM and its closest homolog GNOM-like 1 at distinct subdomains on Golgi cisternae. Short-term BFA treatment stabilizes GNOM at the Golgi apparatus, whereas prolonged exposures results in GNOM translocation to trans-Golgi network (TGN)/early endosomes (EEs). Malformed TGN/EE in gnom mutants suggests a role for GNOM in maintaining TGN/EE function. Our results redefine the subcellular action of GNOM and reevaluate the identity and function of recycling endosomes in plants. AU - Naramoto, Satoshi AU - Otegui, Marisa AU - Kutsuna, Natsumaro AU - De Rycke, Riet AU - Dainobu, Tomoko AU - Karampelias, Michael AU - Fujimoto, Masaru AU - Feraru, Elena AU - Miki, Daisuke AU - Fukuda, Hiroo AU - Nakano, Akihiko AU - Friml, Jirí ID - 1897 IS - 7 JF - Plant Cell TI - Insights into the localization and function of the membrane trafficking regulator GNOM ARF-GEF at the Golgi apparatus in Arabidopsis VL - 26 ER - TY - JOUR AB - Asymmetric cell divisions allow stem cells to balance proliferation and differentiation. During embryogenesis, murine epidermis expands rapidly from a single layer of unspecified basal layer progenitors to a stratified, differentiated epithelium. Morphogenesis involves perpendicular (asymmetric) divisions and the spindle orientation protein LGN, but little is known about how the apical localization of LGN is regulated. Here, we combine conventional genetics and lentiviral-mediated in vivo RNAi to explore the functions of the LGN-interacting proteins Par3, mInsc and Gα i3. Whereas loss of each gene alone leads to randomized division angles, combined loss of Gnai3 and mInsc causes a phenotype of mostly planar divisions, akin to loss of LGN. These findings lend experimental support for the hitherto untested model that Par3-mInsc and Gα i3 act cooperatively to polarize LGN and promote perpendicular divisions. Finally, we uncover a developmental switch between delamination-driven early stratification and spindle-orientation-dependent differentiation that occurs around E15, revealing a two-step mechanism underlying epidermal maturation. AU - Williams, Scott AU - Ratliff, Lyndsay AU - Postiglione, Maria P AU - Knoblich, Juergen AU - Fuchs, Elaine ID - 1899 IS - 8 JF - Nature Cell Biology TI - Par3-mInsc and Gα i3 cooperate to promote oriented epidermal cell divisions through LGN VL - 16 ER - TY - JOUR AB - Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported invivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission upto ~1 kHz. Presynaptic APs are ultrafast, with ~100μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca2+ channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling. AU - Ritzau Jost, Andreas AU - Delvendahl, Igor AU - Rings, Annika AU - Byczkowicz, Niklas AU - Harada, Harumi AU - Shigemoto, Ryuichi AU - Hirrlinger, Johannes AU - Eilers, Jens AU - Hallermann, Stefan ID - 1898 IS - 1 JF - Neuron TI - Ultrafast action potentials mediate kilohertz signaling at a central synapse VL - 84 ER - TY - JOUR AB - In this paper, we introduce a novel scene representation for the visualization of large-scale point clouds accompanied by a set of high-resolution photographs. Many real-world applications deal with very densely sampled point-cloud data, which are augmented with photographs that often reveal lighting variations and inaccuracies in registration. Consequently, the high-quality representation of the captured data, i.e., both point clouds and photographs together, is a challenging and time-consuming task. We propose a two-phase approach, in which the first (preprocessing) phase generates multiple overlapping surface patches and handles the problem of seamless texture generation locally for each patch. The second phase stitches these patches at render-time to produce a high-quality visualization of the data. As a result of the proposed localization of the global texturing problem, our algorithm is more than an order of magnitude faster than equivalent mesh-based texturing techniques. Furthermore, since our preprocessing phase requires only a minor fraction of the whole data set at once, we provide maximum flexibility when dealing with growing data sets. AU - Arikan, Murat AU - Preiner, Reinhold AU - Scheiblauer, Claus AU - Jeschke, Stefan AU - Wimmer, Michael ID - 1906 IS - 9 JF - IEEE Transactions on Visualization and Computer Graphics TI - Large-scale