@article{1086, abstract = {Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.}, author = {Di Giglio, Maria and Muttenthaler, Markus and Harpsøe, Kasper and Liutkeviciute, Zita and Keov, Peter and Eder, Thomas and Rattei, Thomas and Arrowsmith, Sarah and Wray, Susan and Marek, Ales and Elbert, Tomas and Alewood, Paul and Gloriam, David and Gruber, Christian}, journal = {Scientific Reports}, pages = {41002}, publisher = {Nature Publishing Group}, title = {{Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide}}, doi = {10.1038/srep41002}, volume = {7}, year = {2017}, } @article{1084, abstract = {BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities.}, author = {Fang, Chong and Nagy-Staron, Anna A and Grafe, Martin and Heermann, Ralf and Jung, Kirsten and Gebhard, Susanne and Mascher, Thorsten}, issn = { 0950382X}, journal = {Molecular Microbiology}, number = {1}, pages = {16 -- 31}, publisher = {Wiley-Blackwell}, title = {{Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis}}, doi = {10.1111/mmi.13597}, volume = {104}, year = {2017}, } @article{1079, abstract = {We study the ionization problem in the Thomas-Fermi-Dirac-von Weizsäcker theory for atoms and molecules. We prove the nonexistence of minimizers for the energy functional when the number of electrons is large and the total nuclear charge is small. This nonexistence result also applies to external potentials decaying faster than the Coulomb potential. In the case of arbitrary nuclear charges, we obtain the nonexistence of stable minimizers and radial minimizers.}, author = {Nam, Phan and Van Den Bosch, Hanne}, issn = {13850172}, journal = {Mathematical Physics, Analysis and Geometry}, number = {2}, publisher = {Springer}, title = {{Nonexistence in Thomas Fermi-Dirac-von Weizsäcker theory with small nuclear charges}}, doi = {10.1007/s11040-017-9238-0}, volume = {20}, year = {2017}, } @article{1077, abstract = {Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the fX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.}, author = {Fernandes Redondo, Rodrigo A and Vladar, Harold and Włodarski, Tomasz and Bollback, Jonathan P}, issn = {17425689}, journal = {Journal of the Royal Society Interface}, number = {126}, publisher = {Royal Society of London}, title = {{Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family}}, doi = {10.1098/rsif.2016.0139}, volume = {14}, year = {2017}, } @article{1067, abstract = {Embryo morphogenesis relies on highly coordinated movements of different tissues. However, remarkably little is known about how tissues coordinate their movements to shape the embryo. In zebrafish embryogenesis, coordinated tissue movements first become apparent during “doming,” when the blastoderm begins to spread over the yolk sac, a process involving coordinated epithelial surface cell layer expansion and mesenchymal deep cell intercalations. Here, we find that active surface cell expansion represents the key process coordinating tissue movements during doming. By using a combination of theory and experiments, we show that epithelial surface cells not only trigger blastoderm expansion by reducing tissue surface tension, but also drive blastoderm thinning by inducing tissue contraction through radial deep cell intercalations. Thus, coordinated tissue expansion and thinning during doming relies on surface cells simultaneously controlling tissue surface tension and radial tissue contraction.}, author = {Morita, Hitoshi and Grigolon, Silvia and Bock, Martin and Krens, Gabriel and Salbreux, Guillaume and Heisenberg, Carl-Philipp J}, issn = {15345807}, journal = {Developmental Cell}, number = {4}, pages = {354 -- 366}, publisher = {Cell Press}, title = {{The physical basis of coordinated tissue spreading in zebrafish gastrulation}}, doi = {10.1016/j.devcel.2017.01.010}, volume = {40}, year = {2017}, } @article{1074, abstract = {Recently it has become feasible to detect long blocks of nearly identical sequence shared between pairs of genomes. These IBD blocks are direct traces of recent coalescence events and, as such, contain ample signal to infer recent demography. Here, we examine sharing of such blocks in two-dimensional populations with local migration. Using a diffusion approximation to trace genetic ancestry, we derive analytical formulae for patterns of isolation by distance of IBD blocks, which can also incorporate recent population density changes. We introduce an inference scheme that uses a composite likelihood approach to fit these formulae. We then extensively evaluate our theory and inference method on a range of scenarios using simulated data. We first validate the diffusion approximation by showing that the theoretical results closely match the simulated block sharing patterns. We then demonstrate that our inference scheme can accurately and robustly infer dispersal rate and effective density, as well as bounds on recent dynamics of population density. To demonstrate an application, we use our estimation scheme to explore the fit of a diffusion model to Eastern European samples in the POPRES data set. We show that ancestry diffusing with a rate of σ ≈ 50–100 km/√gen during the last centuries, combined with accelerating population growth, can explain the observed exponential decay of block sharing with increasing pairwise sample distance.}, author = {Ringbauer, Harald and Coop, Graham and Barton, Nicholas H}, issn = {00166731}, journal = {Genetics}, number = {3}, pages = {1335 -- 1351}, publisher = {Genetics Society of America}, title = {{Inferring recent demography from isolation by distance of long shared sequence blocks}}, doi = {10.1534/genetics.116.196220}, volume = {205}, year = {2017}, } @article{1076, abstract = {Signatures of the Coulomb corrections in the photoelectron momentum distribution during laser-induced ionization of atoms or ions in tunneling and multiphoton regimes are investigated analytically in the case of a one-dimensional problem. A high-order Coulomb-corrected strong-field approximation is applied, where the exact continuum state in the S matrix is approximated by the eikonal Coulomb-Volkov state including the second-order corrections to the eikonal. Although without high-order corrections our theory coincides with the known analytical R-matrix (ARM) theory, we propose a simplified procedure for the matrix element derivation. Rather than matching the eikonal Coulomb-Volkov wave function with the bound state as in the ARM theory to remove the Coulomb singularity, we calculate the matrix element via the saddle-point integration method by time as well as by coordinate, and in this way avoiding the Coulomb singularity. The momentum shift in the photoelectron momentum distribution with respect to the ARM theory due to high-order corrections is analyzed for tunneling and multiphoton regimes. The relation of the quantum corrections to the tunneling delay time is discussed.}, author = {Klaiber, Michael and Daněk, Jiří and Yakaboylu, Enderalp and Hatsagortsyan, Karen and Keitel, Christoph}, issn = {24699926}, journal = { Physical Review A - Atomic, Molecular, and Optical Physics}, number = {2}, publisher = {American Physical Society}, title = {{Strong-field ionization via a high-order Coulomb-corrected strong-field approximation}}, doi = {10.1103/PhysRevA.95.023403}, volume = {95}, year = {2017}, } @article{1072, abstract = {Given a finite set of points in Rn and a radius parameter, we study the Čech, Delaunay–Čech, Delaunay (or alpha), and Wrap complexes in the light of generalized discrete Morse theory. Establishing the Čech and Delaunay complexes as sublevel sets of generalized discrete Morse functions, we prove that the four complexes are simple-homotopy equivalent by a sequence of simplicial collapses, which are explicitly described by a single discrete gradient field.}, author = {Bauer, Ulrich and Edelsbrunner, Herbert}, journal = {Transactions of the American Mathematical Society}, number = {5}, pages = {3741 -- 3762}, publisher = {American Mathematical Society}, title = {{The Morse theory of Čech and delaunay complexes}}, doi = {10.1090/tran/6991}, volume = {369}, year = {2017}, } @article{1073, abstract = {Let X and Y be finite simplicial sets (e.g. finite simplicial complexes), both equipped with a free simplicial action of a finite group G. Assuming that Y is d-connected and dimX≤2d, for some d≥1, we provide an algorithm that computes the set of all equivariant homotopy classes of equivariant continuous maps |X|→|Y|; the existence of such a map can be decided even for dimX≤2d+1. This yields the first algorithm for deciding topological embeddability of a k-dimensional finite simplicial complex into Rn under the condition k≤23n−1. More generally, we present an algorithm that, given a lifting-extension problem satisfying an appropriate stability assumption, computes the set of all homotopy classes of solutions. This result is new even in the non-equivariant situation.}, author = {Čadek, Martin and Krcál, Marek and Vokřínek, Lukáš}, issn = {01795376}, journal = {Discrete & Computational Geometry}, number = {4}, pages = {915 -- 965}, publisher = {Springer}, title = {{Algorithmic solvability of the lifting extension problem}}, doi = {10.1007/s00454-016-9855-6}, volume = {54}, year = {2017}, } @article{1061, abstract = {Background: Metabolic engineering and synthetic biology of cyanobacteria offer a promising sustainable alternative approach for fossil-based ethylene production, by using sunlight via oxygenic photosynthesis, to convert carbon dioxide directly into ethylene. Towards this, both well-studied cyanobacteria, i.e., Synechocystis sp PCC 6803 and Synechococcus elongatus PCC 7942, have been engineered to produce ethylene by introducing the ethylene-forming enzyme (Efe) from Pseudomonas syringae pv. phaseolicola PK2 (the Kudzu strain), which catalyzes the conversion of the ubiquitous tricarboxylic acid cycle intermediate 2-oxoglutarate into ethylene. Results: This study focuses on Synechocystis sp PCC 6803 and shows stable ethylene production through the integration of a codon-optimized version of the efe gene under control of the Ptrc promoter and the core Shine-Dalgarno sequence (5\'-AGGAGG-3\') as the ribosome-binding site (RBS), at the slr0168 neutral site. We have increased ethylene production twofold by RBS screening and further investigated improving ethylene production from a single gene copy of efe, using multiple tandem promoters and by putting our best construct on an RSF1010-based broad-host-self-replicating plasmid, which has a higher copy number than the genome. Moreover, to raise the intracellular amounts of the key Efe substrate, 2-oxoglutarate, from which ethylene is formed, we constructed a glycogen-synthesis knockout mutant (glgC) and introduced the ethylene biosynthetic pathway in it. Under nitrogen limiting conditions, the glycogen knockout strain has increased intracellular 2-oxoglutarate levels; however, surprisingly, ethylene production was lower in this strain than in the wild-type background. Conclusion: Making use of different RBS sequences, production of ethylene ranging over a 20-fold difference has been achieved. However, a further increase of production through multiple tandem promoters and a broad-host plasmid was not achieved speculating that the transcription strength and the gene copy number are not the limiting factors in our system.}, author = {Veetil, Vinod and Angermayr, Andreas and Hellingwerf, Klaas}, issn = {14752859}, journal = {Microbial Cell Factories}, number = {1}, publisher = {BioMed Central}, title = {{Ethylene production with engineered Synechocystis sp PCC 6803 strains}}, doi = {10.1186/s12934-017-0645-5}, volume = {16}, year = {2017}, } @article{1065, abstract = {We consider the problem of reachability in pushdown graphs. We study the problem for pushdown graphs with constant treewidth. Even for pushdown graphs with treewidth 1, for the reachability problem we establish the following: (i) the problem is PTIME-complete, and (ii) any subcubic algorithm for the problem would contradict the k-clique conjecture and imply faster combinatorial algorithms for cliques in graphs.}, author = {Chatterjee, Krishnendu and Osang, Georg F}, issn = {00200190}, journal = {Information Processing Letters}, pages = {25 -- 29}, publisher = {Elsevier}, title = {{Pushdown reachability with constant treewidth}}, doi = {10.1016/j.ipl.2017.02.003}, volume = {122}, year = {2017}, } @article{1062, abstract = {Mouse chromaffin cells (MCCs) generate action potential (AP) firing that regulates the Ca2+‐dependent release of catecholamines (CAs). Recent findings indicate that MCCs possess a variety of spontaneous firing modes that span from the common ‘tonic‐irregular’ to the less frequent ‘burst’ firing. This latter is evident in a small fraction of MCCs but occurs regularly when Nav1.3/1.7 channels are made less available or when the Slo1β2‐subunit responsible for BK channel inactivation is deleted. Burst firing causes large increases of Ca2+‐entry and potentiates CA release by ∼3.5‐fold and thus may be a key mechanism for regulating MCC function. With the aim to uncover a physiological role for burst‐firing we investigated the effects of acidosis on MCC activity. Lowering the extracellular pH (pHo) from 7.4 to 7.0 and 6.6 induces cell depolarizations of 10–15 mV that generate repeated bursts. Bursts at pHo 6.6 lasted ∼330 ms, occurred at 1–2 Hz and caused an ∼7‐fold increase of CA cumulative release. Burst firing originates from the inhibition of the pH‐sensitive TASK‐1/TASK‐3 channels and from a 40% BK channel conductance reduction at pHo 7.0. The same pHo had little or no effect on Nav, Cav, Kv and SK channels that support AP firing in MCCs. Burst firing of pHo 6.6 could be mimicked by mixtures of the TASK‐1 blocker A1899 (300 nm) and BK blocker paxilline (300 nm) and could be prevented by blocking L‐type channels by adding 3 μm nifedipine. Mixtures of the two blockers raised cumulative CA‐secretion even more than low pHo (∼12‐fold), showing that the action of protons on vesicle release is mainly a result of the ionic conductance changes that increase Ca2+‐entry during bursts. Our data provide direct evidence suggesting that MCCs respond to low pHo with sustained depolarization, burst firing and enhanced CA‐secretion, thus mimicking the physiological response of CCs to acute acidosis and hyperkalaemia generated during heavy exercise and muscle fatigue.}, author = {Guarina, Laura and Vandael, David H and Carabelli, Valentina and Carbone, Emilio}, journal = {Journal of Physiology}, number = {8}, pages = {2587 -- 2609 }, publisher = {Wiley-Blackwell}, title = {{Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells}}, doi = {10.1113/JP273735}, volume = {595}, year = {2017}, } @article{1063, abstract = {Severe environmental change can drive a population extinct unless the population adapts in time to the new conditions (“evolutionary rescue”). How does biparental sexual reproduction influence the chances of population persistence compared to clonal reproduction or selfing? In this article, we set up a one‐locus two‐allele model for adaptation in diploid species, where rescue is contingent on the establishment of the mutant homozygote. Reproduction can occur by random mating, selfing, or clonally. Random mating generates and destroys the rescue mutant; selfing is efficient at generating it but at the same time depletes the heterozygote, which can lead to a low mutant frequency in the standing genetic variation. Due to these (and other) antagonistic effects, we find a nontrivial dependence of population survival on the rate of sex/selfing, which is strongly influenced by the dominance coefficient of the mutation before and after the environmental change. Importantly, since mating with the wild‐type breaks the mutant homozygote up, a slow decay of the wild‐type population size can impede rescue in randomly mating populations.