@inproceedings{313, abstract = {Tunneling of a particle through a potential barrier remains one of the most remarkable quantum phenomena. Owing to advances in laser technology, electric fields comparable to those electrons experience in atoms are readily generated and open opportunities to dynamically investigate the process of electron tunneling through the potential barrier formed by the superposition of both laser and atomic fields. Attosecond-time and angstrom-space resolution of the strong laser-field technique allow to address fundamental questions related to tunneling, which are still open and debated: Which time is spent under the barrier and what momentum is picked up by the particle in the meantime? In this combined experimental and theoretical study we demonstrate that for strong-field ionization the leading quantum mechanical Wigner treatment for the time resolved description of tunneling is valid. We achieve a high sensitivity on the tunneling barrier and unambiguously isolate its effects by performing a differential study of two systems with almost identical tunneling geometry. Moreover, working with a low frequency laser, we essentially limit the non-adiabaticity of the process as a major source of uncertainty. The agreement between experiment and theory implies two substantial corrections with respect to the widely employed quasiclassical treatment: In addition to a non-vanishing longitudinal momentum along the laser field-direction we provide clear evidence for a non-zero tunneling time delay. This addresses also the fundamental question how the transition occurs from the tunnel barrier to free space classical evolution of the ejected electron.}, author = {Camus, Nicolas and Yakaboylu, Enderalp and Fechner, Lutz and Klaiber, Michael and Laux, Martin and Mi, Yonghao and Hatsagortsyan, Karen and Pfeifer, Thomas and Keitel, Cristoph and Moshammer, Robert}, issn = {17426588}, location = {Kazan, Russian Federation}, number = {1}, publisher = {American Physical Society}, title = {{Experimental evidence for Wigner's tunneling time}}, doi = {10.1088/1742-6596/999/1/012004}, volume = {999}, year = {2017}, } @article{601, abstract = {The conserved polymerase-Associated factor 1 complex (Paf1C) plays multiple roles in chromatin transcription and genomic regulation. Paf1C comprises the five subunits Paf1, Leo1, Ctr9, Cdc73 and Rtf1, and binds to the RNA polymerase II (Pol II) transcription elongation complex (EC). Here we report the reconstitution of Paf1C from Saccharomyces cerevisiae, and a structural analysis of Paf1C bound to a Pol II EC containing the elongation factor TFIIS. Cryo-electron microscopy and crosslinking data reveal that Paf1C is highly mobile and extends over the outer Pol II surface from the Rpb2 to the Rpb3 subunit. The Paf1-Leo1 heterodimer and Cdc73 form opposite ends of Paf1C, whereas Ctr9 bridges between them. Consistent with the structural observations, the initiation factor TFIIF impairs Paf1C binding to Pol II, whereas the elongation factor TFIIS enhances it. We further show that Paf1C is globally required for normal mRNA transcription in yeast. These results provide a three-dimensional framework for further analysis of Paf1C function in transcription through chromatin. }, author = {Xu, Youwei and Bernecky, Carrie A and Lee, Chung and Maier, Kerstin and Schwalb, Björn and Tegunov, Dimitri and Plitzko, Jürgen and Urlaub, Henning and Cramer, Patrick}, issn = {20411723}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Architecture of the RNA polymerase II-Paf1C-TFIIS transcription elongation complex}}, doi = {10.1038/ncomms15741}, volume = {8}, year = {2017}, } @article{6013, abstract = {The first hundred attoseconds of the electron dynamics during strong field tunneling ionization are investigated. We quantify theoretically how the electron’s classical trajectories in the continuum emerge from the tunneling process and test the results with those achieved in parallel from attoclock measurements. An especially high sensitivity on the tunneling barrier is accomplished here by comparing the momentum distributions of two atomic species of slightly deviating atomic potentials (argon and krypton) being ionized under absolutely identical conditions with near-infrared laser pulses (1300 nm). The agreement between experiment and theory provides clear evidence for a nonzero tunneling time delay and a nonvanishing longitudinal momentum of the electron at the “tunnel exit.”}, author = {Camus, Nicolas and Yakaboylu, Enderalp and Fechner, Lutz and Klaiber, Michael and Laux, Martin and Mi, Yonghao and Hatsagortsyan, Karen Z. and Pfeifer, Thomas and Keitel, Christoph H. and Moshammer, Robert}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {2}, publisher = {American Physical Society}, title = {{Experimental evidence for quantum tunneling time}}, doi = {10.1103/PhysRevLett.119.023201}, volume = {119}, year = {2017}, } @article{603, abstract = {During transcription, RNA polymerase II (Pol II) associates with the conserved elongation factor DSIF. DSIF renders the elongation complex stable and functions during Pol II pausing and RNA processing. We combined cryo-EM and X-ray crystallography to determine the structure of the mammalian Pol II-DSIF elongation complex at a nominal resolution of 3.4. Human DSIF has a modular structure with two domains forming a DNA clamp, two domains forming an RNA clamp, and one domain buttressing the RNA clamp. The clamps maintain the transcription bubble, position upstream DNA, and retain the RNA transcript in the exit tunnel. The mobile C-terminal region of DSIF is located near exiting RNA, where it can recruit factors for RNA processing. The structure provides insight into the roles of DSIF during mRNA synthesis.}, author = {Bernecky, Carrie A and Plitzko, Jürgen and Cramer, Patrick}, issn = {15459993}, journal = {Nature Structural and Molecular Biology}, number = {10}, pages = {809 -- 815}, publisher = {Nature Publishing Group}, title = {{Structure of a transcribing RNA polymerase II-DSIF complex reveals a multidentate DNA-RNA clamp}}, doi = {10.1038/nsmb.3465}, volume = {24}, year = {2017}, } @inproceedings{605, abstract = {Position based cryptography (PBC), proposed in the seminal work of Chandran, Goyal, Moriarty, and Ostrovsky (SIAM J. Computing, 2014), aims at constructing cryptographic schemes in which the identity of the user is his geographic position. Chandran et al. construct PBC schemes for secure positioning and position-based key agreement in the bounded-storage model (Maurer, J. Cryptology, 1992). Apart from bounded memory, their security proofs need a strong additional restriction on the power of the adversary: he cannot compute joint functions of his inputs. Removing this assumption is left as an open problem. We show that an answer to this question would resolve a long standing open problem in multiparty communication complexity: finding a function that is hard to compute with low communication complexity in the simultaneous message model, but easy to compute in the fully adaptive model. On a more positive side: we also show some implications in the other direction, i.e.: we prove that lower bounds on the communication complexity of certain multiparty problems imply existence of PBC primitives. Using this result we then show two attractive ways to “bypass” our hardness result: the first uses the random oracle model, the second weakens the locality requirement in the bounded-storage model to online computability. The random oracle construction is arguably one of the simplest proposed so far in this area. Our results indicate that constructing improved provably secure protocols for PBC requires a better understanding of multiparty communication complexity. This is yet another example where negative results in one area (in our case: lower bounds in multiparty communication complexity) can be used to construct secure cryptographic schemes.}, author = {Brody, Joshua and Dziembowski, Stefan and Faust, Sebastian and Pietrzak, Krzysztof Z}, editor = {Kalai, Yael and Reyzin, Leonid}, isbn = {978-331970499-9}, location = {Baltimore, MD, United States}, pages = {56 -- 81}, publisher = {Springer}, title = {{Position based cryptography and multiparty communication complexity}}, doi = {10.1007/978-3-319-70500-2_3}, volume = {10677}, year = {2017}, } @inbook{604, abstract = {In several settings of physics and chemistry one has to deal with molecules interacting with some kind of an external environment, be it a gas, a solution, or a crystal surface. Understanding molecular processes in the presence of such a many-particle bath is inherently challenging, and usually requires large-scale numerical computations. Here, we present an alternative approach to the problem, based on the notion of the angulon quasiparticle. We show that molecules rotating inside superfluid helium nanodroplets and Bose–Einstein condensates form angulons, and therefore can be described by straightforward solutions of a simple microscopic Hamiltonian. Casting the problem in the language of angulons allows us not only to greatly simplify it, but also to gain insights into the origins of the observed phenomena and to make predictions for future experimental studies.}, author = {Lemeshko, Mikhail and Schmidt, Richard}, booktitle = {Cold Chemistry: Molecular Scattering and Reactivity Near Absolute Zero }, editor = {Dulieu, Oliver and Osterwalder, Andreas}, issn = {20413181}, pages = {444 -- 495}, publisher = {The Royal Society of Chemistry}, title = {{Molecular impurities interacting with a many-particle environment: From ultracold gases to helium nanodroplets}}, doi = {10.1039/9781782626800-00444}, volume = {11}, year = {2017}, } @article{6059, abstract = {Neutrophils or polymorphonuclear cells (PMN) eliminate bacteria via phagocytosis and/or NETosis. Apartfrom these conventional roles, PMN also have immune-regulatory functions. They can transdifferentiateand upregulate MHCII as well as ligands for costimulatory receptors which enables them to behave asantigen presenting cells (APC). The initial step for activating T-cells is the formation of an immunesynapse between T-cells and antigen-presenting cells. However, the immune synapse that develops atthe PMN/T-cell contact zone is as yet hardly investigated due to the non-availability of methods foranalysis of large number of PMN interactions. In order to overcome these obstacles, we introduce herea workflow to analyse the immune synapse of primary human PMN and T-cells using multispectral imag-ing flow cytometry (InFlow microscopy) and super-resolution microscopy. For that purpose, we used CD3and CD66b as the lineage markers for T-cells and PMN, respectively. Thereafter, we applied and criticallydiscussed various ‘‘masks” for identification of T-cell PMN interactions. Using this approach, we foundthat a small fraction of transdifferentiated PMN (CD66b+CD86high) formed stable PMN/T-cell conjugates.Interestingly, while both CD3 and CD66b accumulation in the immune synapse was dependent on thematuration state of the PMN, only CD3 accumulation was greatly enhanced by the presence of superanti-gen. The actin cytoskeleton was weakly rearranged at the PMN side on the immune synapse upon contactwith a T-cell in the presence of superantigen. A more detailed analysis using super-resolution microscopy(structured-illumination microscopy, SIM) confirmed this finding. Together, we present an InFlow micro-scopy based approach for the large scale analysis of PMN/T-cell interactions and – combined with SIM – apossibility for an in-depth analysis of protein translocation at the site of interactions.}, author = {Balta, Emre and Stopp, Julian A and Castelletti, Laura and Kirchgessner, Henning and Samstag, Yvonne and Wabnitz, Guido H.}, issn = {1046-2023}, journal = {Methods}, number = {1}, pages = {25--38}, publisher = {Elsevier}, title = {{Qualitative and quantitative analysis of PMN/T-cell interactions by InFlow and super-resolution microscopy}}, doi = {10.1016/j.ymeth.2016.09.013}, volume = {112}, year = {2017}, } @inproceedings{609, abstract = {Several cryptographic schemes and applications are based on functions that are both reasonably efficient to compute and moderately hard to invert, including client puzzles for Denial-of-Service protection, password protection via salted hashes, or recent proof-of-work blockchain systems. Despite their wide use, a definition of this concept has not yet been distilled and formalized explicitly. Instead, either the applications are proven directly based on the assumptions underlying the function, or some property of the function is proven, but the security of the application is argued only informally. The goal of this work is to provide a (universal) definition that decouples the efforts of designing new moderately hard functions and of building protocols based on them, serving as an interface between the two. On a technical level, beyond the mentioned definitions, we instantiate the model for four different notions of hardness. We extend the work of Alwen and Serbinenko (STOC 2015) by providing a general tool for proving security for the first notion of memory-hard functions that allows for provably secure applications. The tool allows us to recover all of the graph-theoretic techniques developed for proving security under the older, non-composable, notion of security used by Alwen and Serbinenko. As an application of our definition of moderately hard functions, we prove the security of two different schemes for proofs of effort (PoE). We also formalize and instantiate the concept of a non-interactive proof of effort (niPoE), in which the proof is not bound to a particular communication context but rather any bit-string chosen by the prover.}, author = {Alwen, Joel F and Tackmann, Björn}, editor = {Kalai, Yael and Reyzin, Leonid}, isbn = {978-331970499-9}, location = {Baltimore, MD, United States}, pages = {493 -- 526}, publisher = {Springer}, title = {{Moderately hard functions: Definition, instantiations, and applications}}, doi = {10.1007/978-3-319-70500-2_17}, volume = {10677}, year = {2017}, } @article{610, abstract = {The fact that the complete graph K5 does not embed in the plane has been generalized in two independent directions. On the one hand, the solution of the classical Heawood problem for graphs on surfaces established that the complete graph Kn embeds in a closed surface M (other than the Klein bottle) if and only if (n−3)(n−4) ≤ 6b1(M), where b1(M) is the first Z2-Betti number of M. On the other hand, van Kampen and Flores proved that the k-skeleton of the n-dimensional simplex (the higher-dimensional analogue of Kn+1) embeds in R2k if and only if n ≤ 2k + 1. Two decades ago, Kühnel conjectured that the k-skeleton of the n-simplex embeds in a compact, (k − 1)-connected 2k-manifold with kth Z2-Betti number bk only if the following generalized Heawood inequality holds: (k+1 n−k−1) ≤ (k+1 2k+1)bk. This is a common generalization of the case of graphs on surfaces as well as the van Kampen–Flores theorem. In the spirit of Kühnel’s conjecture, we prove that if the k-skeleton of the n-simplex embeds in a compact 2k-manifold with kth Z2-Betti number bk, then n ≤ 2bk(k 2k+2)+2k+4. This bound is weaker than the generalized Heawood inequality, but does not require the assumption that M is (k−1)-connected. Our results generalize to maps without q-covered points, in the spirit of Tverberg’s theorem, for q a prime power. Our proof uses a result of Volovikov about maps that satisfy a certain homological triviality condition.}, author = {Goaoc, Xavier and Mabillard, Isaac and Paták, Pavel and Patakova, Zuzana and Tancer, Martin and Wagner, Uli}, journal = {Israel Journal of Mathematics}, number = {2}, pages = {841 -- 866}, publisher = {Springer}, title = {{On generalized Heawood inequalities for manifolds: A van Kampen–Flores type nonembeddability result}}, doi = {10.1007/s11856-017-1607-7}, volume = {222}, year = {2017}, } @article{6115, abstract = {Animals adjust their behavioral priorities according to momentary needs and prior experience. We show that Caenorhabditis elegans changes how it processes sensory information according to the oxygen environment it experienced recently. C. elegans acclimated to 7% O2 are aroused by CO2 and repelled by pheromones that attract animals acclimated to 21% O2. This behavioral plasticity arises from prolonged activity differences in a circuit that continuously signals O2 levels. A sustained change in the activity of O2-sensing neurons reprograms the properties of their postsynaptic partners, the RMG hub interneurons. RMG is gap-junctionally coupled to the ASK and ADL pheromone sensors that respectively drive pheromone attraction and repulsion. Prior O2 experience has opposite effects on the pheromone responsiveness of these neurons. These circuit changes provide a physiological correlate of altered pheromone valence. Our results suggest C. elegans stores a memory of recent O2 experience in the RMG circuit and illustrate how a circuit is flexibly sculpted to guide behavioral decisions in a context-dependent manner.