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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - TY - JOUR AB - We reveal the existence of continuous families of guided single-mode solitons in planar waveguides with weakly nonlinear active core and absorbing boundaries. Stable propagation of TE and TM-polarized solitons is accompanied by attenuation of all other modes, i.e., the waveguide features properties of conservative and dissipative systems. If the linear spectrum of the waveguide possesses exceptional points, which occurs in the case of TM polarization, an originally focusing (defocusing) material nonlinearity may become effectively defocusing (focusing). This occurs due to the geometric phase of the carried eigenmode when the surface impedance encircles the exceptional point. In its turn, the change of the effective nonlinearity ensures the existence of dark (bright) solitons in spite of focusing (defocusing) Kerr nonlinearity of the core. The existence of an exceptional point can also result in anomalous enhancement of the effective nonlinearity. In terms of practical applications, the nonlinearity of the reported waveguide can be manipulated by controlling the properties of the absorbing cladding. AU - Midya, Bikashkali AU - Konotop, Vladimir ID - 939 IS - 3 JF - Physical Review Letters SN - 00319007 TI - Waveguides with absorbing boundaries: Nonlinearity controlled by an exceptional point and solitons VL - 119 ER - TY - GEN AB - Egg laying rates and infection loads of C. obscurior queens AU - Giehr, Julia AU - Grasse, Anna V AU - Cremer, Sylvia AU - Heinze, Jürgen AU - Schrempf, Alexandra ID - 9853 TI - Raw data from ant queens increase their reproductive efforts after pathogen infection ER - TY - JOUR AB - Polymicrobial infections constitute small ecosystems that accommodate several bacterial species. Commonly, these bacteria are investigated in isolation. However, it is unknown to what extent the isolates interact and whether their interactions alter bacterial growth and ecosystem resilience in the presence and absence of antibiotics. We quantified the complete ecological interaction network for 72 bacterial isolates collected from 23 individuals diagnosed with polymicrobial urinary tract infections and found that most interactions cluster based on evolutionary relatedness. Statistical network analysis revealed that competitive and cooperative reciprocal interactions are enriched in the global network, while cooperative interactions are depleted in the individual host community networks. A population dynamics model parameterized by our measurements suggests that interactions restrict community stability, explaining the observed species diversity of these communities. We further show that the clinical isolates frequently protect each other from clinically relevant antibiotics. Together, these results highlight that ecological interactions are crucial for the growth and survival of bacteria in polymicrobial infection communities and affect their assembly and resilience. AU - De Vos, Marjon AU - Zagórski, Marcin P AU - Mcnally, Alan AU - Bollenbach, Mark Tobias ID - 822 IS - 40 JF - PNAS SN - 00278424 TI - Interaction networks, ecological stability, and collective antibiotic tolerance in polymicrobial infections VL - 114 ER - TY - CONF AB - We present an efficient algorithm to compute Euler characteristic curves of gray scale images of arbitrary dimension. In various applications the Euler characteristic curve is used as a descriptor of an image. Our algorithm is the first streaming algorithm for Euler characteristic curves. The usage of streaming removes the necessity to store the entire image in RAM. Experiments show that our implementation handles terabyte scale images on commodity hardware. Due to lock-free parallelism, it scales well with the number of processor cores. Additionally, we put the concept of the Euler characteristic curve in the wider context of computational topology. In particular, we explain the connection with persistence diagrams. AU - Heiss, Teresa AU - Wagner, Hubert ED - Felsberg, Michael ED - Heyden, Anders ED - Krüger, Norbert ID - 833 SN - 03029743 TI - Streaming algorithm for Euler characteristic curves of multidimensional images VL - 10424 ER - TY - JOUR AB - Thermal and many-body localized phases are separated by a dynamical phase transition of a new kind. We analyze the distribution of off-diagonal matrix elements of local operators across this transition in two different models of disordered spin chains. We show that the behavior of matrix elements can be used to characterize the breakdown of thermalization and to extract the many-body Thouless energy. We find that upon increasing the disorder strength the system enters a critical region around the many-body localization transition. The properties of the system in this region are: (i) the Thouless energy becomes smaller than the level spacing, (ii) the matrix elements show critical dependence on the energy difference, and (iii) the matrix elements, viewed as amplitudes of a fictitious wave function, exhibit strong multifractality. This critical region decreases with the system size, which we interpret as evidence for a diverging correlation length at the many-body localization transition. Our findings show that the correlation length becomes larger than the accessible system sizes in a broad range of disorder strength values and shed light on the critical behavior near the many-body localization transition. AU - Serbyn, Maksym AU - Zlatko, Papic AU - Abanin, Dmitry ID - 834 IS - 10 JF - Physical Review B - Condensed Matter and Materials Physics SN - 24699950 TI - Thouless energy and multifractality across the many-body localization transition VL - 96 ER - TY - JOUR AB - The resolution of a linear system with positive integer variables is a basic yet difficult computational problem with many applications. We consider sparse uncorrelated random systems parametrised by the density c and the ratio α=N/M between number of variables N and number of constraints M. By means of ensemble calculations we show that the space of feasible solutions endows a Van-Der-Waals phase diagram in the plane (c, α). We give numerical evidence that the associated computational problems become more difficult across the critical point and in particular in the coexistence region. AU - Colabrese, Simona AU - De Martino, Daniele AU - Leuzzi, Luca AU - Marinari, Enzo ID - 823 IS - 9 JF - Journal of Statistical Mechanics: Theory and Experiment SN - 17425468 TI - Phase transitions in integer linear problems VL - 2017 ER - TY - JOUR AB - In shear flows at transitional Reynolds numbers, localized patches of turbulence, known as puffs, coexist with the laminar flow. Recently, Avila et al. (Phys. Rev. Lett., vol. 110, 2013, 224502) discovered two spatially localized relative periodic solutions for pipe flow, which appeared in a saddle-node bifurcation at low Reynolds number. Combining slicing methods for continuous symmetry reduction with Poincaré sections for the first time in a shear flow setting, we compute and visualize the unstable manifold of the lower-branch solution and show that it extends towards the neighbourhood of the upper-branch solution. Surprisingly, this connection even persists far above the bifurcation point and appears to mediate the first stage of the puff generation: amplification of streamwise localized fluctuations. When the state-space trajectories on the unstable manifold reach the vicinity of the upper branch, corresponding fluctuations expand in space and eventually take the usual shape of a puff. AU - Budanur, Nazmi B AU - Hof, Björn ID - 824 JF - Journal of Fluid Mechanics SN - 00221120 TI - Heteroclinic path to spatially localized chaos in pipe flow VL - 827 ER - TY - JOUR AB - Membrane traffic at the trans-Golgi network (TGN) is crucial for correctly distributing various