TY - JOUR AB - We investigate fundamental nonlinear dynamics of ferrofluidic Taylor-Couette flow - flow confined be-tween two concentric independently rotating cylinders - consider small aspect ratio by solving the ferro-hydrodynamical equations, carrying out systematic bifurcation analysis. Without magnetic field, we find steady flow patterns, previously observed with a simple fluid, such as those containing normal one- or two vortex cells, as well as anomalous one-cell and twin-cell flow states. However, when a symmetry-breaking transverse magnetic field is present, all flow states exhibit stimulated, finite two-fold mode. Various bifurcations between steady and unsteady states can occur, corresponding to the transitions between the two-cell and one-cell states. While unsteady, axially oscillating flow states can arise, we also detect the emergence of new unsteady flow states. In particular, we uncover two new states: one contains only the azimuthally oscillating solution in the configuration of the twin-cell flow state, and an-other a rotating flow state. Topologically, these flow states are a limit cycle and a quasiperiodic solution on a two-torus, respectively. Emergence of new flow states in addition to observed ones with classical fluid, indicates that richer but potentially more controllable dynamics in ferrofluidic flows, as such flow states depend on the external magnetic field. AU - Altmeyer, Sebastian AU - Do, Younghae AU - Lai, Ying ID - 1160 JF - Scientific Reports SN - 20452322 TI - Dynamics of ferrofluidic flow in the Taylor-Couette system with a small aspect ratio VL - 7 ER - TY - JOUR AB - Selected universal experimental properties of high-temperature superconducting (HTS) cuprates have been singled out in the last decade. One of the pivotal challenges in this field is the designation of a consistent interpretation framework within which we can describe quantitatively the universal features of those systems. Here we analyze in a detailed manner the principal experimental data and compare them quantitatively with the approach based on a single-band model of strongly correlated electrons supplemented with strong antiferromagnetic (super)exchange interaction (the so-called t−J−U model). The model rationale is provided by estimating its microscopic parameters on the basis of the three-band approach for the Cu-O plane. We use our original full Gutzwiller wave-function solution by going beyond the renormalized mean-field theory (RMFT) in a systematic manner. Our approach reproduces very well the observed hole doping (δ) dependence of the kinetic-energy gain in the superconducting phase, one of the principal non-Bardeen-Cooper-Schrieffer features of the cuprates. The calculated Fermi velocity in the nodal direction is practically δ-independent and its universal value agrees very well with that determined experimentally. Also, a weak doping dependence of the Fermi wave vector leads to an almost constant value of the effective mass in a pure superconducting phase which is both observed in experiment and reproduced within our approach. An assessment of the currently used models (t−J, Hubbard) is carried out and the results of the canonical RMFT as a zeroth-order solution are provided for comparison to illustrate the necessity of the introduced higher-order contributions. AU - Spałek, Jozef AU - Zegrodnik, Michał AU - Kaczmarczyk, Jan ID - 1162 IS - 2 JF - Physical Review B - Condensed Matter and Materials Physics SN - 24699950 TI - Universal properties of high temperature superconductors from real space pairing t-J-U model and its quantitative comparison with experiment VL - 95 ER - TY - JOUR AB - We propose a new memetic strategy that can solve the multi-physics, complex inverse problems, formulated as the multi-objective optimization ones, in which objectives are misfits between the measured and simulated states of various governing processes. The multi-deme structure of the strategy allows for both, intensive, relatively cheap exploration with a moderate accuracy and more accurate search many regions of Pareto set in parallel. The special type of selection operator prefers the coherent alternative solutions, eliminating artifacts appearing in the particular processes. The additional accuracy increment is obtained by the parallel convex searches applied to the local scalarizations of the misfit vector. The strategy is dedicated for solving ill-conditioned problems, for which inverting the single physical process can lead to the ambiguous results. The skill of the selection in artifact elimination is shown on the benchmark problem, while the whole strategy was applied for identification of oil deposits, where the misfits are related to various frequencies of the magnetic and electric waves of the magnetotelluric measurements. 2016 Elsevier B.V. AU - Gajda-Zagorska, Ewa P AU - Schaefer, Robert AU - Smołka, Maciej AU - Pardo, David AU - Alvarez Aramberri, Julen ID - 1152 JF - Journal of Computational Science SN - 18777503 TI - A multi objective memetic inverse solver reinforced by local optimization methods VL - 18 ER - TY - JOUR AB - Optimum experimental design theory has recently been extended for parameter estimation in copula models. The use of these models allows one to gain in flexibility by considering the model parameter set split into marginal and dependence parameters. However, this separation also leads to the natural issue of estimating only a subset of all model parameters. In this work, we treat this problem with the application of the (Formula presented.)-optimality to copula models. First, we provide an extension of the corresponding equivalence theory. Then, we analyze a wide range of flexible copula models to highlight the usefulness of (Formula presented.)