}, author = {Fenk, Lorenz A. and de Bono, Mario}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {16}, pages = {4195--4200}, publisher = {National Academy of Sciences}, title = {{Memory of recent oxygen experience switches pheromone valence inCaenorhabditis elegans}}, doi = {10.1073/pnas.1618934114}, volume = {114}, year = {2017}, } @article{6117, abstract = {Interleukin-17 (IL-17) is a major pro-inflammatory cytokine: it mediates responses to pathogens or tissue damage, and drives autoimmune diseases. Little is known about its role in the nervous system. Here we show that IL-17 has neuromodulator-like properties in Caenorhabditis elegans. IL-17 can act directly on neurons to alter their response properties and contribution to behaviour. Using unbiased genetic screens, we delineate an IL-17 signalling pathway and show that it acts in the RMG hub interneurons. Disrupting IL-17 signalling reduces RMG responsiveness to input from oxygen sensors, and renders sustained escape from 21% oxygen transient and contingent on additional stimuli. Over-activating IL-17 receptors abnormally heightens responses to 21% oxygen in RMG neurons and whole animals. IL-17 deficiency can be bypassed by optogenetic stimulation of RMG. Inducing IL-17 expression in adults can rescue mutant defects within 6 h. These findings reveal a non-immunological role of IL-17 modulating circuit function and behaviour.}, author = {Chen, Changchun and Itakura, Eisuke and Nelson, Geoffrey M. and Sheng, Ming and Laurent, Patrick and Fenk, Lorenz A. and Butcher, Rebecca A. and Hegde, Ramanujan S. and de Bono, Mario}, issn = {0028-0836}, journal = {Nature}, number = {7639}, pages = {43--48}, publisher = {Springer Nature}, title = {{IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses}}, doi = {10.1038/nature20818}, volume = {542}, year = {2017}, } @article{611, abstract = {Small RNAs (sRNAs) regulate genes in plants and animals. Here, we show that population-wide differences in color patterns in snapdragon flowers are caused by an inverted duplication that generates sRNAs. The complexity and size of the transcripts indicate that the duplication represents an intermediate on the pathway to microRNA evolution. The sRNAs repress a pigment biosynthesis gene, creating a yellow highlight at the site of pollinator entry. The inverted duplication exhibits steep clines in allele frequency in a natural hybrid zone, showing that the allele is under selection. Thus, regulatory interactions of evolutionarily recent sRNAs can be acted upon by selection and contribute to the evolution of phenotypic diversity.}, author = {Bradley, Desmond and Xu, Ping and Mohorianu, Irina and Whibley, Annabel and Field, David and Tavares, Hugo and Couchman, Matthew and Copsey, Lucy and Carpenter, Rosemary and Li, Miaomiao and Li, Qun and Xue, Yongbiao and Dalmay, Tamas and Coen, Enrico}, issn = {00368075}, journal = {Science}, number = {6365}, pages = {925 -- 928}, publisher = {American Association for the Advancement of Science}, title = {{Evolution of flower color pattern through selection on regulatory small RNAs}}, doi = {10.1126/science.aao3526}, volume = {358}, year = {2017}, } @article{6113, author = {Oda, Shigekazu and Toyoshima, Yu and de Bono, Mario}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {23}, pages = {E4658--E4665}, publisher = {National Academy of Sciences}, title = {{Modulation of sensory information processing by a neuroglobin in Caenorhabditis elegans}}, doi = {10.1073/pnas.1614596114}, volume = {114}, year = {2017}, } @article{613, abstract = {Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior.}, author = {Chait, Remy P and Ruess, Jakob and Bergmiller, Tobias and Tkacik, Gasper and Guet, Calin C}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Shaping bacterial population behavior through computer interfaced control of individual cells}}, doi = {10.1038/s41467-017-01683-1}, volume = {8}, year = {2017}, } @article{615, abstract = {We show that the Dyson Brownian Motion exhibits local universality after a very short time assuming that local rigidity and level repulsion of the eigenvalues hold. These conditions are verified, hence bulk spectral universality is proven, for a large class of Wigner-like matrices, including deformed Wigner ensembles and ensembles with non-stochastic variance matrices whose limiting densities differ from Wigner's semicircle law.}, author = {Erdös, László and Schnelli, Kevin}, issn = {02460203}, journal = {Annales de l'institut Henri Poincare (B) Probability and Statistics}, number = {4}, pages = {1606 -- 1656}, publisher = {Institute of Mathematical Statistics}, title = {{Universality for random matrix flows with time dependent density}}, doi = {10.1214/16-AIHP765}, volume = {53}, year = {2017}, } @article{618, abstract = {Background: Increasing temperatures are predicted to strongly impact host-parasite interactions, but empirical tests are rare. Host species that are naturally exposed to a broad temperature spectrum offer the possibility to investigate the effects of elevated temperatures on hosts and parasites. Using three-spined sticklebacks, Gasterosteus aculeatus L., and tapeworms, Schistocephalus solidus (Müller, 1776), originating from a cold and a warm water site of a volcanic lake, we subjected sympatric and allopatric host-parasite combinations to cold and warm conditions in a fully crossed design. We predicted that warm temperatures would promote the development of the parasites, while the hosts might benefit from cooler temperatures. We further expected adaptations to the local temperature and mutual adaptations of local host-parasite pairs. Results: Overall, S. solidus parasites grew faster at warm temperatures and stickleback hosts at cold temperatures. On a finer scale, we observed that parasites were able to exploit their hosts more efficiently at the parasite’s temperature of origin. In contrast, host tolerance towards parasite infection was higher when sticklebacks were infected with parasites at the parasite’s ‘foreign’ temperature. Cold-origin sticklebacks tended to grow faster and parasite infection induced a stronger immune response. Conclusions: Our results suggest that increasing environmental temperatures promote the parasite rather than the host and that host tolerance is dependent on the interaction between parasite infection and temperature. Sticklebacks might use tolerance mechanisms towards parasite infection in combination with their high plasticity towards temperature changes to cope with increasing parasite infection pressures and rising temperatures.}, author = {Franke, Frederik and Armitage, Sophie and Kutzer, Megan and Kurtz, Joachim and Scharsack, Jörn}, issn = {17563305}, journal = {Parasites & Vectors}, number = {252}, publisher = {BioMed Central}, title = {{Environmental temperature variation influences fitness trade-offs in a fish-tapeworm association }}, doi = {10.1186/s13071-017-2192-7}, volume = {10}, year = {2017}, } @inbook{623, abstract = {Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research. Extracerebral influences on the physiology could begin in utero and contribute to changes in the brain and in the development of other body systems and further lead to epigenetic changes. Therefore, multiple recent studies have aimed at elucidating the role of gene-environment interactions in ASD. Here we provide an overview on the extracerebral systems that might play an important associative role in ASD and review evidence regarding the potential roles of inflammation, trace metals, metabolism, genetic susceptibility, enteric nervous system function and the microbiota of the gastrointestinal (GI) tract on the development of endophenotypes in animal models of ASD. By influencing environmental conditions, it might be possible to reduce or limit the severity of ASD pathology.}, author = {Hill Yardin, Elisa and Mckeown, Sonja and Novarino, Gaia and Grabrucker, Andreas}, booktitle = {Translational Anatomy and Cell Biology of Autism Spectrum Disorder}, editor = {Schmeisser, Michael and Boekers, Tobias}, isbn = {978-3-319-52496-2}, issn = {03015556}, pages = {159 -- 187}, publisher = {Springer}, title = {{Extracerebral dysfunction in animal models of autism spectrum disorder}}, doi = {10.1007/978-3-319-52498-6_9}, volume = {224}, year = {2017}, } @article{626, abstract = {Our focus here is on the infinitesimal model. In this model, one or several quantitative traits are described as the sum of a genetic and a non-genetic component, the first being distributed within families as a normal random variable centred at the average of the parental genetic components, and with a variance independent of the parental traits. Thus, the variance that segregates within families is not perturbed by selection, and can be predicted from the variance components. This does not necessarily imply that the trait distribution across the whole population should be Gaussian, and indeed selection or population structure may have a substantial effect on the overall trait distribution. One of our main aims is to identify some general conditions on the allelic effects for the infinitesimal model to be accurate. We first review the long history of the infinitesimal model in quantitative genetics. Then we formulate the model at the phenotypic level in terms of individual trait values and relationships between individuals, but including different evolutionary processes: genetic drift, recombination, selection, mutation, population structure, …. We give a range of examples of its application to evolutionary questions related to stabilising selection, assortative mating, effective population size and response to selection, habitat preference and speciation. We provide a mathematical justification of the model as the limit as the number M of underlying loci tends to infinity of a model with Mendelian inheritance, mutation and environmental noise, when the genetic component of the trait is purely additive. We also show how the model generalises to include epistatic effects. We prove in particular that, within each family, the genetic components of the individual trait values in the current generation are indeed normally distributed with a variance independent of ancestral traits, up to an error of order 1∕M. Simulations suggest that in some cases the convergence may be as fast as 1∕M.}, author = {Barton, Nicholas H and Etheridge, Alison and Véber, Amandine}, issn = {00405809}, journal = {Theoretical Population Biology}, pages = {50 -- 73}, publisher = {Academic Press}, title = {{The infinitesimal model: Definition derivation and implications}}, doi = {10.1016/j.tpb.2017.06.001}, volume = {118}, year = {2017}, } @inbook{625, abstract = {In the analysis of reactive systems a quantitative objective assigns a real value to every trace of the system. The value decision problem for a quantitative objective requires a trace whose value is at least a given threshold, and the exact value decision problem requires a trace whose value is exactly the threshold. We compare the computational complexity of the value and exact value decision problems for classical quantitative objectives, such as sum, discounted sum, energy, and mean-payoff for two standard models of reactive systems, namely, graphs and graph games.}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Henzinger, Thomas A}, booktitle = {Models, Algorithms, Logics and Tools}, editor = {Aceto, Luca and Bacci, Giorgio and Ingólfsdóttir, Anna and Legay, Axel and Mardare, Radu}, isbn = {978-3-319-63120-2}, issn = {0302-9743}, pages = {367 -- 381}, publisher = {Springer}, title = {{The cost of exactness in quantitative reachability}}, doi = {10.1007/978-3-319-63121-9_18}, volume = {10460}, year = {2017}, } @article{624, abstract = {Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allows Escherichia coli to alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin module mazEF that is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigate mazEF expression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest that mazEF transcription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in the grcA reporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein.}, author = {Nikolic, Nela and Didara, Zrinka and Moll, Isabella}, issn = {21678359}, journal = {PeerJ}, number = {9}, publisher = {PeerJ}, title = {{MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations}}, doi = {10.7717/peerj.3830}, volume = {2017}, year = {2017}, } @inproceedings{628, abstract = {We consider the problem of developing automated techniques for solving recurrence relations to aid the expected-runtime analysis of programs. The motivation is that several classical textbook algorithms have quite efficient expected-runtime complexity, whereas the corresponding worst-case bounds are either inefficient (e.g., Quick-Sort), or completely ineffective (e.g., Coupon-Collector). Since the main focus of expected-runtime analysis is to obtain efficient bounds, we consider bounds that are either logarithmic, linear or almost-linear (O(log n), O(n), O(n · log n), respectively, where n represents the input size). Our main contribution is an efficient (simple linear-time algorithm) sound approach for deriving such expected-runtime bounds for the analysis of recurrence relations induced by randomized algorithms. The experimental results show that our approach can efficiently derive asymptotically optimal expected-runtime bounds for recurrences of classical randomized algorithms, including Randomized-Search, Quick-Sort, Quick-Select, Coupon-Collector, where the worst-case bounds are either inefficient (such as linear as compared to logarithmic expected-runtime complexity, or quadratic as compared to linear or almost-linear expected-runtime complexity), or ineffective.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Murhekar, Aniket}, editor = {Majumdar, Rupak and Kunčak, Viktor}, isbn = {978-331963386-2}, location = {Heidelberg, Germany}, pages = {118 -- 139}, publisher = {Springer}, title = {{Automated recurrence analysis for almost linear expected runtime bounds}}, doi = {10.1007/978-3-319-63387-9_6}, volume = {10426}, year = {2017}, } @inbook{629, abstract = {Even simple cells like bacteria have precisely regulated cellular anatomies, which allow them to grow, divide and to respond to internal or external cues with high fidelity. How spatial and temporal intracellular organization in prokaryotic cells is achieved and maintained on the basis of locally interacting proteins still remains largely a mystery. Bulk biochemical assays with purified components and in vivo experiments help us to approach key cellular processes from two opposite ends, in terms of minimal and maximal complexity. However, to understand how cellular phenomena emerge, that are more than the sum of their parts, we have to assemble cellular subsystems step by step from the bottom up. Here, we review recent in vitro reconstitution experiments with proteins of the bacterial cell division machinery and illustrate how they help to shed light on fundamental cellular mechanisms that constitute spatiotemporal order and regulate cell division.}, author = {Loose, Martin and Zieske, Katja and Schwille, Petra}, booktitle = {Prokaryotic Cytoskeletons}, pages = {419 -- 444}, publisher = {Springer}, title = {{Reconstitution of protein dynamics involved in bacterial cell division}}, doi = {10.1007/978-3-319-53047-5_15}, volume = {84}, year = {2017}, } @inproceedings{630, abstract = {Background: Standards have become available to share semantically encoded vital parameters from medical devices, as required for example by personal healthcare records. Standardised sharing of biosignal data largely remains open. Objectives: The goal of this work is to explore available biosignal file format and data exchange standards and profiles, and to conceptualise end-To-end solutions. Methods: The authors reviewed and discussed available biosignal file format standards with other members of international standards development organisations (SDOs). Results: A raw concept for standards based acquisition, storage, archiving and sharing of biosignals was developed. The GDF format may serve for storing biosignals. Signals can then be shared using FHIR resources and may be stored on FHIR servers or in DICOM archives, with DICOM waveforms as one possible format. Conclusion: Currently a group of international SDOs (e.g. HL7, IHE, DICOM, IEEE) is engaged in intensive discussions. This discussion extends existing work that already was adopted by large implementer communities. The concept presented here only reports the current status of the discussion in Austria. The discussion will continue internationally, with results to be expected over the coming years.