point-cloud visualization through localized textured surface reconstruction VL - 20 ER - TY - JOUR AB - The unprecedented polymorphism in the major histocompatibility complex (MHC) genes is thought to be maintained by balancing selection from parasites. However, do parasites also drive divergence at MHC loci between host populations, or do the effects of balancing selection maintain similarities among populations? We examined MHC variation in populations of the livebearing fish Poecilia mexicana and characterized their parasite communities. Poecilia mexicana populations in the Cueva del Azufre system are locally adapted to darkness and the presence of toxic hydrogen sulphide, representing highly divergent ecotypes or incipient species. Parasite communities differed significantly across populations, and populations with higher parasite loads had higher levels of diversity at class II MHC genes. However, despite different parasite communities, marked divergence in adaptive traits and in neutral genetic markers, we found MHC alleles to be remarkably similar among host populations. Our findings indicate that balancing selection from parasites maintains immunogenetic diversity of hosts, but this process does not promote MHC divergence in this system. On the contrary, we suggest that balancing selection on immunogenetic loci may outweigh divergent selection causing divergence, thereby hindering host divergence and speciation. Our findings support the hypothesis that balancing selection maintains MHC similarities among lineages during and after speciation (trans-species evolution). AU - Tobler, Michael AU - Plath, Martin AU - Riesch, Rüdiger AU - Schlupp, Ingo AU - Grasse, Anna V AU - Munimanda, Gopi AU - Setzer, C AU - Penn, Dustin AU - Moodley, Yoshan ID - 1905 IS - 5 JF - Journal of Evolutionary Biology SN - 1010-061X TI - Selection from parasites favours immunogenetic diversity but not divergence among locally adapted host populations VL - 27 ER - TY - JOUR AB - In the 1960s-1980s, determination of bacterial growth rates was an important tool in microbial genetics, biochemistry, molecular biology, and microbial physiology. The exciting technical developments of the 1990s and the 2000s eclipsed that tool; as a result, many investigators today lack experience with growth rate measurements. Recently, investigators in a number of areas have started to use measurements of bacterial growth rates for a variety of purposes. Those measurements have been greatly facilitated by the availability of microwell plate readers that permit the simultaneous measurements on up to 384 different cultures. Only the exponential (logarithmic) portions of the resulting growth curves are useful for determining growth rates, and manual determination of that portion and calculation of growth rates can be tedious for high-throughput purposes. Here, we introduce the program GrowthRates that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase. GrowthRates is freely available for Macintosh, Windows, and Linux.We discuss the effects of culture volume, the classical bacterial growth curve, and the differences between determinations in rich media and minimal (mineral salts) media. This protocol covers calibration of the plate reader, growth of culture inocula for both rich and minimal media, and experimental setup. As a guide to reliability, we report typical day-to-day variation in growth rates and variation within experiments with respect to position of wells within the plates. AU - Hall, Barry AU - Acar, Hande AU - Nandipati, Anna AU - Barlow, Miriam ID - 1902 IS - 1 JF - Molecular Biology and Evolution SN - 0737-4038 TI - Growth rates made easy VL - 31 ER - TY - JOUR AB - In plants, the patterning of stem cell-enriched meristems requires a graded auxin response maximum that emerges from the concerted action of polar auxin transport, auxin biosynthesis, auxin metabolism, and cellular auxin response machinery. However, mechanisms underlying this auxin response maximum-mediated root stem cell maintenance are not fully understood. Here, we present unexpected evidence that WUSCHEL-RELATED HOMEOBOX 5 (WOX5) transcription factor modulates expression of auxin biosynthetic genes in the quiescent center (QC) of the root and thus provides a robust mechanism for the maintenance of auxin response maximum in the root tip. This WOX5 