membrane proteins to their destination. Polarly localized auxin efflux proteins, including PIN-FORMED1 (PIN1), are dynamically transported between the endosomes and the plasma membrane (PM) in the plant cells. The intracellular trafficking of PIN1 protein is sensitive to a fungal toxin brefeldin A (BFA), which is known to inhibit guanine-nucleotide exchange factors for ADP ribosylation factors (ARF GEFs) such as GNOM. However, the molecular details of the BFA-sensitive trafficking pathway have not been revealed fully. In a previous study, we have identified an Arabidopsis mutant BFA-visualized endocytic trafficking defective 3 (ben3) which exhibited reduced sensitivity to BFA in terms of BFA-induced intracellular PIN1 agglomeration. Here, we show that BEN3 encodes a member of BIG family ARF GEFs, BIG2. Fluorescent proteins tagged BEN3/BIG2 co-localized with markers for TGN / early endosome (EE). Inspection of conditionally induced de novo synthesized PIN1 confirmed that its secretion to the PM is BFA-sensitive and established BEN3/BIG2 as a crucial component of this BFA action at the level of TGN/EE. Furthermore, ben3 mutation alleviated BFA-induced agglomeration of another TGN-localized ARF GEF BEN1/MIN7. Taken together our results suggest that BEN3/BIG2 is an ARF GEF component, which confers BFA sensitivity to the TGN/EE in Arabidopsis. AU - Kitakura, Saeko AU - Adamowski, Maciek AU - Matsuura, Yuki AU - Santuari, Luca AU - Kouno, Hirotaka AU - Arima, Kohei AU - Hardtke, Christian AU - Friml, Jirí AU - Kakimoto, Tatsuo AU - Tanaka, Hirokazu ID - 799 IS - 10 JF - Plant and Cell Physiology SN - 00320781 TI - BEN3/BIG2 ARF GEF is involved in brefeldin a-sensitive trafficking at the trans-Golgi network/early endosome in Arabidopsis thaliana VL - 58 ER - TY - JOUR AB - Gamma oscillations (30–150 Hz) in neuronal networks are associated with the processing and recall of information. We measured local field potentials in the dentate gyrus of freely moving mice and found that gamma activity occurs in bursts, which are highly heterogeneous in their spatial extensions, ranging from focal to global coherent events. Synaptic communication among perisomatic-inhibitory interneurons (PIIs) is thought to play an important role in the generation of hippocampal gamma patterns. However, how neuronal circuits can generate synchronous oscillations at different spatial scales is unknown. We analyzed paired recordings in dentate gyrus slices and show that synaptic signaling at interneuron-interneuron synapses is distance dependent. Synaptic strength declines whereas the duration of inhibitory signals increases with axonal distance among interconnected PIIs. Using neuronal network modeling, we show that distance-dependent inhibition generates multiple highly synchronous focal gamma bursts allowing the network to process complex inputs in parallel in flexibly organized neuronal centers. AU - Strüber, Michael AU - Sauer, Jonas AU - Jonas, Peter M AU - Bartos, Marlene ID - 800 IS - 1 JF - Nature Communications SN - 20411723 TI - Distance-dependent inhibition facilitates focality of gamma oscillations in the dentate gyrus VL - 8 ER - TY - JOUR AB - Eukaryotic cells store their chromosomes in a single nucleus. This is important to maintain genomic integrity, as chromosomes packaged into separate nuclei (micronuclei) are prone to massive DNA damage. During mitosis, higher eukaryotes disassemble their nucleus and release individualized chromosomes for segregation. How numerous chromosomes subsequently reform a single nucleus has remained unclear. Using image-based screening of human cells, we identified barrier-to-autointegration factor (BAF) as a key factor guiding membranes to form a single nucleus. Unexpectedly, nuclear assembly does not require BAF?s association with inner nuclear membrane proteins but instead relies on BAF?s ability to bridge distant DNA sites. Live-cell imaging and in vitro reconstitution showed that BAF enriches around the mitotic chromosome ensemble to induce a densely cross-bridged chromatin layer that is mechanically stiff and limits membranes to the surface. Our study reveals that BAF-mediated changes in chromosome mechanics underlie nuclear assembly with broad implications for proper genome function. AU - Samwer, Matthias AU - Schneider, Maximilian AU - Hoefler, Rudolf AU - Schmalhorst, Philipp S AU - Jude, Julian AU - Zuber, Johannes AU - Gerlic, Daniel ID - 803 IS - 5 JF - Cell SN - 00928674 TI - DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes VL - 170 ER - TY - JOUR AB - Polysaccharides (carbohydrates) are key regulators of a large number of cell biological processes. However, precise biochemical or genetic manipulation of these often complex structures is laborious and hampers experimental structure–function studies. Molecular Dynamics (MD) simulations provide a valuable alternative tool to generate and test hypotheses on saccharide function. Yet, currently used MD force fields often overestimate the aggregation propensity of polysaccharides, affecting the usability of those simulations. Here we tested MARTINI, a popular coarse-grained (CG) force field for biological macromolecules, for its ability to accurately represent molecular forces between saccharides. To this end, we calculated a thermodynamic solution property, the second virial coefficient of the osmotic pressure (B22). Comparison with light scattering experiments revealed a nonphysical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the nonbonded solute–solute, solute–water, and water–water interactions. This finding also applies to smaller oligosaccharides which were all found to aggregate in simulations even at moderate concentrations, well below their solubility limit. Finally, we explored the influence of the Lennard-Jones (LJ) interaction between saccharide molecules and propose a simple scaling of the LJ interaction strength that makes MARTINI more reliable for the simulation of saccharides. AU - Schmalhorst, Philipp S AU - Deluweit, Felix AU - Scherrers, Roger AU - Heisenberg, Carl-Philipp J AU - Sikora, Mateusz K ID - 804 IS - 10 JF - Journal of Chemical Theory and Computation SN - 15499618 TI - Overcoming the limitations of the MARTINI force field in simulations of polysaccharides VL - 13 ER - TY - JOUR AB - Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synaptic N-methyl-D-Aspartate receptor (NMDAR) function, and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse. Using single-molecule tracking, we found that mGluR5 was significantly more mobile at synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic surface co-clustering of mGluR5 and NMDAR. This correlated with a reduced amplitude of synaptic NMDAR currents, a lack of their mGluR5-Activated long-Term depression, and NMDAR/hippocampus dependent cognitive deficits. These synaptic and behavioral phenomena were reversed by knocking down Homer1a in Fmr1 KO mice. Our study provides a mechanistic link between changes of mGluR5 dynamics and pathological phenotypes of FXS, unveiling novel targets for mGluR5-based therapeutics. AU - Aloisi, Elisabetta AU - Le Corf, Katy AU - Dupuis, Julien AU - Zhang, Pei AU - Ginger, Melanie AU - Labrousse, Virginie AU - Spatuzza, Michela AU - Georg Haberl, Matthias AU - Costa, Lara AU - Shigemoto, Ryuichi AU - Tappe Theodor, Anke AU - Drago, Fillippo AU - Vincenzo Piazza, Pier AU - Mulle, Christophe AU - Groc, Laurent AU - Ciranna, Lucia AU - Catania, Maria AU - Frick, Andreas ID - 746 IS - 1 JF - Nature Communications SN - 20411723 TI - Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice VL - 8 ER - TY - JOUR AB - Synaptotagmin 7 (Syt7) is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, Syt7 is strongly expressed in fast-spiking, parvalbumin-expressing GABAergic interneurons, and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. To resolve this apparent contradiction, we examined the