}, author = {Uecker, Hildegard}, issn = {00143820}, journal = {Evolution}, number = {4}, pages = {845 -- 858}, publisher = {Wiley-Blackwell}, title = {{Evolutionary rescue in randomly mating, selfing, and clonal populations}}, doi = {10.1111/evo.13191}, volume = {71}, year = {2017}, } @article{1066, abstract = {Simulation is an attractive alternative to language inclusion for automata as it is an under-approximation of language inclusion, but usually has much lower complexity. Simulation has also been extended in two orthogonal directions, namely, (1) fair simulation, for simulation over specified set of infinite runs; and (2) quantitative simulation, for simulation between weighted automata. While fair trace inclusion is PSPACE-complete, fair simulation can be computed in polynomial time. For weighted automata, the (quantitative) language inclusion problem is undecidable in general, whereas the (quantitative) simulation reduces to quantitative games, which admit pseudo-polynomial time algorithms. In this work, we study (quantitative) simulation for weighted automata with Büchi acceptance conditions, i.e., we generalize fair simulation from non-weighted automata to weighted automata. We show that imposing Büchi acceptance conditions on weighted automata changes many fundamental properties of the simulation games, yet they still admit pseudo-polynomial time algorithms.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan and Velner, Yaron}, journal = {Information and Computation}, number = {2}, pages = {143 -- 166}, publisher = {Elsevier}, title = {{Quantitative fair simulation games}}, doi = {10.1016/j.ic.2016.10.006}, volume = {254}, year = {2017}, } @article{1023, abstract = {We consider products of independent square non-Hermitian random matrices. More precisely, let X1,…, Xn be independent N × N random matrices with independent entries (real or complex with independent real and imaginary parts) with zero mean and variance 1/N. Soshnikov-O’Rourke [19] and Götze-Tikhomirov [15] showed that the empirical spectral distribution of the product of n random matrices with iid entries converges to (equation found). We prove that if the entries of the matrices X1,…, Xn are independent (but not necessarily identically distributed) and satisfy uniform subexponential decay condition, then in the bulk the convergence of the ESD of X1,…, Xn to (0.1) holds up to the scale N–1/2+ε.}, author = {Nemish, Yuriy}, issn = {10836489}, journal = {Electronic Journal of Probability}, publisher = {Institute of Mathematical Statistics}, title = {{Local law for the product of independent non-Hermitian random matrices with independent entries}}, doi = {10.1214/17-EJP38}, volume = {22}, year = {2017}, } @article{1022, abstract = {We introduce a multiscale topological description of the Megaparsec web-like cosmic matter distribution. Betti numbers and topological persistence offer a powerful means of describing the rich connectivity structure of the cosmic web and of its multiscale arrangement of matter and galaxies. Emanating from algebraic topology and Morse theory, Betti numbers and persistence diagrams represent an extension and deepening of the cosmologically familiar topological genus measure and the related geometric Minkowski functionals. In addition to a description of the mathematical background, this study presents the computational procedure for computing Betti numbers and persistence diagrams for density field filtrations. The field may be computed starting from a discrete spatial distribution of galaxies or simulation particles. The main emphasis of this study concerns an extensive and systematic exploration of the imprint of different web-like morphologies and different levels of multiscale clustering in the corresponding computed Betti numbers and persistence diagrams. To this end, we use Voronoi clustering models as templates for a rich variety of web-like configurations and the fractal-like Soneira-Peebles models exemplify a range of multiscale configurations. We have identified the clear imprint of cluster nodes, filaments, walls, and voids in persistence diagrams, along with that of the nested hierarchy of structures in multiscale point distributions. We conclude by outlining the potential of persistent topology for understanding the connectivity structure of the cosmic web, in large simulations of cosmic structure formation and in the challenging context of the observed galaxy distribution in large galaxy surveys.}, author = {Pranav, Pratyush and Edelsbrunner, Herbert and Van De Weygaert, Rien and Vegter, Gert and Kerber, Michael and Jones, Bernard and Wintraecken, Mathijs}, issn = {00358711}, journal = {Monthly Notices of the Royal Astronomical Society}, number = {4}, pages = {4281 -- 4310}, publisher = {Oxford University Press}, title = {{The topology of the cosmic web in terms of persistent Betti numbers}}, doi = {10.1093/mnras/stw2862}, volume = {465}, year = {2017}, } @article{1026, abstract = {The optogenetic revolution enabled spatially-precise and temporally-precise control over protein function, signaling pathway activation, and animal behavior with tremendous success in the dissection of signaling networks and neural circuits. Very recently, optogenetic methods have been paired with optical reporters in novel drug screening platforms. In these all-optical platforms, light remotely activated ion channels and kinases thereby obviating the use of electrophysiology or reagents. Consequences were remarkable operational simplicity, throughput, and cost-effectiveness that culminated in the identification of new drug candidates. These blueprints for all-optical assays also revealed potential pitfalls and inspire all-optical variants of other screens, such as those that aim at better understanding dynamic drug action or orphan protein function.}, author = {Agus, Viviana and Janovjak, Harald L}, issn = {09581669}, journal = {Current Opinion in Biotechnology}, pages = {8 -- 14}, publisher = {Elsevier}, title = {{Optogenetic methods in drug screening: Technologies and applications}}, doi = {10.1016/j.copbio.2017.02.006}, volume = {48}, year = {2017}, } @article{1020, abstract = {Cellulose is the most abundant biopolymer on Earth. Cellulose fibers, such as the one extracted form cotton or woodpulp, have been used by humankind for hundreds of years to make textiles and paper. Here we show how, by engineering light-matter interaction, we can optimize light scattering using exclusively cellulose nanocrystals. The produced material is sustainable, biocompatible, and when compared to ordinary microfiber-based paper, it shows enhanced scattering strength (×4), yielding a transport mean free path as low as 3.5 μm in the visible light range. The experimental results are in a good agreement with the theoretical predictions obtained with a diffusive model for light propagation.}, author = {Caixeiro, Soraya and Peruzzo, Matilda and Onelli, Olimpia and Vignolini, Silvia and Sapienza, Riccardo}, issn = {19448244}, journal = {ACS Applied Materials and Interfaces}, number = {9}, pages = {7885 -- 7890}, publisher = {American Chemical Society}, title = {{Disordered cellulose based nanostructures for enhanced light scattering}}, doi = {10.1021/acsami.6b15986}, volume = {9}, year = {2017}, } @article{1021, abstract = {Most flows in nature and engineering are turbulent because of their large velocities and spatial scales. Laboratory experiments on rotating quasi-Keplerian flows, for which the angular velocity decreases radially but the angular momentum increases, are however laminar at Reynolds numbers exceeding one million. This is in apparent contradiction to direct numerical simulations showing that in these experiments turbulence transition is triggered by the axial boundaries. We here show numerically that as the Reynolds number increases, turbulence becomes progressively confined to the boundary layers and the flow in the bulk fully relaminarizes. Our findings support that turbulence is unlikely to occur in isothermal constant-density quasi-Keplerian flows.}, author = {Lopez Alonso, Jose M and Avila, Marc}, issn = {00221120}, journal = {Journal of Fluid Mechanics}, pages = {21 -- 34}, publisher = {Cambridge University Press}, title = {{Boundary layer turbulence in experiments on quasi Keplerian flows}}, doi = {10.1017/jfm.2017.109}, volume = {817}, year = {2017}, } @article{1025, abstract = {Many organ surfaces are covered by a protective epithelial-cell layer. It emerges that such layers are maintained by cell stretching that triggers cell division mediated by the force-sensitive ion-channel protein Piezo1. See Letter p.118}, author = {Heisenberg, Carl-Philipp J}, issn = {00280836}, journal = {Nature}, number = {7643}, pages = {43 -- 44}, publisher = {Nature Publishing Group}, title = {{Cell biology: Stretched divisions}}, doi = {10.1038/nature21502}, volume = {543}, year = {2017}, } @article{1017, abstract = {The development of the vertebrate central nervous system is reliant on a complex cascade of biological processes that include mitotic division, relocation of migrating neurons, and the extension of dendritic and axonal processes. Each of these cellular events requires the diverse functional repertoire of the microtubule cytoskeleton for the generation of forces, assembly of macromolecular complexes and transport of molecules and organelles. The tubulins are a multi-gene family that encode for the constituents of microtubules, and have been implicated in a spectrum of neurological disorders. Evidence is building that different tubulins tune the functional properties of the microtubule cytoskeleton dependent on the cell type, developmental profile and subcellular localisation. Here we review of the origins of the functional specification of the tubulin gene family in the developing brain at a transcriptional, translational, and post-transcriptional level. We remind the reader that tubulins are not just loading controls for your average Western blot.}, author = {Breuss, Martin and Leca, Ines and Gstrein, Thomas and Hansen, Andi H and Keays, David}, issn = {10447431}, journal = {Molecular and Cellular Neuroscience}, pages = {58 -- 67}, publisher = {Academic Press}, title = {{Tubulins and brain development: The origins of functional specification}}, doi = {10.1016/j.mcn.2017.03.002}, volume = {84}, year = {2017}, } @article{1015, abstract = {Vortices are commonly observed in the context of classical hydrodynamics: from whirlpools after stirring the coffee in a cup to a violent atmospheric phenomenon such as a tornado, all classical vortices are characterized by an arbitrary circulation value of the local velocity field. On the other hand the appearance of vortices with quantized circulation represents one of the fundamental signatures of macroscopic quantum phenomena. In two-dimensional superfluids quantized vortices play a key role in determining finite-temperature properties, as the superfluid phase and the normal state are separated by a vortex unbinding transition, the Berezinskii-Kosterlitz-Thouless transition. Very recent experiments with two-dimensional superfluid fermions motivate the present work: we present theoretical results based on the renormalization group showing that the universal jump of the superfluid density and the critical temperature crucially depend on the interaction strength, providing a strong benchmark for forthcoming investigations.}, author = {Bighin, Giacomo and Salasnich, Luca}, issn = {20452322}, journal = {Scientific Reports}, publisher = {Nature Publishing Group}, title = {{Vortices and antivortices in two-dimensional ultracold Fermi gases}}, doi = {10.1038/srep45702}, volume = {7}, year = {2017}, } @article{1016, abstract = {The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly referred to as the tubulinopathies. Here we report the addition of recessive quadrupedalism, also known as Uner Tan syndrome (UTS), to the growing list of diseases caused by tubulin variants. Analysis of a consanguineous UTS family identified a biallelic TUBB2B mutation, resulting in a p.R390Q amino acid substitution. In addition to the identifying quadrupedal locomotion, all three patients showed severe cerebellar hypoplasia. None, however, displayed the basal ganglia malformations typically associated with TUBB2B mutations. Functional analysis of the R390Q substitution revealed that it did not affect the ability of β-tubulin to fold or become assembled into the α/β-heterodimer, nor did it influence the incorporation of mutant-containing heterodimers into microtubule polymers. The 390Q mutation in S. cerevisiae TUB2 did not affect growth under basal conditions, but did result in increased sensitivity to microtubule-depolymerizing drugs, indicative of a mild impact of this mutation on microtubule function. The TUBB2B mutation described here represents an unusual recessive mode of inheritance for missense-mediated tubulinopathies and reinforces the sensitivity of the developing cerebellum to microtubule defects.}, author = {Breuss, Martin and Nguyen, Thai and Srivatsan, Anjana and Leca, Ines and Tian, Guoling and Fritz, Tanja and Hansen, Andi H and Musaev, Damir and Mcevoy Venneri, Jennifer and Kiely, James and Rosti, Rasim and Scott, Eric and Tan, Uner and Kolodner, Richard and Cowan, Nicholas and Keays, David and Gleeson, Joseph}, issn = {09646906}, journal = {Human Molecular Genetics}, number = {2}, pages = {258 -- 269}, publisher = {Oxford University Press}, title = {{Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability}}, doi = {10.1093/hmg/ddw383}, volume = {26}, year = {2017}, } @article{1018, abstract = {In plants, the multistep phosphorelay (MSP) pathway mediates a range of regulatory processes, including those activated by cytokinins. The crosstalk between cytokinin response and light is known for a long time. However, the molecular mechanism underlying the interactionbetween light and cytokinin signaling remains elusive. In the screen for upstream regulators we identified a LONG PALE HYPOCOTYL (LPH) gene whose activity is indispensable for spatiotemporally correct expression of CYTOKININ INDEPENDENT-1 (CKI1), encoding the constitutively active sensor histidine kinase that activates MSP signaling. lph is a new allele of HEME OXYGENASE 1 (HY1) which encodes the key protein in the biosynthesis of phytochromobilin, a cofactor of photoconvertiblephytochromes. Our analysis confirmed the light-dependent regulation oftheCKI1 expression pattern. We show that CKI1 expression is under the control of phytochrome A (phyA), functioning as a dual (both positive and negative) regulator of CKI1 expression, presumably via the phyA-regulated transcription factors PHYTOCHROME INTERACTING FACTOR 3 (PIF3) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1). Changes in CKI1 expression observed in lph/hy1-7 and phy mutants correlatewithmisregulation of MSP signaling, changedcytokinin sensitivity and developmental aberrations,previously shown to be associated with cytokinin and/or CKI1 action. Besides that, we demonstrate novel role of phyA-dependent CKI1 expression in the hypocotyl elongation and hook development during skotomorphogenesis. Based on these results, we propose that the light-dependent regulation of CKI1 provides a plausible mechanistic link underlying the well-known interaction between light- and cytokinin-controlled plant development.}, author = {Dobisova, Tereza and Hrdinova, Vendula and Cuesta, Candela and Michlickova, Sarka and Urbankova, Ivana and Hejatkova, Romana and Zadnikova, Petra and Pernisová, Markéta and Benková, Eva and Hejátko, Jan}, journal = {Plant Physiology}, number = {1}, pages = {387 -- 404}, publisher = {American Society of Plant Biologists}, title = {{Light regulated expression of sensor histidine kinase CKI1 controls cytokinin related development}}, doi = {10.1104/pp.16.01964}, volume = {174}, year = {2017}, } @article{1019, abstract = {As a consequence of its difference in copy number between males and females, the X chromosome is subject to unique evolutionary forces and gene regulatory mechanisms. Previous studies of Drosophila melanogaster have shown that the expression of X-linked, testis-specific reporter genes is suppressed in the male germline. However, it is not known whether this phenomenon is restricted to testis-expressed genes or if it is a more general property of genes with tissue-specific expression, which are also underrepresented on the X chromosome. To test this, we compared the expression of three tissue-specific reporter genes (ovary, accessory gland and Malpighian tubule) inserted at various autosomal and X-chromosomal locations. In contrast to testis-specific reporter genes, we found no reduction of X-linked expression in any of the other tissues. In accessory gland and Malpighian tubule, we detected higher expression of the X-linked reporter genes, which suggests that they are at least partially dosage compensated. We found no difference in the tissue-specificity of X-linked and autosomal reporter genes. These findings indicate that, in general, the X chromosome is not a detrimental environment for tissue-specific gene expression and that the suppression of X-linked expression is limited to the male germline.