-optimality in many possible scenarios. Finally, we discuss how the usage of the introduced design criterion also relates to the more general issue of copula selection and optimal design for model discrimination. AU - Perrone, Elisa AU - Rappold, Andreas AU - Müller, Werner ID - 1168 IS - 3 JF - Statistical Methods and Applications TI - D inf s optimality in copula models VL - 26 ER - TY - JOUR AB - We investigate the effect of the electron-hole (e-h) symmetry breaking on d-wave superconductivity induced by non-local effects of correlations in the generalized Hubbard model. The symmetry breaking is introduced in a two-fold manner: by the next-to-nearest neighbor hopping of electrons and by the charge-bond interaction - the off-diagonal term of the Coulomb potential. Both terms lead to a pronounced asymmetry of the superconducting order parameter. The next-to-nearest neighbor hopping enhances superconductivity for h-doping, while diminishes it for e-doping. The charge-bond interaction alone leads to the opposite effect and, additionally, to the kinetic-energy gain upon condensation in the underdoped regime. With both terms included, with similar amplitudes, the height of the superconducting dome and the critical doping remain in favor of h-doping. The influence of the charge-bond interaction on deviations from symmetry of the shape of the gap at the Fermi surface in the momentum space is briefly discussed. AU - Wysokiński, Marcin AU - Kaczmarczyk, Jan ID - 1163 IS - 8 JF - Journal of Physics: Condensed Matter SN - 09538984 TI - Unconventional superconductivity in generalized Hubbard model role of electron–hole symmetry breaking terms VL - 29 ER - TY - JOUR AB - We introduce the Voronoi functional of a triangulation of a finite set of points in the Euclidean plane and prove that among all geometric triangulations of the point set, the Delaunay triangulation maximizes the functional. This result neither extends to topological triangulations in the plane nor to geometric triangulations in three and higher dimensions. AU - Edelsbrunner, Herbert AU - Glazyrin, Alexey AU - Musin, Oleg AU - Nikitenko, Anton ID - 1173 IS - 5 JF - Combinatorica SN - 02099683 TI - The Voronoi functional is maximized by the Delaunay triangulation in the plane VL - 37 ER - TY - JOUR AB - Coordinated changes of cell shape are often the result of the excitable, wave-like dynamics of the actin cytoskeleton. New work shows that, in migrating cells, protrusion waves arise from mechanochemical crosstalk between adhesion sites, membrane tension and the actin protrusive machinery. AU - Müller, Jan AU - Sixt, Michael K ID - 1161 IS - 1 JF - Current Biology SN - 09609822 TI - Cell migration: Making the waves VL - 27 ER - TY - CONF AB - Time-triggered switched networks are a deterministic communication infrastructure used by real-time distributed embedded systems. Due to the criticality of the applications running over them, developers need to ensure that end-to-end communication is dependable and predictable. Traditional approaches assume static networks that are not flexible to changes caused by reconfigurations or, more importantly, faults, which are dealt with in the application using redundancy. We adopt the concept of handling faults in the switches from non-real-time networks while maintaining the required predictability. We study a class of forwarding schemes that can handle various types of failures. We consider probabilistic failures. We study a class of forwarding schemes that can handle various types of failures. We consider probabilistic failures. For a given network with a forwarding scheme and a constant ℓ, we compute the {\em score} of the scheme, namely the probability (induced by faults) that at least ℓ messages arrive on time. We reduce the scoring problem to a reachability problem on a Markov chain with a "product-like" structure. Its special structure allows us to reason about it symbolically, and reduce the scoring problem to #SAT. Our solution is generic and can be adapted to different networks and other contexts. Also, we show the computational complexity of the scoring problem is #P-complete, and we study methods to estimate the score. We evaluate the effectiveness of our techniques with an implementation. AU - Avni, Guy AU - Goel, Shubham AU - Henzinger, Thomas A AU - Rodríguez Navas, Guillermo ID - 1116 SN - 03029743 TI - Computing scores of forwarding schemes in switched networks with probabilistic faults VL - 10206 ER - TY - JOUR AB - Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV+ interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo. AU - Gan, Jian AU - Weng, Shih-Ming AU - Pernia-Andrade, Alejandro AU - Csicsvari, Jozsef L AU - Jonas, Peter M ID - 1118 IS - 2 JF - Neuron TI - Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo VL - 93 ER - TY - JOUR AB - GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-author AU - Chen, Chong AU - Arai, Itaru AU - Satterield, Rachel AU - Young, Samuel AU - Jonas, Peter M ID - 1117 IS - 3 JF - Cell Reports SN - 22111247 TI - Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse VL - 18 ER - TY - JOUR AB - The hippocampus is thought to initiate systems-wide mnemonic processes through the reactivation of previously acquired spatial and episodic memory traces, which can recruit the entorhinal cortex as a first stage of memory redistribution to other brain areas. Hippocampal reactivation occurs during sharp wave-ripples, in which synchronous network firing encodes sequences of places.We investigated the coordination of this replay by recording assembly activity simultaneously in the CA1 region of the hippocampus and superficial layers of the medial entorhinal cortex. We found that entorhinal cell assemblies can replay trajectories independently of the hippocampus and sharp wave-ripples. This suggests that the hippocampus is not the sole initiator of spatial and episodic memory trace reactivation. Memory systems involved in these processes may include nonhierarchical, parallel components. AU - O'Neill, Joseph AU - Boccara, Charlotte AU - Stella, Federico AU - Schönenberger, Philipp AU - Csicsvari, Jozsef L ID - 1132 IS - 6321 JF - Science SN - 00368075 TI - Superficial layers of the medial entorhinal cortex replay independently of the hippocampus VL - 355 ER - TY - JOUR AB - The existence of a self-localization transition in the polaron problem has been under an active debate ever since Landau suggested it 83 years ago. Here we reveal the self-localization transition for the rotational analogue of the polaron -- the angulon quasiparticle. We show that, unlike for the polarons, self-localization of angulons occurs at finite impurity-bath coupling already at the mean-field level. The transition is accompanied by the spherical-symmetry breaking of the angulon ground state and a discontinuity in the first derivative of the ground-state energy. Moreover, the type of the symmetry breaking is dictated by the symmetry of the microscopic impurity-bath interaction, which leads to a number of distinct self-localized states. The predicted effects can potentially be addressed in experiments on cold molecules trapped in superfluid helium droplets and ultracold quantum gases, as