effects of genetic elimination of Syt7 on synaptic transmission at the GABAergic basket cell (BC)-Purkinje cell (PC) synapse in cerebellum. Our results indicate that at the BC-PC synapse, Syt7 contributes to asynchronous release, pool replenishment, and facilitation. In combination, these three effects ensure efficient transmitter release during high-frequency activity and guarantee frequency independence of inhibition. Our results identify a distinct function of Syt7: ensuring the efficiency of high-frequency inhibitory synaptic transmission AU - Chen, Chong AU - Satterfield, Rachel AU - Young, Samuel AU - Jonas, Peter M ID - 749 IS - 8 JF - Cell Reports SN - 22111247 TI - Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses VL - 21 ER - TY - JOUR AB - In evolutionary game theory interactions between individuals are often assumed obligatory. However, in many real-life situations, individuals can decide to opt out of an interaction depending on the information they have about the opponent. We consider a simple evolutionary game theoretic model to study such a scenario, where at each encounter between two individuals the type of the opponent (cooperator/defector) is known with some probability, and where each individual either accepts or opts out of the interaction. If the type of the opponent is unknown, a trustful individual accepts the interaction, whereas a suspicious individual opts out of the interaction. If either of the two individuals opt out both individuals remain without an interaction. We show that in the prisoners dilemma optional interactions along with suspicious behaviour facilitates the emergence of trustful cooperation. AU - Priklopil, Tadeas AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 744 JF - Journal of Theoretical Biology SN - 00225193 TI - Optional interactions and suspicious behaviour facilitates trustful cooperation in prisoners dilemma VL - 433 ER - TY - JOUR AB - Fluid flows in nature and applications are frequently subject to periodic velocity modulations. Surprisingly, even for the generic case of flow through a straight pipe, there is little consensus regarding the influence of pulsation on the transition threshold to turbulence: while most studies predict a monotonically increasing threshold with pulsation frequency (i.e. Womersley number, ), others observe a decreasing threshold for identical parameters and only observe an increasing threshold at low . In the present study we apply recent advances in the understanding of transition in steady shear flows to pulsating pipe flow. For moderate pulsation amplitudes we find that the first instability encountered is subcritical (i.e. requiring finite amplitude disturbances) and gives rise to localized patches of turbulence ('puffs') analogous to steady pipe flow. By monitoring the impact of pulsation on the lifetime of turbulence we map the onset of turbulence in parameter space. Transition in pulsatile flow can be separated into three regimes. At small Womersley numbers the dynamics is dominated by the decay turbulence suffers during the slower part of the cycle and hence transition is delayed significantly. As shown in this regime thresholds closely agree with estimates based on a quasi-steady flow assumption only taking puff decay rates into account. The transition point predicted in the zero limit equals to the critical point for steady pipe flow offset by the oscillation Reynolds number (i.e. the dimensionless oscillation amplitude). In the high frequency limit on the other hand, puff lifetimes are identical to those in steady pipe flow and hence the transition threshold appears to be unaffected by flow pulsation. In the intermediate frequency regime the transition threshold sharply drops (with increasing ) from the decay dominated (quasi-steady) threshold to the steady pipe flow level. AU - Xu, Duo AU - Warnecke, Sascha AU - Song, Baofang AU - Ma, Xingyu AU - Hof, Björn ID - 745 JF - Journal of Fluid Mechanics SN - 00221120 TI - Transition to turbulence in pulsating pipe flow VL - 831 ER - TY - JOUR AB - Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate, antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase, while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons, which was prevented by the B2 receptor antagonist. In vivo studies indicate that microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic reticulum, and membrane depolarization; these effects are translated in vivo by bradycardia. AU - Brǎiloiu, Eugen AU - Mcguire, Matthew AU - Shuler, Shadaria AU - Deliu, Elena AU - Barr, Jeffrey AU - Abood, Mary AU - Brailoiu, Gabriela ID - 747 JF - Neuroscience SN - 03064522 TI - Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus VL - 365 ER - TY - THES AB - Cell-cell contact formation constitutes the first step in the emergence of multicellularity in evolution, thereby allowing the differentiation of specialized cell types. In metazoan development, cell-cell contact formation is thought to influence cell fate specification, and cell fate specification has been implicated in cell-cell contact formation. However, remarkably little is yet known about whether and how the interaction and feedback between cell-cell contact formation and cell fate specification affect development. Here we identify a positive feedback loop between cell-cell contact duration, morphogen signaling and mesendoderm cell fate specification during zebrafish gastrulation. We show that long lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for proper ppl cell fate specification. We further show that Nodal signalling romotes ppl cell-cell contact duration, thereby generating an effective positive feedback loop between ppl cell-cell contact duration and cell fate specification. Finally, by using a combination of theoretical modeling and experimentation, we show that this feedback loop determines whether anterior axial mesendoderm cells become ppl progenitors or, instead, turn into endoderm progenitors. Our findings reveal that the gene regulatory networks leading to cell fate diversification within the developing embryo are controlled by the interdependent activities of cell-cell signaling and contact formation. AU - Barone, Vanessa ID - 961 SN - 2663-337X TI - Cell adhesion and cell fate: An effective feedback loop during zebrafish gastrulation ER - TY - JOUR AB - Social insect societies are long-standing models for understanding social behaviour and evolution. Unlike other advanced biological societies (such as the multicellular body), the component parts of social insect societies can be easily deconstructed and manipulated. Recent methodological and theoretical innovations have exploited this trait to address an expanded range of biological questions. We illustrate the broadening range of biological insight coming from social insect biology with four examples. These new frontiers promote open-minded, interdisciplinary exploration of one of the richest and most complex of biological phenomena: sociality. AU - Kennedy, Patrick AU - Baron, Gemma AU - Qiu, Bitao AU - Freitak, Dalial AU - Helantera, Heikki AU - Hunt, Edmund AU - Manfredini, Fabio AU - O'Shea Wheller, Thomas AU - Patalano, Solenn AU - Pull, Christopher AU - Sasaki, Takao AU - Taylor, Daisy AU - Wyatt, Christopher AU - Sumner, Seirian ID - 734 IS - 11 JF - Trends in Ecology and Evolution SN - 01695347 TI - Deconstructing superorganisms and societies to address big questions in biology VL - 32 ER - TY - THES AB - Contagious diseases must transmit from infectious to susceptible hosts in order to reproduce. Whilst vectored pathogens can rely on intermediaries to find new hosts for them, many infectious pathogens require close contact or direct interaction between hosts for transmission. Hence, this means that conspecifics are often the main source of infection for most animals and so, in theory, animals should avoid conspecifics