}, author = {Sauermann, Stefan and David, Veronika and Schlögl, Alois and Egelkraut, Reinhard and Frohner, Matthias and Pohn, Birgit and Urbauer, Philipp and Mense, Alexander}, isbn = {978-161499758-0}, location = {Vienna, Austria}, pages = {356 -- 362}, publisher = {IOS Press}, title = {{Biosignals standards and FHIR: The way to go}}, doi = {10.3233/978-1-61499-759-7-356}, volume = {236}, year = {2017}, } @article{632, abstract = {We consider a 2D quantum system of N bosons in a trapping potential |x|s, interacting via a pair potential of the form N2β−1 w(Nβ x). We show that for all 0 < β < (s + 1)/(s + 2), the leading order behavior of ground states of the many-body system is described in the large N limit by the corresponding cubic nonlinear Schrödinger energy functional. Our result covers the focusing case (w < 0) where even the stability of the many-body system is not obvious. This answers an open question mentioned by X. Chen and J. Holmer for harmonic traps (s = 2). Together with the BBGKY hierarchy approach used by these authors, our result implies the convergence of the many-body quantum dynamics to the focusing NLS equation with harmonic trap for all 0 < β < 3/4. }, author = {Lewin, Mathieu and Nam, Phan and Rougerie, Nicolas}, journal = {Proceedings of the American Mathematical Society}, number = {6}, pages = {2441 -- 2454}, publisher = {American Mathematical Society}, title = {{A note on 2D focusing many boson systems}}, doi = {10.1090/proc/13468}, volume = {145}, year = {2017}, } @inbook{634, abstract = {As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental condition, long-time consensus was that its hallmark features are irreversible. However, several studies from recent years using defined mouse models of ASD have provided clear evidence that in mice neurobiological and behavioural alterations can be ameliorated or even reversed by genetic restoration or pharmacological treatment either before or after symptom onset. Here, we review findings on genetic and pharmacological reversibility of phenotypes in mouse models of ASD. Our review should give a comprehensive overview on both aspects and encourage future studies to better understand the underlying molecular mechanisms that might be translatable from animals to humans.}, author = {Schroeder, Jan and Deliu, Elena and Novarino, Gaia and Schmeisser, Michael}, booktitle = {Translational Anatomy and Cell Biology of Autism Spectrum Disorder}, editor = {Schmeisser, Michael and Boekers, Tobias}, pages = {189 -- 211}, publisher = {Springer}, title = {{Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder}}, doi = {10.1007/978-3-319-52498-6_10}, volume = {224}, year = {2017}, } @inproceedings{633, abstract = {A Rapidly-exploring Random Tree (RRT) is an algorithm which can search a non-convex region of space by incrementally building a space-filling tree. The tree is constructed from random points drawn from system’s state space and is biased to grow towards large unexplored areas in the system. RRT can provide better coverage of a system’s possible behaviors compared with random simulations, but is more lightweight than full reachability analysis. In this paper, we explore some of the design decisions encountered while implementing a hybrid extension of the RRT algorithm, which have not been elaborated on before. In particular, we focus on handling non-determinism, which arises due to discrete transitions. We introduce the notion of important points to account for this phenomena. We showcase our ideas using heater and navigation benchmarks.}, author = {Bak, Stanley and Bogomolov, Sergiy and Henzinger, Thomas A and Kumar, Aviral}, editor = {Abate, Alessandro and Bodo, Sylvie}, isbn = {978-331963500-2}, location = {Heidelberg, Germany}, pages = {83 -- 89}, publisher = {Springer}, title = {{Challenges and tool implementation of hybrid rapidly exploring random trees}}, doi = {10.1007/978-3-319-63501-9_6}, volume = {10381}, year = {2017}, } @inproceedings{635, abstract = {Memory-hard functions (MHFs) are hash algorithms whose evaluation cost is dominated by memory cost. As memory, unlike computation, costs about the same across different platforms, MHFs cannot be evaluated at significantly lower cost on dedicated hardware like ASICs. MHFs have found widespread applications including password hashing, key derivation, and proofs-of-work. This paper focuses on scrypt, a simple candidate MHF designed by Percival, and described in RFC 7914. It has been used within a number of cryptocurrencies (e.g., Litecoin and Dogecoin) and has been an inspiration for Argon2d, one of the winners of the recent password-hashing competition. Despite its popularity, no rigorous lower bounds on its memory complexity are known. We prove that scrypt is optimally memory-hard, i.e., its cumulative memory complexity (cmc) in the parallel random oracle model is Ω(n2w), where w and n are the output length and number of invocations of the underlying hash function, respectively. High cmc is a strong security target for MHFs introduced by Alwen and Serbinenko (STOC’15) which implies high memory cost even for adversaries who can amortize the cost over many evaluations and evaluate the underlying hash functions many times in parallel. Our proof is the first showing optimal memory-hardness for any MHF. Our result improves both quantitatively and qualitatively upon the recent work by Alwen et al. (EUROCRYPT’16) who proved a weaker lower bound of Ω(n2w/ log2 n) for a restricted class of adversaries.}, author = {Alwen, Joel F and Chen, Binchi and Pietrzak, Krzysztof Z and Reyzin, Leonid and Tessaro, Stefano}, editor = {Coron, Jean-Sébastien and Buus Nielsen, Jesper}, isbn = {978-331956616-0}, location = {Paris, France}, pages = {33 -- 62}, publisher = {Springer}, title = {{Scrypt is maximally memory hard}}, doi = {10.1007/978-3-319-56617-7_2}, volume = {10212}, year = {2017}, } @inproceedings{636, abstract = {Signal regular expressions can specify sequential properties of real-valued signals based on threshold conditions, regular operations, and duration constraints. In this paper we endow them with a quantitative semantics which indicates how robustly a signal matches or does not match a given expression. First, we show that this semantics is a safe approximation of a distance between the signal and the language defined by the expression. Then, we consider the robust matching problem, that is, computing the quantitative semantics of every segment of a given signal relative to an expression. We present an algorithm that solves this problem for piecewise-constant and piecewise-linear signals and show that for such signals the robustness map is a piecewise-linear function. The availability of an indicator describing how robustly a signal segment matches some regular pattern provides a general framework for quantitative monitoring of cyber-physical systems.}, author = {Bakhirkin, Alexey and Ferrere, Thomas and Maler, Oded and Ulus, Dogan}, editor = {Abate, Alessandro and Geeraerts, Gilles}, isbn = {978-331965764-6}, location = {Berlin, Germany}, pages = {189 -- 206}, publisher = {Springer}, title = {{On the quantitative semantics of regular expressions over real-valued signals}}, doi = {10.1007/978-3-319-65765-3_11}, volume = {10419}, year = {2017}, } @proceedings{638, abstract = {This book constitutes the refereed proceedings of the 9th InternationalWorkshop on Numerical Software Verification, NSV 2016, held in Toronto, ON, Canada in July 2011 - colocated with CAV 2016, the 28th International Conference on Computer Aided Verification. The NSV workshop is dedicated to the development of logical and mathematical techniques for the reasoning about programmability and reliability.}, editor = {Bogomolov, Sergiy and Martel, Matthieu and Prabhakar, Pavithra}, issn = {0302-9743}, location = {Toronto, ON, Canada}, publisher = {Springer}, title = {{Numerical Software Verification}}, doi = {10.1007/978-3-319-54292-8}, volume = {10152}, year = {2017}, } @inproceedings{640, abstract = {Data-independent Memory Hard Functions (iMHFS) are finding a growing number of applications in security; especially in the domain of password hashing. An important property of a concrete iMHF is specified by fixing a directed acyclic graph (DAG) Gn on n nodes. The quality of that iMHF is then captured by the following two pebbling complexities of Gn: – The parallel cumulative pebbling complexity Π∥cc(Gn) must be as high as possible (to ensure that the amortized cost of computing the function on dedicated hardware is dominated by the cost of memory). – The sequential space-time pebbling complexity Πst(Gn) should be as close as possible to Π∥cc(Gn) (to ensure that using many cores in parallel and amortizing over many instances does not give much of an advantage). In this paper we construct a family of DAGs with best possible parameters in an asymptotic sense, i.e., where Π∥cc(Gn) = Ω(n2/ log(n)) (which matches a known upper bound) and Πst(Gn) is within a constant factor of Π∥cc(Gn). Our analysis relies on a new connection between the pebbling complexity of a DAG and its depth-robustness (DR) – a well studied combinatorial property. We show that high DR is sufficient for high Π∥cc. Alwen and Blocki (CRYPTO’16) showed that high DR is necessary and so, together, these results fully characterize DAGs with high Π∥cc in terms of DR. Complementing these results, we provide new upper and lower bounds on the Π∥cc of several important candidate iMHFs from the literature. We give the first lower bounds on the memory hardness of the Catena and Balloon Hashing functions in a parallel model of computation and we give the first lower bounds of any kind for (a version) of Argon2i. Finally we describe a new class of pebbling attacks improving on those of Alwen and Blocki (CRYPTO’16). By instantiating these attacks we upperbound the Π∥cc of the Password Hashing Competition winner Argon2i and one of the Balloon Hashing functions by O (n1.71). We also show an upper bound of O(n1.625) for the Catena functions and the two remaining Balloon Hashing functions.}, author = {Alwen, Joel F and Blocki, Jeremiah and Pietrzak, Krzysztof Z}, editor = {Coron, Jean-Sébastien and Buus Nielsen, Jesper}, isbn = {978-331956616-0}, location = {Paris, France}, pages = {3 -- 32}, publisher = {Springer}, title = {{Depth-robust graphs and their cumulative memory complexity}}, doi = {10.1007/978-3-319-56617-7_1}, volume = {10212}, year = {2017}, } @inproceedings{641, abstract = {We introduce two novel methods for learning parameters of graphical models for image labelling. The following two tasks underline both methods: (i) perturb model parameters based on given features and ground truth labelings, so as to exactly reproduce these labelings as optima of the local polytope relaxation of the labelling problem; (ii) train a predictor for the perturbed model parameters so that improved model parameters can be applied to the labelling of novel data. Our first method implements task (i) by inverse linear programming and task (ii) using a regressor e.g. a Gaussian process. Our second approach simultaneously solves tasks (i) and (ii) in a joint manner, while being restricted to linearly parameterised predictors. Experiments demonstrate the merits of both approaches.}, author = {Trajkovska, Vera and Swoboda, Paul and Åström, Freddie and Petra, Stefanie}, editor = {Lauze, François and Dong, Yiqiu and Bjorholm Dahl, Anders}, isbn = {978-331958770-7}, location = {Kolding, Denmark}, pages = {323 -- 334}, publisher = {Springer}, title = {{Graphical model parameter learning by inverse linear programming}}, doi = {10.1007/978-3-319-58771-4_26}, volume = {10302}, year = {2017}, } @misc{6426, abstract = {Synchronous programs are easy to specify because the side effects of an operation are finished by the time the invocation of the operation returns to the caller. Asynchronous programs, on the other hand, are difficult to specify because there are side effects due to pending computation scheduled as a result of the invocation of an operation. They are also difficult to verify because of the large number of possible interleavings of concurrent asynchronous computation threads. We show that specifications and correctness proofs for asynchronous programs can be structured by introducing the fiction, for proof purposes, that intermediate, non-quiescent states of asynchronous operations can be ignored. Then, the task of specification becomes relatively simple and the task of verification can be naturally decomposed into smaller sub-tasks. The sub-tasks iteratively summarize, guided by the structure of an asynchronous program, the atomic effect of non-atomic operations and the synchronous effect of asynchronous operations. This structuring of specifications and proofs corresponds to the introduction of multiple layers of stepwise refinement for asynchronous programs. We present the first proof rule, called synchronization, to reduce asynchronous invocations on a lower layer to synchronous invocations on a higher layer. We implemented our proof method in CIVL and evaluated it on a collection of benchmark programs.}, author = {Henzinger, Thomas A and Kragl, Bernhard and Qadeer, Shaz}, issn = {2664-1690}, pages = {28}, publisher = {IST Austria}, title = {{Synchronizing the asynchronous}}, doi = {10.15479/AT:IST-2018-853-v2-2}, year = {2017}, } @article{643, abstract = {It has been reported that nicotinamide-overload induces oxidative stress associated with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance tests (GTT) were carried out in adult Sprague-Dawley rats treated with or without cumulative doses of B vitamins. More specifically, insulin tolerance tests (ITT) were also carried out in adult Sprague-Dawley rats treated with or without cumulative doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration significantly increased the plasma H2O2 levels associated with high insulin levels. Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration of nicotinic acid, another form of Vitamin B3, also significantly increased plasma insulin level and H2O2 generation. Moreover, cumulative administration of nicotinic acid or nicotinamide impaired glucose metabolism. This study suggested that excess Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance.}, author = {Sun, Wuping and Zhai, Ming-Zhu and Zhou, Qian and Qian, Chengrui and Jiang, Changyu}, issn = {03044920}, journal = {Chinese Journal of Physiology}, number = {4}, pages = {207 -- 214}, publisher = {Chinese Physiological Society}, title = {{Effects of B vitamins overload on plasma insulin level and hydrogen peroxide generation in rats}}, doi = {10.4077/CJP.2017.BAF469}, volume = {60}, year = {2017}, } @article{642, abstract = {Cauchy problems with SPDEs on the whole space are localized to Cauchy problems on a ball of radius R. This localization reduces various kinds of spatial approximation schemes to finite dimensional problems. The error is shown to be exponentially small. As an application, a numerical scheme is presented which combines the localization and the space and time discretization, and thus is fully implementable.}, author = {Gerencser, Mate and Gyöngy, István}, issn = {00255718}, journal = {Mathematics of Computation}, number = {307}, pages = {2373 -- 2397}, publisher = {American Mathematical Society}, title = {{Localization errors in solving stochastic partial differential equations in the whole space}}, doi = {10.1090/mcom/3201}, volume = {86}, year = {2017}, } @inproceedings{645, abstract = {Markov decision processes (MDPs) are standard models for probabilistic systems with non-deterministic behaviours. Long-run average rewards provide a mathematically elegant formalism for expressing long term performance. Value iteration (VI) is one of the simplest and most efficient algorithmic approaches to MDPs with other properties, such as reachability objectives. Unfortunately, a naive extension of VI does not work for MDPs with long-run average rewards, as there is no known stopping criterion. In this work our contributions are threefold. (1) We refute a conjecture related to stopping criteria for MDPs with long-run average rewards. (2) We present two practical algorithms for MDPs with long-run average rewards based on VI. First, we show that a combination of applying VI locally for each maximal end-component (MEC) and VI for reachability objectives can provide approximation guarantees. Second, extending the above approach with a simulation-guided on-demand variant of VI, we present an anytime algorithm that is able to deal with very large models. (3) Finally, we present experimental results showing that our methods significantly outperform the standard approaches on several benchmarks.