well as on electronic excitations in solids and Bose-Einstein condensates. AU - Li, Xiang AU - Seiringer, Robert AU - Lemeshko, Mikhail ID - 1120 IS - 3 JF - Physical Review A SN - 24699926 TI - Angular self-localization of impurities rotating in a bosonic bath VL - 95 ER - TY - JOUR AB - It is a common knowledge that an effective interaction of a quantum impurity with an electromagnetic field can be screened by surrounding charge carriers, whether mobile or static. Here we demonstrate that very strong, "anomalous" screening can take place in the presence of a neutral, weakly polarizable environment, due to an exchange of orbital angular momentum between the impurity and the bath. Furthermore, we show that it is possible to generalize all phenomena related to isolated impurities in an external field to the case when a many-body environment is present, by casting the problem in terms of the angulon quasiparticle. As a result, the relevant observables such as the effective Rabi frequency, geometric phase, and impurity spatial alignment are straightforward to evaluate in terms of a single parameter: the angular-momentum-dependent screening factor. AU - Yakaboylu, Enderalp AU - Lemeshko, Mikhail ID - 1133 IS - 8 JF - Physical Review Letters SN - 00319007 TI - Anomalous screening of quantum impurities by a neutral environment VL - 118 ER - TY - JOUR AB - Understanding the behavior of molecules interacting with superfluid helium represents a formidable challenge and, in general, requires approaches relying on large-scale numerical simulations. Here we demonstrate that experimental data collected over the last 20 years provide evidence that molecules immersed in superfluid helium form recently-predicted angulon quasiparticles [Phys. Rev. Lett. 114, 203001 (2015)]. Most importantly, casting the many-body problem in terms of angulons amounts to a drastic simplification and yields effective molecular moments of inertia as straightforward analytic solutions of a simple microscopic Hamiltonian. The outcome of the angulon theory is in good agreement with experiment for a broad range of molecular impurities, from heavy to medium-mass to light species. These results pave the way to understanding molecular rotation in liquid and crystalline phases in terms of the angulon quasiparticle. AU - Lemeshko, Mikhail ID - 1119 IS - 9 JF - Physical Review Letters SN - 00319007 TI - Quasiparticle approach to molecules interacting with quantum solvents VL - 118 ER - TY - JOUR AB - The phytohormone auxin is a major determinant and regulatory component important for plant development. Auxin transport between cells is mediated by a complex system of transporters such as AUX1/LAX, PIN, and ABCB proteins, and their localization and activity is thought to be influenced by phosphatases and kinases. Flavonols have been shown to alter auxin transport activity and changes in flavonol accumulation in the Arabidopsis thaliana rol1-2 mutant cause defects in auxin transport and seedling development. A new mutation in ROOTS CURL IN NPA 1 (RCN1), encoding a regulatory subunit of the phosphatase PP2A, was found to suppress the growth defects of rol1-2 without changing the flavonol content. rol1-2 rcn1-3 double mutants show wild type-like auxin transport activity while levels of free auxin are not affected by rcn1-3. In the rol1-2 mutant, PIN2 shows a flavonol-induced basal-to-apical shift in polar localization which is reversed in the rol1-2 rcn1-3 to basal localization. In vivo analysis of PINOID action, a kinase known to influence PIN protein localization in a PP2A-antagonistic manner, revealed a negative impact of flavonols on PINOID activity. Together, these data suggest that flavonols affect auxin transport by modifying the antagonistic kinase/phosphatase equilibrium. AU - Kuhn, Benjamin AU - Nodzyński, Tomasz AU - Errafi, Sanae AU - Bucher, Rahel AU - Gupta, Shibu AU - Aryal, Bibek AU - Dobrev, Petre AU - Bigler, Laurent AU - Geisler, Markus AU - Zažímalová, Eva AU - Friml, Jirí AU - Ringli, Christoph ID - 1110 JF - Scientific Reports SN - 20452322 TI - Flavonol-induced changes in PIN2 polarity and auxin transport in the Arabidopsis thaliana rol1-2 mutant require phosphatase activity VL - 7 ER - TY - JOUR AB - In the early visual system, cells of the same type perform the same computation in different places of the visual field. How these cells code together a complex visual scene is unclear. A common assumption is that cells of a single-type extract a single-stimulus feature to form a feature map, but this has rarely been observed directly. Using large-scale recordings in the rat retina, we show that a homogeneous population of fast OFF ganglion cells simultaneously encodes two radically different features of a visual scene. Cells close to a moving object code quasilinearly for its position, while distant cells remain largely invariant to the object's position and, instead, respond nonlinearly to changes in the object's speed. We develop a quantitative model that accounts for this effect and identify a disinhibitory circuit that mediates it. Ganglion cells of a single type thus do not code for one, but two features simultaneously. This richer, flexible neural map might also be present in other sensory systems. AU - Deny, Stephane AU - Ferrari, Ulisse AU - Mace, Emilie AU - Yger, Pierre AU - Caplette, Romain AU - Picaud, Serge AU - Tkacik, Gasper AU - Marre, Olivier ID - 1104 IS - 1 JF - Nature Communications SN - 20411723 TI - Multiplexed computations in retinal ganglion cells of a single type VL - 8 ER - TY - JOUR AB - Nonequilibrium phase transitions exist in damped-driven open quantum systems when the continuous tuning of an external parameter leads to a transition between two robust steady states. In second-order transitions this change is abrupt at a critical point, whereas in first-order transitions the two phases can coexist in a critical hysteresis domain. Here, we report the observation of a first-order dissipative quantum phase transition in a driven circuit quantum electrodynamics system. It takes place when the photon blockade of the driven cavity-atom system is broken by increasing the drive power. The observed experimental signature is a bimodal phase space distribution with varying weights controlled by the drive strength. Our measurements show an improved stabilization of the classical attractors up to the millisecond range when the size of the quantum system is increased from one to three artificial atoms. The