}, author = {Argyridou, Eliza and Huylmans, Ann K and Königer, Annabella and Parsch, John}, issn = {0018067X}, journal = {Heredity}, number = {1}, pages = {27 -- 34}, publisher = {Nature Publishing Group}, title = {{X-linkage is not a general inhibitor of tissue-specific gene expression in Drosophila melanogaster}}, doi = {10.1038/hdy.2017.12}, volume = {119}, year = {2017}, } @article{1014, abstract = {We consider the large-scale regularity of solutions to second-order linear elliptic equations with random coefficient fields. In contrast to previous works on regularity theory for random elliptic operators, our interest is in the regularity at the boundary: We consider problems posed on the half-space with homogeneous Dirichlet boundary conditions and derive an associated C1,α-type large-scale regularity theory in the form of a corresponding decay estimate for the homogenization-adapted tilt-excess. This regularity theory entails an associated Liouville-type theorem. The results are based on the existence of homogenization correctors adapted to the half-space setting, which we construct-by an entirely deterministic argument-as a modification of the homogenization corrector on the whole space. This adaption procedure is carried out inductively on larger scales, crucially relying on the regularity theory already established on smaller scales.}, author = {Fischer, Julian L and Raithel, Claudia}, issn = {00361410}, journal = {SIAM Journal on Mathematical Analysis}, number = {1}, pages = {82 -- 114}, publisher = {Society for Industrial and Applied Mathematics }, title = {{Liouville principles and a large-scale regularity theory for random elliptic operators on the half-space}}, doi = {10.1137/16M1070384}, volume = {49}, year = {2017}, } @misc{9861, abstract = {As a consequence of its difference in copy number between males and females, the X chromosome is subject to unique evolutionary forces and gene regulatory mechanisms. Previous studies of Drosophila melanogaster have shown that the expression of X-linked, testis-specific reporter genes is suppressed in the male germline. However, it is not known whether this phenomenon is restricted to testis-expressed genes or if it is a more general property of genes with tissue-specific expression, which are also underrepresented on the X chromosome. To test this, we compared the expression of three tissue-specific reporter genes (ovary, accessory gland and Malpighian tubule) inserted at various autosomal and X-chromosomal locations. In contrast to testis-specific reporter genes, we found no reduction of X-linked expression in any of the other tissues. In accessory gland and Malpighian tubule, we detected higher expression of the X-linked reporter genes, which suggests that they are at least partially dosage compensated. We found no difference in the tissue-specificity of X-linked and autosomal reporter genes. These findings indicate that, in general, the X chromosome is not a detrimental environment for tissue-specific gene expression and that the suppression of X-linked expression is limited to the male germline.}, author = {Argyridou, Eliza and Huylmans, Ann K and Königer, Annabella and Parsch, John}, publisher = {Dryad}, title = {{Data from: X-linkage is not a general inhibitor of tissue-specific gene expression in Drosophila melanogaster}}, doi = {10.5061/dryad.02f6r}, year = {2017}, } @article{1006, abstract = {Background: The phenomenon of immune priming, i.e. enhanced protection following a secondary exposure to a pathogen, has now been demonstrated in a wide range of invertebrate species. Despite accumulating phenotypic evidence, knowledge of its mechanistic underpinnings is currently very limited. Here we used the system of the red flour beetle, Tribolium castaneum and the insect pathogen Bacillus thuringiensis (Bt) to further our molecular understanding of the oral immune priming phenomenon. We addressed how ingestion of bacterial cues (derived from spore supernatants) of an orally pathogenic and non-pathogenic Bt strain affects gene expression upon later challenge exposure, using a whole-transcriptome sequencing approach. Results: Whereas gene expression of individuals primed with the orally non-pathogenic strain showed minor changes to controls, we found that priming with the pathogenic strain induced regulation of a large set of distinct genes, many of which are known immune candidates. Intriguingly, the immune repertoire activated upon priming and subsequent challenge qualitatively differed from the one mounted upon infection with Bt without previous priming. Moreover, a large subset of priming-specific genes showed an inverse regulation compared to their regulation upon challenge only. Conclusions: Our data demonstrate that gene expression upon infection is strongly affected by previous immune priming. We hypothesise that this shift in gene expression indicates activation of a more targeted and efficient response towards a previously encountered pathogen, in anticipation of potential secondary encounter.}, author = {Greenwood, Jenny and Milutinovic, Barbara and Peuß, Robert and Behrens, Sarah and Essar, Daniela and Rosenstiel, Philip and Schulenburg, Hinrich and Kurtz, Joachim}, issn = {14712164}, journal = {BMC Genomics}, number = {1}, pages = {329}, publisher = {BioMed Central}, title = {{Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae}}, doi = {10.1186/s12864-017-3705-7}, volume = {18}, year = {2017}, } @inproceedings{1011, abstract = {Pushdown systems (PDSs) and recursive state machines (RSMs), which are linearly equivalent, are standard models for interprocedural analysis. Yet RSMs are more convenient as they (a) explicitly model function calls and returns, and (b) specify many natural parameters for algorithmic analysis, e.g., the number of entries and exits. We consider a general framework where RSM transitions are labeled from a semiring and path properties are algebraic with semiring operations, which can model, e.g., interprocedural reachability and dataflow analysis problems. Our main contributions are new algorithms for several fundamental problems. As compared to a direct translation of RSMs to PDSs and the best-known existing bounds of PDSs, our analysis algorithm improves the complexity for finite-height semirings (that subsumes reachability and standard dataflow properties). We further consider the problem of extracting distance values from the representation structures computed by our algorithm, and give efficient algorithms that distinguish the complexity of a one-time preprocessing from the complexity of each individual query. Another advantage of our algorithm is that our improvements carry over to the concurrent setting, where we improve the bestknown complexity for the context-bounded analysis of concurrent RSMs. Finally, we provide a prototype implementation that gives a significant speed-up on several benchmarks from the SLAM/SDV project.}, author = {Chatterjee, Krishnendu and Kragl, Bernhard and Mishra, Samarth and Pavlogiannis, Andreas}, editor = {Yang, Hongseok}, issn = {03029743}, location = {Uppsala, Sweden}, pages = {287 -- 313}, publisher = {Springer}, title = {{Faster algorithms for weighted recursive state machines}}, doi = {10.1007/978-3-662-54434-1_11}, volume = {10201}, year = {2017}, } @article{1004, abstract = {The fundamental tasks of the root system are, besides anchoring, mediating interactions between plant and soil and providing the plant with water and nutrients. The architecture of the root system is controlled by endogenous mechanisms that constantly integrate environmental signals, such as availability of nutrients and water. Extremely important for efficient soil exploitation and survival under less favorable conditions is the developmental flexibility of the root system that is largely determined by its postembryonic branching capacity. Modulation of initiation and outgrowth of lateral roots provides roots with an exceptional plasticity, allows optimal adjustment to underground heterogeneity, and enables effective soil exploitation and use of resources. Here we discuss recent advances in understanding the molecular mechanisms that shape the plant root system and integrate external cues to adapt to the changing environment.}, author = {Ötvös, Krisztina and Benková, Eva}, issn = {0959437X}, journal = {Current Opinion in Genetics & Development}, pages = {82 -- 89}, publisher = {Elsevier}, title = {{Spatiotemporal mechanisms of root branching}}, doi = {10.1016/j.gde.2017.03.010}, volume = {45}, year = {2017}, } @article{1010, abstract = {We prove a local law in the bulk of the spectrum for random Gram matrices XX∗, a generalization of sample covariance matrices, where X is a large matrix with independent, centered entries with arbitrary variances. The limiting eigenvalue density that generalizes the Marchenko-Pastur law is determined by solving a system of nonlinear equations. Our entrywise and averaged local laws are on the optimal scale with the optimal error bounds. They hold both in the square case (hard edge) and in the properly rectangular case (soft edge). In the latter case we also establish a macroscopic gap away from zero in the spectrum of XX∗. }, author = {Alt, Johannes and Erdös, László and Krüger, Torben H}, issn = {10836489}, journal = {Electronic Journal of Probability}, publisher = {Institute of Mathematical Statistics}, title = {{Local law for random Gram matrices}}, doi = {10.1214/17-EJP42}, volume = {22}, year = {2017}, } @inproceedings{1009, abstract = {A standard objective in partially-observable Markov decision processes (POMDPs) is to find a policy that maximizes the expected discounted-sum payoff. However, such policies may still permit unlikely but highly undesirable outcomes, which is problematic especially in safety-critical applications. Recently, there has been a surge of interest in POMDPs where the goal is to maximize the probability to ensure that the payoff is at least a given threshold, but these approaches do not consider any optimization beyond satisfying this threshold constraint. In this work we go beyond both the “expectation” and “threshold” approaches and consider a “guaranteed payoff optimization (GPO)” problem for POMDPs, where we are given a threshold t and the objective is to find a policy σ such that a) each possible outcome of σ yields a discounted-sum payoff of at least t, and b) the expected discounted-sum payoff of σ is optimal (or near-optimal) among all policies satisfying a). We present a practical approach to tackle the GPO problem and evaluate it on standard POMDP benchmarks.}, author = {Chatterjee, Krishnendu and Novotny, Petr and Pérez, Guillermo and Raskin, Jean and Zikelic, Djordje}, booktitle = {Proceedings of the 31st AAAI Conference on Artificial Intelligence}, location = {San Francisco, CA, United States}, pages = {3725 -- 3732}, publisher = {AAAI Press}, title = {{Optimizing expectation with guarantees in POMDPs}}, volume = {5}, year = {2017}, } @misc{9859, abstract = {Lists of all differentially expressed genes in the different priming-challenge treatments (compared to the fully naïve control; xlsx file). Relevant columns include the following: sample_1 and sample_2 – treatment groups being compared; Normalised FPKM sample_1 and sample_2 – FPKM of samples being compared; log2(fold_change) – log2(FPKM sample 2/FPKM sample 1), i.e. negative means sample 1 upregulated compared with sample 2, positive means sample 2 upregulated compared with sample 1; cuffdiff test_statistic – test statistic of differential expression test; p_value – p-value of differential expression test; q_value (FDR correction) – adjusted P-value of differential expression test. (XLSX 598 kb)}, author = {Greenwood, Jenny and Milutinovic, Barbara and Peuß, Robert and Behrens, Sarah and Essar, Daniela and Rosenstiel, Philip and Schulenburg, Hinrich and Kurtz, Joachim}, publisher = {Springer Nature}, title = {{Additional file 1: Table S1. of Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae}}, doi = {10.6084/m9.figshare.c.3756974_d1.v1}, year = {2017}, } @misc{9860, author = {Greenwood, Jenny and Milutinovic, Barbara and Peuß, Robert and Behrens, Sarah and Essar, Daniela and Rosenstiel, Philip and Schulenburg, Hinrich and Kurtz, Joachim}, publisher = {Springer Nature}, title = {{Additional file 5: Table S3. of Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae}}, doi = {10.6084/m9.figshare.c.3756974_d5.v1}, year = {2017}, } @inproceedings{1002, abstract = { We present an interactive design system to create functional mechanical objects. Our computational approach allows novice users to retarget an existing mechanical template to a user-specified input shape. Our proposed representation for a mechanical template encodes a parameterized mechanism, mechanical constraints that ensure a physically valid configuration, spatial relationships of mechanical parts to the user-provided shape, and functional constraints that specify an intended functionality. We provide an intuitive interface and optimization-in-the-loop approach for finding a valid configuration of the mechanism and the shape to ensure that higher-level functional goals are met. Our algorithm interactively optimizes the mechanism while the user manipulates the placement of mechanical components and the shape. Our system allows users to efficiently explore various design choices and to synthesize customized mechanical objects that can be fabricated with rapid prototyping technologies. We demonstrate the efficacy of our approach by retargeting various mechanical templates to different shapes and fabricating the resulting functional mechanical objects. }, author = {Zhang, Ran and Auzinger, Thomas and Ceylan, Duygu and Li, Wilmot and Bickel, Bernd}, issn = {07300301}, location = {Los Angeles, CA, United States }, number = {4}, publisher = {ACM}, title = {{Functionality-aware retargeting of mechanisms to 3D shapes}}, doi = {10.1145/3072959.3073710}, volume = {36}, year = {2017}, } @inproceedings{1001, abstract = {We present a computational approach for designing CurveUps, curvy shells that form from an initially flat state. They consist of small rigid tiles that are tightly held together by two pre-stretched elastic sheets attached to them. Our method allows the realization of smooth, doubly curved surfaces that can be fabricated as a flat piece. Once released, the restoring forces of the pre-stretched sheets support the object to take shape in 3D. CurveUps are structurally stable in their target configuration. The design process starts with a target surface. Our method generates a tile layout in 2D and optimizes the distribution, shape, and attachment areas of the tiles to obtain a configuration that is fabricable and in which the curved up state closely matches the target. Our approach is based on an efficient approximate model and a local optimization strategy for an otherwise intractable nonlinear optimization problem. We demonstrate the effectiveness of our approach for a wide range of shapes, all realized as physical prototypes.}, author = {Guseinov, Ruslan and Miguel, Eder and Bickel, Bernd}, location = {Los Angeles, CA, United States}, number = {4}, publisher = {ACM}, title = {{CurveUps: Shaping objects from flat plates with tension-actuated curvature}}, doi = {10.1145/3072959.3073709}, volume = {36}, year = {2017}, } @inproceedings{1003, abstract = {Network games (NGs) are played on directed graphs and are extensively used in network design and analysis. Search problems for NGs include finding special strategy profiles such as a Nash equilibrium and a globally optimal solution. The networks modeled by NGs may be huge. In formal verification, abstraction has proven to be an extremely effective technique for reasoning about systems with big and even infinite state spaces. We describe an abstraction-refinement methodology for reasoning about NGs. Our methodology is based on an abstraction function that maps the state space of an NG to a much smaller state space. We search for a global optimum and a Nash equilibrium by reasoning on an under- and an overapproximation defined on top of this smaller state space. When the approximations are too coarse to find such profiles, we refine the abstraction function. Our experimental results demonstrate the efficiency of the methodology.