to reduce their risk of infection. Of course, in reality animals must interact with one another, as a bare minimum, to mate. However, being social provides many additional benefits and group living has become a taxonomically diverse and widespread trait. How then do social animals overcome the issue of increased disease? Over the last few decades, the social insects (ants, termites and some bees and wasps) have become a model system for studying disease in social animals. On paper, a social insect colony should be particularly susceptible to disease, given that they often contain thousands of potential hosts that are closely related and frequently interact, as well as exhibiting stable environmental conditions that encourage microbial growth. Yet, disease outbreaks appear to be rare and attempts to eradicate pest species using pathogens have failed time and again. Evolutionary biologists investigating this observation have discovered that the reduced disease susceptibility in social insects is, in part, due to collectively performed disease defences of the workers. These defences act like a “social immune system” for the colony, resulting in a per capita decrease in disease, termed social immunity. Our understanding of social immunity, and its importance in relation to the immunological defences of each insect, continues to grow, but there remain many open questions. In this thesis I have studied disease defence in garden ants. In the first data chapter, I use the invasive garden ant, Lasius neglectus, to investigate how colonies mitigate lethal infections and prevent them from spreading systemically. I find that ants have evolved ‘destructive disinfection’ – a behaviour that uses endogenously produced acidic poison to kill diseased brood and to prevent the pathogen from replicating. In the second experimental chapter, I continue to study the use of poison in invasive garden ant colonies, finding that it is sprayed prophylactically within the nest. However, this spraying has negative effects on developing pupae when they have had their cocoons artificially removed. Hence, I suggest that acidic nest sanitation may be maintaining larval cocoon spinning in this species. In the next experimental chapter, I investigated how colony founding black garden ant queens (Lasius niger) prevent disease when a co-foundress dies. I show that ant queens prophylactically perform undertaking behaviours, similar to those performed by the workers in mature nests. When a co-foundress was infected, these undertaking behaviours improved the survival of the healthy queen. In the final data chapter, I explored how immunocompetence (measured as antifungal activity) changes as incipient black garden ant colonies grow and mature, from the solitary queen phase to colonies with several hundred workers. Queen and worker antifungal activity varied throughout this time period, but despite social immunity, did not decrease as colonies matured. In addition to the above data chapters, this thesis includes two co-authored reviews. In the first, we examine the state of the art in the field of social immunity and how it might develop in the future. In the second, we identify several challenges and open questions in the study of disease defence in animals. We highlight how social insects offer a unique model to tackle some of these problems, as disease defence can be studied from the cell to the society. AU - Pull, Christopher ID - 819 SN - 2663-337X TI - Disease defence in garden ants ER - TY - JOUR AB - Background: Social insects form densely crowded societies in environments with high pathogen loads, but have evolved collective defences that mitigate the impact of disease. However, colony-founding queens lack this protection and suffer high rates of mortality. The impact of pathogens may be exacerbated in species where queens found colonies together, as healthy individuals may contract pathogens from infectious co-founders. Therefore, we tested whether ant queens avoid founding colonies with pathogen-exposed conspecifics and how they might limit disease transmission from infectious individuals. Results: Using Lasius Niger queens and a naturally infecting fungal pathogen Metarhizium brunneum, we observed that queens were equally likely to found colonies with another pathogen-exposed or sham-treated queen. However, when one queen died, the surviving individual performed biting, burial and removal of the corpse. These undertaking behaviours were performed prophylactically, i.e. targeted equally towards non-infected and infected corpses, as well as carried out before infected corpses became infectious. Biting and burial reduced the risk of the queens contracting and dying from disease from an infectious corpse of a dead co-foundress. Conclusions: We show that co-founding ant queens express undertaking behaviours that, in mature colonies, are performed exclusively by workers. Such infection avoidance behaviours act before the queens can contract the disease and will therefore improve the overall chance of colony founding success in ant queens. AU - Pull, Christopher AU - Cremer, Sylvia ID - 732 IS - 1 JF - BMC Evolutionary Biology SN - 14712148 TI - Co-founding ant queens prevent disease by performing prophylactic undertaking behaviour VL - 17 ER - TY - JOUR AB - The morphogenesis of branched organs remains a subject of abiding interest. Although much is known about the underlying signaling pathways, it remains unclear how macroscopic features of branched organs, including their size, network topology, and spatial patterning, are encoded. Here, we show that, in mouse mammary gland, kidney, and human prostate, these features can be explained quantitatively within a single unifying framework of branching and annihilating random walks. Based on quantitative analyses of large-scale organ reconstructions and proliferation kinetics measurements, we propose that morphogenesis follows from the proliferative activity of equipotent tips that stochastically branch and randomly explore their environment but compete neutrally for space, becoming proliferatively inactive when in proximity with neighboring ducts. These results show that complex branched epithelial structures develop as a self-organized process, reliant upon a strikingly simple but generic rule, without recourse to a rigid and deterministic sequence of genetically programmed events. AU - Hannezo, Edouard B AU - Scheele, Colinda AU - Moad, Mohammad AU - Drogo, Nicholas AU - Heer, Rakesh AU - Sampogna, Rosemary AU - Van Rheenen, Jacco AU - Simons, Benjamin ID - 726 IS - 1 JF - Cell SN - 00928674 TI - A unifying theory of branching morphogenesis VL - 171 ER - TY - JOUR AB - In this work maximum entropy distributions in the space of steady states of metabolic networks are considered upon constraining the first and second moments of the growth rate. Coexistence of fast and slow phenotypes, with bimodal flux distributions, emerges upon considering control on the average growth (optimization) and its fluctuations (heterogeneity). This is applied to the carbon catabolic core of Escherichia coli where it quantifies the metabolic activity of slow growing phenotypes and it provides a quantitative map with metabolic fluxes, opening the possibility to detect coexistence from flux data. A preliminary analysis on data for E. coli cultures in standard conditions shows degeneracy for the inferred parameters that extend in the coexistence region. AU - De Martino, Daniele ID - 548 IS - 6 JF - Physical Review E SN - 2470-0045 TI - Maximum entropy modeling of metabolic networks by constraining growth-rate moments predicts coexistence of phenotypes VL - 96 ER - TY - JOUR AB - We present a numerical study of wavy supercritical cylindrical Couette flow between counter-rotating cylinders in which the wavy pattern propagates either prograde with the inner cylinder or retrograde opposite the