formation of such robust pointer states could be used for new quantum measurement schemes or to investigate multiphoton phases of finite-size, nonlinear, open quantum systems. AU - Fink, Johannes M AU - Dombi, András AU - Vukics, András AU - Wallraff, Andreas AU - Domokos, Peter ID - 1114 IS - 1 JF - Physical Review X SN - 21603308 TI - Observation of the photon blockade breakdown phase transition VL - 7 ER - TY - JOUR AB - Adaptation depends critically on the effects of new mutations and their dependency on the genetic background in which they occur. These two factors can be summarized by the fitness landscape. However, it would require testing all mutations in all backgrounds, making the definition and analysis of fitness landscapes mostly inaccessible. Instead of postulating a particular fitness landscape, we address this problem by considering general classes of landscapes and calculating an upper limit for the time it takes for a population to reach a fitness peak, circumventing the need to have full knowledge about the fitness landscape. We analyze populations in the weak-mutation regime and characterize the conditions that enable them to quickly reach the fitness peak as a function of the number of sites under selection. We show that for additive landscapes there is a critical selection strength enabling populations to reach high-fitness genotypes, regardless of the distribution of effects. This threshold scales with the number of sites under selection, effectively setting a limit to adaptation, and results from the inevitable increase in deleterious mutational pressure as the population adapts in a space of discrete genotypes. Furthermore, we show that for the class of all unimodal landscapes this condition is sufficient but not necessary for rapid adaptation, as in some highly epistatic landscapes the critical strength does not depend on the number of sites under selection; effectively removing this barrier to adaptation. AU - Heredia, Jorge AU - Trubenova, Barbora AU - Sudholt, Dirk AU - Paixao, Tiago ID - 1111 IS - 2 JF - Genetics SN - 00166731 TI - Selection limits to adaptive walks on correlated landscapes VL - 205 ER - TY - JOUR AB - Rotation of molecules embedded in He nanodroplets is explored by a combination of fs laser-induced alignment experiments and angulon quasiparticle theory. We demonstrate that at low fluence of the fs alignment pulse, the molecule and its solvation shell can be set into coherent collective rotation lasting long enough to form revivals. With increasing fluence, however, the revivals disappear -- instead, rotational dynamics as rapid as for an isolated molecule is observed during the first few picoseconds. Classical calculations trace this phenomenon to transient decoupling of the molecule from its He shell. Our results open novel opportunities for studying non-equilibrium solute-solvent dynamics and quantum thermalization. AU - Shepperson, Benjamin AU - Søndergaard, Anders AU - Christiansen, Lars AU - Kaczmarczyk, Jan AU - Zillich, Robert AU - Lemeshko, Mikhail AU - Stapelfeldt, Henrik ID - 1109 IS - 20 JF - Physical Review Letters TI - Laser-induced rotation of iodine molecules in helium nanodroplets: Revivals and breaking-free VL - 118 ER - TY - JOUR AB - Using extensive direct numerical simulations, the dynamics of laminar-turbulent fronts in pipe flow is investigated for Reynolds numbers between and 5500. We here investigate the physical distinction between the fronts of weak and strong slugs both by analysing the turbulent kinetic energy budget and by comparing the downstream front motion to the advection speed of bulk turbulent structures. Our study shows that weak downstream fronts travel slower than turbulent structures in the bulk and correspond to decaying turbulence at the front. At the downstream front speed becomes faster than the advection speed, marking the onset of strong fronts. In contrast to weak fronts, turbulent eddies are generated at strong fronts by feeding on the downstream laminar flow. Our study also suggests that temporal fluctuations of production and dissipation at the downstream laminar-turbulent front drive the dynamical switches between the two types of front observed up to. AU - Song, Baofang AU - Barkley, Dwight AU - Hof, Björn AU - Avila, Marc ID - 1087 JF - Journal of Fluid Mechanics SN - 00221120 TI - Speed and structure of turbulent fronts in pipe flow VL - 813 ER - TY - JOUR AB - We discuss properties of distributions that are multivariate totally positive of order two (MTP2) related to conditional independence. In particular, we show that any independence model generated by an MTP2 distribution is a compositional semigraphoid which is upward-stable and singleton-transitive. In addition, we prove that any MTP2 distribution satisfying an appropriate support condition is faithful to its concentration graph. Finally, we analyze factorization properties of MTP2 distributions and discuss ways of constructing MTP2 distributions; in particular we give conditions on the log-linear parameters of a discrete distribution which ensure MTP2 and characterize conditional Gaussian distributions which satisfy MTP2. AU - Fallat, Shaun AU - Lauritzen, Steffen AU - Sadeghi, Kayvan AU - Uhler, Caroline AU - Wermuth, Nanny AU - Zwiernik, Piotr ID - 1089 IS - 3 JF - Annals of Statistics SN - 00905364 TI - Total positivity in Markov structures VL - 45 ER - TY - JOUR AB - Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications. Genome-wide sequencing data has enabled modern phylogenomic methods to accurately dissect subclones and their phylogenies from noisy and impure bulk tumour samples at unprecedented depth. However, existing methods are not designed to infer metastatic seeding patterns. Here we develop a tool, called Treeomics, to reconstruct the phylogeny of metastases and map subclones to their anatomic locations. Treeomics infers comprehensive seeding patterns for pancreatic, ovarian, and prostate cancers. Moreover, Treeomics correctly disambiguates true seeding patterns from sequencing artifacts; 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumour heterogeneity among distinct samples. In silico benchmarking on simulated tumour phylogenies across a wide range of sample purities (15–95%) and sequencing depths (25-800 × ) demonstrates the accuracy of Treeomics compared with existing methods. AU - Reiter, Johannes AU - Makohon Moore, Alvin AU - Gerold, Jeffrey AU - Božić, Ivana AU - Chatterjee, Krishnendu AU - Iacobuzio