}, author = {Avni, Guy and Guha, Shibashis and Kupferman, Orna}, issn = {10450823}, location = {Melbourne, Australia}, pages = {70 -- 76}, publisher = {AAAI Press}, title = {{An abstraction-refinement methodology for reasoning about network games}}, doi = {10.24963/ijcai.2017/11}, year = {2017}, } @inproceedings{1000, abstract = {We study probabilistic models of natural images and extend the autoregressive family of PixelCNN models by incorporating latent variables. Subsequently, we describe two new generative image models that exploit different image transformations as latent variables: a quantized grayscale view of the image or a multi-resolution image pyramid. The proposed models tackle two known shortcomings of existing PixelCNN models: 1) their tendency to focus on low-level image details, while largely ignoring high-level image information, such as object shapes, and 2) their computationally costly procedure for image sampling. We experimentally demonstrate benefits of our LatentPixelCNN models, in particular showing that they produce much more realistically looking image samples than previous state-of-the-art probabilistic models. }, author = {Kolesnikov, Alexander and Lampert, Christoph}, booktitle = {34th International Conference on Machine Learning}, isbn = {978-151085514-4}, location = {Sydney, Australia}, pages = {1905 -- 1914}, publisher = {JMLR}, title = {{PixelCNN models with auxiliary variables for natural image modeling}}, volume = {70}, year = {2017}, } @inproceedings{998, abstract = {A major open problem on the road to artificial intelligence is the development of incrementally learning systems that learn about more and more concepts over time from a stream of data. In this work, we introduce a new training strategy, iCaRL, that allows learning in such a class-incremental way: only the training data for a small number of classes has to be present at the same time and new classes can be added progressively. iCaRL learns strong classifiers and a data representation simultaneously. This distinguishes it from earlier works that were fundamentally limited to fixed data representations and therefore incompatible with deep learning architectures. We show by experiments on CIFAR-100 and ImageNet ILSVRC 2012 data that iCaRL can learn many classes incrementally over a long period of time where other strategies quickly fail. }, author = {Rebuffi, Sylvestre Alvise and Kolesnikov, Alexander and Sperl, Georg and Lampert, Christoph}, isbn = {978-153860457-1}, location = {Honolulu, HA, United States}, pages = {5533 -- 5542}, publisher = {IEEE}, title = {{iCaRL: Incremental classifier and representation learning}}, doi = {10.1109/CVPR.2017.587}, volume = {2017}, year = {2017}, } @article{990, abstract = {Assortative mating is an important driver of speciation in populations with gene flow and is predicted to evolve under certain conditions in few-locus models. However, the evolution of assortment is less understood for mating based on quantitative traits, which are often characterized by high genetic variability and extensive linkage disequilibrium between trait loci. We explore this scenario for a two-deme model with migration, by considering a single polygenic trait subject to divergent viability selection across demes, as well as assortative mating and sexual selection within demes, and investigate how trait divergence is shaped by various evolutionary forces. Our analysis reveals the existence of sharp thresholds of assortment strength, at which divergence increases dramatically. We also study the evolution of assortment via invasion of modifiers of mate discrimination and show that the ES assortment strength has an intermediate value under a range of migration-selection parameters, even in diverged populations, due to subtle effects which depend sensitively on the extent of phenotypic variation within these populations. The evolutionary dynamics of the polygenic trait is studied using the hypergeometric and infinitesimal models. We further investigate the sensitivity of our results to the assumptions of the hypergeometric model, using individual-based simulations.}, author = {Sachdeva, Himani and Barton, Nicholas H}, issn = {00143820}, journal = {Evolution; International Journal of Organic Evolution}, number = {6}, pages = {1478 -- 1493 }, publisher = {Wiley-Blackwell}, title = {{Divergence and evolution of assortative mating in a polygenic trait model of speciation with gene flow}}, doi = {10.1111/evo.13252}, volume = {71}, year = {2017}, } @article{988, abstract = {The current-phase relation (CPR) of a Josephson junction (JJ) determines how the supercurrent evolves with the superconducting phase difference across the junction. Knowledge of the CPR is essential in order to understand the response of a JJ to various external parameters. Despite the rising interest in ultraclean encapsulated graphene JJs, the CPR of such junctions remains unknown. Here, we use a fully gate-tunable graphene superconducting quantum intereference device (SQUID) to determine the CPR of ballistic graphene JJs. Each of the two JJs in the SQUID is made with graphene encapsulated in hexagonal boron nitride. By independently controlling the critical current of the JJs, we can operate the SQUID either in a symmetric or asymmetric configuration. The highly asymmetric SQUID allows us to phase-bias one of the JJs and thereby directly obtain its CPR. The CPR is found to be skewed, deviating significantly from a sinusoidal form. The skewness can be tuned with the gate voltage and oscillates in antiphase with Fabry-Pérot resistance oscillations of the ballistic graphene cavity. We compare our experiments with tight-binding calculations that include realistic graphene-superconductor interfaces and find a good qualitative agreement.}, author = {Nanda, Gaurav and Aguilera Servin, Juan L and Rakyta, Péter and Kormányos, Andor and Kleiner, Reinhold and Koelle, Dieter and Watanabe, Kazuo and Taniguchi, Takashi and Vandersypen, Lieven and Goswami, Srijit}, issn = {15306984}, journal = {Nano Letters}, number = {6}, pages = {3396 -- 3401}, publisher = {American Chemical Society}, title = {{Current-phase relation of ballistic graphene Josephson junctions}}, doi = {10.1021/acs.nanolett.7b00097}, volume = {17}, year = {2017}, } @article{993, abstract = {In real-world applications, observations are often constrained to a small fraction of a system. Such spatial subsampling can be caused by the inaccessibility or the sheer size of the system, and cannot be overcome by longer sampling. Spatial subsampling can strongly bias inferences about a system’s aggregated properties. To overcome the bias, we derive analytically a subsampling scaling framework that is applicable to different observables, including distributions of neuronal avalanches, of number of people infected during an epidemic outbreak, and of node degrees. We demonstrate how to infer the correct distributions of the underlying full system, how to apply it to distinguish critical from subcritical systems, and how to disentangle subsampling and finite size effects. Lastly, we apply subsampling scaling to neuronal avalanche models and to recordings from developing neural networks. We show that only mature, but not young networks follow power-law scaling, indicating self-organization to criticality during development.}, author = {Levina (Martius), Anna and Priesemann, Viola}, issn = {20411723}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Subsampling scaling}}, doi = {10.1038/ncomms15140}, volume = {8}, year = {2017}, } @article{995, abstract = {Recently it was shown that an impurity exchanging orbital angular momentum with a surrounding bath can be described in terms of the angulon quasiparticle [Phys. Rev. Lett. 118, 095301 (2017)]. The angulon consists of a quantum rotor dressed by a many-particle field of boson excitations, and can be formed out of, for example, a molecule or a nonspherical atom in superfluid helium, or out of an electron coupled to lattice phonons or a Bose condensate. Here we develop an approach to the angulon based on the path-integral formalism, which sets the ground for a systematic, perturbative treatment of the angulon problem. The resulting perturbation series can be interpreted in terms of Feynman diagrams, from which, in turn, one can derive a set of diagrammatic rules. These rules extend the machinery of the graphical theory of angular momentum - well known from theoretical atomic spectroscopy - to the case where an environment with an infinite number of degrees of freedom is present. In particular, we show that each diagram can be interpreted as a 'skeleton', which enforces angular momentum conservation, dressed by an additional many-body contribution. This connection between the angulon theory and the graphical theory of angular momentum is particularly important as it allows to systematically and substantially simplify the analytical representation of each diagram. In order to exemplify the technique, we calculate the 1- and 2-loop contributions to the angulon self-energy, the spectral function, and the quasiparticle weight. The diagrammatic theory we develop paves the way to investigate next-to-leading order quantities in a more compact way compared to the variational approaches.}, author = {Bighin, Giacomo and Lemeshko, Mikhail}, issn = {24699950}, journal = {Physical Review B - Condensed Matter and Materials Physics}, number = {8}, publisher = {American Physical Society}, title = {{Diagrammatic approach to orbital quantum impurities interacting with a many-particle environment}}, doi = {10.1103/PhysRevB.96.085410}, volume = {96}, year = {2017}, } @inproceedings{989, abstract = {We present a generalized optimal transport model in which the mass-preserving constraint for the L2-Wasserstein distance is relaxed by introducing a source term in the continuity equation. The source term is also incorporated in the path energy by means of its squared L2-norm in time of a functional with linear growth in space. This extension of the original transport model enables local density modulations, which is a desirable feature in applications such as image warping and blending. A key advantage of the use of a functional with linear growth in space is that it allows for singular sources and sinks, which can be supported on points or lines. On a technical level, the L2-norm in time ensures a disintegration of the source in time, which we use to obtain the well-posedness of the model and the existence of geodesic paths. The numerical discretization is based on the proximal splitting approach [18] and selected numerical test cases show the potential of the proposed approach. Furthermore, the approach is applied to the warping and blending of textures.}, author = {Maas, Jan and Rumpf, Martin and Simon, Stefan}, editor = {Lauze, François and Dong, Yiqiu and Bjorholm Dahl, Anders}, issn = {03029743}, location = {Kolding, Denmark}, pages = {563 -- 577}, publisher = {Springer}, title = {{Transport based image morphing with intensity modulation}}, doi = {10.1007/978-3-319-58771-4_45}, volume = {10302}, year = {2017}, } @article{994, abstract = {The formation of vortices is usually considered to be the main mechanism of angular momentum disposal in superfluids. Recently, it was predicted that a superfluid can acquire angular momentum via an alternative, microscopic route -- namely, through interaction with rotating impurities, forming so-called `angulon quasiparticles' [Phys. Rev. Lett. 114, 203001 (2015)]. The angulon instabilities correspond to transfer of a small number of angular momentum quanta from the impurity to the superfluid, as opposed to vortex instabilities, where angular momentum is quantized in units of ℏ per atom. Furthermore, since conventional impurities (such as molecules) represent three-dimensional (3D) rotors, the angular momentum transferred is intrinsically 3D as well, as opposed to a merely planar rotation which is inherent to vortices. Herein we show that the angulon theory can explain the anomalous broadening of the spectroscopic lines observed for CH 3 and NH 3 molecules in superfluid helium nanodroplets, thereby providing a fingerprint of the emerging angulon instabilities in experiment.}, author = {Cherepanov, Igor and Lemeshko, Mikhail}, journal = {Physical Review Materials}, number = {3}, publisher = {American Physical Society}, title = {{Fingerprints of angulon instabilities in the spectra of matrix-isolated molecules}}, doi = {10.1103/PhysRevMaterials.1.035602}, volume = {1}, year = {2017}, } @article{991, abstract = {Synaptotagmin 7 (Syt7) was originally identified as a slow Ca2+ sensor for lysosome fusion, but its function at fast synapses is controversial. The paper by Luo and Südhof (2017) in this issue of Neuron shows that at the calyx of Held in the auditory brainstem Syt7 triggers asynchronous release during stimulus trains, resulting in reliable and temporally precise high-frequency transmission. Thus, a slow Ca2+ sensor contributes to the fast signaling properties of the calyx synapse.}, author = {Chen, Chong and Jonas, Peter M}, issn = {08966273}, journal = {Neuron}, number = {4}, pages = {694 -- 696}, publisher = {Elsevier}, title = {{Synaptotagmins: That’s why so many}}, doi = {10.1016/j.neuron.2017.05.011}, volume = {94}, year = {2017}, } @article{954, abstract = {Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for.}, author = {Lagator, Mato and Paixao, Tiago and Barton, Nicholas H and Bollback, Jonathan P and Guet, Calin C}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{On the mechanistic nature of epistasis in a canonical cis-regulatory element}}, doi = {10.7554/eLife.25192}, volume = {6}, year = {2017}, } @article{955, abstract = {Gene expression is controlled by networks of regulatory proteins that interact specifically with external signals and DNA regulatory sequences. These interactions force the network components to co-evolve so as to continually maintain function. Yet, existing models of evolution mostly focus on isolated genetic elements. In contrast, we study the essential process by which regulatory networks grow: the duplication and subsequent specialization of network components. We synthesize a biophysical model of molecular interactions with the evolutionary framework to find the conditions and pathways by which new regulatory functions emerge. We show that specialization of new network components is usually slow, but can be drastically accelerated in the presence of regulatory crosstalk and mutations that promote promiscuous interactions between network components.}, author = {Friedlander, Tamar and Prizak, Roshan and Barton, Nicholas H and Tkacik, Gasper}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Evolution of new regulatory functions on biophysically realistic fitness landscapes}}, doi = {10.1038/s41467-017-00238-8}, volume = {8}, year = {2017}, } @inproceedings{962, abstract = {We present a new algorithm for model counting of a class of string constraints. In addition to the classic operation of concatenation, our class includes some recursively defined operations such as Kleene closure, and replacement of substrings. Additionally, our class also includes length constraints on the string expressions, which means, by requiring reasoning about numbers, that we face a multi-sorted logic. In the end, our string constraints are motivated by their use in programming for web applications. Our algorithm comprises two novel features: the ability to use a technique of (1) partial derivatives for constraints that are already in a solved form, i.e. a form where its (string) satisfiability is clearly displayed, and (2) non-progression, where cyclic reasoning in the reduction process may be terminated (thus allowing for the algorithm to look elsewhere). Finally, we experimentally compare our model counter with two recent works on model counting of similar constraints, SMC [18] and ABC [5], to demonstrate its superior performance.