rotation of the inner cylinder. The wave propagation reversals from prograde to retrograde and vice versa occur at distinct values of the inner cylinder Reynolds number when the associated frequency of the wavy instability vanishes. The reversal occurs for both twofold and threefold symmetric wavy vortices. Moreover, the wave propagation reversal only occurs for sufficiently strong counter-rotation. The flow pattern reversal appears to be intrinsic in the system as either periodic boundary conditions or fixed end wall boundary conditions for different system sizes always result in the wave propagation reversal. We present a detailed bifurcation sequence and parameter space diagram with respect to retrograde behavior of wavy flows. The retrograde propagation of the instability occurs when the inner Reynolds number is about two times the outer Reynolds number. The mechanism for the retrograde propagation is associated with the inviscidly unstable region near the inner cylinder and the direction of the global average azimuthal velocity. Flow dynamics, spatio-temporal behavior, global mean angular velocity, and torque of the flow with the wavy pattern are explored. AU - Altmeyer, Sebastian AU - Lueptow, Richard ID - 673 IS - 5 JF - Physical Review E SN - 2470-0045 TI - Wave propagation reversal for wavy vortices in wide gap counter rotating cylindrical Couette flow VL - 95 ER - TY - JOUR AB - We consider last passage percolation (LPP) models with exponentially distributed random variables, which are linked to the totally asymmetric simple exclusion process (TASEP). The competition interface for LPP was introduced and studied in Ferrari and Pimentel (2005a) for cases where the corresponding exclusion process had a rarefaction fan. Here we consider situations with a shock and determine the law of the fluctuations of the competition interface around its deter- ministic law of large number position. We also study the multipoint distribution of the LPP around the shock, extending our one-point result of Ferrari and Nejjar (2015). AU - Ferrari, Patrik AU - Nejjar, Peter ID - 447 JF - Revista Latino-Americana de Probabilidade e Estatística TI - Fluctuations of the competition interface in presence of shocks VL - 9 ER - TY - JOUR AB - PURPOSE. Gene therapy of retinal ganglion cells (RGCs) has promise as a powerful therapeutic for the rescue and regeneration of these cells after optic nerve damage. However, early after damage, RGCs undergo atrophic changes, including gene silencing. It is not known if these changes will deleteriously affect transduction and transgene expression, or if the therapeutic protein can influence reactivation of the endogenous genome. METHODS. Double-transgenic mice carrying a Rosa26-(LoxP)-tdTomato reporter, and a mutant allele for the proapoptotic Bax gene were reared. The Bax mutant blocks apoptosis, but RGCs still exhibit nuclear atrophy and gene silencing. At times ranging from 1 hour to 4 weeks after optic nerve crush (ONC), eyes received an intravitreal injection of AAV2 virus carrying the Cre recombinase. Successful transduction was monitored by expression of the tdTomato reporter. Immunostaining was used to localize tdTomato expression in select cell types. RESULTS. Successful transduction of RGCs was achieved at all time points after ONC using AAV2 expressing Cre from the phosphoglycerate kinase (Pgk) promoter, but not the CMV promoter. ONC promoted an increase in the transduction of cell types in the inner nuclear layer, including Müller cells and rod bipolar neurons. There was minimal evidence of transduction of amacrine cells and astrocytes in the inner retina or optic nerve. CONCLUSIONS. Damaged RGCs can be transduced and at least some endogenous genes can be subsequently activated. Optic nerve damage may change retinal architecture to allow greater penetration of an AAV2 virus to transduce several additional cell types in the inner nuclear layer. AU - Nickells, Robert AU - Schmitt, Heather AU - Maes, Margaret E AU - Schlamp, Cassandra ID - 557 IS - 14 JF - Investigative Ophthalmology and Visual Science SN - 01460404 TI - AAV2 mediated transduction of the mouse retina after optic nerve injury VL - 58 ER - TY - JOUR AB - Recently it was shown that molecules rotating in superfluid helium can be described in terms of the angulon quasiparticles (Phys. Rev. Lett. 118, 095301 (2017)). Here we demonstrate that in the experimentally realized regime the angulon can be seen as a point charge on a 2-sphere interacting with a gauge field of a non-abelian magnetic monopole. Unlike in several other settings, the gauge fields of the angulon problem emerge in the real coordinate space, as opposed to the momentum space or some effective parameter space. Furthermore, we find a topological transition associated with making the monopole abelian, which takes place in the vicinity of the previously reported angulon instabilities. These results pave the way for studying topological phenomena in experiments on molecules trapped in superfluid helium nanodroplets, as well as on other realizations of orbital impurity problems. AU - Yakaboylu, Enderalp AU - Deuchert, Andreas AU - Lemeshko, Mikhail ID - 997 IS - 23 JF - Physical Review Letters SN - 0031-9007 TI - Emergence of non-abelian magnetic monopoles in a quantum impurity problem VL - 119 ER - TY - CONF AB - We develop a probabilistic technique for colorizing grayscale natural images. In light of the intrinsic uncertainty of this task, the proposed probabilistic framework has numerous desirable properties. In particular, our model is able to produce multiple plausible and vivid colorizations for a given grayscale image and is one of the first colorization models to provide a proper stochastic sampling scheme. Moreover, our training procedure is supported by a rigorous theoretical framework that does not require any ad hoc heuristics and allows for efficient modeling and learning of the joint pixel color distribution.We demonstrate strong quantitative and qualitative experimental results on the CIFAR-10 dataset and the challenging ILSVRC 2012 dataset. AU - Royer, Amélie AU - Kolesnikov, Alexander AU - Lampert, Christoph ID - 911 TI - Probabilistic image colorization ER - TY - JOUR AB - Beige adipocytes are a new type of recruitable brownish adipocytes, with highly mitochondrial membrane uncoupling protein 1 expression and thermogenesis. Beige adipocytes were found among white adipocytes, especially in subcutaneous white adipose tissue (sWAT). Therefore, beige adipocytes may be involved in the regulation of energy metabolism and fat deposition. Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the thermogenic function of brown adiposytes. However, the involvement of TRPM8 in the thermogenic function of WAT remains unexplored. Our data revealed that TRPM8 was expressed in mouse white adipocytes at mRNA, protein and functional levels. The mRNA expression of Trpm8 was significantly increased in the differentiated white adipocytes than pre-adipocytes. Moreover, activation of TRPM8 by menthol enhanced the expression of thermogenic genes in cultured white aidpocytes. And menthol-induced increases of the thermogenic genes in white adipocytes was inhibited by either KT5720 (a protein kinase A inhibitor) or BAPTA-AM. In addition, high fat diet (HFD)-induced obesity in mice was significantly recovered by co-treatment with menthol. Dietary menthol enhanced WAT "browning" and improved glucose metabolism in HFD-induced obesity mice as well. Therefore, we concluded that TRPM8 might be involved in WAT "browning" by increasing the expression levels of genes related to thermogenesis and energy metabolism. And dietary menthol could be a novel approach for combating human obesity and related metabolic diseases. AU - Jiang, Changyu AU - Zhai, Ming-Zhu AU - Yan, Dong AU - Li, Da AU - Li, Chen AU - Zhang, Yonghong AU - Xiao, Lizu AU - Xiong, Donglin AU - Deng, Qiwen AU - Sun, Wuping ID - 627 IS - 43 JF - Oncotarget SN - 1949-2553 TI - Dietary menthol-induced TRPM8 activation enhances WAT “browning” and ameliorates diet-induced obesity VL - 8 ER - TY - JOUR AB - A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input. AU - Lang, Moritz AU - Sontag, Eduardo ID - 1007 JF - Automatica SN - 0005-1098 TI - Zeros of nonlinear systems with input invariances VL - 81C ER - TY - CONF AB - In this work we study the learnability of stochastic processes with respect to the conditional risk, i.e. the existence of a learning algorithm that improves its next-step performance with the amount of observed data. We introduce a notion of pairwise discrepancy between conditional distributions at different times steps and show how certain properties of these discrepancies can be used to construct a successful learning algorithm. Our main results are two theorems that establish criteria for learnability for many classes of stochastic processes, including all special cases studied previously in the literature. AU - Zimin, Alexander AU - Lampert, Christoph ID - 1108 TI - Learning theory for conditional risk minimization VL - 54 ER - TY - JOUR AB - We study the lengths of curves passing through a fixed number of points on the boundary of a convex shape in the plane. We show that, for any convex shape K, there exist four points on the boundary of K such that the length of any curve passing through these points is at least half of the perimeter of K. It is also shown that the same statement does not remain valid with the additional constraint that the points are extreme points of K. Moreover, the factor ½ cannot be achieved with any fixed number of extreme points. We conclude the paper with a few other inequalities related to the perimeter of a convex shape. AU - Akopyan, Arseniy AU - Vysotsky, Vladislav ID - 909 IS - 7 JF - The American Mathematical Monthly SN - 00029890 TI - On the lengths of curves passing through boundary points of a planar convex shape VL - 124 ER - TY - CONF AB - Parallel implementations of stochastic gradient descent (SGD) have received significant research attention, thanks to its excellent scalability properties. A fundamental barrier when parallelizing SGD is the high bandwidth cost of communicating gradient updates between nodes; consequently, several lossy compresion heuristics have been proposed, by which nodes only communicate quantized gradients. Although effective in practice, these heuristics do not always converge. In this paper, we propose Quantized SGD (QSGD), a family of compression schemes with convergence guarantees and good practical performance. QSGD allows the user to smoothly trade off communication bandwidth and convergence time: nodes can adjust the number of bits sent per iteration, at the cost of possibly higher variance. We show that this trade-off is inherent, in the sense that improving it past some threshold would violate information-theoretic lower bounds. QSGD guarantees convergence for convex and non-convex objectives, under asynchrony, and can be extended to stochastic variance-reduced techniques. When applied to training deep neural networks for image classification and automated speech recognition, QSGD leads to significant reductions in end-to-end training time. For instance, on 16GPUs, we can train the ResNet-152 network to full accuracy on ImageNet 1.8 × faster than the full-precision variant. AU - Alistarh, Dan-Adrian AU - Grubic, Demjan AU - Li, Jerry AU - Tomioka, Ryota AU - Vojnović, Milan ID - 431 SN - 10495258 TI - QSGD: Communication-efficient SGD via gradient quantization and encoding VL - 2017 ER - TY - CONF AB - Model checking is usually based on a comprehensive traversal of the state space. Causality-based model checking is a radically different approach that instead analyzes the cause-effect relationships in a program. We give an overview on a new class of model checking algorithms that capture the causal relationships in a special data structure called concurrent traces. Concurrent traces identify key events in an execution history and link them through their cause-effect relationships. The model checker builds a tableau of concurrent traces, where the case splits represent different causal explanations of a hypothetical error. Causality-based model checking has been implemented in the ARCTOR tool, and applied to previously intractable multi-threaded benchmarks. AU - Finkbeiner, Bernd AU - Kupriyanov, Andrey ID - 549 SN - 2075-2180 T2 - Electronic Proceedings in Theoretical Computer Science TI - Causality-based model checking VL - 259 ER - TY - CONF AB - In multi-task learning, a learner is given a collection of prediction tasks and needs to solve all of them. In contrast to previous work, which required that annotated training data must be available for all tasks, we consider a new setting, in which for some tasks, potentially most of them, only unlabeled training data is provided. Consequently, to solve all tasks, information must be transferred between tasks with labels and tasks without labels. Focusing on an instance-based transfer method we analyze two variants of this setting: when the set of labeled tasks is fixed, and when it can be actively selected by the learner. We state and prove a generalization bound that covers both scenarios and derive from it an algorithm for making the choice of labeled tasks (in the active case) and for transferring information between the tasks in a principled way. We also illustrate the effectiveness of the algorithm on synthetic and real data. AU - Pentina, Anastasia AU - Lampert, Christoph ID - 999 SN - 9781510855144 TI - Multi-task learning with labeled and unlabeled tasks VL - 70 ER - TY - JOUR AB - The social insects bees, wasps, ants, and termites are species-rich, occur in many habitats, and often constitute a large part of the biomass. Many are also invasive, including species of termites, the red imported fire ant, and the Argentine ant. While invasive social insects have been a problem in Southern Europe for some time, Central Europa was free of invasive ant species until recently because most ants are adapted to warmer climates. Only in the 1990s, did Lasius neglectus, a close relative of the common black garden ant, arrive in Germany. First described in 1990 based on individuals collected in Budapest, the species has since been detected for example in France, Germany, Spain, England, and Kyrgyzstan. The species is spread with soil during construction work or plantings, and L. neglectus therefore is often found in parks and botanical gardens. Another invasive ant now spreading in southern Germany is Formica fuscocinerea, which occurs along rivers, including in the sandy floodplains of the river Isar. As is typical of pioneer species, F. fuscocinerea quickly becomes extremely abundant and therefore causes problems for example on playgrounds in Munich. All invasive ant species are characterized by cooperation across nests, leading to strongly interconnected, very large super-colonies. The resulting dominance results in the extinction of native ant species as well as other arthropod species and thus in the reduction of biodiversity. AU - Cremer, Sylvia ID - 459 JF - Rundgespräche Forum Ökologie SN - 2366-2875 TI - Invasive Ameisen in Europa: Wie sie sich ausbreiten und die heimische Fauna verändern VL - 46 ER - TY - CONF AB - Recently there has been significant interest in training machine-learning models at low precision: by reducing precision, one can reduce computation and communication by one order of magnitude. We examine training at reduced precision, both from a theoretical and practical perspective, and ask: is it possible to train models at end-to-end low precision with provable guarantees? Can this lead to consistent order-of-magnitude speedups? We mainly focus on linear models, and the answer is yes for