action is balanced through the activity of indole-3-acetic acid 17 (IAA17) auxin response repressor. Our combined genetic, cell biology, and computational modeling studies revealed a previously uncharacterized feedback loop linking WOX5-mediated auxin production to IAA17-dependent repression of auxin responses. This WOX5-IAA17 feedback circuit further assures the maintenance of auxin response maximum in the root tip and thereby contributes to the maintenance of distal stem cell (DSC) populations. Our experimental studies and in silico computer simulations both demonstrate that the WOX5-IAA17 feedback circuit is essential for the maintenance of auxin gradient in the root tip and the auxin-mediated root DSC differentiation. AU - Tian, Huiyu AU - Wabnik, Krzysztof T AU - Niu, Tiantian AU - Li, Hongjiang AU - Yu, Qianqian AU - Pollmann, Stephan AU - Vanneste, Steffen AU - Govaerts, Willy AU - Rolčík, Jakub AU - Geisler, Markus AU - Friml, Jirí AU - Ding, Zhaojun ID - 1901 IS - 2 JF - Molecular Plant TI - WOX5-IAA17 feedback circuit-mediated cellular auxin response is crucial for the patterning of root stem cell niches in arabidopsis VL - 7 ER - TY - JOUR AB - We prove a Strichartz inequality for a system of orthonormal functions, with an optimal behavior of the constant in the limit of a large number of functions. The estimate generalizes the usual Strichartz inequality, in the same fashion as the Lieb-Thirring inequality generalizes the Sobolev inequality. As an application, we consider the Schrödinger equation with a time-dependent potential and we show the existence of the wave operator in Schatten spaces. AU - Frank, Rupert AU - Lewin, Mathieu AU - Lieb, Élliott AU - Seiringer, Robert ID - 1904 IS - 7 JF - Journal of the European Mathematical Society TI - Strichartz inequality for orthonormal functions VL - 16 ER - TY - JOUR AB - Epithelial cell layers need to be tightly regulated to maintain their integrity and correct function. Cell integration into epithelial sheets is now shown to depend on the N-WASP-regulated stabilization of cortical F-actin, which generates distinct patterns of apical-lateral contractility at E-cadherin-based cell-cell junctions. AU - Behrndt, Martin AU - Heisenberg, Carl-Philipp J ID - 1900 IS - 2 JF - Nature Cell Biology TI - Lateral junction dynamics lead the way out VL - 16 ER - TY - JOUR AB - Summary: Phenotypes are often environmentally dependent, which requires organisms to track environmental change. The challenge for organisms is to construct phenotypes using the most accurate environmental cue. Here, we use a quantitative genetic model of adaptation by additive genetic variance, within- and transgenerational plasticity via linear reaction norms and indirect genetic effects respectively. We show how the relative influence on the eventual phenotype of these components depends on the predictability of environmental change (fast or slow, sinusoidal or stochastic) and the developmental lag τ between when the environment is perceived and when selection acts. We then decompose expected mean fitness into three components (variance load, adaptation and fluctuation load) to study the fitness costs of within- and transgenerational plasticity. A strongly negative maternal effect coefficient m minimizes the variance load, but a strongly positive m minimises the fluctuation load. The adaptation term is maximized closer to zero, with positive or negative m preferred under different environmental scenarios. Phenotypic plasticity is higher when τ is shorter and when the environment changes frequently between seasonal extremes. Expected mean population fitness is highest away from highest observed levels of phenotypic plasticity. Within- and transgenerational plasticity act in concert to deliver well-adapted phenotypes, which emphasizes the need to study both simultaneously when investigating phenotypic evolution. AU - Ezard, Thomas AU - Prizak, Roshan AU - Hoyle, Rebecca ID - 1909 IS - 3 JF - Functional Ecology TI - The fitness costs of adaptation via phenotypic plasticity and maternal effects VL - 28 ER - TY - JOUR AB - angerhans cells (LCs) are a unique subset of dendritic cells (DCs) that express epithelial adhesion molecules, allowing them to form contacts with epithelial cells and reside in epidermal/epithelial tissues. The dynamic regulation of epithelial