}, author = {Trinh, Minh and Chu, Duc Hiep and Jaffar, Joxan}, editor = {Majumdar, Rupak and Kunčak, Viktor}, issn = {03029743}, location = {Heidelberg, Germany}, pages = {399 -- 418}, publisher = {Springer}, title = {{Model counting for recursively-defined strings}}, doi = {10.1007/978-3-319-63390-9_21}, volume = {10427}, year = {2017}, } @article{953, abstract = {The role of natural selection in the evolution of adaptive phenotypes has undergone constant probing by evolutionary biologists, employing both theoretical and empirical approaches. As Darwin noted, natural selection can act together with other processes, including random changes in the frequencies of phenotypic differences that are not under strong selection, and changes in the environment, which may reflect evolutionary changes in the organisms themselves. As understanding of genetics developed after 1900, the new genetic discoveries were incorporated into evolutionary biology. The resulting general principles were summarized by Julian Huxley in his 1942 book Evolution: the modern synthesis. Here, we examine how recent advances in genetics, developmental biology and molecular biology, including epigenetics, relate to today's understanding of the evolution of adaptations. We illustrate how careful genetic studies have repeatedly shown that apparently puzzling results in a wide diversity of organisms involve processes that are consistent with neo-Darwinism. They do not support important roles in adaptation for processes such as directed mutation or the inheritance of acquired characters, and therefore no radical revision of our understanding of the mechanism of adaptive evolution is needed.}, author = {Charlesworth, Deborah and Barton, Nicholas H and Charlesworth, Brian}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1855}, publisher = {Royal Society, The}, title = {{The sources of adaptive evolution}}, doi = {10.1098/rspb.2016.2864}, volume = {284}, year = {2017}, } @article{959, abstract = {In this work it is shown that scale-free tails in metabolic flux distributions inferred in stationary models are an artifact due to reactions involved in thermodynamically unfeasible cycles, unbounded by physical constraints and in principle able to perform work without expenditure of free energy. After implementing thermodynamic constraints by removing such loops, metabolic flux distributions scale meaningfully with the physical limiting factors, acquiring in turn a richer multimodal structure potentially leading to symmetry breaking while optimizing for objective functions.}, author = {De Martino, Daniele}, issn = {24700045}, journal = { Physical Review E Statistical Nonlinear and Soft Matter Physics }, number = {6}, pages = {062419}, publisher = {American Institute of Physics}, title = {{Scales and multimodal flux distributions in stationary metabolic network models via thermodynamics}}, doi = {10.1103/PhysRevE.95.062419}, volume = {95}, year = {2017}, } @article{956, abstract = {We study a class of ergodic quantum Markov semigroups on finite-dimensional unital C⁎-algebras. These semigroups have a unique stationary state σ, and we are concerned with those that satisfy a quantum detailed balance condition with respect to σ. We show that the evolution on the set of states that is given by such a quantum Markov semigroup is gradient flow for the relative entropy with respect to σ in a particular Riemannian metric on the set of states. This metric is a non-commutative analog of the 2-Wasserstein metric, and in several interesting cases we are able to show, in analogy with work of Otto on gradient flows with respect to the classical 2-Wasserstein metric, that the relative entropy is strictly and uniformly convex with respect to the Riemannian metric introduced here. As a consequence, we obtain a number of new inequalities for the decay of relative entropy for ergodic quantum Markov semigroups with detailed balance.}, author = {Carlen, Eric and Maas, Jan}, issn = {00221236}, journal = {Journal of Functional Analysis}, number = {5}, pages = {1810 -- 1869}, publisher = {Academic Press}, title = {{Gradient flow and entropy inequalities for quantum Markov semigroups with detailed balance}}, doi = {10.1016/j.jfa.2017.05.003}, volume = {273}, year = {2017}, } @article{952, abstract = {A novel strategy for controlling the spread of arboviral diseases such as dengue, Zika and chikungunya is to transform mosquito populations with virus-suppressing Wolbachia. In general, Wolbachia transinfected into mosquitoes induce fitness costs through lower viability or fecundity. These maternally inherited bacteria also produce a frequency-dependent advantage for infected females by inducing cytoplasmic incompatibility (CI), which kills the embryos produced by uninfected females mated to infected males. These competing effects, a frequency-dependent advantage and frequency-independent costs, produce bistable Wolbachia frequency dynamics. Above a threshold frequency, denoted pˆ, CI drives fitness-decreasing Wolbachia transinfections through local populations; but below pˆ, infection frequencies tend to decline to zero. If pˆ is not too high, CI also drives spatial spread once infections become established over sufficiently large areas. We illustrate how simple models provide testable predictions concerning the spatial and temporal dynamics of Wolbachia introductions, focusing on rate of spatial spread, the shape of spreading waves, and the conditions for initiating spread from local introductions. First, we consider the robustness of diffusion-based predictions to incorporating two important features of wMel-Aedes aegypti biology that may be inconsistent with the diffusion approximations, namely fast local dynamics induced by complete CI (i.e., all embryos produced from incompatible crosses die) and long-tailed, non-Gaussian dispersal. With complete CI, our numerical analyses show that long-tailed dispersal changes wave-width predictions only slightly; but it can significantly reduce wave speed relative to the diffusion prediction; it also allows smaller local introductions to initiate spatial spread. Second, we use approximations for pˆ and dispersal distances to predict the outcome of 2013 releases of wMel-infected Aedes aegypti in Cairns, Australia, Third, we describe new data from Ae. aegypti populations near Cairns, Australia that demonstrate long-distance dispersal and provide an approximate lower bound on pˆ for wMel in northeastern Australia. Finally, we apply our analyses to produce operational guidelines for efficient transformation of vector populations over large areas. We demonstrate that even very slow spatial spread, on the order of 10-20 m/month (as predicted), can produce area-wide population transformation within a few years following initial releases covering about 20-30% of the target area.}, author = {Turelli, Michael and Barton, Nicholas H}, issn = {00405809}, journal = {Theoretical Population Biology}, pages = {45 -- 60}, publisher = {Elsevier}, title = {{Deploying dengue-suppressing Wolbachia: Robust models predict slow but effective spatial spread in Aedes aegypti}}, doi = {10.1016/j.tpb.2017.03.003}, volume = {115}, year = {2017}, } @article{951, abstract = {Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100–200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transfo}, author = {Schmidt, Tom and Barton, Nicholas H and Rasic, Gordana and Turley, Andrew and Montgomery, Brian and Iturbe Ormaetxe, Inaki and Cook, Peter and Ryan, Peter and Ritchie, Scott and Hoffmann, Ary and O’Neill, Scott and Turelli, Michael}, issn = {15449173}, journal = {PLoS Biology}, number = {5}, publisher = {Public Library of Science}, title = {{Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes Aegypti}}, doi = {10.1371/journal.pbio.2001894}, volume = {15}, year = {2017}, } @article{947, abstract = {Viewing the ways a living cell can organize its metabolism as the phase space of a physical system, regulation can be seen as the ability to reduce the entropy of that space by selecting specific cellular configurations that are, in some sense, optimal. Here we quantify the amount of regulation required to control a cell's growth rate by a maximum-entropy approach to the space of underlying metabolic phenotypes, where a configuration corresponds to a metabolic flux pattern as described by genome-scale models. We link the mean growth rate achieved by a population of cells to the minimal amount of metabolic regulation needed to achieve it through a phase diagram that highlights how growth suppression can be as costly (in regulatory terms) as growth enhancement. Moreover, we provide an interpretation of the inverse temperature β controlling maximum-entropy distributions based on the underlying growth dynamics. Specifically, we show that the asymptotic value of β for a cell population can be expected to depend on (i) the carrying capacity of the environment, (ii) the initial size of the colony, and (iii) the probability distribution from which the inoculum was sampled. Results obtained for E. coli and human cells are found to be remarkably consistent with empirical evidence.}, author = {De Martino, Daniele and Capuani, Fabrizio and De Martino, Andrea}, issn = {24700045}, journal = { Physical Review E Statistical Nonlinear and Soft Matter Physics }, number = {1}, publisher = {American Institute of Physics}, title = {{Quantifying the entropic cost of cellular growth control}}, doi = {10.1103/PhysRevE.96.010401}, volume = {96}, year = {2017}, } @misc{9858, author = {Schmidt, Tom and Barton, Nicholas H and Rasic, Gordana and Turley, Andrew and Montgomery, Brian and Iturbe Ormaetxe, Inaki and Cook, Peter and Ryan, Peter and Ritchie, Scott and Hoffmann, Ary and O’Neill, Scott and Turelli, Michael}, publisher = {Public Library of Science}, title = {{Excel file with data on mosquito densities, Wolbachia infection status and housing characteristics}}, doi = {10.1371/journal.pbio.2001894.s016}, year = {2017}, } @misc{9857, author = {Schmidt, Tom and Barton, Nicholas H and Rasic, Gordana and Turley, Andrew and Montgomery, Brian and Iturbe Ormaetxe, Inaki and Cook, Peter and Ryan, Peter and Ritchie, Scott and Hoffmann, Ary and O’Neill, Scott and Turelli, Michael}, publisher = {Public Library of Science }, title = {{Supporting information concerning observed wMel frequencies and analyses of habitat variables}}, doi = {10.1371/journal.pbio.2001894.s015}, year = {2017}, } @misc{9856, author = {Schmidt, Tom and Barton, Nicholas H and Rasic, Gordana and Turley, Andrew and Montgomery, Brian and Iturbe Ormaetxe, Inaki and Cook, Peter and Ryan, Peter and Ritchie, Scott and Hoffmann, Ary and O’Neill, Scott and Turelli, Michael}, publisher = {Public Library of Science}, title = {{Supporting Information concerning additional likelihood analyses and results}}, doi = {10.1371/journal.pbio.2001894.s014}, year = {2017}, } @article{945, abstract = {While chromosome-wide dosage compensation of the X chromosome has been found in many species, studies in ZW clades have indicated that compensation of the Z is more localized and/or incomplete. In the ZW Lepidoptera, some species show complete compensation of the Z chromosome, while others lack full equalization, but what drives these inconsistencies is unclear. Here, we compare patterns of male and female gene expression on the Z chromosome of two closely related butterfly species, Papilio xuthus and Papilio machaon, and in multiple tissues of two moths species, Plodia interpunctella and Bombyx mori, which were previously found to differ in the extent to which they equalize Z-linked gene expression between the sexes. We find that, while some species and tissues seem to have incomplete dosage compensation, this is in fact due to the accumulation of male-biased genes and the depletion of female-biased genes on the Z chromosome. Once this is accounted for, the Z chromosome is fully compensated in all four species, through the up-regulation of Z expression in females and in some cases additional down-regulation in males. We further find that both sex-biased genes and Z-linked genes have increased rates of expression divergence in this clade, and that this can lead to fast shifts in patterns of gene expression even between closely related species. Taken together, these results show that the uneven distribution of sex-biased genes on sex chromosomes can confound conclusions about dosage compensation and that Z chromosome-wide dosage compensation is not only possible but ubiquitous among Lepidoptera.}, author = {Huylmans, Ann K and Macon, Ariana and Vicoso, Beatriz}, issn = {07374038}, journal = {Molecular Biology and Evolution}, number = {10}, pages = {2637 -- 2649}, publisher = {Oxford University Press}, title = {{Global dosage compensation is ubiquitous in Lepidoptera, but counteracted by the masculinization of the Z chromosome}}, doi = {10.1093/molbev/msx190}, volume = {34}, year = {2017}, } @article{751, abstract = {The basement membrane (BM) is a thin layer of extracellular matrix (ECM) beneath nearly all epithelial cell types that is critical for cellular and tissue function. It is composed of numerous components conserved among all bilaterians [1]; however, it is unknown how all of these components are generated and subsequently constructed to form a fully mature BM in the living animal. Although BM formation is thought to simply involve a process of self-assembly [2], this concept suffers from a number of logistical issues when considering its construction in vivo. First, incorporation of BM components appears to be hierarchical [3-5], yet it is unclear whether their production during embryogenesis must also be regulated in a temporal fashion. Second, many BM proteins are produced not only by the cells residing on the BM but also by surrounding cell types [6-9], and it is unclear how large, possibly insoluble protein complexes [10] are delivered into the matrix. Here we exploit our ability to live image and genetically dissect de novo BM formation during Drosophila development. This reveals that there is a temporal hierarchy of BM protein production that is essential for proper component incorporation. Furthermore, we show that BM components require secretion by migrating macrophages (hemocytes) during their developmental dispersal, which is critical for embryogenesis. Indeed, hemocyte migration is essential to deliver a subset of ECM components evenly throughout the embryo. This reveals that de novo BM construction requires a combination of both production and distribution logistics allowing for the timely delivery of core components.}, author = {Matsubayashi, Yutaka and Louani, Adam and Dragu, Anca and Sanchez Sanchez, Besaiz and Serna Morales, Eduardo and Yolland, Lawrence and György, Attila and Vizcay, Gema and Fleck, Roland and Heddleston, John and Chew, Teng and Siekhaus, Daria E and Stramer, Brian}, issn = {09609822}, journal = {Current Biology}, number = {22}, pages = {3526 -- 3534e.4}, publisher = {Cell Press}, title = {{A moving source of matrix components is essential for De Novo basement membrane formation}}, doi = {10.1016/j.cub.2017.10.001}, volume = {27}, year = {2017}, } @article{798, abstract = {Nonreciprocal circuit elements form an integral part of modern measurement and communication systems. Mathematically they require breaking of time-reversal symmetry, typically achieved using magnetic materials and more recently using the quantum Hall effect, parametric permittivity modulation or Josephson nonlinearities. Here we demonstrate an on-chip magnetic-free circulator based on reservoir-engineered electromechanic interactions. Directional circulation is achieved with controlled phase-sensitive interference of six distinct electro-mechanical signal conversion paths. The presented circulator is compact, its silicon-on-insulator platform is compatible with both superconducting qubits and silicon photonics, and its noise performance is close to the quantum limit. With a high dynamic range, a tunable bandwidth of up to 30 MHz and an in situ reconfigurability as beam splitter or wavelength converter, it could pave the way for superconducting qubit processors with multiplexed on-chip signal processing and readout.