linear models. We develop a simple framework called ZipML based on one simple but novel strategy called double sampling. Our ZipML framework is able to execute training at low precision with no bias, guaranteeing convergence, whereas naive quanti- zation would introduce significant bias. We val- idate our framework across a range of applica- tions, and show that it enables an FPGA proto- type that is up to 6.5 × faster than an implemen- tation using full 32-bit precision. We further de- velop a variance-optimal stochastic quantization strategy and show that it can make a significant difference in a variety of settings. When applied to linear models together with double sampling, we save up to another 1.7 × in data movement compared with uniform quantization. When training deep networks with quantized models, we achieve higher accuracy than the state-of-the- art XNOR-Net. AU - Zhang, Hantian AU - Li, Jerry AU - Kara, Kaan AU - Alistarh, Dan-Adrian AU - Liu, Ji AU - Zhang, Ce ID - 432 SN - 978-151085514-4 T2 - Proceedings of Machine Learning Research TI - ZipML: Training linear models with end-to-end low precision, and a little bit of deep learning VL - 70 ER - TY - CONF AB - We consider the problem of estimating the partition function Z(β)=∑xexp(−β(H(x)) of a Gibbs distribution with a Hamilton H(⋅), or more precisely the logarithm of the ratio q=lnZ(0)/Z(β). It has been recently shown how to approximate q with high probability assuming the existence of an oracle that produces samples from the Gibbs distribution for a given parameter value in [0,β]. The current best known approach due to Huber [9] uses O(qlnn⋅[lnq+lnlnn+ε−2]) oracle calls on average where ε is the desired accuracy of approximation and H(⋅) is assumed to lie in {0}∪[1,n]. We improve the complexity to O(qlnn⋅ε−2) oracle calls. We also show that the same complexity can be achieved if exact oracles are replaced with approximate sampling oracles that are within O(ε2qlnn) variation distance from exact oracles. Finally, we prove a lower bound of Ω(q⋅ε−2) oracle calls under a natural model of computation. AU - Kolmogorov, Vladimir ID - 274 T2 - Proceedings of the 31st Conference On Learning Theory TI - A faster approximation algorithm for the Gibbs partition function VL - 75 ER - TY - JOUR AB - Auf der Suche nach einem Bibliothekssystem entschied sich die Forschungseinrichtung IST Austria im Jahr 2014 für das Open-Source-Produkt Koha. In einem ersten Schritt wurden zunächst Grundfunktionen aktiviert um im Anschluss diverse zusätzliche Tools zum Einsatz zu bringen. Die große Flexibilität des Systems erlaubt maßgeschneiderte Lösungen für unterschiedlichste Institutionen. Trotz Herausforderungen kann die Bibliothek auf eine erfolgreiche Implementierung zurückblicken. AU - Villányi, Márton ID - 1030 IS - 1 JF - Informationspraxis SN - 2297-3249 TI - Ein freies Bibliothekssystem für wissenschaftliche Bibliotheken – Werkstattbericht der IST Austria Library VL - 3 ER - TY - JOUR AB - DNA methylation regulates eukaryotic gene expression and is extensively reprogrammed during animal development. However, whether developmental methylation reprogramming during the sporophytic life cycle of flowering plants regulates genes is presently unknown. Here we report a distinctive gene-targeted RNA-directed DNA methylation (RdDM) activity in the Arabidopsis thaliana male sexual lineage that regulates gene expression in meiocytes. Loss of sexual-lineage-specific RdDM causes mis-splicing of the MPS1 gene (also known as PRD2), thereby disrupting meiosis. Our results establish a regulatory paradigm in which de novo methylation creates a cell-lineage-specific epigenetic signature that controls gene expression and contributes to cellular function in flowering plants. AU - Walker, James AU - Gao, Hongbo AU - Zhang, Jingyi AU - Aldridge, Billy AU - Vickers, Martin AU - Higgins, James D. AU - Feng, Xiaoqi ID - 12193 IS - 1 JF - Nature Genetics KW - Genetics SN - 1061-4036 TI - Sexual-lineage-specific DNA methylation regulates meiosis in Arabidopsis VL - 50 ER - TY - CONF AB - Termination is one of the basic liveness properties, and we study the termination problem for probabilistic programs with real-valued variables. Previous works focused on the qualitative problem that asks whether an input program terminates with probability~1 (almost-sure termination). A powerful approach for this qualitative problem is the notion of ranking supermartingales with respect to a given set of invariants. The quantitative problem (probabilistic termination) asks for bounds on the termination probability. A fundamental and conceptual drawback of the existing approaches to address probabilistic termination is that even though the supermartingales consider the probabilistic behavior of the programs, the invariants are obtained completely ignoring the probabilistic aspect. In this work we address the probabilistic termination problem for linear-arithmetic probabilistic programs with nondeterminism. We define the notion of {\em stochastic invariants}, which are constraints along with a probability bound that the constraints hold. We introduce a concept of {\em repulsing supermartingales}. First, we show that repulsing supermartingales can be used to obtain bounds on the probability of the stochastic invariants. Second, we show the effectiveness of repulsing supermartingales in the following three ways: (1)~With a combination of ranking and repulsing supermartingales we can compute lower bounds on the probability of termination; (2)~repulsing supermartingales provide witnesses for refutation of almost-sure termination; and (3)~with a combination of ranking and repulsing supermartingales we can establish persistence properties of probabilistic programs. We also present results on related computational problems and an experimental evaluation of our approach on academic examples. AU - Chatterjee, Krishnendu AU - Novotny, Petr AU - Zikelic, Djordje ID - 1194 IS - 1 SN - 07308566 TI - Stochastic invariants for probabilistic termination VL - 52 ER - TY - CHAP AB - Development of vascular tissue is a remarkable example of intercellular communication and coordinated development involving hormonal signaling and tissue polarity. Thus far, studies on vascular patterning and regeneration have been conducted mainly in trees—woody plants—with a well-developed layer of vascular cambium and secondary tissues. Trees are difficult to use as genetic models, i.e., due to long generation time, unstable environmental conditions, and lack of available mutants and transgenic lines. Therefore, the use of the main genetic model plant Arabidopsis thaliana (L.) Heynh., with a wealth of available marker and transgenic lines, provides a unique opportunity to address molecular mechanism of vascular tissue formation and regeneration. With specific treatments, the tiny weed Arabidopsis can serve as a model to understand the growth of mighty trees and interconnect a tree physiology with molecular genetics and cell biology of Arabidopsis. AU - Mazur, Ewa AU - Friml, Jirí ED - Jurić, Snježana ID - 545 T2 - Plant Engineering TI - Vascular tissue development and regeneration in the model plant arabidopsis ER - TY - JOUR AB - The mammalian cerebral cortex is responsible for higher cognitive functions such as perception, consciousness, and acquiring and processing information. The neocortex is organized into six distinct laminae, each composed of a rich diversity of cell types which assemble into highly complex cortical circuits. Radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. Here, we discuss recent discoveries emerging from clonal lineage analysis at the single RGP cell level that provide us with an inaugural quantitative framework of RGP lineage progression. We further discuss the importance of the relative contribution of intrinsic gene functions and non-cell-autonomous or community effects in