adhesion plays a decisive role in the life cycle of LCs. It controls whether LCs remain immature and sessile within the epidermis or mature and egress to initiate immune responses. So far, the molecular machinery regulating epithelial adhesion molecules during LC maturation remains elusive. Here, we generated pure populations of immature human LCs in vitro to systematically probe for gene-expression changes during LC maturation. LCs down-regulate a set of epithelial genes including E-cadherin, while they upregulate the mesenchymal marker N-cadherin known to facilitate cell migration. In addition, N-cadherin is constitutively expressed by monocyte-derived DCs known to exhibit characteristics of both inflammatory-type and interstitial/dermal DCs. Moreover, the transcription factors ZEB1 and ZEB2 (ZEB is zinc-finger E-box-binding homeobox) are upregulated in migratory LCs. ZEB1 and ZEB2 have been shown to induce epithelial-to-mesenchymal transition (EMT) and invasive behavior in cancer cells undergoing metastasis. Our results provide the first hint that the molecular EMT machinery might facilitate LC mobilization. Moreover, our study suggests that N-cadherin plays a role during DC migration. AU - Konradi, Sabine AU - Yasmin, Nighat AU - Haslwanter, Denise AU - Weber, Michele AU - Gesslbauer, Bernd AU - Sixt, Michael K AU - Strobl, Herbert ID - 1910 IS - 2 JF - European Journal of Immunology TI - Langerhans cell maturation is accompanied by induction of N-cadherin and the transcriptional regulators of epithelial-mesenchymal transition ZEB1/2 VL - 44 ER - TY - CONF AB - Most cryptographic security proofs require showing that two systems are indistinguishable. A central tool in such proofs is that of a game, where winning the game means provoking a certain condition, and it is shown that the two systems considered cannot be distinguished unless this condition is provoked. Upper bounding the probability of winning such a game, i.e., provoking this condition, for an arbitrary strategy is usually hard, except in the special case where the best strategy for winning such a game is known to be non-adaptive. A sufficient criterion for ensuring the optimality of non-adaptive strategies is that of conditional equivalence to a system, a notion introduced in [1]. In this paper, we show that this criterion is not necessary to ensure the optimality of non-adaptive strategies by giving two results of independent interest: 1) the optimality of non-adaptive strategies is not preserved under parallel composition; 2) in contrast, conditional equivalence is preserved under parallel composition. AU - Demay, Grégory AU - Gazi, Peter AU - Maurer, Ueli AU - Tackmann, Björn ID - 1907 T2 - IEEE International Symposium on Information Theory TI - Optimality of non-adaptive strategies: The case of parallel games ER - TY - JOUR AB - In large populations, multiple beneficial mutations may be simultaneously spreading. In asexual populations, these mutations must either arise on the same background or compete against each other. In sexual populations, recombination can bring together beneficial alleles from different backgrounds, but tightly linked alleles may still greatly interfere with each other. We show for well-mixed populations that when this interference is strong, the genome can be seen as consisting of many effectively asexual stretches linked together. The rate at which beneficial alleles fix is thus roughly proportional to the rate of recombination and depends only logarithmically on the mutation supply and the strength of selection. Our scaling arguments also allow us to predict, with reasonable accuracy, the fitness distribution of fixed mutations when the mutational effect sizes are broad. We focus on the regime in which crossovers occur more frequently than beneficial mutations, as is likely to be the case for many natural populations. AU - Weissman, Daniel AU - Hallatschek, Oskar ID - 1908 IS - 4 JF - Genetics TI - The rate of adaptation in large sexual populations with linear chromosomes VL - 196 ER - TY - JOUR AB - The topological Tverberg theorem has been generalized in several directions by setting extra restrictions on the Tverberg partitions. Restricted Tverberg partitions, defined by the idea that certain points cannot be in the same part, are encoded with graphs. When two points are adjacent in the