Donahue, Christine AU - Vogelstein, Bert AU - Nowak, Martin ID - 1080 JF - Nature Communications SN - 20411723 TI - Reconstructing metastatic seeding patterns of human cancers VL - 8 ER - TY - JOUR AB - Sex chromosomes evolve once recombination is halted between a homologous pair of chromosomes. The dominant model of sex chromosome evolution posits that recombination is suppressed between emerging X and Y chromosomes in order to resolve sexual conflict. Here we test this model using whole genome and transcriptome resequencing data in the guppy, a model for sexual selection with many Y-linked colour traits. We show that although the nascent Y chromosome encompasses nearly half of the linkage group, there has been no perceptible degradation of Y chromosome gene content or activity. Using replicate wild populations with differing levels of sexually antagonistic selection for colour, we also show that sexual selection leads to greater expansion of the non-recombining region and increased Y chromosome divergence. These results provide empirical support for longstanding models of sex chromosome catalysis, and suggest an important role for sexual selection and sexual conflict in genome evolution. AU - Wright, Alison AU - Darolti, Iulia AU - Bloch, Natasha AU - Oostra, Vicencio AU - Sandkam, Benjamin AU - Buechel, Séverine AU - Kolm, Niclas AU - Breden, Felix AU - Vicoso, Beatriz AU - Mank, Judith ID - 1085 JF - Nature Communications SN - 20411723 TI - Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation VL - 8 ER - TY - JOUR AB - 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. AU - Di Giglio, Maria AU - Muttenthaler, Markus AU - Harpsøe, Kasper AU - Liutkeviciute, Zita AU - Keov, Peter AU - Eder, Thomas AU - Rattei, Thomas AU - Arrowsmith, Sarah AU - Wray, Susan AU - Marek, Ales AU - Elbert, Tomas AU - Alewood, Paul AU - Gloriam, David AU - Gruber, Christian ID - 1086 JF - Scientific Reports TI - Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide VL - 7 ER - TY - JOUR AB - 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. AU - Fang, Chong AU - Nagy-Staron, Anna A AU - Grafe, Martin AU - Heermann, Ralf AU - Jung, Kirsten AU - Gebhard, Susanne AU - Mascher, Thorsten ID - 1084 IS - 1 JF - Molecular Microbiology SN - 0950382X TI - Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis VL - 104 ER - TY - JOUR AB - 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. AU - Nam, Phan AU - Van Den Bosch, Hanne ID - 1079 IS - 2 JF - Mathematical Physics, Analysis and Geometry SN - 13850172 TI - Nonexistence in Thomas Fermi-Dirac-von Weizsäcker theory with small nuclear charges VL - 20 ER - TY - JOUR AB - 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. AU - Fernandes Redondo, Rodrigo A AU - Vladar, Harold AU - Włodarski, Tomasz AU - Bollback, Jonathan P ID - 1077 IS - 126 JF - Journal of the Royal Society Interface SN - 17425689 TI - Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family VL - 14 ER - TY - JOUR AB - 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. AU - Morita, Hitoshi AU - Grigolon, Silvia AU - Bock, Martin AU - Krens, Gabriel AU - Salbreux, Guillaume AU - Heisenberg, Carl-Philipp J ID - 1067 IS - 4 JF - Developmental Cell SN - 15345807 TI - The physical basis of coordinated tissue spreading in zebrafish gastrulation VL - 40 ER - TY - JOUR AB - 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. AU - Ringbauer, Harald AU - Coop, Graham AU - Barton, Nicholas H ID - 1074 IS - 3 JF - Genetics SN - 00166731 TI - Inferring recent demography from isolation by distance of long shared sequence blocks VL - 205 ER - TY - JOUR AB - 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. AU - Klaiber, Michael AU - Daněk, Jiří AU - Yakaboylu, Enderalp AU - Hatsagortsyan, Karen AU - Keitel, Christoph ID - 1076 IS - 2 JF - Physical Review A - Atomic, Molecular, and Optical Physics SN - 24699926 TI - Strong-field ionization via a high-order Coulomb-corrected strong-field approximation VL - 95 ER - TY - JOUR AB - 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. AU - Bauer, Ulrich AU - Edelsbrunner, Herbert ID - 1072 IS - 5 JF - Transactions of the American Mathematical Society TI - The Morse theory of Čech and delaunay complexes VL - 369 ER - TY - JOUR AB - 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. AU - Čadek, Martin AU - Krcál, Marek AU - Vokřínek, Lukáš ID - 1073 IS - 4 JF - Discrete & Computational Geometry SN - 01795376 TI - Algorithmic solvability of the lifting extension problem VL - 54 ER - TY - JOUR AB - 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. AU - Chatterjee, Krishnendu AU - Osang, Georg F ID - 1065 JF - Information Processing Letters SN - 00200190 TI - Pushdown reachability with constant treewidth VL - 122 ER - TY - JOUR AB - 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. AU - Uecker, Hildegard ID - 1063 IS - 4 JF - Evolution SN - 00143820 TI - Evolutionary rescue in randomly mating, selfing, and clonal populations VL - 71 ER - TY - JOUR AB - 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. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Otop, Jan AU - Velner, Yaron ID - 1066 IS - 2 JF - Information and Computation TI - Quantitative fair simulation games VL - 254 ER - TY - JOUR AB - 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. AU - Nemish, Yuriy ID - 1023 JF - Electronic Journal of Probability SN - 10836489 TI - Local law for the product of independent non-Hermitian random matrices with independent entries VL - 22 ER - TY - JOUR AB - 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. AU - Pranav, Pratyush AU - Edelsbrunner, Herbert AU - Van De Weygaert, Rien AU - Vegter, Gert AU - Kerber, Michael AU - Jones, Bernard AU - Wintraecken, Mathijs ID - 1022 IS - 4 JF - Monthly Notices of the Royal Astronomical Society SN - 00358711 TI - The topology of the cosmic web in terms of persistent Betti numbers VL - 465 ER - TY - JOUR AB - 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. AU - Agus, Viviana AU - Janovjak, Harald L ID - 1026 JF - Current Opinion in Biotechnology SN - 09581669 TI - Optogenetic methods in drug screening: Technologies and applications VL - 48 ER - TY - JOUR AB - 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. AU - Caixeiro, Soraya AU - Peruzzo, Matilda AU - Onelli, Olimpia AU - Vignolini, Silvia AU - Sapienza, Riccardo ID - 1020 IS - 9 JF - ACS Applied Materials and Interfaces SN - 19448244 TI - Disordered cellulose based nanostructures for enhanced light