}, author = {Ashok, Pranav and Chatterjee, Krishnendu and Daca, Przemyslaw and Kretinsky, Jan and Meggendorfer, Tobias}, editor = {Majumdar, Rupak and Kunčak, Viktor}, isbn = {978-331963386-2}, location = {Heidelberg, Germany}, pages = {201 -- 221}, publisher = {Springer}, title = {{Value iteration for long run average reward in markov decision processes}}, doi = {10.1007/978-3-319-63387-9_10}, volume = {10426}, year = {2017}, } @article{644, abstract = {An instance of the valued constraint satisfaction problem (VCSP) is given by a finite set of variables, a finite domain of labels, and a sum of functions, each function depending on a subset of the variables. Each function can take finite values specifying costs of assignments of labels to its variables or the infinite value, which indicates an infeasible assignment. The goal is to find an assignment of labels to the variables that minimizes the sum. We study, assuming that P 6= NP, how the complexity of this very general problem depends on the set of functions allowed in the instances, the so-called constraint language. The case when all allowed functions take values in f0;1g corresponds to ordinary CSPs, where one deals only with the feasibility issue, and there is no optimization. This case is the subject of the algebraic CSP dichotomy conjecture predicting for which constraint languages CSPs are tractable (i.e., solvable in polynomial time) and for which they are NP-hard. The case when all allowed functions take only finite values corresponds to a finitevalued CSP, where the feasibility aspect is trivial and one deals only with the optimization issue. The complexity of finite-valued CSPs was fully classified by Thapper and Živný. An algebraic necessary condition for tractability of a general-valued CSP with a fixed constraint language was recently given by Kozik and Ochremiak. As our main result, we prove that if a constraint language satisfies this algebraic necessary condition, and the feasibility CSP (i.e., the problem of deciding whether a given instance has a feasible solution) corresponding to the VCSP with this language is tractable, then the VCSP is tractable. The algorithm is a simple combination of the assumed algorithm for the feasibility CSP and the standard LP relaxation. As a corollary, we obtain that a dichotomy for ordinary CSPs would imply a dichotomy for general-valued CSPs.}, author = {Kolmogorov, Vladimir and Krokhin, Andrei and Rolinek, Michal}, journal = {SIAM Journal on Computing}, number = {3}, pages = {1087 -- 1110}, publisher = {SIAM}, title = {{The complexity of general-valued CSPs}}, doi = {10.1137/16M1091836}, volume = {46}, year = {2017}, } @inproceedings{646, abstract = {We present a novel convex relaxation and a corresponding inference algorithm for the non-binary discrete tomography problem, that is, reconstructing discrete-valued images from few linear measurements. In contrast to state of the art approaches that split the problem into a continuous reconstruction problem for the linear measurement constraints and a discrete labeling problem to enforce discrete-valued reconstructions, we propose a joint formulation that addresses both problems simultaneously, resulting in a tighter convex relaxation. For this purpose a constrained graphical model is set up and evaluated using a novel relaxation optimized by dual decomposition. We evaluate our approach experimentally and show superior solutions both mathematically (tighter relaxation) and experimentally in comparison to previously proposed relaxations.}, author = {Kuske, Jan and Swoboda, Paul and Petra, Stefanie}, editor = {Lauze, François and Dong, Yiqiu and Bjorholm Dahl, Anders}, isbn = {978-331958770-7}, location = {Kolding, Denmark}, pages = {235 -- 246}, publisher = {Springer}, title = {{A novel convex relaxation for non binary discrete tomography}}, doi = {10.1007/978-3-319-58771-4_19}, volume = {10302}, year = {2017}, } @inproceedings{648, abstract = {Pseudoentropy has found a lot of important applications to cryptography and complexity theory. In this paper we focus on the foundational problem that has not been investigated so far, namely by how much pseudoentropy (the amount seen by computationally bounded attackers) differs from its information-theoretic counterpart (seen by unbounded observers), given certain limits on attacker’s computational power? We provide the following answer for HILL pseudoentropy, which exhibits a threshold behavior around the size exponential in the entropy amount:– If the attacker size (s) and advantage () satisfy s (formula presented) where k is the claimed amount of pseudoentropy, then the pseudoentropy boils down to the information-theoretic smooth entropy. – If s (formula presented) then pseudoentropy could be arbitrarily bigger than the information-theoretic smooth entropy. Besides answering the posted question, we show an elegant application of our result to the complexity theory, namely that it implies the clas-sical result on the existence of functions hard to approximate (due to Pippenger). In our approach we utilize non-constructive techniques: the duality of linear programming and the probabilistic method.}, author = {Skórski, Maciej}, editor = {Jäger, Gerhard and Steila, Silvia}, isbn = {978-331955910-0}, location = {Bern, Switzerland}, pages = {600 -- 613}, publisher = {Springer}, title = {{On the complexity of breaking pseudoentropy}}, doi = {10.1007/978-3-319-55911-7_43}, volume = {10185}, year = {2017}, } @inbook{649, abstract = {We give a short overview on a recently developed notion of Ricci curvature for discrete spaces. This notion relies on geodesic convexity properties of the relative entropy along geodesics in the space of probability densities, for a metric which is similar to (but different from) the 2-Wasserstein metric. The theory can be considered as a discrete counterpart to the theory of Ricci curvature for geodesic measure spaces developed by Lott–Sturm–Villani.}, author = {Maas, Jan}, booktitle = {Modern Approaches to Discrete Curvature}, editor = {Najman, Laurent and Romon, Pascal}, isbn = {978-3-319-58001-2}, issn = {978-3-319-58002-9}, pages = {159 -- 174}, publisher = {Springer}, title = {{Entropic Ricci curvature for discrete spaces}}, doi = {10.1007/978-3-319-58002-9_5}, volume = {2184}, year = {2017}, } @inproceedings{650, abstract = {In this work we present a short and unified proof for the Strong and Weak Regularity Lemma, based on the cryptographic tech-nique called low-complexity approximations. In short, both problems reduce to a task of finding constructively an approximation for a certain target function under a class of distinguishers (test functions), where dis-tinguishers are combinations of simple rectangle-indicators. In our case these approximations can be learned by a simple iterative procedure, which yields a unified and simple proof, achieving for any graph with density d and any approximation parameter the partition size. The novelty in our proof is: (a) a simple approach which yields both strong and weaker variant, and (b) improvements when d = o(1). At an abstract level, our proof can be seen a refinement and simplification of the “analytic” proof given by Lovasz and Szegedy.}, author = {Skórski, Maciej}, editor = {Jäger, Gerhard and Steila, Silvia}, issn = {03029743}, location = {Bern, Switzerland}, pages = {586 -- 599}, publisher = {Springer}, title = {{A cryptographic view of regularity lemmas: Simpler unified proofs and refined bounds}}, doi = {10.1007/978-3-319-55911-7_42}, volume = {10185}, year = {2017}, } @inproceedings{6519, abstract = {Graph games with omega-regular winning conditions provide a mathematical framework to analyze a wide range of problems in the analysis of reactive systems and programs (such as the synthesis of reactive systems, program repair, and the verification of branching time properties). Parity conditions are canonical forms to specify omega-regular winning conditions. Graph games with parity conditions are equivalent to mu-calculus model checking, and thus a very important algorithmic problem. Symbolic algorithms are of great significance because they provide scalable algorithms for the analysis of large finite-state systems, as well as algorithms for the analysis of infinite-state systems with finite quotient. A set-based symbolic algorithm uses the basic set operations and the one-step predecessor operators. We consider graph games with n vertices and parity conditions with c priorities (equivalently, a mu-calculus formula with c alternations of least and greatest fixed points). While many explicit algorithms exist for graph games with parity conditions, for set-based symbolic algorithms there are only two algorithms (notice that we use space to refer to the number of sets stored by a symbolic algorithm): (a) the basic algorithm that requires O(n^c) symbolic operations and linear space; and (b) an improved algorithm that requires O(n^{c/2+1}) symbolic operations but also O(n^{c/2+1}) space (i.e., exponential space). In this work we present two set-based symbolic algorithms for parity games: (a) our first algorithm requires O(n^{c/2+1}) symbolic operations and only requires linear space; and (b) developing on our first algorithm, we present an algorithm that requires O(n^{c/3+1}) symbolic operations and only linear space. We also present the first linear space set-based symbolic algorithm for parity games that requires at most a sub-exponential number of symbolic operations. }, author = {Chatterjee, Krishnendu and Dvorák, Wolfgang and Henzinger, Monika H and Loitzenbauer, Veronika}, location = {Stockholm, Sweden}, publisher = {Schloss Dagstuhl -Leibniz-Zentrum fuer Informatik}, title = {{Improved set-based symbolic algorithms for parity games}}, doi = {10.4230/LIPICS.CSL.2017.18}, volume = {82}, year = {2017}, } @inproceedings{6517, abstract = {A (possibly degenerate) drawing of a graph G in the plane is approximable by an embedding if it can be turned into an embedding by an arbitrarily small perturbation. We show that testing, whether a drawing of a planar graph G in the plane is approximable by an embedding, can be carried out in polynomial time, if a desired embedding of G belongs to a fixed isotopy class, i.e., the rotation system (or equivalently the faces) of the embedding of G and the choice of outer face are fixed. In other words, we show that c-planarity with embedded pipes is tractable for graphs with fixed embeddings. To the best of our knowledge an analogous result was previously known essentially only when G is a cycle.}, author = {Fulek, Radoslav}, location = {Phuket, Thailand}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Embedding graphs into embedded graphs}}, doi = {10.4230/LIPICS.ISAAC.2017.34}, volume = {92}, year = {2017}, } @inproceedings{652, abstract = {We present an approach that enables robots to self-organize their sensorimotor behavior from scratch without providing specific information about neither the robot nor its environment. This is achieved by a simple neural control law that increases the consistency between external sensor dynamics and internal neural dynamics of the utterly simple controller. In this way, the embodiment and the agent-environment coupling are the only source of individual development. We show how an anthropomorphic tendon driven arm-shoulder system develops different behaviors depending on that coupling. For instance: Given a bottle half-filled with water, the arm starts to shake it, driven by the physical response of the water. When attaching a brush, the arm can be manipulated into wiping a table, and when connected to a revolvable wheel it finds out how to rotate it. Thus, the robot may be said to discover the affordances of the world. When allowing two (simulated) humanoid robots to interact physically, they engage into a joint behavior development leading to, for instance, spontaneous cooperation. More social effects are observed if the robots can visually perceive each other. Although, as an observer, it is tempting to attribute an apparent intentionality, there is nothing of the kind put in. As a conclusion, we argue that emergent behavior may be much less rooted in explicit intentions, internal motivations, or specific reward systems than is commonly believed.}, author = {Der, Ralf and Martius, Georg S}, isbn = {978-150905069-7}, location = {Cergy-Pontoise, France}, publisher = {IEEE}, title = {{Dynamical self consistency leads to behavioral development and emergent social interactions in robots}}, doi = {10.1109/DEVLRN.2016.7846789}, year = {2017}, } @article{651, abstract = {Superhydrophobic surfaces reduce the frictional drag between water and solid materials, but this effect is often temporary. The realization of sustained drag reduction has applications for water vehicles and pipeline flows. }, author = {Hof, Björn}, issn = {00280836}, journal = {Nature}, number = {7636}, pages = {161 -- 162}, publisher = {Nature Publishing Group}, title = {{Fluid dynamics: Water flows out of touch}}, doi = {10.1038/541161a}, volume = {541}, year = {2017}, } @article{653, abstract = {The extent of heterogeneity among driver gene mutations present in naturally occurring metastases - that is, treatment-naive metastatic disease - is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity. Even with respect to these passenger mutations, our analysis suggests that the genetic similarity among the founding cells of metastases was higher than that expected for any two cells randomly taken from a normal tissue. The uniformity of known driver gene mutations among metastases in the same patient has critical and encouraging implications for the success of future targeted therapies in advanced-stage disease.}, author = {Makohon Moore, Alvin and Zhang, Ming and Reiter, Johannes and Božić, Ivana and Allen, Benjamin and Kundu, Deepanjan and Chatterjee, Krishnendu and Wong, Fay and Jiao, Yuchen and Kohutek, Zachary and Hong, Jungeui and Attiyeh, Marc and Javier, Breanna and Wood, Laura and Hruban, Ralph and Nowak, Martin and Papadopoulos, Nickolas and Kinzler, Kenneth and Vogelstein, Bert and Iacobuzio Donahue, Christine}, issn = {10614036}, journal = {Nature Genetics}, number = {3}, pages = {358 -- 366}, publisher = {Nature Publishing Group}, title = {{Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer}}, doi = {10.1038/ng.3764}, volume = {49}, year = {2017}, } @inproceedings{6527, abstract = {A memory-hard function (MHF) ƒn with parameter n can be computed in sequential time and space n. Simultaneously, a high amortized parallel area-time complexity (aAT) is incurred per evaluation. In practice, MHFs are used to limit the rate at which an adversary (using a custom computational device) can evaluate a security sensitive function that still occasionally needs to be evaluated by honest users (using an off-the-shelf general purpose device). The most prevalent examples of such sensitive functions are Key Derivation Functions (KDFs) and password hashing algorithms where rate limits help mitigate off-line dictionary attacks. As the honest users' inputs to these functions are often (low-entropy) passwords special attention is given to a class of side-channel resistant MHFs called iMHFs. Essentially all iMHFs can be viewed as some mode of operation (making n calls to some round function) given by a directed acyclic graph (DAG) with very low indegree. Recently, a combinatorial property of a DAG has been identified (called "depth-robustness") which results in good provable security for an iMHF based on that DAG. Depth-robust DAGs have also proven useful in other cryptographic applications. Unfortunately, up till now, all known very depth-robust DAGs are impractically complicated and little is known about their exact (i.e. non-asymptotic) depth-robustness both in theory and in practice. In this work we build and analyze (both formally and empirically) several exceedingly simple and efficient to navigate practical DAGs for use in iMHFs and other applications. For each DAG we: *Prove that their depth-robustness is asymptotically maximal. *Prove bounds of at least 3 orders of magnitude better on their exact depth-robustness compared to known bounds for other practical iMHF. *Implement and empirically evaluate their depth-robustness and aAT against a variety of state-of-the art (and several new) depth-reduction and low aAT attacks. We find that, against all attacks, the new DAGs perform significantly better in practice than Argon2i, the most widely deployed iMHF in practice. Along the way we also improve the best known empirical attacks on the aAT of Argon2i by implementing and testing several heuristic versions of a (hitherto purely theoretical) depth-reduction attack. Finally, we demonstrate practicality of our constructions by modifying the Argon2i code base to use one of the new high aAT DAGs. Experimental benchmarks on a standard off-the-shelf CPU show that the new modifications do not adversely affect the impressive throughput of Argon2i (despite seemingly enjoying significantly higher aAT). }, author = {Alwen, Joel F and Blocki, Jeremiah and Harsha, Ben}, booktitle = {Proceedings of the 2017 ACM SIGSAC Conference on Computer and Communications Security}, isbn = {9781450349468}, location = {Dallas, TX, USA}, pages = {1001--1017}, publisher = {ACM Press}, title = {{Practical graphs for optimal side-channel resistant memory-hard functions}}, doi = {10.1145/3133956.3134031}, year = {2017}, } @article{654, abstract = {In November 2016, developmental biologists, synthetic biologists and engineers gathered in Paris for a meeting called ‘Engineering the embryo’. The participants shared an interest in exploring how synthetic systems can reveal new principles of embryonic development, and how the in vitro manipulation and modeling of development using stem cells can be used to integrate ideas and expertise from physics, developmental biology and tissue engineering. As we review here, the conference pinpointed some of the challenges arising at the intersection of these fields, along with great enthusiasm for finding new approaches and collaborations.