}, author = {Barzanjeh, Shabir and Wulf, Matthias and Peruzzo, Matilda and Kalaee, Mahmoud and Dieterle, Paul and Painter, Oskar and Fink, Johannes M}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Mechanical on chip microwave circulator}}, doi = {10.1038/s41467-017-01304-x}, volume = {8}, year = {2017}, } @inproceedings{791, abstract = {Consider the following random process: we are given n queues, into which elements of increasing labels are inserted uniformly at random. To remove an element, we pick two queues at random, and remove the element of lower label (higher priority) among the two. The cost of a removal is the rank of the label removed, among labels still present in any of the queues, that is, the distance from the optimal choice at each step. Variants of this strategy are prevalent in state-of-the-art concurrent priority queue implementations. Nonetheless, it is not known whether such implementations provide any rank guarantees, even in a sequential model. We answer this question, showing that this strategy provides surprisingly strong guarantees: Although the single-choice process, where we always insert and remove from a single randomly chosen queue, has degrading cost, going to infinity as we increase the number of steps, in the two choice process, the expected rank of a removed element is O(n) while the expected worst-case cost is O(n log n). These bounds are tight, and hold irrespective of the number of steps for which we run the process. The argument is based on a new technical connection between "heavily loaded" balls-into-bins processes and priority scheduling. Our analytic results inspire a new concurrent priority queue implementation, which improves upon the state of the art in terms of practical performance.}, author = {Alistarh, Dan-Adrian and Kopinsky, Justin and Li, Jerry and Nadiradze, Giorgi}, booktitle = {Proceedings of the ACM Symposium on Principles of Distributed Computing}, isbn = {978-145034992-5}, location = {Washington, WA, USA}, pages = {283 -- 292}, publisher = {ACM}, title = {{The power of choice in priority scheduling}}, doi = {10.1145/3087801.3087810}, volume = {Part F129314}, year = {2017}, } @article{792, abstract = {The chaotic dynamics of low-dimensional systems, such as Lorenz or Rössler flows, is guided by the infinity of periodic orbits embedded in their strange attractors. Whether this is also the case for the infinite-dimensional dynamics of Navier–Stokes equations has long been speculated, and is a topic of ongoing study. Periodic and relative periodic solutions have been shown to be involved in transitions to turbulence. Their relevance to turbulent dynamics – specifically, whether periodic orbits play the same role in high-dimensional nonlinear systems like the Navier–Stokes equations as they do in lower-dimensional systems – is the focus of the present investigation. We perform here a detailed study of pipe flow relative periodic orbits with energies and mean dissipations close to turbulent values. We outline several approaches to reduction of the translational symmetry of the system. We study pipe flow in a minimal computational cell at Re=2500, and report a library of invariant solutions found with the aid of the method of slices. Detailed study of the unstable manifolds of a sample of these solutions is consistent with the picture that relative periodic orbits are embedded in the chaotic saddle and that they guide the turbulent dynamics.}, author = {Budanur, Nazmi B and Short, Kimberly and Farazmand, Mohammad and Willis, Ashley and Cvitanović, Predrag}, issn = {00221120}, journal = {Journal of Fluid Mechanics}, pages = {274 -- 301}, publisher = {Cambridge University Press}, title = {{Relative periodic orbits form the backbone of turbulent pipe flow}}, doi = {10.1017/jfm.2017.699}, volume = {833}, year = {2017}, } @article{796, abstract = {We present the fabrication and characterization of an aluminum transmon qubit on a silicon-on-insulator substrate. Key to the qubit fabrication is the use of an anhydrous hydrofluoric vapor process which selectively removes the lossy silicon oxide buried underneath the silicon device layer. For a 5.6 GHz qubit measured dispersively by a 7.1 GHz resonator, we find T1 = 3.5 μs and T∗2 = 2.2 μs. This process in principle permits the co-fabrication of silicon photonic and mechanical elements, providing a route towards chip-scale integration of electro-opto-mechanical transducers for quantum networking of superconducting microwave quantum circuits. The additional processing steps are compatible with established fabrication techniques for aluminum transmon qubits on silicon.}, author = {Keller, Andrew J and Dieterle, Paul and Fang, Michael and Berger, Brett and Fink, Johannes M and Painter, Oskar}, issn = {00036951}, journal = {Applied Physics Letters}, number = {4}, publisher = {American Institute of Physics}, title = {{Al transmon qubits on silicon on insulator for quantum device integration}}, doi = {10.1063/1.4994661}, volume = {111}, year = {2017}, } @article{793, abstract = {Let P be a finite point set in the plane. A cordinary triangle in P is a subset of P consisting of three non-collinear points such that each of the three lines determined by the three points contains at most c points of P . Motivated by a question of Erdös, and answering a question of de Zeeuw, we prove that there exists a constant c > 0such that P contains a c-ordinary triangle, provided that P is not contained in the union of two lines. Furthermore, the number of c-ordinary triangles in P is Ω(| P |). }, author = {Fulek, Radoslav and Mojarrad, Hossein and Naszódi, Márton and Solymosi, József and Stich, Sebastian and Szedlák, May}, issn = {09257721}, journal = {Computational Geometry: Theory and Applications}, pages = {28 -- 31}, publisher = {Elsevier}, title = {{On the existence of ordinary triangles}}, doi = {10.1016/j.comgeo.2017.07.002}, volume = {66}, year = {2017}, } @article{794, abstract = {We show that c-planarity is solvable in quadratic time for flat clustered graphs with three clusters if the combinatorial embedding of the underlying graph is fixed. In simpler graph-theoretical terms our result can be viewed as follows. Given a graph G with the vertex set partitioned into three parts embedded on a 2-sphere, our algorithm decides if we can augment G by adding edges without creating an edge-crossing so that in the resulting spherical graph the vertices of each part induce a connected sub-graph. We proceed by a reduction to the problem of testing the existence of a perfect matching in planar bipartite graphs. We formulate our result in a slightly more general setting of cyclic clustered graphs, i.e., the simple graph obtained by contracting each cluster, where we disregard loops and multi-edges, is a cycle.}, author = {Fulek, Radoslav}, journal = {Computational Geometry: Theory and Applications}, pages = {1 -- 13}, publisher = {Elsevier}, title = {{C-planarity of embedded cyclic c-graphs}}, doi = {10.1016/j.comgeo.2017.06.016}, volume = {66}, year = {2017}, } @article{736, abstract = {The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner.}, author = {Rubio, María and Matsui, Ko and Fukazawa, Yugo and Kamasawa, Naomi and Harada, Harumi and Itakura, Makoto and Molnár, Elek and Abe, Manabu and Sakimura, Kenji and Shigemoto, Ryuichi}, issn = {18632653}, journal = {Brain Structure and Function}, number = {8}, pages = {3375 -- 3393}, publisher = {Springer}, title = {{The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells}}, doi = {10.1007/s00429-017-1408-0}, volume = {222}, year = {2017}, } @article{740, abstract = {Developments in bioengineering and molecular biology have introduced a palette of genetically encoded probes for identification of specific cell populations in electron microscopy. These probes can be targeted to distinct cellular compartments, rendering them electron dense through a subsequent chemical reaction. These electron densities strongly increase the local contrast in samples prepared for electron microscopy, allowing three major advances in ultrastructural mapping of circuits: genetic identification of circuit components, targeted imaging of regions of interest and automated analysis of the tagged circuits. Together, the gains from these advances can decrease the time required for the analysis of targeted circuit motifs by over two orders of magnitude. These genetic encoded tags for electron microscopy promise to simplify the analysis of circuit motifs and become a central tool for structure‐function studies of synaptic connections in the brain. We review the current state‐of‐the‐art with an emphasis on connectomics, the quantitative analysis of neuronal structures and motifs.}, author = {Shigemoto, Ryuichi and Jösch, Maximilian A}, issn = {17597684}, journal = {WIREs Developmental Biology}, number = {6}, publisher = {Wiley-Blackwell}, title = {{The genetic encoded toolbox for electron microscopy and connectomics}}, doi = {10.1002/wdev.288}, volume = {6}, year = {2017}, } @article{741, abstract = {We prove that a system of N fermions interacting with an additional particle via point interactions is stable if the ratio of the mass of the additional particle to the one of the fermions is larger than some critical m*. The value of m* is independent of N and turns out to be less than 1. This fact has important implications for the stability of the unitary Fermi gas. We also characterize the domain of the Hamiltonian of this model, and establish the validity of the Tan relations for all wave functions in the domain.}, author = {Moser, Thomas and Seiringer, Robert}, issn = {00103616}, journal = {Communications in Mathematical Physics}, number = {1}, pages = {329 -- 355}, publisher = {Springer}, title = {{Stability of a fermionic N+1 particle system with point interactions}}, doi = {10.1007/s00220-017-2980-0}, volume = {356}, year = {2017}, } @article{739, abstract = {We study the norm approximation to the Schrödinger dynamics of N bosons in with an interaction potential of the form . Assuming that in the initial state the particles outside of the condensate form a quasi-free state with finite kinetic energy, we show that in the large N limit, the fluctuations around the condensate can be effectively described using Bogoliubov approximation for all . The range of β is expected to be optimal for this large class of initial states.}, author = {Nam, Phan and Napiórkowski, Marcin M}, issn = {00217824}, journal = {Journal de Mathématiques Pures et Appliquées}, number = {5}, pages = {662 -- 688}, publisher = {Elsevier}, title = {{A note on the validity of Bogoliubov correction to mean field dynamics}}, doi = {10.1016/j.matpur.2017.05.013}, volume = {108}, year = {2017}, } @article{737, abstract = {We generalize Brazas’ topology on the fundamental group to the whole universal path space X˜ i.e., to the set of homotopy classes of all based paths. We develop basic properties of the new notion and provide a complete comparison of the obtained topology with the established topologies, in particular with the Lasso topology and the CO topology, i.e., the topology that is induced by the compact-open topology. It turns out that the new topology is the finest topology contained in the CO topology, for which the action of the fundamental group on the universal path space is a continuous group action.}, author = {Virk, Ziga and Zastrow, Andreas}, issn = {01668641}, journal = {Topology and its Applications}, pages = {186 -- 196}, publisher = {Elsevier}, title = {{A new topology on the universal path space}}, doi = {10.1016/j.topol.2017.09.015}, volume = {231}, year = {2017}, } @article{733, abstract = {Let A and B be two N by N deterministic Hermitian matrices and let U be an N by N Haar distributed unitary matrix. It is well known that the spectral distribution of the sum H = A + UBU∗ converges weakly to the free additive convolution of the spectral distributions of A and B, as N tends to infinity. We establish the optimal convergence rate in the bulk of the spectrum.}, author = {Bao, Zhigang and Erdös, László and Schnelli, Kevin}, journal = {Advances in Mathematics}, pages = {251 -- 291}, publisher = {Academic Press}, title = {{Convergence rate for spectral distribution of addition of random matrices}}, doi = {10.1016/j.aim.2017.08.028}, volume = {319}, year = {2017}, } @article{840, abstract = {Heavy holes confined in quantum dots are predicted to be promising candidates for the realization of spin qubits with long coherence times. Here we focus on such heavy-hole states confined in germanium hut wires. By tuning the growth density of the latter we can realize a T-like structure between two neighboring wires. Such a structure allows the realization of a charge sensor, which is electrostatically and tunnel coupled to a quantum dot, with charge-transfer signals as high as 0.3 e. By integrating the T-like structure into a radiofrequency reflectometry setup, single-shot measurements allowing the extraction of hole tunneling times are performed. The extracted tunneling times of less than 10 μs are attributed to the small effective mass of Ge heavy-hole states and pave the way toward projective spin readout measurements.}, author = {Vukusic, Lada and Kukucka, Josip and Watzinger, Hannes and Katsaros, Georgios}, issn = {15306984}, journal = {Nano Letters}, number = {9}, pages = {5706 -- 5710}, publisher = {American Chemical Society}, title = {{Fast hole tunneling times in germanium hut wires probed by single-shot reflectometry}}, doi = {10.1021/acs.nanolett.7b02627}, volume = {17}, year = {2017}, } @article{914, abstract = {Infections with potentially lethal pathogens may negatively affect an individual’s lifespan and decrease its reproductive value. The terminal investment hypothesis predicts that individuals faced with a reduced survival should invest more into reproduction instead of maintenance and growth. Several studies suggest that individuals are indeed able to estimate their body condition and to increase their reproductive effort with approaching death, while other studies gave ambiguous results. We investigate whether queens of a perennial social insect (ant) are able to boost their reproduction following infection with an obligate killing pathogen. Social insect queens are special with regard to reproduction and aging, as they outlive conspecific non-reproductive workers. Moreover, in the ant Cardiocondyla obscurior, fecundity increases with queen age. However, it remained unclear whether this reflects negative reproductive senescence or terminal investment in response to approaching death. Here, we test whether queens of C. obscurior react to infection with the entomopathogenic fungus Metarhizium brunneum by an increased egg-laying rate. We show that a fungal infection triggers a reinforced investment in reproduction in queens. This adjustment of the reproductive rate by ant queens is consistent with predictions of the terminal investment hypothesis and is reported for the first time in a social insect.}, author = {Giehr, Julia and Grasse, Anna V and Cremer, Sylvia and Heinze, Jürgen and Schrempf, Alexandra}, issn = {20545703}, journal = {Royal Society Open Science}, number = {7}, publisher = {Royal Society, The}, title = {{Ant queens increase their reproductive efforts after pathogen infection}}, doi = {10.1098/rsos.170547}, volume = {4}, year = {2017}, } @article{910, abstract = {Frequency-independent selection is generally considered as a force that acts to reduce the genetic variation in evolving populations, yet rigorous arguments for this idea are scarce. When selection fluctuates in time, it is unclear whether frequency-independent selection may maintain genetic polymorphism without invoking additional mechanisms. We show that constant frequency-independent selection with arbitrary epistasis on a well-mixed haploid population eliminates genetic variation if we assume linkage equilibrium between alleles. To this end, we introduce the notion of frequency-independent selection at the level of alleles, which is sufficient to prove our claim and contains the notion of frequency-independent selection on haploids. When selection and recombination are weak but of the same order, there may be strong linkage disequilibrium; numerical calculations show that stable equilibria are highly unlikely. Using the example of a diallelic two-locus model, we then demonstrate that frequency-independent selection that fluctuates in time can maintain stable polymorphism if linkage disequilibrium changes its sign periodically. We put our findings in the context of results from the existing literature and point out those scenarios in which the possible role of frequency-independent selection in maintaining genetic variation remains unclear. }, author = {Novak, Sebastian and Barton, Nicholas H}, journal = {Genetics}, number = {2}, pages = {653 -- 668}, publisher = {Genetics Society of America}, title = {{When does frequency-independent selection maintain genetic variation?