scattering VL - 9 ER - TY - JOUR AB - 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. AU - Lopez Alonso, Jose M AU - Avila, Marc ID - 1021 JF - Journal of Fluid Mechanics SN - 00221120 TI - Boundary layer turbulence in experiments on quasi Keplerian flows VL - 817 ER - TY - JOUR AB - 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 AU - Heisenberg, Carl-Philipp J ID - 1025 IS - 7643 JF - Nature SN - 00280836 TI - Cell biology: Stretched divisions VL - 543 ER - TY - JOUR AB - 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. AU - Breuss, Martin AU - Leca, Ines AU - Gstrein, Thomas AU - Hansen, Andi H AU - Keays, David ID - 1017 JF - Molecular and Cellular Neuroscience SN - 10447431 TI - Tubulins and brain development: The origins of functional specification VL - 84 ER - TY - JOUR AB - 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. AU - Bighin, Giacomo AU - Salasnich, Luca ID - 1015 JF - Scientific Reports SN - 20452322 TI - Vortices and antivortices in two-dimensional ultracold Fermi gases VL - 7 ER - TY - JOUR AB - 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. AU - Breuss, Martin AU - Nguyen, Thai AU - Srivatsan, Anjana AU - Leca, Ines AU - Tian, Guoling AU - Fritz, Tanja AU - Hansen, Andi H AU - Musaev, Damir AU - Mcevoy Venneri, Jennifer AU - Kiely, James AU - Rosti, Rasim AU - Scott, Eric AU - Tan, Uner AU - Kolodner, Richard AU - Cowan, Nicholas AU - Keays, David AU - Gleeson, Joseph ID - 1016 IS - 2 JF - Human Molecular Genetics SN - 09646906 TI - Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability VL - 26 ER - TY - JOUR AB - 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. AU - Dobisova, Tereza AU - Hrdinova, Vendula AU - Cuesta, Candela AU - Michlickova, Sarka AU - Urbankova, Ivana AU - Hejatkova, Romana AU - Zadnikova, Petra AU - Pernisová, Markéta AU - Benková, Eva AU - Hejátko, Jan ID - 1018 IS - 1 JF - Plant Physiology TI - Light regulated expression of sensor histidine kinase CKI1 controls cytokinin related development VL - 174 ER - TY - JOUR AB - 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. AU - Argyridou, Eliza AU - Huylmans, Ann K AU - Königer, Annabella AU - Parsch, John ID - 1019 IS - 1 JF - Heredity SN - 0018067X TI - X-linkage is not a general inhibitor of tissue-specific gene expression in Drosophila melanogaster VL - 119 ER - TY - GEN AB - 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. AU - Argyridou, Eliza AU - Huylmans, Ann K AU - Königer, Annabella AU - Parsch, John ID - 9861 TI - Data from: X-linkage is not a general inhibitor of tissue-specific gene expression in Drosophila melanogaster ER - TY - JOUR AB - 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. AU - Greenwood, Jenny AU - Milutinovic, Barbara AU - Peuß, Robert AU - Behrens, Sarah AU - Essar, Daniela AU - Rosenstiel, Philip AU - Schulenburg, Hinrich AU - Kurtz, Joachim ID - 1006 IS - 1 JF - BMC Genomics SN - 14712164 TI - Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae VL - 18 ER - TY - CONF AB - 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. AU - Chatterjee, Krishnendu AU - Kragl, Bernhard AU - Mishra, Samarth AU - Pavlogiannis, Andreas ED - Yang, Hongseok ID - 1011 SN - 03029743 TI - Faster algorithms for weighted recursive state machines VL - 10201 ER - TY - JOUR AB - 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. AU - Ötvös, Krisztina AU - Benková, Eva ID - 1004 JF - Current Opinion in Genetics & Development SN - 0959437X TI - Spatiotemporal mechanisms of root branching VL - 45 ER - TY - JOUR AB - 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∗. AU - Alt, Johannes AU - Erdös, László AU - Krüger, Torben H ID - 1010 JF - Electronic Journal of Probability SN - 10836489 TI - Local law for random Gram matrices VL - 22 ER - TY - CONF AB - 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. AU - Chatterjee, Krishnendu AU - Novotny, Petr AU - Pérez, Guillermo AU - Raskin, Jean AU - Zikelic, Djordje ID - 1009 T2 - Proceedings of the 31st AAAI Conference on Artificial Intelligence TI - Optimizing expectation with guarantees in POMDPs VL - 5 ER - TY - GEN AB - 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) AU - Greenwood, Jenny AU - Milutinovic, Barbara AU - Peuß, Robert AU - Behrens, Sarah AU - Essar, Daniela AU - Rosenstiel, Philip AU - Schulenburg, Hinrich AU - Kurtz, Joachim ID - 9859 TI - Additional file 1: Table S1. of Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae ER - TY - GEN AU - Greenwood, Jenny AU - Milutinovic, Barbara AU - Peuß, Robert AU - Behrens, Sarah AU - Essar, Daniela AU - Rosenstiel, Philip AU - Schulenburg, Hinrich AU - Kurtz, Joachim ID - 9860 TI - Additional file 5: Table S3. of Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae ER - TY - CONF AB - 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. AU - Zhang, Ran AU - Auzinger, Thomas AU - Ceylan, Duygu AU - Li, Wilmot AU - Bickel, Bernd ID - 1002 IS - 4 SN - 07300301 TI - Functionality-aware retargeting of mechanisms to 3D shapes VL - 36 ER - TY - CONF AB - 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. AU - Guseinov, Ruslan AU - Miguel, Eder AU - Bickel, Bernd ID - 1001 IS - 4 TI - CurveUps: Shaping objects from flat plates with tension-actuated curvature VL - 36 ER - TY - CONF AB - Network games (NGs) are played on directed graphs and are extensively used in network design and analysis. Search problems for NGs include finding special strategy profiles such as a Nash equilibrium and a globally optimal solution. The networks modeled by NGs may be huge. In formal verification, abstraction has proven to be an extremely effective technique for reasoning about systems with big and even infinite state spaces. We describe an abstraction-refinement methodology for reasoning about NGs. Our methodology is based on an abstraction function that maps the state space of an NG to a much smaller state space. We search for a global optimum and a Nash equilibrium by reasoning on an under- and an 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. AU - Avni, Guy AU - Guha, Shibashis AU - Kupferman, Orna ID - 1003 SN - 10450823 TI - An abstraction-refinement methodology for reasoning about network games ER - TY - CONF AB - 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. AU - Kolesnikov, Alexander AU - Lampert, Christoph ID - 1000 SN - 978-151085514-4 T2 - 34th International Conference on Machine Learning TI - PixelCNN models with auxiliary variables for natural image modeling VL - 70 ER - TY - CONF AB - 