}, author = {Kicheva, Anna and Rivron, Nicolas}, issn = {09501991}, journal = {Development}, number = {5}, pages = {733 -- 736}, publisher = {Company of Biologists}, title = {{Creating to understand – developmental biology meets engineering in Paris}}, doi = {10.1242/dev.144915}, volume = {144}, year = {2017}, } @inproceedings{6526, abstract = {This paper studies the complexity of estimating Rényi divergences of discrete distributions: p observed from samples and the baseline distribution q known a priori. Extending the results of Acharya et al. (SODA'15) on estimating Rényi entropy, we present improved estimation techniques together with upper and lower bounds on the sample complexity. We show that, contrarily to estimating Rényi entropy where a sublinear (in the alphabet size) number of samples suffices, the sample complexity is heavily dependent on events occurring unlikely in q, and is unbounded in general (no matter what an estimation technique is used). For any divergence of integer order bigger than 1, we provide upper and lower bounds on the number of samples dependent on probabilities of p and q (the lower bounds hold for non-integer orders as well). We conclude that the worst-case sample complexity is polynomial in the alphabet size if and only if the probabilities of q are non-negligible. This gives theoretical insights into heuristics used in the applied literature to handle numerical instability, which occurs for small probabilities of q. Our result shows that they should be handled with care not only because of numerical issues, but also because of a blow up in the sample complexity.}, author = {Skórski, Maciej}, booktitle = {2017 IEEE International Symposium on Information Theory (ISIT)}, isbn = {9781509040964}, location = {Aachen, Germany}, publisher = {IEEE}, title = {{On the complexity of estimating Rènyi divergences}}, doi = {10.1109/isit.2017.8006529}, year = {2017}, } @article{655, abstract = {The bacterial flagellum is a self-assembling nanomachine. The external flagellar filament, several times longer than a bacterial cell body, is made of a few tens of thousands subunits of a single protein: flagellin. A fundamental problem concerns the molecular mechanism of how the flagellum grows outside the cell, where no discernible energy source is available. Here, we monitored the dynamic assembly of individual flagella using in situ labelling and real-time immunostaining of elongating flagellar filaments. We report that the rate of flagellum growth, initially ~1,700 amino acids per second, decreases with length and that the previously proposed chain mechanism does not contribute to the filament elongation dynamics. Inhibition of the proton motive force-dependent export apparatus revealed a major contribution of substrate injection in driving filament elongation. The combination of experimental and mathematical evidence demonstrates that a simple, injection-diffusion mechanism controls bacterial flagella growth outside the cell.}, author = {Renault, Thibaud and Abraham, Anthony and Bergmiller, Tobias and Paradis, Guillaume and Rainville, Simon and Charpentier, Emmanuelle and Guet, Calin C and Tu, Yuhai and Namba, Keiichi and Keener, James and Minamino, Tohru and Erhardt, Marc}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Bacterial flagella grow through an injection diffusion mechanism}}, doi = {10.7554/eLife.23136}, volume = {6}, year = {2017}, } @article{657, abstract = {Plant organs are typically organized into three main tissue layers. The middle ground tissue layer comprises the majority of the plant body and serves a wide range of functions, including photosynthesis, selective nutrient uptake and storage, and gravity sensing. Ground tissue patterning and maintenance in Arabidopsis are controlled by a well-established gene network revolving around the key regulator SHORT-ROOT (SHR). In contrast, it is completely unknown how ground tissue identity is first specified from totipotent precursor cells in the embryo. The plant signaling molecule auxin, acting through AUXIN RESPONSE FACTOR (ARF) transcription factors, is critical for embryo patterning. The auxin effector ARF5/MONOPTEROS (MP) acts both cell-autonomously and noncell-autonomously to control embryonic vascular tissue formation and root initiation, respectively. Here we show that auxin response and ARF activity cell-autonomously control the asymmetric division of the first ground tissue cells. By identifying embryonic target genes, we show that MP transcriptionally initiates the ground tissue lineage and acts upstream of the regulatory network that controls ground tissue patterning and maintenance. Strikingly, whereas the SHR network depends on MP, this MP function is, at least in part, SHR independent. Our study therefore identifies auxin response as a regulator of ground tissue specification in the embryonic root, and reveals that ground tissue initiation and maintenance use different regulators and mechanisms. Moreover, our data provide a framework for the simultaneous formation of multiple cell types by the same transcriptional regulator.}, author = {Möller, Barbara and Ten Hove, Colette and Xiang, Daoquan and Williams, Nerys and López, Lorena and Yoshida, Saiko and Smit, Margot and Datla, Raju and Weijers, Dolf}, issn = {00278424}, journal = {PNAS}, number = {12}, pages = {E2533 -- E2539}, publisher = {National Academy of Sciences}, title = {{Auxin response cell autonomously controls ground tissue initiation in the early arabidopsis embryo}}, doi = {10.1073/pnas.1616493114}, volume = {114}, year = {2017}, } @article{656, abstract = {Human neurons transplanted into a mouse model for Alzheimer’s disease show human-specific vulnerability to β-amyloid plaques and may help to identify new therapeutic targets.}, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {381}, publisher = {American Association for the Advancement of Science}, title = {{Modeling Alzheimer's disease in mice with human neurons}}, doi = {10.1126/scitranslmed.aam9867}, volume = {9}, year = {2017}, } @article{658, abstract = {With the accelerated development of robot technologies, control becomes one of the central themes of research. In traditional approaches, the controller, by its internal functionality, finds appropriate actions on the basis of specific objectives for the task at hand. While very successful in many applications, self-organized control schemes seem to be favored in large complex systems with unknown dynamics or which are difficult to model. Reasons are the expected scalability, robustness, and resilience of self-organizing systems. The paper presents a self-learning neurocontroller based on extrinsic differential plasticity introduced recently, applying it to an anthropomorphic musculoskeletal robot arm with attached objects of unknown physical dynamics. The central finding of the paper is the following effect: by the mere feedback through the internal dynamics of the object, the robot is learning to relate each of the objects with a very specific sensorimotor pattern. Specifically, an attached pendulum pilots the arm into a circular motion, a half-filled bottle produces axis oriented shaking behavior, a wheel is getting rotated, and wiping patterns emerge automatically in a table-plus-brush setting. By these object-specific dynamical patterns, the robot may be said to recognize the object's identity, or in other words, it discovers dynamical affordances of objects. Furthermore, when including hand coordinates obtained from a camera, a dedicated hand-eye coordination self-organizes spontaneously. These phenomena are discussed from a specific dynamical system perspective. Central is the dedicated working regime at the border to instability with its potentially infinite reservoir of (limit cycle) attractors "waiting" to be excited. Besides converging toward one of these attractors, variate behavior is also arising from a self-induced attractor morphing driven by the learning rule. We claim that experimental investigations with this anthropomorphic, self-learning robot not only generate interesting and potentially useful behaviors, but may also help to better understand what subjective human muscle feelings are, how they can be rooted in sensorimotor patterns, and how these concepts may feed back on robotics.}, author = {Der, Ralf and Martius, Georg S}, issn = {16625218}, journal = {Frontiers in Neurorobotics}, number = {MAR}, publisher = {Frontiers Research Foundation}, title = {{Self organized behavior generation for musculoskeletal robots}}, doi = {10.3389/fnbot.2017.00008}, volume = {11}, year = {2017}, } @article{659, abstract = {Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.}, author = {Kage, Frieda and Winterhoff, Moritz and Dimchev, Vanessa and Müller, Jan and Thalheim, Tobias and Freise, Anika and Brühmann, Stefan and Kollasser, Jana and Block, Jennifer and Dimchev, Georgi A and Geyer, Matthias and Schnittler, Hams and Brakebusch, Cord and Stradal, Theresia and Carlier, Marie and Sixt, Michael K and Käs, Josef and Faix, Jan and Rottner, Klemens}, issn = {20411723}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{FMNL formins boost lamellipodial force generation}}, doi = {10.1038/ncomms14832}, volume = {8}, year = {2017}, } @article{660, abstract = {Growing microtubules are protected from depolymerization by the presence of a GTP or GDP/Pi cap. End-binding proteins of the EB1 family bind to the stabilizing cap, allowing monitoring of its size in real time. The cap size has been shown to correlate with instantaneous microtubule stability. Here we have quantitatively characterized the properties of cap size fluctuations during steadystate growth and have developed a theory predicting their timescale and amplitude from the kinetics of microtubule growth and cap maturation. In contrast to growth speed fluctuations, cap size fluctuations show a characteristic timescale, which is defined by the lifetime of the cap sites. Growth fluctuations affect the amplitude of cap size fluctuations; however, cap size does not affect growth speed, indicating that microtubules are far from instability during most of their time of growth. Our theory provides the basis for a quantitative understanding of microtubule stability fluctuations during steady-state growth.}, author = {Rickman, Jamie and Düllberg, Christian F and Cade, Nicholas and Griffin, Lewis and Surrey, Thomas}, issn = {00278424}, journal = {PNAS}, number = {13}, pages = {3427 -- 3432}, publisher = {National Academy of Sciences}, title = {{Steady state EB cap size fluctuations are determined by stochastic microtubule growth and maturation}}, doi = {10.1073/pnas.1620274114}, volume = {114}, year = {2017}, } @article{662, abstract = {We report a direct-numerical-simulation study of the Taylor-Couette flow in the quasi-Keplerian regime at shear Reynolds numbers up to (105). Quasi-Keplerian rotating flow has been investigated for decades as a simplified model system to study the origin of turbulence in accretion disks that is not fully understood. The flow in this study is axially periodic and thus the experimental end-wall effects on the stability of the flow are avoided. Using optimal linear perturbations as initial conditions, our simulations find no sustained turbulence: the strong initial perturbations distort the velocity profile and trigger turbulence that eventually decays.}, author = {Shi, Liang and Hof, Björn and Rampp, Markus and Avila, Marc}, issn = {10706631}, journal = {Physics of Fluids}, number = {4}, publisher = {American Institute of Physics}, title = {{Hydrodynamic turbulence in quasi Keplerian rotating flows}}, doi = {10.1063/1.4981525}, volume = {29}, year = {2017}, } @inproceedings{663, abstract = {In this paper, we propose an approach to automatically compute invariant clusters for nonlinear semialgebraic hybrid systems. An invariant cluster for an ordinary differential equation (ODE) is a multivariate polynomial invariant g(u→, x→) = 0, parametric in u→, which can yield an infinite number of concrete invariants by assigning different values to u→ so that every trajectory of the system can be overapproximated precisely by the intersection of a group of concrete invariants. For semialgebraic systems, which involve ODEs with multivariate polynomial right-hand sides, given a template multivariate polynomial g(u→, x→), an invariant cluster can be obtained by first computing the remainder of the Lie derivative of g(u→, x→) divided by g(u→, x→) and then solving the system of polynomial equations obtained from the coefficients of the remainder. Based on invariant clusters and sum-of-squares (SOS) programming, we present a new method for the safety verification of hybrid systems. Experiments on nonlinear benchmark systems from biology and control theory show that our approach is efficient. }, author = {Kong, Hui and Bogomolov, Sergiy and Schilling, Christian and Jiang, Yu and Henzinger, Thomas A}, booktitle = {Proceedings of the 20th International Conference on Hybrid Systems}, isbn = {978-145034590-3}, location = {Pittsburgh, PA, United States}, pages = {163 -- 172}, publisher = {ACM}, title = {{Safety verification of nonlinear hybrid systems based on invariant clusters}}, doi = {10.1145/3049797.3049814}, year = {2017}, } @article{667, abstract = {Perinatal exposure to penicillin may result in longlasting gut and behavioral changes.}, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {387}, publisher = {American Association for the Advancement of Science}, title = {{The antisocial side of antibiotics}}, doi = {10.1126/scitranslmed.aan2786}, volume = {9}, year = {2017}, } @article{668, abstract = {Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading.}, author = {Horsthemke, Markus and Bachg, Anne and Groll, Katharina and Moyzio, Sven and Müther, Barbara and Hemkemeyer, Sandra and Wedlich Söldner, Roland and Sixt, Michael K and Tacke, Sebastian and Bähler, Martin and Hanley, Peter}, issn = {00219258}, journal = {Journal of Biological Chemistry}, number = {17}, pages = {7258 -- 7273}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion}}, doi = {10.1074/jbc.M116.766923}, volume = {292}, year = {2017}, } @article{669, abstract = {The exocyst, a eukaryotic tethering complex, coregulates targeted exocytosis as an effector of small GTPases in polarized cell growth. In land plants, several exocyst subunits are encoded by double or triple paralogs, culminating in tens of EXO70 paralogs. Out of 23 Arabidopsis thaliana EXO70 isoforms, we analyzed seven isoforms expressed in pollen. Genetic and microscopic analyses of single mutants in EXO70A2, EXO70C1, EXO70C2, EXO70F1, EXO70H3, EXO70H5, and EXO70H6 genes revealed that only a loss-of-function EXO70C2 allele resulted in a significant male-specific transmission defect (segregation 40%:51%:9%) due to aberrant pollen tube growth. Mutant pollen tubes grown in vitro exhibited an enhanced growth rate and a decreased thickness of the tip cell wall, causing tip bursts. However, exo70C2 pollen tubes could frequently recover and restart their speedy elongation, resulting in a repetitive stop-and-go growth dynamics. A pollenspecific depletion of the closest paralog, EXO70C1, using artificial microRNA in the exo70C2 mutant background, resulted in a complete pollen-specific transmission defect, suggesting redundant functions of EXO70C1 and EXO70C2. Both EXO70C1 and EXO70C2, GFP tagged and expressed under the control of their native promoters, localized in the cytoplasm of pollen grains, pollen tubes, and also root trichoblast cells. The expression of EXO70C2-GFP complemented the aberrant growth of exo70C2 pollen tubes. The absent EXO70C2 interactions with core exocyst subunits in the yeast two-hybrid assay, cytoplasmic localization, and genetic effect suggest an unconventional EXO70 function possibly as a regulator of exocytosis outside the exocyst complex. In conclusion, EXO70C2 is a novel factor contributing to the regulation of optimal tip growth of Arabidopsis pollen tubes. }, author = {Synek, Lukáš and Vukašinović, Nemanja and Kulich, Ivan and Hála, Michal and Aldorfová, Klára and Fendrych, Matyas and Žárský, Viktor}, issn = {00320889}, journal = {Plant Physiology}, number = {1}, pages = {223 -- 240}, publisher = {American Society of Plant Biologists}, title = {{EXO70C2 is a key regulatory factor for optimal tip growth of pollen}}, doi = {10.1104/pp.16.01282}, volume = {174}, year = {2017}, } @inproceedings{6679, abstract = {Polar codes represent one of the major recent breakthroughs in coding theory and, because of their attractive features, they have been selected for the incoming 5G standard. As such, a lot of attention has been devoted to the development of decoding algorithms with good error performance and efficient hardware implementation. One of the leading candidates in this regard is represented by successive-cancellation list (SCL) decoding. However, its hardware implementation requires a large amount of memory. Recently, a partitioned SCL (PSCL) decoder has been proposed to significantly reduce the memory consumption [1]. In this paper, we examine the paradigm of PSCL decoding from both theoretical and practical standpoints: (i) by changing the construction of the code, we are able to improve the performance at no additional computational, latency or memory cost, (ii) we present an optimal scheme to allocate cyclic redundancy checks (CRCs), and (iii) we provide an upper bound on the list size that allows MAP performance.