graph, they are not in the same part. If the restrictions are too harsh, then the topological Tverberg theorem fails. The colored Tverberg theorem corresponds to graphs constructed as disjoint unions of small complete graphs. Hell studied the case of paths and cycles. In graph theory these partitions are usually viewed as graph colorings. As explored by Aharoni, Haxell, Meshulam and others there are fundamental connections between several notions of graph colorings and topological combinatorics. For ordinary graph colorings it is enough to require that the number of colors q satisfy q>Δ, where Δ is the maximal degree of the graph. It was proven by the first author using equivariant topology that if q>Δ 2 then the topological Tverberg theorem still works. It is conjectured that q>KΔ is also enough for some constant K, and in this paper we prove a fixed-parameter version of that conjecture. The required topological connectivity results are proven with shellability, which also strengthens some previous partial results where the topological connectivity was proven with the nerve lemma. AU - Engström, Alexander AU - Noren, Patrik ID - 1911 IS - 1 JF - Discrete & Computational Geometry TI - Tverberg's Theorem and Graph Coloring VL - 51 ER - TY - JOUR AB - Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease. AU - Novarino, Gaia AU - Fenstermaker, Ali AU - Zaki, Maha AU - Hofree, Matan AU - Silhavy, Jennifer AU - Heiberg, Andrew AU - Abdellateef, Mostafa AU - Rosti, Başak AU - Scott, Eric AU - Mansour, Lobna AU - Masri, Amira AU - Kayserili, Hülya AU - Al Aama, Jumana AU - Abdel Salam, Ghada AU - Karminejad, Ariana AU - Kara, Majdi AU - Kara, Bülent AU - Bozorgmehri, Bita AU - Ben Omran, Tawfeg AU - Mojahedi, Faezeh AU - Mahmoud, Iman AU - Bouslam, Naïma AU - Bouhouche, Ahmed AU - Benomar, Ali AU - Hanein, Sylvain AU - Raymond, Laure AU - Forlani, Sylvie AU - Mascaro, Massimo AU - Selim, Laila AU - Shehata, Nabil AU - Al Allawi, Nasir AU - Bindu, Parayil AU - Azam, Matloob AU - Günel, Murat AU - Caglayan, Ahmet AU - Bilgüvar, Kaya AU - Tolun, Aslihan AU - Issa, Mahmoud AU - Schroth, Jana AU - Spencer, Emily AU - Rosti, Rasim AU - Akizu, Naiara AU - Vaux, Keith AU - Johansen, Anide AU - Koh, Alice AU - Megahed, Hisham AU - Dürr, Alexandra AU - Brice, Alexis AU - Stévanin, Giovanni AU - Gabriel, Stacy AU - Ideker, Trey AU - Gleeson, Joseph ID - 1916 IS - 6170 JF - Science TI - Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders VL - 343 ER - TY - JOUR AB - Auxin-binding protein 1 (ABP1) was discovered nearly 40 years ago and was shown to be essential for plant development and morphogenesis, but its mode of action remains unclear. Here, we report that the plasma membrane-localized transmembrane kinase (TMK) receptor-like kinases interact with ABP1 and transduce auxin signal to activate plasma membrane-associated ROPs [Rho-like guanosine triphosphatases (GTPase) from plants], leading to changes in the cytoskeleton and the shape of leaf pavement cells in Arabidopsis. The interaction between ABP1 and TMK at the cell surface is induced by auxin and requires ABP1 sensing of auxin. These findings show that TMK proteins and ABP1 form a cell surface auxin perception complex that activates ROP signaling pathways, regulating nontranscriptional cytoplasmic responses and associated fundamental processes. AU - Xu, Tongda AU - Dai, Ning AU - Chen, Jisheng AU - Nagawa, Shingo AU - Cao, Min AU - Li, Hongjiang AU - Zhou, Zimin AU - Chen, Xu AU - De Rycke, Riet AU - Rakusová, Hana AU - Wang, Wen AU - Jones, Alan AU - Friml, Jirí AU - Patterson, Sara AU - Bleecker, Anthony AU - Yang, Zhenbiao ID - 1917 IS - 6174 JF - Science TI - Cell surface ABP1-TMK auxin sensing complex activates ROP GTPase signaling VL - 343 ER - TY - JOUR AB - Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-termadaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short- and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation. AU - Wang, Wen AU - Nakadate, Kazuhiko AU - Masugi Tokita, Miwako AU - Shutoh, Fumihiro AU - Aziz, Wajeeha AU - Tarusawa, Etsuko AU - Lörincz, Andrea AU - Molnár, Elek AU - Kesaf, Sebnem AU - Li, Yunqing AU - Fukazawa, Yugo AU - Nagao, Soichi AU - Shigemoto, Ryuichi ID - 1920 IS - 1 JF - PNAS TI - Distinct cerebellar engrams in short-term and long-term motor learning VL - 111 ER - TY - JOUR AB - ROPs (Rho of plants) belong to a large family of plant-specific Rho-like small GTPases that function as essential molecular switches to control diverse cellular processes including cytoskeleton organization, cell polarization, cytokinesis, cell differentiation and vesicle trafficking. Although the machineries of vesicle trafficking and cell polarity in plants have been individually well addressed, how ROPs co-ordinate those processes is still largely unclear. Recent progress has been made towards an understanding of the coordination of ROP signalling and trafficking of PIN (PINFORMED) transporters for the plant hormone auxin in both root and leaf pavement cells. PIN transporters constantly shuttle between the endosomal compartments and the polar plasma membrane domains, therefore the modulation of PIN-dependent auxin transport between cells is a main developmental output of ROP-regulated vesicle trafficking. The present review focuses on these cellular mechanisms, especially the integration of ROP-based vesicle trafficking and plant cell polarity. AU - Chen, Xu AU - Friml, Jirí ID - 1915 IS - 1 JF - Biochemical Society Transactions SN - 0300-5127 TI - Rho-GTPase-regulated vesicle trafficking in plant cell polarity VL - 42 ER - TY - JOUR AB - Long-lasting memories are formed when the stimulus is temporally distributed (spacing effect). However, the synaptic mechanisms underlying this robust phenomenon and the precise time course of the synaptic modifications that occur during learning remain unclear. Here we examined the adaptation of horizontal optokinetic response in mice that underwent 1 h of massed and spaced training at varying intervals. Despite similar acquisition by all training protocols, 1 h of spacing produced the highest memory retention at 24 h, which lasted for 1 mo. The distinct kinetics of memory are strongly correlated with the reduction of floccular parallel fiber-Purkinje cell synapses but not with AMPA receptor (AMPAR) number and synapse size. After the spaced training, we observed 25%, 23%, and 12% reduction in AMPAR density, synapse size, and synapse number, respectively. Four hours after the spaced training, half of the synapses and Purkinje cell spines had been eliminated, whereas AMPAR density and synapse size were recovered in remaining synapses. Surprisingly, massed training also produced long-term memory and halving of synapses; however, this occurred slowly over days, and the memory lasted for only 1 wk. This distinct kinetics of structural plasticity may serve as a basis for unique temporal profiles in the formation and decay of memory with or without intervals. AU - Aziz, Wajeeha AU - Wang, Wen AU - Kesaf, Sebnem AU - Mohamed, Alsayed AU - Fukazawa, Yugo AU - Shigemoto, Ryuichi ID - 1919 IS - 1 JF - PNAS TI - Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning VL - 111 ER - TY - JOUR AB - As the nuclear charge Z is continuously decreased an N-electron atom undergoes a binding-unbinding transition. We investigate whether the electrons remain bound and whether the radius of the system stays finite as the critical value Zc is approached. Existence of a ground state at Zc is shown under the condition Zc < N-K, where K is the maximal number of electrons that can be removed at Zc without changing the energy. AU - Bellazzini, Jacopo AU - Frank, Rupert AU - Lieb, Élliott AU - Seiringer, Robert ID - 1918 IS - 1 JF - Reviews in Mathematical Physics TI - Existence of ground states for negative ions at the binding threshold VL - 26 ER - TY - JOUR AB - Targeting membrane proteins for degradation requires the sequential action of ESCRT sub-complexes ESCRT-0 to ESCRT-III. Although this machinery is generally conserved among kingdoms, plants lack the essential ESCRT-0 components. A new report closes this gap by identifying a novel protein family that substitutes for ESCRT-0 function in plants. AU - Sauer, Michael AU - Friml, Jirí ID - 1914 IS - 1 JF - Current Biology TI - Plant biology: Gatekeepers of the road to protein perdition VL - 24 ER - TY - JOUR AB - In the past decade carbon nanotubes (CNTs) have been widely studied as a potential drug-delivery system, especially with functionality for cellular targeting. Yet, little is known about the actual process of docking to cell receptors and transport dynamics after internalization. Here we performed single-particle