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. AU - Rebuffi, Sylvestre Alvise AU - Kolesnikov, Alexander AU - Sperl, Georg AU - Lampert, Christoph ID - 998 SN - 978-153860457-1 TI - iCaRL: Incremental classifier and representation learning VL - 2017 ER - TY - JOUR AB - 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. AU - Sachdeva, Himani AU - Barton, Nicholas H ID - 990 IS - 6 JF - Evolution; International Journal of Organic Evolution SN - 00143820 TI - Divergence and evolution of assortative mating in a polygenic trait model of speciation with gene flow VL - 71 ER - TY - JOUR AB - 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. AU - Nanda, Gaurav AU - Aguilera Servin, Juan L AU - Rakyta, Péter AU - Kormányos, Andor AU - Kleiner, Reinhold AU - Koelle, Dieter AU - Watanabe, Kazuo AU - Taniguchi, Takashi AU - Vandersypen, Lieven AU - Goswami, Srijit ID - 988 IS - 6 JF - Nano Letters SN - 15306984 TI - Current-phase relation of ballistic graphene Josephson junctions VL - 17 ER - TY - JOUR AB - 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. AU - Levina (Martius), Anna AU - Priesemann, Viola ID - 993 JF - Nature Communications SN - 20411723 TI - Subsampling scaling VL - 8 ER - TY - JOUR AB - 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. AU - Bighin, Giacomo AU - Lemeshko, Mikhail ID - 995 IS - 8 JF - Physical Review B - Condensed Matter and Materials Physics SN - 24699950 TI - Diagrammatic approach to orbital quantum impurities interacting with a many-particle environment VL - 96 ER - TY - CONF AB - 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. AU - Maas, Jan AU - Rumpf, Martin AU - Simon, Stefan ED - Lauze, François ED - Dong, Yiqiu ED - Bjorholm Dahl, Anders ID - 989 SN - 03029743 TI - Transport based image morphing with intensity modulation VL - 10302 ER - TY - JOUR AB - 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. AU - Cherepanov, Igor AU - Lemeshko, Mikhail ID - 994 IS - 3 JF - Physical Review Materials TI - Fingerprints of angulon instabilities in the spectra of matrix-isolated molecules VL - 1 ER - TY - JOUR AB - 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. AU - Chen, Chong AU - Jonas, Peter M ID - 991 IS - 4 JF - Neuron SN - 08966273 TI - Synaptotagmins: That’s why so many VL - 94 ER - TY - JOUR AB - 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. AU - Lagator, Mato AU - Paixao, Tiago AU - Barton, Nicholas H AU - Bollback, Jonathan P AU - Guet, Calin C ID - 954 JF - eLife SN - 2050084X TI - On the mechanistic nature of epistasis in a canonical cis-regulatory element VL - 6 ER - TY - JOUR AB - 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. AU - Friedlander, Tamar AU - Prizak, Roshan AU - Barton, Nicholas H AU - Tkacik, Gasper ID - 955 IS - 1 JF - Nature Communications SN - 20411723 TI - Evolution of new regulatory functions on biophysically realistic fitness landscapes VL - 8 ER - TY - CONF AB - 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. AU - Trinh, Minh AU - Chu, Duc Hiep AU - Jaffar, Joxan ED - Majumdar, Rupak ED - Kunčak, Viktor ID - 962 SN - 03029743 TI - Model counting for recursively-defined strings VL - 10427 ER - TY - JOUR AB - 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. AU - Charlesworth, Deborah AU - Barton, Nicholas H AU - Charlesworth, Brian ID - 953 IS - 1855 JF - Proceedings of the Royal Society of London Series B Biological Sciences TI - The sources of adaptive evolution VL - 284 ER - TY - JOUR AB - 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. AU - De Martino, Daniele ID - 959 IS - 6 JF - Physical Review E Statistical Nonlinear and Soft Matter Physics SN - 24700045 TI - Scales and multimodal flux distributions in stationary metabolic network models via thermodynamics VL - 95 ER - TY - JOUR AB - 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. AU - Carlen, Eric AU - Maas, Jan ID - 956 IS - 5 JF - Journal of Functional Analysis SN - 00221236 TI - Gradient flow and entropy inequalities for quantum Markov semigroups with detailed balance VL - 273 ER - TY - JOUR AB - 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. AU - Turelli, Michael AU - Barton, Nicholas H ID - 952 JF - Theoretical Population Biology SN - 00405809 TI - Deploying dengue-suppressing Wolbachia: Robust models predict slow but effective spatial spread in Aedes aegypti VL - 115 ER - TY - JOUR AB - 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 AU - Schmidt, Tom AU - Barton, Nicholas H AU - Rasic, Gordana AU - Turley, Andrew AU - Montgomery, Brian AU - Iturbe Ormaetxe, Inaki AU - Cook, Peter AU - Ryan, Peter AU - Ritchie, Scott AU - Hoffmann, Ary AU - O’Neill, Scott AU - Turelli, Michael ID - 951 IS - 5 JF - PLoS Biology SN - 15449173 TI - Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes Aegypti VL - 15 ER - TY - JOUR AB - 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. AU - De Martino, Daniele AU - Capuani, Fabrizio AU - De Martino, Andrea ID - 947 IS - 1 JF - Physical Review E Statistical Nonlinear and Soft Matter Physics SN - 24700045 TI - Quantifying the entropic cost of cellular growth control VL - 96 ER - TY - GEN AU - Schmidt, Tom AU - Barton, Nicholas H AU - Rasic, Gordana AU - Turley, Andrew AU - Montgomery, Brian AU - Iturbe Ormaetxe, Inaki AU - Cook, Peter AU - Ryan, Peter AU - Ritchie, Scott AU - Hoffmann, Ary AU - O’Neill, Scott AU - Turelli, Michael ID - 9858 TI - Excel file with data on mosquito densities, Wolbachia infection status and housing characteristics ER - TY - GEN AU - Schmidt, Tom AU - Barton, Nicholas H AU - Rasic, Gordana AU - Turley, Andrew AU - Montgomery, Brian AU - Iturbe Ormaetxe, Inaki AU - Cook, Peter AU - Ryan, Peter AU - Ritchie, Scott AU - Hoffmann, Ary AU - O’Neill, Scott AU - Turelli, Michael ID - 9857 TI - Supporting information concerning observed wMel frequencies and analyses of habitat variables ER - TY - GEN AU - Schmidt, Tom AU - Barton, Nicholas H AU - Rasic, Gordana AU - Turley, Andrew AU - Montgomery, Brian AU - Iturbe Ormaetxe, Inaki AU - Cook, Peter AU - Ryan, Peter AU - Ritchie, Scott AU - Hoffmann, Ary AU - O’Neill, Scott AU - Turelli, Michael ID - 9856 TI - Supporting Information concerning additional likelihood analyses and results ER - TY - JOUR AB - 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. AU - Huylmans, Ann K AU - Macon, Ariana AU - Vicoso, Beatriz ID - 945 IS - 10 JF - Molecular Biology and Evolution SN - 07374038 TI - Global dosage compensation is ubiquitous in Lepidoptera, but counteracted by the masculinization