}, author = {Hashemi, Seyyed Ali and Mondelli, Marco and Hassani, Hamed and Urbanke, Ruediger and Gross, Warren}, booktitle = {2017 IEEE Global Communications Conference}, location = {Singapore, Singapore}, pages = {1--7}, publisher = {IEEE}, title = {{Partitioned list decoding of polar codes: Analysis and improvement of finite length performance}}, doi = {10.1109/glocom.2017.8254940}, year = {2017}, } @article{671, abstract = {Humans routinely use conditionally cooperative strategies when interacting in repeated social dilemmas. They are more likely to cooperate if others cooperated before, and are ready to retaliate if others defected. To capture the emergence of reciprocity, most previous models consider subjects who can only choose from a restricted set of representative strategies, or who react to the outcome of the very last round only. As players memorize more rounds, the dimension of the strategy space increases exponentially. This increasing computational complexity renders simulations for individuals with higher cognitive abilities infeasible, especially if multiplayer interactions are taken into account. Here, we take an axiomatic approach instead. We propose several properties that a robust cooperative strategy for a repeated multiplayer dilemma should have. These properties naturally lead to a unique class of cooperative strategies, which contains the classical Win-Stay Lose-Shift rule as a special case. A comprehensive numerical analysis for the prisoner's dilemma and for the public goods game suggests that strategies of this class readily evolve across various memory-n spaces. Our results reveal that successful strategies depend not only on how cooperative others were in the past but also on the respective context of cooperation.}, author = {Hilbe, Christian and Martinez, Vaquero and Chatterjee, Krishnendu and Nowak, Martin}, issn = {00278424}, journal = {PNAS}, number = {18}, pages = {4715 -- 4720}, publisher = {National Academy of Sciences}, title = {{Memory-n strategies of direct reciprocity}}, doi = {10.1073/pnas.1621239114}, volume = {114}, year = {2017}, } @article{670, abstract = {We propose an efficient method to model paper tearing in the context of interactive modeling. The method uses geometrical information to automatically detect potential starting points of tears. We further introduce a new hybrid geometrical and physical-based method to compute the trajectory of tears while procedurally synthesizing high resolution details of the tearing path using a texture based approach. The results obtained are compared with real paper and with previous studies on the expected geometric paths of paper that tears.}, author = {Schreck, Camille and Rohmer, Damien and Hahmann, Stefanie}, issn = {01677055}, journal = {Computer Graphics Forum}, number = {2}, pages = {95 -- 106}, publisher = {Wiley}, title = {{Interactive paper tearing}}, doi = {10.1111/cgf.13110}, volume = {36}, year = {2017}, } @article{672, abstract = {Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration.}, author = {Vaahtomeri, Kari and Brown, Markus and Hauschild, Robert and De Vries, Ingrid and Leithner, Alexander F and Mehling, Matthias and Kaufmann, Walter and Sixt, Michael K}, issn = {22111247}, journal = {Cell Reports}, number = {5}, pages = {902 -- 909}, publisher = {Cell Press}, title = {{Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia}}, doi = {10.1016/j.celrep.2017.04.027}, volume = {19}, year = {2017}, } @inproceedings{6729, abstract = {Consider the problem of constructing a polar code of block length N for the transmission over a given channel W. Typically this requires to compute the reliability of all the N synthetic channels and then to include those that are sufficiently reliable. However, we know from [1], [2] that there is a partial order among the synthetic channels. Hence, it is natural to ask whether we can exploit it to reduce the computational burden of the construction problem. We show that, if we take advantage of the partial order [1], [2], we can construct a polar code by computing the reliability of roughly N/ log 3/2 N synthetic channels. Such a set of synthetic channels is universal, in the sense that it allows one to construct polar codes for any W, and it can be identified by solving a maximum matching problem on a bipartite graph. Our proof technique consists in reducing the construction problem to the problem of computing the maximum cardinality of an antichain for a suitable partially ordered set. As such, this method is general and it can be used to further improve the complexity of the construction problem in case a new partial order on the synthetic channels of polar codes is discovered.}, author = {Mondelli, Marco and Hassani, S. Hamed and Urbanke, Rudiger}, booktitle = {2017 IEEE International Symposium on Information Theory }, isbn = {9781509040964}, issn = {2157-8117}, location = {Aachen, Germany}, pages = {1853--1857}, publisher = {IEEE}, title = {{Construction of polar codes with sublinear complexity}}, doi = {10.1109/isit.2017.8006850}, year = {2017}, } @article{6730, abstract = {We introduce a new approach to proving that a sequence of deterministic linear codes achieves capacity on an erasure channel under maximum a posteriori decoding. Rather than relying on the precise structure of the codes, our method exploits code symmetry. In particular, the technique applies to any sequence of linear codes where the blocklengths are strictly increasing, the code rates converge, and the permutation group of each code is doubly transitive. In other words, we show that symmetry alone implies near-optimal performance. An important consequence of this result is that a sequence of Reed-Muller codes with increasing block length and converging rate achieves capacity. This possibility has been suggested previously in the literature but it has only been proven for cases where the limiting code rate is 0 or 1. Moreover, these results extend naturally to all affine-invariant codes and, thus, to extended primitive narrow-sense BCH codes. This also resolves, in the affirmative, the existence question for capacity-achieving sequences of binary cyclic codes. The primary tools used in the proof are the sharp threshold property for symmetric monotone Boolean functions and the area theorem for extrinsic information transfer functions.}, author = {Kudekar, Shrinivas and Kumar, Santhosh and Mondelli, Marco and Pfister, Henry D. and Sasoglu, Eren and Urbanke, Ridiger L.}, issn = {1557-9654}, journal = {IEEE Transactions on Information Theory}, number = {7}, pages = {4298--4316}, publisher = {IEEE}, title = {{Reed–Muller codes achieve capacity on erasure channels}}, doi = {10.1109/tit.2017.2673829}, volume = {63}, year = {2017}, } @article{674, abstract = {Navigation of cells along gradients of guidance cues is a determining step in many developmental and immunological processes. Gradients can either be soluble or immobilized to tissues as demonstrated for the haptotactic migration of dendritic cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate how gradient characteristics govern cellular response patterns, we here introduce an in vitro system allowing to track migratory responses of DCs to precisely controlled immobilized gradients of CCL21. We find that haptotactic sensing depends on the absolute CCL21 concentration and local steepness of the gradient, consistent with a scenario where DC directionality is governed by the signal-to-noise ratio of CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore, we find that CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. These findings suggest that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal guidance in vivo.}, author = {Schwarz, Jan and Bierbaum, Veronika and Vaahtomeri, Kari and Hauschild, Robert and Brown, Markus and De Vries, Ingrid and Leithner, Alexander F and Reversat, Anne and Merrin, Jack and Tarrant, Teresa and Bollenbach, Tobias and Sixt, Michael K}, issn = {09609822}, journal = {Current Biology}, number = {9}, pages = {1314 -- 1325}, publisher = {Cell Press}, title = {{Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6}}, doi = {10.1016/j.cub.2017.04.004}, volume = {27}, year = {2017}, } @inproceedings{6731, abstract = {We present a rate-compatible polar coding scheme that achieves the capacity of any family of channels. Our solution generalizes the previous results [1], [2] that provide capacity-achieving rate-compatible polar codes for a degraded family of channels. The motivation for our extension comes from the fact that in many practical scenarios, e.g., MIMO systems and non-Gaussian interference, the channels cannot be ordered by degradation. The main technical contribution of this paper consists in removing the degradation condition. To do so, we exploit the ideas coming from the construction of universal polar codes. Our scheme possesses the usual attractive features of polar codes: low complexity code construction, encoding, and decoding; super-polynomial scaling of the error probability with the block length; and absence of error floors. On the negative side, the scaling of the gap to capacity with the block length is slower than in standard polar codes, and we prove an upper bound on the scaling exponent.}, author = {Mondelli, Marco and Hassani, Hamed and Maric, Ivana and Hui, Dennis and Hong, Song-Nam}, booktitle = {2017 IEEE Wireless Communications and Networking Conference Workshops }, isbn = {9781509059089}, location = {San Francisco, CA, USA}, publisher = {IEEE}, title = {{Capacity-achieving rate-compatible polar codes for general channels}}, doi = {10.1109/wcncw.2017.7919107}, year = {2017}, } @article{677, abstract = {The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR—DNA end resection and presynaptic filament formation. Importantly, the second function is linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic filament formation and HR are restored in INO80-C-deficient mutants, suggesting that presynaptic filament formation is the crucial INO80-C function during HR.}, author = {Lademann, Claudio and Renkawitz, Jörg and Pfander, Boris and Jentsch, Stefan}, issn = {22111247}, journal = {Cell Reports}, number = {7}, pages = {1294 -- 1303}, publisher = {Cell Press}, title = {{The INO80 complex removes H2A.Z to promote presynaptic filament formation during homologous recombination}}, doi = {10.1016/j.celrep.2017.04.051}, volume = {19}, year = {2017}, } @article{678, abstract = {The seminal observation that mechanical signals can elicit changes in biochemical signalling within cells, a process commonly termed mechanosensation and mechanotransduction, has revolutionized our understanding of the role of cell mechanics in various fundamental biological processes, such as cell motility, adhesion, proliferation and differentiation. In this Review, we will discuss how the interplay and feedback between mechanical and biochemical signals control tissue morphogenesis and cell fate specification in embryonic development.}, author = {Petridou, Nicoletta and Spiro, Zoltan P and Heisenberg, Carl-Philipp J}, issn = {14657392}, journal = {Nature Cell Biology}, number = {6}, pages = {581 -- 588}, publisher = {Nature Publishing Group}, title = {{Multiscale force sensing in development}}, doi = {10.1038/ncb3524}, volume = {19}, year = {2017}, } @article{681, abstract = {Two-player games on graphs provide the theoretical framework for many important problems such as reactive synthesis. While the traditional study of two-player zero-sum games has been extended to multi-player games with several notions of equilibria, they are decidable only for perfect-information games, whereas several applications require imperfect-information. In this paper we propose a new notion of equilibria, called doomsday equilibria, which is a strategy profile where all players satisfy their own objective, and if any coalition of players deviates and violates even one of the players' objective, then the objective of every player is violated. We present algorithms and complexity results for deciding the existence of doomsday equilibria for various classes of ω-regular objectives, both for imperfect-information games, and for perfect-information games. We provide optimal complexity bounds for imperfect-information games, and in most cases for perfect-information games.}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Filiot, Emmanuel and Raskin, Jean}, issn = {08905401}, journal = {Information and Computation}, pages = {296 -- 315}, publisher = {Elsevier}, title = {{Doomsday equilibria for omega-regular games}}, doi = {10.1016/j.ic.2016.10.012}, volume = {254}, year = {2017}, } @inproceedings{6841, abstract = {In classical machine learning, regression is treated as a black box process of identifying a suitable function from a hypothesis set without attempting to gain insight into the mechanism connecting inputs and outputs. In the natural sciences, however, finding an interpretable function for a phenomenon is the prime goal as it allows to understand and generalize results. This paper proposes a novel type of function learning network, called equation learner (EQL), that can learn analytical expressions and is able to extrapolate to unseen domains. It is implemented as an end-to-end differentiable feed-forward network and allows for efficient gradient based training. Due to sparsity regularization concise interpretable expressions can be obtained. Often the true underlying source expression is identified.}, author = {Martius, Georg S and Lampert, Christoph}, booktitle = {5th International Conference on Learning Representations, ICLR 2017 - Workshop Track Proceedings}, location = {Toulon, France}, publisher = {International Conference on Learning Representations}, title = {{Extrapolation and learning equations}}, year = {2017}, } @article{684, abstract = {We generalize winning conditions in two-player games by adding a structural acceptance condition called obligations. Obligations are orthogonal to the linear winning conditions that define whether a play is winning. Obligations are a declaration that player 0 can achieve a certain value from a configuration. If the obligation is met, the value of that configuration for player 0 is 1. We define the value in such games and show that obligation games are determined. For Markov chains with Borel objectives and obligations, and finite turn-based stochastic parity games with obligations we give an alternative and simpler characterization of the value function. Based on this simpler definition we show that the decision problem of winning finite turn-based stochastic parity games with obligations is in NP∩co-NP. We also show that obligation games provide a game framework for reasoning about p-automata. © 2017 The Association for Symbolic Logic.}, author = {Chatterjee, Krishnendu and Piterman, Nir}, issn = {1943-5886}, journal = {Journal of Symbolic Logic}, number = {2}, pages = {420 -- 452}, publisher = {Cambridge University Press}, title = {{Obligation blackwell games and p-automata}}, doi = {10.1017/jsl.2016.71}, volume = {82}, year = {2017}, } @article{685, abstract = {By applying methods and principles from the physical sciences to biological problems, D'Arcy Thompson's On Growth and Form demonstrated how mathematical reasoning reveals elegant, simple explanations for seemingly complex processes. This has had a profound influence on subsequent generations of developmental biologists. We discuss how this influence can be traced through twentieth century morphologists, embryologists and theoreticians to current research that explores the molecular and cellular mechanisms of tissue growth and patterning, including our own studies of the vertebrate neural tube.