studies of folic acid (FA) mediated CNT binding to human carcinoma cells and their transport inside the cytosol. In particular, we employed molecular recognition force spectroscopy, an atomic force microscopy based method, to visualize and quantify docking of FA functionalized CNTs to FA binding receptors in terms of binding probability and binding force. We then traced individual fluorescently labeled, FA functionalized CNTs after specific uptake, and created a dynamic 'roadmap' that clearly showed trajectories of directed diffusion and areas of nanotube confinement in the cytosol. Our results demonstrate the potential of a single-molecule approach for investigation of drug-delivery vehicles and their targeting capacity. AU - Lamprecht, Constanze AU - Plochberger, Birgit AU - Ruprecht, Verena AU - Wieser, Stefan AU - Rankl, Christian AU - Heister, Elena AU - Unterauer, Barbara AU - Brameshuber, Mario AU - Danzberger, Jürgen AU - Lukanov, Petar AU - Flahaut, Emmanuel AU - Schütz, Gerhard AU - Hinterdorfer, Peter AU - Ebner, Andreas ID - 1925 IS - 12 JF - Nanotechnology TI - A single-molecule approach to explore binding uptake and transport of cancer cell targeting nanotubes VL - 25 ER - TY - JOUR AB - We derive the equations for a thin, axisymmetric elastic shell subjected to an internal active stress giving rise to active tension and moments within the shell. We discuss the stability of a cylindrical elastic shell and its response to a localized change in internal active stress. This description is relevant to describe the cellular actomyosin cortex, a thin shell at the cell surface behaving elastically at a short timescale and subjected to active internal forces arising from myosin molecular motor activity. We show that the recent observations of cell deformation following detachment of adherent cells (Maître J-L et al 2012 Science 338 253-6) are well accounted for by this mechanical description. The actin cortex elastic and bending moduli can be obtained from a quantitative analysis of cell shapes observed in these experiments. Our approach thus provides a non-invasive, imaging-based method for the extraction of cellular physical parameters. AU - Berthoumieux, Hélène AU - Maître, Jean-Léon AU - Heisenberg, Carl-Philipp J AU - Paluch, Ewa AU - Julicher, Frank AU - Salbreux, Guillaume ID - 1923 JF - New Journal of Physics TI - Active elastic thin shell theory for cellular deformations VL - 16 ER - TY - JOUR AB - Cell polarity manifested by asymmetric distribution of cargoes, such as receptors and transporters, within the plasma membrane (PM) is crucial for essential functions in multicellular organisms. In plants, cell polarity (re)establishment is intimately linked to patterning processes. Despite the importance of cell polarity, its underlying mechanisms are still largely unknown, including the definition and distinctiveness of the polar domains within the PM. Here, we show in Arabidopsis thaliana that the signaling membrane components, the phosphoinositides phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4, 5-bisphosphate [PtdIns(4, 5)P2] as well as PtdIns4P 5-kinases mediating their interconversion, are specifically enriched at apical and basal polar plasma membrane domains. The PtdIns4P 5-kinases PIP5K1 and PIP5K2 are redundantly required for polar localization of specifically apical and basal cargoes, such as PIN-FORMED transporters for the plant hormone auxin. As a consequence of the polarity defects, instructive auxin gradients as well as embryonic and postembryonic patterning are severely compromised. Furthermore, auxin itself regulates PIP5K transcription and PtdIns4P and PtdIns(4, 5)P2 levels, in particular their association with polar PM domains. Our results provide insight into the polar domain-delineating mechanisms in plant cells that depend on apical and basal distribution of membrane lipids and are essential for embryonic and postembryonic patterning. AU - Tejos, Ricardo AU - Sauer, Michael AU - Vanneste, Steffen AU - Palacios-Gomez, MiriamPalacios AU - Li, Hongjiang AU - Heilmann, Mareike AU - Van Wijk, Ringo AU - Vermeer, Joop AU - Heilmann, Ingo AU - Munnik, Teun AU - Friml, Jirí ID - 1921 IS - 5 JF - Plant Cell TI - Bipolar plasma membrane distribution of phosphoinositides and their requirement for auxin-mediated cell polarity and patterning in Arabidopsis