of the Z chromosome VL - 34 ER - TY - JOUR AB - 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. AU - Matsubayashi, Yutaka AU - Louani, Adam AU - Dragu, Anca AU - Sanchez Sanchez, Besaiz AU - Serna Morales, Eduardo AU - Yolland, Lawrence AU - György, Attila AU - Vizcay, Gema AU - Fleck, Roland AU - Heddleston, John AU - Chew, Teng AU - Siekhaus, Daria E AU - Stramer, Brian ID - 751 IS - 22 JF - Current Biology SN - 09609822 TI - A moving source of matrix components is essential for De Novo basement membrane formation VL - 27 ER - TY - JOUR AB - 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. AU - Barzanjeh, Shabir AU - Wulf, Matthias AU - Peruzzo, Matilda AU - Kalaee, Mahmoud AU - Dieterle, Paul AU - Painter, Oskar AU - Fink, Johannes M ID - 798 IS - 1 JF - Nature Communications SN - 20411723 TI - Mechanical on chip microwave circulator VL - 8 ER - TY - CONF AB - 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. AU - Alistarh, Dan-Adrian AU - Kopinsky, Justin AU - Li, Jerry AU - Nadiradze, Giorgi ID - 791 SN - 978-145034992-5 T2 - Proceedings of the ACM Symposium on Principles of Distributed Computing TI - The power of choice in priority scheduling VL - Part F129314 ER - TY - JOUR AB - 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. AU - Budanur, Nazmi B AU - Short, Kimberly AU - Farazmand, Mohammad AU - Willis, Ashley AU - Cvitanović, Predrag ID - 792 JF - Journal of Fluid Mechanics SN - 00221120 TI - Relative periodic orbits form the backbone of turbulent pipe flow VL - 833 ER - TY - JOUR AB - 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. AU - Keller, Andrew J AU - Dieterle, Paul AU - Fang, Michael AU - Berger, Brett AU - Fink, Johannes M AU - Painter, Oskar ID - 796 IS - 4 JF - Applied Physics Letters SN - 00036951 TI - Al transmon qubits on silicon on insulator for quantum device integration VL - 111 ER - TY - JOUR AB - 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 |). AU - Fulek, Radoslav AU - Mojarrad, Hossein AU - Naszódi, Márton AU - Solymosi, József AU - Stich, Sebastian AU - Szedlák, May ID - 793 JF - Computational Geometry: Theory and Applications SN - 09257721 TI - On the existence of ordinary triangles VL - 66 ER - TY - JOUR AB - 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. AU - Fulek, Radoslav ID - 794 JF - Computational Geometry: Theory and Applications TI - C-planarity of embedded cyclic c-graphs VL - 66 ER - TY - JOUR AB - 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. AU - Rubio, María AU - Matsui, Ko AU - Fukazawa, Yugo AU - Kamasawa, Naomi AU - Harada, Harumi AU - Itakura, Makoto AU - Molnár, Elek AU - Abe, Manabu AU - Sakimura, Kenji AU - Shigemoto, Ryuichi ID - 736 IS - 8 JF - Brain Structure and Function SN - 18632653 TI - The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells VL - 222 ER - TY - JOUR AB - 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. AU - Shigemoto, Ryuichi AU - Jösch, Maximilian A ID - 740 IS - 6 JF - WIREs Developmental Biology SN - 17597684 TI - The genetic encoded toolbox for electron microscopy and connectomics VL - 6 ER - TY - JOUR AB - 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. AU - Moser, Thomas AU - Seiringer, Robert ID - 741 IS - 1 JF - Communications in Mathematical Physics SN - 00103616 TI - Stability of a fermionic N+1 particle system with point interactions VL - 356 ER - TY - JOUR AB - 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. AU - Nam, Phan AU - Napiórkowski, Marcin M ID - 739 IS - 5 JF - Journal de Mathématiques Pures et Appliquées SN - 00217824 TI - A note on the validity of Bogoliubov correction to mean field dynamics VL - 108 ER - TY - JOUR AB - 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. AU - Virk, Ziga AU - Zastrow, Andreas ID - 737 JF - Topology and its Applications SN - 01668641 TI - A new topology on the universal path space VL - 231 ER - TY - JOUR AB - 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. AU - Bao, Zhigang AU - Erdös, László AU - Schnelli, Kevin ID - 733 JF - Advances in Mathematics TI - Convergence rate for spectral distribution of addition of random matrices VL - 319 ER - TY - JOUR AB - 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. AU - Vukusic, Lada AU - Kukucka, Josip AU - Watzinger, Hannes AU - Katsaros, Georgios ID - 840 IS - 9 JF - Nano Letters SN - 15306984 TI - Fast hole tunneling times in germanium hut wires probed by single-shot reflectometry VL - 17 ER - TY - JOUR AB - 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. AU - Giehr, Julia AU - Grasse, Anna V AU - Cremer, Sylvia AU - Heinze, Jürgen AU - Schrempf, Alexandra ID - 914 IS - 7 JF - Royal Society Open Science SN - 20545703 TI - Ant queens increase their reproductive efforts after pathogen infection VL - 4 ER - TY - JOUR AB - 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. AU - Novak, Sebastian AU - Barton, Nicholas H ID - 910 IS - 2 JF - Genetics TI - When does frequency-independent selection maintain genetic variation? VL - 207 ER - TY - CONF AB - 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. AU - Ethier, Marc AU - Jablonski, Grzegorz AU - Mrozek, Marian ID - 836 SN - 978-331956930-7 T2 - Special Sessions in Applications of Computer Algebra TI - Finding eigenvalues of self-maps with the Kronecker canonical form VL - 198 ER - TY - CONF AB - 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. AU - Swoboda, Paul AU - Rother, Carsten AU - Abu Alhaija, Carsten AU - Kainmueller, Dagmar AU - Savchynskyy, Bogdan ID - 916 SN - 978-153860457-1 TI - A study of lagrangean decompositions and dual ascent solvers for graph matching VL - 2017 ER - TY - CONF AB - 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. AU - Swoboda, Paul AU - Andres, Bjoern ID - 915 SN - 978-153860457-1 TI - A message passing algorithm for the minimum cost multicut problem VL - 2017 ER - TY - CONF AB - 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. AU - Swoboda, Paul AU - Kuske, Jan AU - Savchynskyy, Bogdan ID - 917 SN - 978-153860457-1 TI - A dual ascent framework for Lagrangean decomposition of combinatorial problems VL - 2017 ER - TY - JOUR AB - 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. AU - Zagórski, Marcin P AU - Tabata, Yoji AU - Brandenberg, Nathalie AU - Lutolf, Matthias AU - Tkacik, Gasper AU - Bollenbach, Tobias AU - Briscoe, James AU - Kicheva, Anna ID - 943 IS - 6345 JF - Science SN - 00368075 TI - Decoding of position in the developing neural tube from antiparallel morphogen gradients VL - 356 ER -