}, author = {Briscoe, James and Kicheva, Anna}, issn = {09254773}, journal = {Mechanisms of Development}, pages = {26 -- 31}, publisher = {Elsevier}, title = {{The physics of development 100 years after D'Arcy Thompson's “on growth and form”}}, doi = {10.1016/j.mod.2017.03.005}, volume = {145}, year = {2017}, } @inproceedings{688, abstract = {We show that the framework of topological data analysis can be extended from metrics to general Bregman divergences, widening the scope of possible applications. Examples are the Kullback - Leibler divergence, which is commonly used for comparing text and images, and the Itakura - Saito divergence, popular for speech and sound. In particular, we prove that appropriately generalized čech and Delaunay (alpha) complexes capture the correct homotopy type, namely that of the corresponding union of Bregman balls. Consequently, their filtrations give the correct persistence diagram, namely the one generated by the uniformly growing Bregman balls. Moreover, we show that unlike the metric setting, the filtration of Vietoris-Rips complexes may fail to approximate the persistence diagram. We propose algorithms to compute the thus generalized čech, Vietoris-Rips and Delaunay complexes and experimentally test their efficiency. Lastly, we explain their surprisingly good performance by making a connection with discrete Morse theory. }, author = {Edelsbrunner, Herbert and Wagner, Hubert}, issn = {18688969}, location = {Brisbane, Australia}, pages = {391--3916}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Topological data analysis with Bregman divergences}}, doi = {10.4230/LIPIcs.SoCG.2017.39}, volume = {77}, year = {2017}, } @article{687, abstract = {Pursuing the similarity between the Kontsevich-Soibelman construction of the cohomological Hall algebra (CoHA) of BPS states and Lusztig's construction of canonical bases for quantum enveloping algebras, and the similarity between the integrality conjecture for motivic Donaldson-Thomas invariants and the PBW theorem for quantum enveloping algebras, we build a coproduct on the CoHA associated to a quiver with potential. We also prove a cohomological dimensional reduction theorem, further linking a special class of CoHAs with Yangians, and explaining how to connect the study of character varieties with the study of CoHAs.}, author = {Davison, Ben}, issn = {00335606}, journal = {Quarterly Journal of Mathematics}, number = {2}, pages = {635 -- 703}, publisher = {Oxford University Press}, title = {{The critical CoHA of a quiver with potential}}, doi = {10.1093/qmath/haw053}, volume = {68}, year = {2017}, } @article{686, abstract = {Tissues are thought to behave like fluids with a given surface tension. Differences in tissue surface tension (TST) have been proposed to trigger cell sorting and tissue envelopment. D'Arcy Thompson in his seminal book ‘On Growth and Form’ has introduced this concept of differential TST as a key physical mechanism dictating tissue formation and organization within the developing organism. Over the past century, many studies have picked up the concept of differential TST and analyzed the role and cell biological basis of TST in development, underlining the importance and influence of this concept in developmental biology.}, author = {Heisenberg, Carl-Philipp J}, issn = {09254773}, journal = {Mechanisms of Development}, pages = {32 -- 37}, publisher = {Elsevier}, title = {{D'Arcy Thompson's ‘on growth and form’: From soap bubbles to tissue self organization}}, doi = {10.1016/j.mod.2017.03.006}, volume = {145}, year = {2017}, } @article{689, abstract = {Rett syndrome modeling in monkey mirrors the human disorder.}, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {393}, publisher = {American Association for the Advancement of Science}, title = {{Rett syndrome modeling goes simian}}, doi = {10.1126/scitranslmed.aan8196}, volume = {9}, year = {2017}, } @article{693, abstract = {Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such “simple synapses” indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Cav2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Cav2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1–10) and 2.03 at 4 wk (range: 1–4), whereas the mean numbers of Cav2.1 clusters were 2.84 at 2 wk (range: 1–8) and 2.37 at 4 wk (range: 1–5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm2 to 0.0234 μm2), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels. }, author = {Miki, Takafumi and Kaufmann, Walter and Malagon, Gerardo and Gomez, Laura and Tabuchi, Katsuhiko and Watanabe, Masahiko and Shigemoto, Ryuichi and Marty, Alain}, issn = {00278424}, journal = {PNAS}, number = {26}, pages = {E5246 -- E5255}, publisher = {National Academy of Sciences}, title = {{Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses}}, doi = {10.1073/pnas.1704470114}, volume = {114}, year = {2017}, } @inproceedings{6932, abstract = {LCLs or locally checkable labelling problems (e.g. maximal independent set, maximal matching, and vertex colouring) in the LOCAL model of computation are very well-understood in cycles (toroidal 1-dimensional grids): every problem has a complexity of O(1), Θ(log* n), or Θ(n), and the design of optimal algorithms can be fully automated. This work develops the complexity theory of LCL problems for toroidal 2-dimensional grids. The complexity classes are the same as in the 1-dimensional case: O(1), Θ(log* n), and Θ(n). However, given an LCL problem it is undecidable whether its complexity is Θ(log* n) or Θ(n) in 2-dimensional grids. Nevertheless, if we correctly guess that the complexity of a problem is Θ(log* n), we can completely automate the design of optimal algorithms. For any problem we can find an algorithm that is of a normal form A' o Sk, where A' is a finite function, Sk is an algorithm for finding a maximal independent set in kth power of the grid, and k is a constant. Finally, partially with the help of automated design tools, we classify the complexity of several concrete LCL problems related to colourings and orientations.}, author = {Brandt, Sebastian and Hirvonen, Juho and Korhonen, Janne H. and Lempiäinen, Tuomo and Östergård, Patric R.J. and Purcell, Christopher and Rybicki, Joel and Suomela, Jukka and Uznański, Przemysław}, isbn = {9781450349925}, location = {Washington, DC, United States}, pages = {101--110}, publisher = {ACM Press}, title = {{LCL problems on grids}}, doi = {10.1145/3087801.3087833}, year = {2017}, } @article{694, abstract = {A change regarding the extent of adhesion - hereafter referred to as adhesion plasticity - between adhesive and less-adhesive states of mammalian cells is important for their behavior. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of human MDA-MB-468 breast carcinoma cells growing in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices. By using transcriptome analysis, we identified the focal adhesion protein tensin3 (Tns3) as a determinant of adhesion plasticity. Tns3 is strongly reduced at mRNA and protein levels in suspension cells. Furthermore, by transiently challenging breast cancer cells to grow under non-adherent conditions markedly reduces Tns3 protein expression, which is regained upon re-adhesion. Stable knockdown of Tns3 in parental MDA-MB-468 cells results in defective adhesion, spreading and migration. Tns3-knockdown cells display impaired structure and dynamics of focal adhesion complexes as determined by immunostaining. Restoration of Tns3 protein expression in suspension cells partially rescues adhesion and focal contact composition. Our work identifies Tns3 as a crucial focal adhesion component regulated by, and functionally contributing to, the switch between adhesive and non-adhesive states in MDA-MB-468 cancer cells.}, author = {Veß, Astrid and Blache, Ulrich and Leitner, Laura and Kurz, Angela and Ehrenpfordt, Anja and Sixt, Michael K and Posern, Guido}, issn = {00219533}, journal = {Journal of Cell Science}, number = {13}, pages = {2172 -- 2184}, publisher = {Company of Biologists}, title = {{A dual phenotype of MDA MB 468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity}}, doi = {10.1242/jcs.200899}, volume = {130}, year = {2017}, } @article{695, abstract = {It has been known since Stefan Vogel's observations in 1969 that solitary female oil bees collect fatty floral oils from specialized oil-secreting plants with the aid of hairy patches on either their legs or abdomen, a reward used as food for their larvae and/or to line their brood cells. Similar adaptations are also known from male oil bees, although the purpose of their oil-collecting behavior has not yet been clarified. Here, we describe a novel pollination system involving male Paratetrapedia oil bees and the tropical herb Anthurium acutifolium. We present ultrastructural morphological details of bee and plant structures involved in this interaction and the composition of floral scents likely mediating pollinator attraction. Inflorescences of A. acutifolium were visited almost exclusively by male P. chocoensis oil bees. The bees mopped with a hairy patch of their abdominal sterna 3 across the inflorescence surface. During this activity on both staminate and pistillate stage inflorescences, bees’ abdomens and legs became loaded with pollen and contacted receptive stigmas. In contrast to what has been observed in other angiosperms visited for the collection of fatty floral oils, the inflorescences/flowers of A. acutifolium do not have structures specialized in oil secretion, i.e., elaiophores. These inflorescences, nonetheless, were strongly scented during the time interval they were visited by the bees. Gas chromatography/mass spectrometry (GC/MS) analyses of dynamic headspace floral samples revealed that inflorescences of both anthetic phases emitted scent bouquets consisting mainly of aliphatic esters, indole and uncommmon terpenoids (megastigmanes). Interestingly enough, our data suggest that the unusual floral scent of A. acutifolium is a perfume reward collected by male P. chocoensis oil bees. This pollination system thus bears a remarkable resemblence with the interactions between perfume-collecting male euglossine bees and their preferred flowers, discovered by Stefan Vogel half a century ago.}, author = {Etl, Florian and Franschitz, Anna and Aguiar, Antonio and Schönenberger, Jürg and Dötterl, Stefan}, issn = {03672530}, journal = {Flora: Morphology, Distribution, Functional Ecology of Plants}, pages = {7 -- 15}, publisher = {Elsevier}, title = {{A perfume collecting male oil bee? Evidences of a novel pollination system involving Anthurium acutifolium Araceae and Paratetrapedia chocoensis Apidae Tapinotaspidini}}, doi = {10.1016/j.flora.2017.02.020}, volume = {232}, year = {2017}, } @inproceedings{697, abstract = {De, Trevisan and Tulsiani [CRYPTO 2010] show that every distribution over n-bit strings which has constant statistical distance to uniform (e.g., the output of a pseudorandom generator mapping n-1 to n bit strings), can be distinguished from the uniform distribution with advantage epsilon by a circuit of size O( 2^n epsilon^2). We generalize this result, showing that a distribution which has less than k bits of min-entropy, can be distinguished from any distribution with k bits of delta-smooth min-entropy with advantage epsilon by a circuit of size O(2^k epsilon^2/delta^2). As a special case, this implies that any distribution with support at most 2^k (e.g., the output of a pseudoentropy generator mapping k to n bit strings) can be distinguished from any given distribution with min-entropy k+1 with advantage epsilon by a circuit of size O(2^k epsilon^2). Our result thus shows that pseudoentropy distributions face basically the same non-uniform attacks as pseudorandom distributions. }, author = {Pietrzak, Krzysztof Z and Skórski, Maciej}, issn = {18688969}, location = {Warsaw, Poland}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Non uniform attacks against pseudoentropy}}, doi = {10.4230/LIPIcs.ICALP.2017.39}, volume = {80}, year = {2017}, } @article{698, abstract = {Extracellular matrix signals from the microenvironment regulate gene expression patterns and cell behavior. Using a combination of experiments and geometric models, we demonstrate correlations between cell geometry, three-dimensional (3D) organization of chromosome territories, and gene expression. Fluorescence in situ hybridization experiments showed that micropatterned fibroblasts cultured on anisotropic versus isotropic substrates resulted in repositioning of specific chromosomes, which contained genes that were differentially regulated by cell geometries. Experiments combined with ellipsoid packing models revealed that the mechanosensitivity of chromosomes was correlated with their orientation in the nucleus. Transcription inhibition experiments suggested that the intermingling degree was more sensitive to global changes in transcription than to chromosome radial positioning and its orientations. These results suggested that cell geometry modulated 3D chromosome arrangement, and their neighborhoods correlated with gene expression patterns in a predictable manner. This is central to understanding geometric control of genetic programs involved in cellular homeostasis and the associated diseases. }, author = {Wang, Yejun and Nagarajan, Mallika and Uhler, Caroline and Shivashankar, Gv}, issn = {10591524}, journal = {Molecular Biology of the Cell}, number = {14}, pages = {1997 -- 2009}, publisher = {American Society for Cell Biology}, title = {{Orientation and repositioning of chromosomes correlate with cell geometry dependent gene expression}}, doi = {10.1091/mbc.E16-12-0825}, volume = {28}, year = {2017}, } @article{699, abstract = {In antagonistic symbioses, such as host–parasite interactions, one population’s success is the other’s loss. In mutualistic symbioses, such as division of labor, both parties can gain, but they might have different preferences over the possible mutualistic arrangements. The rates of evolution of the two populations in a symbiosis are important determinants of which population will be more successful: Faster evolution is thought to be favored in antagonistic symbioses (the “Red Queen effect”), but disfavored in certain mutualistic symbioses (the “Red King effect”). However, it remains unclear which biological parameters drive these effects. Here, we analyze the effects of the various determinants of evolutionary rate: generation time, mutation rate, population size, and the intensity of natural selection. Our main results hold for the case where mutation is infrequent. Slower evolution causes a long-term advantage in an important class of mutualistic interactions. Surprisingly, less intense selection is the strongest driver of this Red King effect, whereas relative mutation rates and generation times have little effect. In antagonistic interactions, faster evolution by any means is beneficial. Our results provide insight into the demographic evolution of symbionts. }, author = {Veller, Carl and Hayward, Laura and Nowak, Martin and Hilbe, Christian}, issn = {00278424}, journal = {PNAS}, number = {27}, pages = {E5396 -- E5405}, publisher = {National Academy of Sciences}, title = {{The red queen and king in finite populations}}, doi = {10.1073/pnas.1702020114}, volume = {114}, year = {2017}, } @article{700, abstract = {Microtubules provide the mechanical force required for chromosome separation during mitosis. However, little is known about the dynamic (high-frequency) mechanical properties of microtubules. Here, we theoretically propose to control the vibrations of a doubly clamped microtubule by tip electrodes and to detect its motion via the optomechanical coupling between the vibrational modes of the microtubule and an optical cavity. In the presence of a red-detuned strong pump laser, this coupling leads to optomechanical-induced transparency of an optical probe field, which can be detected with state-of-the art technology. The center frequency and line width of the transparency peak give the resonance frequency and damping rate of the microtubule, respectively, while the height of the peak reveals information about the microtubule-cavity field coupling. Our method opens the new possibilities to gain information about the physical properties of microtubules, which will enhance our capability to design physical cancer treatment protocols as alternatives to chemotherapeutic drugs.}, author = {Barzanjeh, Shabir and Salari, Vahid and Tuszynski, Jack and Cifra, Michal and Simon, Christoph}, issn = {24700045}, journal = { Physical Review E Statistical Nonlinear and Soft Matter Physics }, number = {1}, publisher = {American Institute of Physics}, title = {{Optomechanical proposal for monitoring microtubule mechanical vibrations}}, doi = {10.1103/PhysRevE.96.012404}, volume = {96}, year = {2017}, } @article{701, abstract = {A d-dimensional simplex S is called a k-reptile (or a k-reptile simplex) if it can be tiled by k simplices with disjoint interiors that are all mutually congruent and similar to S. For d = 2, triangular k-reptiles exist for all k of the form a^2, 3a^2 or a^2+b^2 and they have been completely characterized by Snover, Waiveris, and Williams. On the other hand, the only k-reptile simplices that are known for d ≥ 3, have k = m^d, where m is a positive integer. We substantially simplify the proof by Matoušek and the second author that for d = 3, k-reptile tetrahedra can exist only for k = m^3. We then prove a weaker analogue of this result for d = 4 by showing that four-dimensional k-reptile simplices can exist only for k = m^2.