}}, doi = {10.1534/genetics.117.300129}, volume = {207}, year = {2017}, } @article{835, abstract = {An outstanding question in animal development, tissue homeostasis and disease is how cell populations adapt to sensory inputs. During Drosophila larval development, hematopoietic sites are in direct contact with sensory neuron clusters of the peripheral nervous system (PNS), and blood cells (hemocytes) require the PNS for their survival and recruitment to these microenvironments, known as Hematopoietic Pockets. Here we report that Activin-β, a TGF-β family ligand, is expressed by sensory neurons of the PNS and regulates the proliferation and adhesion of hemocytes. These hemocyte responses depend on PNS activity, as shown by agonist treatment and transient silencing of sensory neurons. Activin-β has a key role in this regulation, which is apparent from reporter expression and mutant analyses. This mechanism of local sensory neurons controlling blood cell adaptation invites evolutionary parallels with vertebrate hematopoietic progenitors and the independent myeloid system of tissue macrophages, whose regulation by local microenvironments remain undefined.}, author = {Makhijani, Kalpana and Alexander, Brandy and Rao, Deepti and Petraki, Sophia and Herboso, Leire and Kukar, Katelyn and Batool, Itrat and Wachner, Stephanie and Gold, Katrina and Wong, Corinna and O'Connor, Michael and Brückner, Katja}, issn = {20411723}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Regulation of Drosophila hematopoietic sites by Activin-β from active sensory neurons}}, doi = {10.1038/ncomms15990}, volume = {8}, year = {2017}, } @inproceedings{836, abstract = {Recent research has examined how to study the topological features of a continuous self-map by means of the persistence of the eigenspaces, for given eigenvalues, of the endomorphism induced in homology over a field. This raised the question of how to select dynamically significant eigenvalues. The present paper aims to answer this question, giving an algorithm that computes the persistence of eigenspaces for every eigenvalue simultaneously, also expressing said eigenspaces as direct sums of “finite” and “singular” subspaces.}, author = {Ethier, Marc and Jablonski, Grzegorz and Mrozek, Marian}, booktitle = {Special Sessions in Applications of Computer Algebra}, isbn = {978-331956930-7}, location = {Kalamata, Greece}, pages = {119 -- 136}, publisher = {Springer}, title = {{Finding eigenvalues of self-maps with the Kronecker canonical form}}, doi = {10.1007/978-3-319-56932-1_8}, volume = {198}, year = {2017}, } @inproceedings{916, abstract = {We study the quadratic assignment problem, in computer vision also known as graph matching. Two leading solvers for this problem optimize the Lagrange decomposition duals with sub-gradient and dual ascent (also known as message passing) updates. We explore this direction further and propose several additional Lagrangean relaxations of the graph matching problem along with corresponding algorithms, which are all based on a common dual ascent framework. Our extensive empirical evaluation gives several theoretical insights and suggests a new state-of-the-art anytime solver for the considered problem. Our improvement over state-of-the-art is particularly visible on a new dataset with large-scale sparse problem instances containing more than 500 graph nodes each.}, author = {Swoboda, Paul and Rother, Carsten and Abu Alhaija, Carsten and Kainmueller, Dagmar and Savchynskyy, Bogdan}, isbn = {978-153860457-1}, location = {Honolulu, HA, United States}, pages = {7062--7071}, publisher = {IEEE}, title = {{A study of lagrangean decompositions and dual ascent solvers for graph matching}}, doi = {10.1109/CVPR.2017.747}, volume = {2017}, year = {2017}, } @inproceedings{915, abstract = {We propose a dual decomposition and linear program relaxation of the NP-hard minimum cost multicut problem. Unlike other polyhedral relaxations of the multicut polytope, it is amenable to efficient optimization by message passing. Like other polyhedral relaxations, it can be tightened efficiently by cutting planes. We define an algorithm that alternates between message passing and efficient separation of cycle- and odd-wheel inequalities. This algorithm is more efficient than state-of-the-art algorithms based on linear programming, including algorithms written in the framework of leading commercial software, as we show in experiments with large instances of the problem from applications in computer vision, biomedical image analysis and data mining.}, author = {Swoboda, Paul and Andres, Bjoern}, isbn = {978-153860457-1}, location = {Honolulu, HA, United States}, pages = {4990--4999}, publisher = {IEEE}, title = {{A message passing algorithm for the minimum cost multicut problem}}, doi = {10.1109/CVPR.2017.530}, volume = {2017}, year = {2017}, } @inproceedings{917, abstract = {We propose a general dual ascent framework for Lagrangean decomposition of combinatorial problems. Although methods of this type have shown their efficiency for a number of problems, so far there was no general algorithm applicable to multiple problem types. In this work, we propose such a general algorithm. It depends on several parameters, which can be used to optimize its performance in each particular setting. We demonstrate efficacy of our method on graph matching and multicut problems, where it outperforms state-of-the-art solvers including those based on subgradient optimization and off-the-shelf linear programming solvers.}, author = {Swoboda, Paul and Kuske, Jan and Savchynskyy, Bogdan}, isbn = {978-153860457-1}, location = {Honolulu, HA, United States}, pages = {4950--4960}, publisher = {IEEE}, title = {{A dual ascent framework for Lagrangean decomposition of combinatorial problems}}, doi = {10.1109/CVPR.2017.526}, volume = {2017}, year = {2017}, } @article{943, abstract = {Like many developing tissues, the vertebrate neural tube is patterned by antiparallel morphogen gradients. To understand how these inputs are interpreted, we measured morphogen signaling and target gene expression in mouse embryos and chick ex vivo assays. From these data, we derived and validated a characteristic decoding map that relates morphogen input to the positional identity of neural progenitors. Analysis of the observed responses indicates that the underlying interpretation strategy minimizes patterning errors in response to the joint input of noisy opposing gradients. We reverse-engineered a transcriptional network that provides a mechanistic basis for the observed cell fate decisions and accounts for the precision and dynamics of pattern formation. Together, our data link opposing gradient dynamics in a growing tissue to precise pattern formation.}, author = {Zagórski, Marcin P and Tabata, Yoji and Brandenberg, Nathalie and Lutolf, Matthias and Tkacik, Gasper and Bollenbach, Tobias and Briscoe, James and Kicheva, Anna}, issn = {00368075}, journal = {Science}, number = {6345}, pages = {1379 -- 1383}, publisher = {American Association for the Advancement of Science}, title = {{Decoding of position in the developing neural tube from antiparallel morphogen gradients}}, doi = {10.1126/science.aam5887}, volume = {356}, year = {2017}, } @article{944, abstract = {The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.}, author = {Beattie, Robert J and Postiglione, Maria P and Burnett, Laura and Laukoter, Susanne and Streicher, Carmen and Pauler, Florian and Xiao, Guanxi and Klezovitch, Olga and Vasioukhin, Valeri and Ghashghaei, Troy and Hippenmeyer, Simon}, issn = {08966273}, journal = {Neuron}, number = {3}, pages = {517 -- 533.e3}, publisher = {Cell Press}, title = {{Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells}}, doi = {10.1016/j.neuron.2017.04.012}, volume = {94}, year = {2017}, } @inproceedings{942, abstract = {A notable class of techniques for automatic program repair is known as semantics-based. Such techniques, e.g., Angelix, infer semantic specifications via symbolic execution, and then use program synthesis to construct new code that satisfies those inferred specifications. However, the obtained specifications are naturally incomplete, leaving the synthesis engine with a difficult task of synthesizing a general solution from a sparse space of many possible solutions that are consistent with the provided specifications but that do not necessarily generalize. We present S3, a new repair synthesis engine that leverages programming-by-examples methodology to synthesize high-quality bug repairs. The novelty in S3 that allows it to tackle the sparse search space to create more general repairs is three-fold: (1) A systematic way to customize and constrain the syntactic search space via a domain-specific language, (2) An efficient enumeration-based search strategy over the constrained search space, and (3) A number of ranking features based on measures of the syntactic and semantic distances between candidate solutions and the original buggy program. We compare S3’s repair effectiveness with state-of-the-art synthesis engines Angelix, Enumerative, and CVC4. S3 can successfully and correctly fix at least three times more bugs than the best baseline on datasets of 52 bugs in small programs, and 100 bugs in real-world large programs. }, author = {Le, Xuan and Chu, Duc Hiep and Lo, David and Le Goues, Claire and Visser, Willem}, isbn = {978-145035105-8}, location = {Paderborn, Germany}, pages = {593 -- 604}, publisher = {ACM}, title = {{S3: Syntax- and semantic-guided repair synthesis via programming by examples}}, doi = {10.1145/3106237.3106309}, volume = {F130154}, year = {2017}, } @article{939, abstract = {We reveal the existence of continuous families of guided single-mode solitons in planar waveguides with weakly nonlinear active core and absorbing boundaries. Stable propagation of TE and TM-polarized solitons is accompanied by attenuation of all other modes, i.e., the waveguide features properties of conservative and dissipative systems. If the linear spectrum of the waveguide possesses exceptional points, which occurs in the case of TM polarization, an originally focusing (defocusing) material nonlinearity may become effectively defocusing (focusing). This occurs due to the geometric phase of the carried eigenmode when the surface impedance encircles the exceptional point. In its turn, the change of the effective nonlinearity ensures the existence of dark (bright) solitons in spite of focusing (defocusing) Kerr nonlinearity of the core. The existence of an exceptional point can also result in anomalous enhancement of the effective nonlinearity. In terms of practical applications, the nonlinearity of the reported waveguide can be manipulated by controlling the properties of the absorbing cladding.}, author = {Midya, Bikashkali and Konotop, Vladimir}, issn = {00319007}, journal = {Physical Review Letters}, number = {3}, publisher = {American Physical Society}, title = {{Waveguides with absorbing boundaries: Nonlinearity controlled by an exceptional point and solitons}}, doi = {10.1103/PhysRevLett.119.033905}, volume = {119}, year = {2017}, } @misc{9853, abstract = {Egg laying rates and infection loads of C. obscurior queens}, author = {Giehr, Julia and Grasse, Anna V and Cremer, Sylvia and Heinze, Jürgen and Schrempf, Alexandra}, publisher = {The Royal Society}, title = {{Raw data from ant queens increase their reproductive efforts after pathogen infection}}, doi = {10.6084/m9.figshare.5117788.v1}, year = {2017}, } @article{822, abstract = {Polymicrobial infections constitute small ecosystems that accommodate several bacterial species. Commonly, these bacteria are investigated in isolation. However, it is unknown to what extent the isolates interact and whether their interactions alter bacterial growth and ecosystem resilience in the presence and absence of antibiotics. We quantified the complete ecological interaction network for 72 bacterial isolates collected from 23 individuals diagnosed with polymicrobial urinary tract infections and found that most interactions cluster based on evolutionary relatedness. Statistical network analysis revealed that competitive and cooperative reciprocal interactions are enriched in the global network, while cooperative interactions are depleted in the individual host community networks. A population dynamics model parameterized by our measurements suggests that interactions restrict community stability, explaining the observed species diversity of these communities. We further show that the clinical isolates frequently protect each other from clinically relevant antibiotics. Together, these results highlight that ecological interactions are crucial for the growth and survival of bacteria in polymicrobial infection communities and affect their assembly and resilience. }, author = {De Vos, Marjon and Zagórski, Marcin P and Mcnally, Alan and Bollenbach, Mark Tobias}, issn = {00278424}, journal = {PNAS}, number = {40}, pages = {10666 -- 10671}, publisher = {National Academy of Sciences}, title = {{Interaction networks, ecological stability, and collective antibiotic tolerance in polymicrobial infections}}, doi = {10.1073/pnas.1713372114}, volume = {114}, year = {2017}, } @inproceedings{833, abstract = {We present an efficient algorithm to compute Euler characteristic curves of gray scale images of arbitrary dimension. In various applications the Euler characteristic curve is used as a descriptor of an image. Our algorithm is the first streaming algorithm for Euler characteristic curves. The usage of streaming removes the necessity to store the entire image in RAM. Experiments show that our implementation handles terabyte scale images on commodity hardware. Due to lock-free parallelism, it scales well with the number of processor cores. Additionally, we put the concept of the Euler characteristic curve in the wider context of computational topology. In particular, we explain the connection with persistence diagrams.}, author = {Heiss, Teresa and Wagner, Hubert}, editor = {Felsberg, Michael and Heyden, Anders and Krüger, Norbert}, issn = {03029743}, location = {Ystad, Sweden}, pages = {397 -- 409}, publisher = {Springer}, title = {{Streaming algorithm for Euler characteristic curves of multidimensional images}}, doi = {10.1007/978-3-319-64689-3_32}, volume = {10424}, year = {2017}, } @article{805, abstract = {During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14.5, while depletion of the alternatively spliced E12 variant did not affect layer-specific neurogenesis. While ChIP-Seq identified a big overlap for E12- and E47-specific binding sites in embryonic NSCs, including sites at the cyclin-dependent kinase inhibitor (CDKI) Cdkn1c gene locus, RNA-Seq revealed a unique transcriptional regulation by each splice variant. E47 activated the expression of the CDKI Cdkn1c through binding to a distal enhancer. Finally, overexpression of E47 in embryonic NSCs in vitro impaired neurite outgrowth and E47 overexpression in vivo by in utero electroporation disturbed proper layer-specific neurogenesis and upregulated p57(KIP2) expression. Overall, this study identified E2A target genes in embryonic NSCs and demonstrates that E47 regulates neuronal differentiation via p57(KIP2).}, author = {Pfurr, Sabrina and Chu, Yu and Bohrer, Christian and Greulich, Franziska and Beattie, Robert J and Mammadzada, Könül and Hils, Miriam and Arnold, Sebastian and Taylor, Verdon and Schachtrup, Kristina and Uhlenhaut, N Henriette and Schachtrup, Christian}, journal = {Development}, pages = {3917 -- 3931}, publisher = {Company of Biologists}, title = {{The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development}}, doi = {10.1242/dev.145698}, volume = {144}, year = {2017}, } @article{834, abstract = {Thermal and many-body localized phases are separated by a dynamical phase transition of a new kind. We analyze the distribution of off-diagonal matrix elements of local operators across this transition in two different models of disordered spin chains. We show that the behavior of matrix elements can be used to characterize the breakdown of thermalization and to extract the many-body Thouless energy. We find that upon increasing the disorder strength the system enters a critical region around the many-body localization transition. The properties of the system in this region are: (i) the Thouless energy becomes smaller than the level spacing, (ii) the matrix elements show critical dependence on the energy difference, and (iii) the matrix elements, viewed as amplitudes of a fictitious wave function, exhibit strong multifractality. This critical region decreases with the system size, which we interpret as evidence for a diverging correlation length at the many-body localization transition. Our findings show that the correlation length becomes larger than the accessible system sizes in a broad range of disorder strength values and shed light on the critical behavior near the many-body localization transition.