regulating RGP proliferation behavior and lineage progression. AU - Beattie, Robert J AU - Hippenmeyer, Simon ID - 621 IS - 24 JF - FEBS letters SN - 00145793 TI - Mechanisms of radial glia progenitor cell lineage progression VL - 591 ER - TY - DATA AB - This data was collected as part of the study [1]. It consists of preprocessed multi-electrode array recording from 160 salamander retinal ganglion cells responding to 297 repeats of a 19 s natural movie. The data is available in two formats: (1) a .mat file containing an array with dimensions “number of repeats” x “number of neurons” x “time in a repeat”; (2) a zipped .txt file containing the same data represented as an array with dimensions “number of neurons” x “number of samples”, where the number of samples is equal to the product of the number of repeats and timebins within a repeat. The time dimension is divided into 20 ms time windows, and the array is binary indicating whether a given cell elicited at least one spike in a given time window during a particular repeat. See the reference below for details regarding collection and preprocessing: [1] Tkačik G, Marre O, Amodei D, Schneidman E, Bialek W, Berry MJ II. Searching for Collective Behavior in a Large Network of Sensory Neurons. PLoS Comput Biol. 2014;10(1):e1003408. AU - Marre, Olivier AU - Tkacik, Gasper AU - Amodei, Dario AU - Schneidman, Elad AU - Bialek, William AU - Berry, Michael ID - 5562 KW - multi-electrode recording KW - retinal ganglion cells TI - Multi-electrode array recording from salamander retinal ganglion cells ER - TY - DATA AB - Graph matching problems as described in "Active Graph Matching for Automatic Joint Segmentation and Annotation of C. Elegans." by Kainmueller, Dagmar and Jug, Florian and Rother, Carsten and Myers, Gene, MICCAI 2014. Problems are in OpenGM2 hdf5 format (see http://hciweb2.iwr.uni-heidelberg.de/opengm/) and a custom text format used by the feature matching solver described in "Feature Correspondence via Graph Matching: Models and Global Optimization." by Lorenzo Torresani, Vladimir Kolmogorov and Carsten Rother, ECCV 2008, code at http://pub.ist.ac.at/~vnk/software/GraphMatching-v1.02.src.zip. AU - Kainmueller, Dagmar AU - Jug, Florian AU - Rother, Carsten AU - Meyers, Gene ID - 5561 KW - graph matching KW - feature matching KW - QAP KW - MAP-inference TI - Graph matching problems for annotating C. Elegans ER - TY - DATA AB - MATLAB code and processed datasets available for reproducing the results in: Lukačišin, M.*, Landon, M.*, Jajoo, R*. (2016) Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast. *equal contributions AU - Lukacisin, Martin ID - 5563 TI - MATLAB analysis code for 'Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast' ER - TY - THES AB - This thesis describes a brittle fracture simulation method for visual effects applications. Building upon a symmetric Galerkin boundary element method, we first compute stress intensity factors following the theory of linear elastic fracture mechanics. We then use these stress intensities to simulate the motion of a propagating crack front at a significantly higher resolution than the overall deformation of the breaking object. Allowing for spatial variations of the material's toughness during crack propagation produces visually realistic, highly-detailed fracture surfaces. Furthermore, we introduce approximations for stress intensities and crack opening displacements, resulting in both practical speed-up and theoretically superior runtime complexity compared to previous methods. While we choose a quasi-static approach to fracture mechanics, ignoring dynamic deformations, we also couple our fracture simulation framework to a standard rigid-body dynamics solver, enabling visual effects artists to simulate both large scale motion, as well as fracturing due to collision forces in a combined system. As fractures inside of an object grow, their geometry must be represented both in the coarse boundary element mesh, as well as at the desired fine output resolution. Using a boundary element method, we avoid complicated volumetric meshing operations. Instead we describe a simple set of surface meshing operations that allow us to progressively add cracks to the mesh of an object and still re-use all previously computed entries of the linear boundary element system matrix. On the high resolution level, we opt for an implicit surface representation. We then describe how to capture fracture surfaces during crack propagation, as well as separate the individual fragments resulting from the fracture process, based on this implicit representation. We show results obtained with our method, either solving the full boundary element system in every time step, or alternatively using our fast approximations. These results demonstrate that both of these methods perform well in basic test cases and produce realistic fracture surfaces. Furthermore we show that our fast approximations substantially out-perform the standard approach in more demanding scenarios. Finally, these two methods naturally combine, using the full solution while the problem size is manageably small and switching to the fast approximations later on. The resulting hybrid method gives the user a direct way to choose between speed and accuracy of the simulation. AU - Hahn, David ID - 839 SN - 2663-337X TI - Brittle fracture simulation with boundary elements for computer graphics ER - TY - JOUR AB - Moths and butterflies (Lepidoptera) usually have a pair of differentiated WZ sex chromosomes. However, in most lineages outside of the division Ditrysia, as well as in the sister order Trichoptera, females lack a W chromosome. The W is therefore thought to have been acquired secondarily. Here we compare the genomes of three Lepidoptera species (one Dytrisia and two non-Dytrisia) to test three models accounting for the origin of the W: (1) a Z-autosome fusion; (2) a sex chromosome turnover; and (3) a non-canonical mechanism (e.g., through the recruitment of a B chromosome). We show that the gene content of the Z is highly conserved across Lepidoptera (rejecting a sex chromosome turnover) and that very few genes moved onto the Z in the common ancestor of the Ditrysia (arguing against a Z-autosome fusion). Our comparative genomics analysis therefore supports the secondary acquisition of the Lepidoptera W by a non-canonical mechanism, and it confirms the extreme stability of well-differentiated sex chromosomes. AU - Fraisse, Christelle AU - Picard, Marion A AU - Vicoso, Beatriz ID - 614 IS - 1 JF - Nature Communications SN - 20411723 TI - The deep conservation of the Lepidoptera Z chromosome suggests a non canonical origin of the W VL - 8 ER - TY - DATA AB - Compressed Fastq files with whole-genome sequencing data of IS-wt strain D and clones from four evolved populations (A11, C08, C10, D08). Information on this data collection is available in the Methods Section of the primary publication. AU - Steinrück, Magdalena AU - Guet, Calin C ID - 5564 TI - Fastq files for "Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection" ER - TY - DATA AB - Includes source codes, test cases, and example data used in the thesis Brittle Fracture Simulation with Boundary Elements for Computer Graphics. Also includes pre-built binaries of the HyENA library, but not sources - please contact the HyENA authors to obtain these sources if required (https://mech.tugraz.at/hyena) AU - Hahn, David ID - 5568 KW - Boundary elements KW - brittle fracture KW - computer graphics KW - fracture simulation TI - Source codes: Brittle fracture simulation with boundary elements for computer graphics ER - TY - DATA AB - The de novo genome assemblies generated for this study, and the associated metadata. AU - Fraisse, Christelle ID - 7163 TI - Supplementary Files for "The deep conservation of the Lepidoptera Z chromosome suggests a non canonical origin of the W" ER -