}, author = {Kynčl, Jan and Patakova, Zuzana}, issn = {10778926}, journal = {The Electronic Journal of Combinatorics}, number = {3}, pages = {1--44}, publisher = {International Press}, title = {{On the nonexistence of k reptile simplices in ℝ^3 and ℝ^4}}, volume = {24}, year = {2017}, } @article{702, abstract = {Leading autism-associated mutation in mouse partially mimics human disorder. }, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {399}, pages = {eaao0972}, publisher = {American Association for the Advancement of Science}, title = {{The riddle of CHD8 haploinsufficiency in autism spectrum disorder}}, doi = {10.1126/scitranslmed.aao0972}, volume = {9}, year = {2017}, } @article{706, abstract = {A hippocampal mossy fiber synapse has a complex structure and is implicated in learning and memory. In this synapse, the mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions and wrap around a multiply-branched spine, forming synaptic junctions. We have recently shown using transmission electron microscopy, immunoelectron microscopy and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities and the density of synaptic vesicles docked to active zones are decreased in the afadin-deficient synapse. We investigated here the roles of afadin in the functional differentiations of the mossy fiber synapse using the afadin-deficient mice. The electrophysiological studies showed that both the release probability of glutamate and the postsynaptic responsiveness to glutamate were markedly reduced, but not completely lost, in the afadin-deficient mossy fiber synapse, whereas neither long-term potentiation nor long-term depression was affected. These results indicate that afadin plays roles in the functional differentiations of the presynapse and the postsynapse of the hippocampal mossy fiber synapse.}, author = {Geng, Xiaoqi and Maruo, Tomohiko and Mandai, Kenji and Supriyanto, Irwan and Miyata, Muneaki and Sakakibara, Shotaro and Mizoguchi, Akira and Takai, Yoshimi and Mori, Masahiro}, issn = {13569597}, journal = {Genes to Cells}, number = {8}, pages = {715 -- 722}, publisher = {Wiley-Blackwell}, title = {{Roles of afadin in functional differentiations of hippocampal mossy fiber synapse}}, doi = {10.1111/gtc.12508}, volume = {22}, year = {2017}, } @article{7064, abstract = {The complex antiferromagnetic orders observed in the honeycomb iridates are a double-edged sword in the search for a quantum spin-liquid: both attesting that the magnetic interactions provide many of the necessary ingredients, while simultaneously impeding access. Focus has naturally been drawn to the unusual magnetic orders that hint at the underlying spin correlations. However, the study of any particular broken symmetry state generally provides little clue about the possibility of other nearby ground states. Here we use magnetic fields approaching 100 Tesla to reveal the extent of the spin correlations in γ-lithium iridate. We find that a small component of field along the magnetic easy-axis melts long-range order, revealing a bistable, strongly correlated spin state. Far from the usual destruction of antiferromagnetism via spin polarization, the high-field state possesses only a small fraction of the total iridium moment, without evidence for long-range order up to the highest attainable magnetic fields.}, author = {Modic, Kimberly A and Ramshaw, B. J. and Betts, J. B. and Breznay, Nicholas P. and Analytis, James G. and McDonald, Ross D. and Shekhter, Arkady}, issn = {2041-1723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{Robust spin correlations at high magnetic fields in the harmonic honeycomb iridates}}, doi = {10.1038/s41467-017-00264-6}, volume = {8}, year = {2017}, } @article{7067, abstract = {Broken fourfold rotational (C4) symmetry is observed in the experimental properties of several classes of unconventional superconductors. It has been proposed that this symmetry breaking is important for superconducting pairing in these materials, but in the high-Tc cuprates this broken symmetry has never been observed on the Fermi surface. Here we report a pronounced anisotropy in the angle dependence of the interlayer magnetoresistance of the underdoped high transition temperature (high-Tc) superconductor YBa2Cu3O6.58, directly revealing broken C4 symmetry on the Fermi surface. Moreover, we demonstrate that this Fermi surface has C2 symmetry of the type produced by a uniaxial or anisotropic density-wave phase. This establishes the central role of C4 symmetry breaking in the Fermi surface reconstruction of YBa2Cu3O6+δ , and suggests a striking degree of universality among unconventional superconductors.}, author = {Ramshaw, B. J. and Harrison, N. and Sebastian, S. E. and Ghannadzadeh, S. and Modic, Kimberly A and Bonn, D. A. and Hardy, W. N. and Liang, Ruixing and Goddard, P. A.}, issn = {2397-4648}, journal = {npj Quantum Materials}, number = {1}, publisher = {Springer Nature}, title = {{Broken rotational symmetry on the Fermi surface of a high-Tc superconductor}}, doi = {10.1038/s41535-017-0013-z}, volume = {2}, year = {2017}, } @article{7066, abstract = {The excitonic insulator phase has long been predicted to form in proximity to a band gap opening in the underlying band structure. The character of the pairing is conjectured to crossover from weak (BCS-like) to strong coupling (BEC-like) as the underlying band structure is tuned from the metallic to the insulating side of the gap opening. Here we report the high-magnetic field phase diagram of graphite to exhibit just such a crossover. By way of comprehensive angle-resolved magnetoresistance measurements, we demonstrate that the underlying band gap opening occurs inside the magnetic field-induced phase, paving the way for a systematic study of the BCS-BEC-like crossover by means of conventional condensed matter probes.}, author = {Zhu, Z. and McDonald, R. D. and Shekhter, A. and Ramshaw, B. J. and Modic, Kimberly A and Balakirev, F. F. and Harrison, N.}, issn = {2045-2322}, journal = {Scientific Reports}, publisher = {Springer Nature}, title = {{Magnetic field tuning of an excitonic insulator between the weak and strong coupling regimes in quantum limit graphite}}, doi = {10.1038/s41598-017-01693-5}, volume = {7}, year = {2017}, } @article{7065, abstract = {Magneto-quantum oscillation experiments in high-temperature superconductors show a strong thermally induced suppression of the oscillation amplitude approaching the critical dopings [B. J. Ramshaw et al., Science 348, 317 (2014); H. Shishido et al., Phys. Rev. Lett. 104, 057008 (2010); P. Walmsley et al., Phys. Rev. Lett. 110, 257002 (2013)]—in support of a quantum-critical origin of their phase diagrams. We suggest that, in addition to a thermodynamic mass enhancement, these experiments may directly indicate the increasing role of quantum fluctuations that suppress the quantum oscillation amplitude through inelastic scattering. We show that the traditional theoretical approaches beyond Lifshitz-Kosevich to calculate the oscillation amplitude in correlated metals result in a contradiction with the third law of thermodynamics and suggest a way to rectify this problem.}, author = {Shekhter, Arkady and Modic, Kimberly A and McDonald, R. D. and Ramshaw, B. J.}, issn = {2469-9969}, journal = {Physical Review B}, number = {12}, publisher = {APS}, title = {{Thermodynamic constraints on the amplitude of quantum oscillations}}, doi = {10.1103/physrevb.95.121106}, volume = {95}, year = {2017}, } @article{707, abstract = {We answer a question of M. Gromov on the waist of the unit ball.}, author = {Akopyan, Arseniy and Karasev, Roman}, issn = {00246093}, journal = {Bulletin of the London Mathematical Society}, number = {4}, pages = {690 -- 693}, publisher = {Wiley-Blackwell}, title = {{A tight estimate for the waist of the ball }}, doi = {10.1112/blms.12062}, volume = {49}, year = {2017}, } @article{708, abstract = {In the developing and adult brain, oligodendrocyte precursor cells (OPCs) are influenced by neuronal activity: they are involved in synaptic signaling with neurons, and their proliferation and differentiation into myelinating glia can be altered by transient changes in neuronal firing. An important question that has been unanswered is whether OPCs can discriminate different patterns of neuronal activity and respond to them in a distinct way. Here, we demonstrate in brain slices that the pattern of neuronal activity determines the functional changes triggered at synapses between axons and OPCs. Furthermore, we show that stimulation of the corpus callosum at different frequencies in vivo affects proliferation and differentiation of OPCs in a dissimilar way. Our findings suggest that neurons do not influence OPCs in “all-or-none” fashion but use their firing pattern to tune the response and behavior of these nonneuronal cells.}, author = {Nagy, Balint and Hovhannisyan, Anahit and Barzan, Ruxandra and Chen, Ting and Kukley, Maria}, issn = {15449173}, journal = {PLoS Biology}, number = {8}, publisher = {Public Library of Science}, title = {{Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum}}, doi = {10.1371/journal.pbio.2001993}, volume = {15}, year = {2017}, } @article{709, abstract = {Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) share the similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo-sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using reverse transcriptase-quantitative PCRs (RT-qPCR). The results demonstrated that all 10 thermoTRPs are expressed in both iBAT and sWAT, and without significant difference in the mRNA expression level of thermoTRPs between these two tissues. Moreover, Trpv1 and Trpv3 mRNA expression levels in both iBAT and sWAT were significantly decreased in high fat diet (HFD)-induced obese mice and db/db (leptin receptor deficient) mice. Trpm2 mRNA expression level was significantly decreased only in sWAT from HFD-induced obese mice and db/db mice. On the other hand, Trpv2 and Trpv4 mRNA expression levels in iBAT and sWAT were significantly increased in HFD-induced obese mice and db/db mice. Taken together, we conclude that all 10 thermoTRPs are expressed in iBAT and sWAT. And several thermoTRPs differentially expressed in adipose tissues from HFD-induced obese mice and db/db mice, suggesting a potential involvement in anti-obesity regulations.}, author = {Sun, Wuping and Li, Chen and Zhang, Yonghong and Jiang, Changyu and Zhai, Ming-Zhu and Zhou, Qian and Xiao, Lizu and Deng, Qiwen}, issn = {10656995}, journal = {Cell Biology International}, number = {8}, pages = {908 -- 913}, publisher = {Wiley-Blackwell}, title = {{Gene expression changes of thermo sensitive transient receptor potential channels in obese mice}}, doi = {10.1002/cbin.10783}, volume = {41}, year = {2017}, } @inproceedings{710, abstract = {We revisit the problem of estimating entropy of discrete distributions from independent samples, studied recently by Acharya, Orlitsky, Suresh and Tyagi (SODA 2015), improving their upper and lower bounds on the necessary sample size n. For estimating Renyi entropy of order alpha, up to constant accuracy and error probability, we show the following * Upper bounds n = O(1) 2^{(1-1/alpha)H_alpha} for integer alpha>1, as the worst case over distributions with Renyi entropy equal to H_alpha. * Lower bounds n = Omega(1) K^{1-1/alpha} for any real alpha>1, with the constant being an inverse polynomial of the accuracy, as the worst case over all distributions on K elements. Our upper bounds essentially replace the alphabet size by a factor exponential in the entropy, which offers improvements especially in low or medium entropy regimes (interesting for example in anomaly detection). As for the lower bounds, our proof explicitly shows how the complexity depends on both alphabet and accuracy, partially solving the open problem posted in previous works. The argument for upper bounds derives a clean identity for the variance of falling-power sum of a multinomial distribution. Our approach for lower bounds utilizes convex optimization to find a distribution with possibly worse estimation performance, and may be of independent interest as a tool to work with Le Cam’s two point method. }, author = {Obremski, Maciej and Skórski, Maciej}, issn = {18688969}, location = {Berkeley, USA}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Renyi entropy estimation revisited}}, doi = {10.4230/LIPIcs.APPROX-RANDOM.2017.20}, volume = {81}, year = {2017}, } @article{713, abstract = {To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta.}, author = {Andergassen, Daniel and Dotter, Christoph and Wenzel, Dyniel and Sigl, Verena and Bammer, Philipp and Muckenhuber, Markus and Mayer, Daniela and Kulinski, Tomasz and Theussl, Hans and Penninger, Josef and Bock, Christoph and Barlow, Denise and Pauler, Florian and Hudson, Quanah}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Mapping the mouse Allelome reveals tissue specific regulation of allelic expression}}, doi = {10.7554/eLife.25125}, volume = {6}, year = {2017}, } @inproceedings{711, abstract = {Nested weighted automata (NWA) present a robust and convenient automata-theoretic formalism for quantitative specifications. Previous works have considered NWA that processed input words only in the forward direction. It is natural to allow the automata to process input words backwards as well, for example, to measure the maximal or average time between a response and the preceding request. We therefore introduce and study bidirectional NWA that can process input words in both directions. First, we show that bidirectional NWA can express interesting quantitative properties that are not expressible by forward-only NWA. Second, for the fundamental decision problems of emptiness and universality, we establish decidability and complexity results for the new framework which match the best-known results for the special case of forward-only NWA. Thus, for NWA, the increased expressiveness of bidirectionality is achieved at no additional computational complexity. This is in stark contrast to the unweighted case, where bidirectional finite automata are no more expressive but exponentially more succinct than their forward-only counterparts.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, issn = {18688969}, location = {Berlin, Germany}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Bidirectional nested weighted automata}}, doi = {10.4230/LIPIcs.CONCUR.2017.5}, volume = {85}, year = {2017}, } @article{712, abstract = {We establish a weak–strong uniqueness principle for solutions to entropy-dissipating reaction–diffusion equations: As long as a strong solution to the reaction–diffusion equation exists, any weak solution and even any renormalized solution must coincide with this strong solution. Our assumptions on the reaction rates are just the entropy condition and local Lipschitz continuity; in particular, we do not impose any growth restrictions on the reaction rates. Therefore, our result applies to any single reversible reaction with mass-action kinetics as well as to systems of reversible reactions with mass-action kinetics satisfying the detailed balance condition. Renormalized solutions are known to exist globally in time for reaction–diffusion equations with entropy-dissipating reaction rates; in contrast, the global-in-time existence of weak solutions is in general still an open problem–even for smooth data–, thereby motivating the study of renormalized solutions. The key ingredient of our result is a careful adjustment of the usual relative entropy functional, whose evolution cannot be controlled properly for weak solutions or renormalized solutions.}, author = {Fischer, Julian L}, issn = {0362546X}, journal = {Nonlinear Analysis: Theory, Methods and Applications}, pages = {181 -- 207}, publisher = {Elsevier}, title = {{Weak–strong uniqueness of solutions to entropy dissipating reaction–diffusion equations}}, doi = {10.1016/j.na.2017.03.001}, volume = {159}, year = {2017}, } @article{714, abstract = {Background HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical channels. The influx of cations depolarizes the membrane promoting additional Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously found that cocaine targets NAcc neurons directly (independent of the inhibition of dopamine transporter) only when IP3-generating mechanisms are concomitantly initiated. When tested here, cocaine produced a dose-dependent potentiation of the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization and a potentiation of the effect of Tat by cocaine, which may be relevant for the reward axis in cocaine-abusing HIV-1-positive patients.}, author = {Brailoiu, Gabriela and Deliu, Elena and Barr, Jeffrey and Console Bram, Linda and Ciuciu, Alexandra and Abood, Mary and Unterwald, Ellen and Brǎiloiu, Eugen}, issn = {03768716}, journal = {Drug and Alcohol Dependence}, pages = {7 -- 14}, publisher = {Elsevier}, title = {{HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens}}, doi = {10.1016/j.drugalcdep.2017.04.015}, volume = {178}, year = {2017}, }