VL - 26 ER - TY - JOUR AB - Germination of Arabidopsis seeds in darkness induces apical hook development, based on a tightly regulated differential growth coordinated by a multiple hormone cross-talk. Here, we endeavoured to clarify the function of brassinosteroids (BRs) and cross-talk with ethylene in hook development. An automated infrared imaging system was developed to study the kinetics of hook development in etiolated Arabidopsis seedlings. To ascertain the photomorphogenic control of hook opening, the system was equipped with an automatic light dimmer. We demonstrate that ethylene and BRs are indispensable for hook formation and maintenance. Ethylene regulation of hook formation functions partly through BRs, with BR feedback inhibition of ethylene action. Conversely, BR-mediated extension of hook maintenance functions partly through ethylene. Furthermore, we revealed that a short light pulse is sufficient to induce rapid hook opening. Our dynamic infrared imaging system allows high-resolution, kinetic imaging of up to 112 seedlings in a single experimental run. At this high throughput, it is ideally suited to rapidly gain insight in pathway networks. We demonstrate that BRs and ethylene cooperatively regulate apical hook development in a phase-dependent manner. Furthermore, we show that light is a predominant regulator of hook opening, inhibiting ethylene- and BR-mediated postponement of hook opening. AU - Smet, Dajo AU - Žádníková, Petra AU - Vandenbussche, Filip AU - Benková, Eva AU - Van Der Straeten, Dominique ID - 1922 IS - 4 JF - New Phytologist TI - Dynamic infrared imaging analysis of apical hook development in Arabidopsis: The case of brassinosteroids VL - 202 ER - TY - CONF AB - Constrained pseudorandom functions have recently been introduced independently by Boneh and Waters (Asiacrypt’13), Kiayias et al. (CCS’13), and Boyle et al. (PKC’14). In a standard pseudorandom function (PRF) a key k is used to evaluate the PRF on all inputs in the domain. Constrained PRFs additionally offer the functionality to delegate “constrained” keys kS which allow to evaluate the PRF only on a subset S of the domain. The three above-mentioned papers all show that the classical GGM construction (J.ACM’86) of a PRF from a pseudorandom generator (PRG) directly yields a constrained PRF where one can compute constrained keys to evaluate the PRF on all inputs with a given prefix. This constrained PRF has already found many interesting applications. Unfortunately, the existing security proofs only show selective security (by a reduction to the security of the underlying PRG). To achieve full security, one has to use complexity leveraging, which loses an exponential factor 2N in security, where N is the input length. The first contribution of this paper is a new reduction that only loses a quasipolynomial factor qlog N, where q is the number of adversarial queries. For this we develop a new proof technique which constructs a distinguisher by interleaving simple guessing steps and hybrid arguments a small number of times. This approach might be of interest also in other contexts where currently the only technique to achieve full security is complexity leveraging. Our second contribution is concerned with another constrained PRF, due to Boneh and Waters, which allows for constrained keys for the more general class of bit-fixing functions. Their security proof also suffers from a 2N loss, which we show is inherent. We construct a meta-reduction which shows that any “simple” reduction of full security from a noninteractive hardness assumption must incur an exponential security loss. AU - Georg Fuchsbauer AU - Konstantinov, Momchil AU - Krzysztof Pietrzak AU - Rao, Vanishree ID - 1927 TI - Adaptive security of constrained PRFs VL - 8874 ER - TY - JOUR AB - We consider cross products of finite graphs with a class of trees that have arbitrarily but finitely long line segments, such as the Fibonacci tree. Such cross products are called tree-strips. We prove that for small disorder random Schrödinger operators on such tree-strips have purely absolutely continuous spectrum in a certain set. AU - Sadel, Christian ID - 1926 IS - 3-4 JF - Mathematical Physics, Analysis and Geometry TI - Absolutely continuous spectrum for random Schrödinger operators on the Fibonacci and similar Tree-strips VL - 17 ER -