}, author = {Serbyn, Maksym and Zlatko, Papic and Abanin, Dmitry}, issn = {24699950}, journal = {Physical Review B - Condensed Matter and Materials Physics}, number = {10}, publisher = {American Physical Society}, title = {{Thouless energy and multifractality across the many-body localization transition}}, doi = {10.1103/PhysRevB.96.104201}, volume = {96}, year = {2017}, } @article{823, abstract = {The resolution of a linear system with positive integer variables is a basic yet difficult computational problem with many applications. We consider sparse uncorrelated random systems parametrised by the density c and the ratio α=N/M between number of variables N and number of constraints M. By means of ensemble calculations we show that the space of feasible solutions endows a Van-Der-Waals phase diagram in the plane (c, α). We give numerical evidence that the associated computational problems become more difficult across the critical point and in particular in the coexistence region.}, author = {Colabrese, Simona and De Martino, Daniele and Leuzzi, Luca and Marinari, Enzo}, issn = {17425468}, journal = { Journal of Statistical Mechanics: Theory and Experiment}, number = {9}, publisher = {IOPscience}, title = {{Phase transitions in integer linear problems}}, doi = {10.1088/1742-5468/aa85c3}, volume = {2017}, year = {2017}, } @article{824, abstract = {In shear flows at transitional Reynolds numbers, localized patches of turbulence, known as puffs, coexist with the laminar flow. Recently, Avila et al. (Phys. Rev. Lett., vol. 110, 2013, 224502) discovered two spatially localized relative periodic solutions for pipe flow, which appeared in a saddle-node bifurcation at low Reynolds number. Combining slicing methods for continuous symmetry reduction with Poincaré sections for the first time in a shear flow setting, we compute and visualize the unstable manifold of the lower-branch solution and show that it extends towards the neighbourhood of the upper-branch solution. Surprisingly, this connection even persists far above the bifurcation point and appears to mediate the first stage of the puff generation: amplification of streamwise localized fluctuations. When the state-space trajectories on the unstable manifold reach the vicinity of the upper branch, corresponding fluctuations expand in space and eventually take the usual shape of a puff.}, author = {Budanur, Nazmi B and Hof, Björn}, issn = {00221120}, journal = {Journal of Fluid Mechanics}, publisher = {Cambridge University Press}, title = {{Heteroclinic path to spatially localized chaos in pipe flow}}, doi = {10.1017/jfm.2017.516}, volume = {827}, year = {2017}, } @article{799, abstract = {Membrane traffic at the trans-Golgi network (TGN) is crucial for correctly distributing various membrane proteins to their destination. Polarly localized auxin efflux proteins, including PIN-FORMED1 (PIN1), are dynamically transported between the endosomes and the plasma membrane (PM) in the plant cells. The intracellular trafficking of PIN1 protein is sensitive to a fungal toxin brefeldin A (BFA), which is known to inhibit guanine-nucleotide exchange factors for ADP ribosylation factors (ARF GEFs) such as GNOM. However, the molecular details of the BFA-sensitive trafficking pathway have not been revealed fully. In a previous study, we have identified an Arabidopsis mutant BFA-visualized endocytic trafficking defective 3 (ben3) which exhibited reduced sensitivity to BFA in terms of BFA-induced intracellular PIN1 agglomeration. Here, we show that BEN3 encodes a member of BIG family ARF GEFs, BIG2. Fluorescent proteins tagged BEN3/BIG2 co-localized with markers for TGN / early endosome (EE). Inspection of conditionally induced de novo synthesized PIN1 confirmed that its secretion to the PM is BFA-sensitive and established BEN3/BIG2 as a crucial component of this BFA action at the level of TGN/EE. Furthermore, ben3 mutation alleviated BFA-induced agglomeration of another TGN-localized ARF GEF BEN1/MIN7. Taken together our results suggest that BEN3/BIG2 is an ARF GEF component, which confers BFA sensitivity to the TGN/EE in Arabidopsis.}, author = {Kitakura, Saeko and Adamowski, Maciek and Matsuura, Yuki and Santuari, Luca and Kouno, Hirotaka and Arima, Kohei and Hardtke, Christian and Friml, Jirí and Kakimoto, Tatsuo and Tanaka, Hirokazu}, issn = {00320781}, journal = {Plant and Cell Physiology}, number = {10}, publisher = {Oxford University Press}, title = {{BEN3/BIG2 ARF GEF is involved in brefeldin a-sensitive trafficking at the trans-Golgi network/early endosome in Arabidopsis thaliana}}, doi = {10.1093/pcp/pcx118}, volume = {58}, year = {2017}, } @article{800, abstract = {Gamma oscillations (30–150 Hz) in neuronal networks are associated with the processing and recall of information. We measured local field potentials in the dentate gyrus of freely moving mice and found that gamma activity occurs in bursts, which are highly heterogeneous in their spatial extensions, ranging from focal to global coherent events. Synaptic communication among perisomatic-inhibitory interneurons (PIIs) is thought to play an important role in the generation of hippocampal gamma patterns. However, how neuronal circuits can generate synchronous oscillations at different spatial scales is unknown. We analyzed paired recordings in dentate gyrus slices and show that synaptic signaling at interneuron-interneuron synapses is distance dependent. Synaptic strength declines whereas the duration of inhibitory signals increases with axonal distance among interconnected PIIs. Using neuronal network modeling, we show that distance-dependent inhibition generates multiple highly synchronous focal gamma bursts allowing the network to process complex inputs in parallel in flexibly organized neuronal centers.}, author = {Strüber, Michael and Sauer, Jonas and Jonas, Peter M and Bartos, Marlene}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Distance-dependent inhibition facilitates focality of gamma oscillations in the dentate gyrus}}, doi = {10.1038/s41467-017-00936-3}, volume = {8}, year = {2017}, } @article{803, abstract = {Eukaryotic cells store their chromosomes in a single nucleus. This is important to maintain genomic integrity, as chromosomes packaged into separate nuclei (micronuclei) are prone to massive DNA damage. During mitosis, higher eukaryotes disassemble their nucleus and release individualized chromosomes for segregation. How numerous chromosomes subsequently reform a single nucleus has remained unclear. Using image-based screening of human cells, we identified barrier-to-autointegration factor (BAF) as a key factor guiding membranes to form a single nucleus. Unexpectedly, nuclear assembly does not require BAF?s association with inner nuclear membrane proteins but instead relies on BAF?s ability to bridge distant DNA sites. Live-cell imaging and in vitro reconstitution showed that BAF enriches around the mitotic chromosome ensemble to induce a densely cross-bridged chromatin layer that is mechanically stiff and limits membranes to the surface. Our study reveals that BAF-mediated changes in chromosome mechanics underlie nuclear assembly with broad implications for proper genome function.}, author = {Samwer, Matthias and Schneider, Maximilian and Hoefler, Rudolf and Schmalhorst, Philipp S and Jude, Julian and Zuber, Johannes and Gerlic, Daniel}, issn = {00928674}, journal = {Cell}, number = {5}, pages = {956 -- 972}, publisher = {Cell Press}, title = {{DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes}}, doi = {10.1016/j.cell.2017.07.038}, volume = {170}, year = {2017}, } @article{804, abstract = {Polysaccharides (carbohydrates) are key regulators of a large number of cell biological processes. However, precise biochemical or genetic manipulation of these often complex structures is laborious and hampers experimental structure–function studies. Molecular Dynamics (MD) simulations provide a valuable alternative tool to generate and test hypotheses on saccharide function. Yet, currently used MD force fields often overestimate the aggregation propensity of polysaccharides, affecting the usability of those simulations. Here we tested MARTINI, a popular coarse-grained (CG) force field for biological macromolecules, for its ability to accurately represent molecular forces between saccharides. To this end, we calculated a thermodynamic solution property, the second virial coefficient of the osmotic pressure (B22). Comparison with light scattering experiments revealed a nonphysical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the nonbonded solute–solute, solute–water, and water–water interactions. This finding also applies to smaller oligosaccharides which were all found to aggregate in simulations even at moderate concentrations, well below their solubility limit. Finally, we explored the influence of the Lennard-Jones (LJ) interaction between saccharide molecules and propose a simple scaling of the LJ interaction strength that makes MARTINI more reliable for the simulation of saccharides.}, author = {Schmalhorst, Philipp S and Deluweit, Felix and Scherrers, Roger and Heisenberg, Carl-Philipp J and Sikora, Mateusz K}, issn = {15499618}, journal = {Journal of Chemical Theory and Computation}, number = {10}, pages = {5039 -- 5053}, publisher = {American Chemical Society}, title = {{Overcoming the limitations of the MARTINI force field in simulations of polysaccharides}}, doi = {10.1021/acs.jctc.7b00374}, volume = {13}, year = {2017}, } @article{746, abstract = {Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synaptic N-methyl-D-Aspartate receptor (NMDAR) function, and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse. Using single-molecule tracking, we found that mGluR5 was significantly more mobile at synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic surface co-clustering of mGluR5 and NMDAR. This correlated with a reduced amplitude of synaptic NMDAR currents, a lack of their mGluR5-Activated long-Term depression, and NMDAR/hippocampus dependent cognitive deficits. These synaptic and behavioral phenomena were reversed by knocking down Homer1a in Fmr1 KO mice. Our study provides a mechanistic link between changes of mGluR5 dynamics and pathological phenotypes of FXS, unveiling novel targets for mGluR5-based therapeutics.}, author = {Aloisi, Elisabetta and Le Corf, Katy and Dupuis, Julien and Zhang, Pei and Ginger, Melanie and Labrousse, Virginie and Spatuzza, Michela and Georg Haberl, Matthias and Costa, Lara and Shigemoto, Ryuichi and Tappe Theodor, Anke and Drago, Fillippo and Vincenzo Piazza, Pier and Mulle, Christophe and Groc, Laurent and Ciranna, Lucia and Catania, Maria and Frick, Andreas}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice}}, doi = {10.1038/s41467-017-01191-2}, volume = {8}, year = {2017}, } @article{749, abstract = {Synaptotagmin 7 (Syt7) is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, Syt7 is strongly expressed in fast-spiking, parvalbumin-expressing GABAergic interneurons, and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. To resolve this apparent contradiction, we examined the effects of genetic elimination of Syt7 on synaptic transmission at the GABAergic basket cell (BC)-Purkinje cell (PC) synapse in cerebellum. Our results indicate that at the BC-PC synapse, Syt7 contributes to asynchronous release, pool replenishment, and facilitation. In combination, these three effects ensure efficient transmitter release during high-frequency activity and guarantee frequency independence of inhibition. Our results identify a distinct function of Syt7: ensuring the efficiency of high-frequency inhibitory synaptic transmission}, author = {Chen, Chong and Satterfield, Rachel and Young, Samuel and Jonas, Peter M}, issn = {22111247}, journal = {Cell Reports}, number = {8}, pages = {2082 -- 2089}, publisher = {Cell Press}, title = {{Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses}}, doi = {10.1016/j.celrep.2017.10.122}, volume = {21}, year = {2017}, } @article{744, abstract = {In evolutionary game theory interactions between individuals are often assumed obligatory. However, in many real-life situations, individuals can decide to opt out of an interaction depending on the information they have about the opponent. We consider a simple evolutionary game theoretic model to study such a scenario, where at each encounter between two individuals the type of the opponent (cooperator/defector) is known with some probability, and where each individual either accepts or opts out of the interaction. If the type of the opponent is unknown, a trustful individual accepts the interaction, whereas a suspicious individual opts out of the interaction. If either of the two individuals opt out both individuals remain without an interaction. We show that in the prisoners dilemma optional interactions along with suspicious behaviour facilitates the emergence of trustful cooperation.}, author = {Priklopil, Tadeas and Chatterjee, Krishnendu and Nowak, Martin}, issn = {00225193}, journal = { Journal of Theoretical Biology}, pages = {64 -- 72}, publisher = {Elsevier}, title = {{Optional interactions and suspicious behaviour facilitates trustful cooperation in prisoners dilemma}}, doi = {10.1016/j.jtbi.2017.08.025}, volume = {433}, year = {2017}, } @article{745, abstract = {Fluid flows in nature and applications are frequently subject to periodic velocity modulations. Surprisingly, even for the generic case of flow through a straight pipe, there is little consensus regarding the influence of pulsation on the transition threshold to turbulence: while most studies predict a monotonically increasing threshold with pulsation frequency (i.e. Womersley number, ), others observe a decreasing threshold for identical parameters and only observe an increasing threshold at low . In the present study we apply recent advances in the understanding of transition in steady shear flows to pulsating pipe flow. For moderate pulsation amplitudes we find that the first instability encountered is subcritical (i.e. requiring finite amplitude disturbances) and gives rise to localized patches of turbulence ('puffs') analogous to steady pipe flow. By monitoring the impact of pulsation on the lifetime of turbulence we map the onset of turbulence in parameter space. Transition in pulsatile flow can be separated into three regimes. At small Womersley numbers the dynamics is dominated by the decay turbulence suffers during the slower part of the cycle and hence transition is delayed significantly. As shown in this regime thresholds closely agree with estimates based on a quasi-steady flow assumption only taking puff decay rates into account. The transition point predicted in the zero limit equals to the critical point for steady pipe flow offset by the oscillation Reynolds number (i.e. the dimensionless oscillation amplitude). In the high frequency limit on the other hand, puff lifetimes are identical to those in steady pipe flow and hence the transition threshold appears to be unaffected by flow pulsation. In the intermediate frequency regime the transition threshold sharply drops (with increasing ) from the decay dominated (quasi-steady) threshold to the steady pipe flow level.}, author = {Xu, Duo and Warnecke, Sascha and Song, Baofang and Ma, Xingyu and Hof, Björn}, issn = {00221120}, journal = {Journal of Fluid Mechanics}, pages = {418 -- 432}, publisher = {Cambridge University Press}, title = {{Transition to turbulence in pulsating pipe flow}}, doi = {10.1017/jfm.2017.620}, volume = {831}, year = {2017}, } @article{747, abstract = {Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate, antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase, while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons, which was prevented by the B2 receptor antagonist. In vivo studies indicate that microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic reticulum, and membrane depolarization; these effects are translated in vivo by bradycardia.}, author = {Brǎiloiu, Eugen and Mcguire, Matthew and Shuler, Shadaria and Deliu, Elena and Barr, Jeffrey and Abood, Mary and Brailoiu, Gabriela}, issn = {03064522}, journal = {Neuroscience}, pages = {23 -- 32}, publisher = {Elsevier}, title = {{Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus}}, doi = {10.1016/j.neuroscience.2017.09.034}, volume = {365}, year = {2017}, }