5,814 research outputs found

    The 2D/3D dynamics of wall-bounded low-Rm magnetohydrodynamic (MHD) turbulence

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    With this experimental study, we give evidence that the dynamics of low-Rm MHD turbulence depends on the diffusion length l_z, which corresponds to the distance over which the Lorentz force is able to diffuse momentum before it is balanced by inertia

    Investigating the DNA methylation landscape of Staphylococcus aureus

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    Staphylococcus aureus is a leading causative agent of healthcare-associated infections. One aspect of the organism that remains unknown is the methylome, specifically that of the whole genome. In prokaryotes, methylation is facilitated by methyltransferases, usually part of the organism’s Restriction Modification system (RM). It is well established that RM are involved in cellular defense but have also been attributed to have secondary regulatory functions in host physiology and virulence by modulating gene expression through DNA methylation in numerous bacterial species. In S. aureus the main RM present are Type I RM Sau1, which potential epigenetic role has not yet been studied. Using PacBio SMRT sequencing this study investigates the variability and distribution of sau1 DNA binding specificity unit (hsdS) alleles and explores the frequency of whole genome 6mA methylation within the species using a historically and phylogenetically variable collection of S. aureus isolates part of the NCTC3000 project. The results revealed lineage specific methylation patterns randomly distributed throughout the chromosome, but preferential methylation of the coding sequence and the core genome. Between the 24 represented STs, the detailed protein structure of 40 different HsdS homologs were characterised and matched to corresponding 6mA target recognition sequences, greatly augmenting the current knowledge of Sau1 methylation signatures. Differential methylation was also investigated in novel ST622 hybrid strains as a natural experiment (variable methylation signatures across an identical sequence region between chimeric and closely related ST45 and ST22 donor strains) effectively looking at the effect of large-scale recombination on whole genome methylation using RNA-Sequencing. Mutagenesis of hsdS and further transcriptomic studies revealed that deletion of 6mA methylation by Sau1 in a set of isogenic mutants in multiple sequence backgrounds causes a pleotropic shift in expression of metabolic genes. This is not likely due to an epigenetic regulatory mechanism, but rather and induced global stress response.""I would first like to acknowledge that this work was funded by the Wellcome ISSF Fund of the University of St Andrews (School of Medicine)."--Acknowledgement

    Estimating demographic parameters for capture-recapture data in the presence of multiple mark types

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    In mark-recapture studies, various techniques can be used to uniquely identify individual animals, such as ringing, tagging or photo-identification using natural markings. In some long-term studies more than one type of marking procedure may be implemented during the study period. In these circumstances, ignoring the different mark types can produce biased survival estimates since the assumption that the different mark types are equally catchable (homogeneous capture probability across mark types) may be incorrect.We implement an integrated approach where we simultaneously analyse data obtained using three different marking techniques, assuming that animals can be cross-classified across the different mark types. We discriminate between competing models using the AIC statistic. This technique also allows us to estimate both relative mark-loss probabilities and relative recapture efficiency rates for the different marking methods.We initially perform a simulation study to explore the different biases that can be introduced if we assume a homogeneous recapture probability over mark type, before applying the method to a real dataset. We make use of data obtained from an intensive long-term observational study of UK female grey seals (Halichoerus grypus) at a single breeding colony, where three different methods are used to identify individuals within a single study: branding, tagging and photo-identification based on seal coat pattern or pelage.Peer reviewe

    Triangular Constellations in Flows

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    Particles advected on the surface of a fluid can exhibit fractal clustering. The local structure of a fractal set is described by its dimension DD, which is the exponent of a power-law relating the mass N{\cal N} in a ball to its radius ε\varepsilon: NεD{\cal N}\sim \varepsilon^D. It is desirable to characterise the {\em shapes} of constellations of points sampling a fractal measure, as well as their masses. The simplest example is the distribution of shapes of triangles formed by triplets of points, which we investigate for fractals generated by chaotic dynamical systems. The most significant parameter describing the triangle shape is the ratio zz of its area to the radius of gyration squared. We show that the probability density of zz has a phase transition: P(z)P(z) is independent of ε\varepsilon and approximately uniform below a critical flow compressibility βc\beta_{\rm c}, which we estimate. For β>βc\beta>\beta_{\rm c} the distribution appears to be described by two power laws: P(z)zα1P(z)\sim z^{\alpha_1} when 1zzc(ε)1\gg z\gg z_{\rm c}(\varepsilon), and P(z)zα2P(z)\sim z^{\alpha_2} when zzc(ε)z\ll z_{\rm c}(\varepsilon)

    The semiotics of printed instructions (graphic signa)

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    This thesis sets out to describe sign systems for communication using Axiomatic Functionalism as its theoretical framework. In doing so, the thesis also provides an important test to the claim of Axiomatic Functionalism that by using its premisses the semiotician (or linguist) has all the necessary "tools" s/he needs for the analysis and description (the one implies the other) of any semiotic system for communication (including Language). Using Axiomatic Functionalism the author attempts to describe a number of graphic semiotic systems for communication. He finds that for an adequate description of the signa (a generic term which includes various types of signs and symbols) in these systems further theoretical notions and definitions are needed. Discussing these the author concludes that for Axiomatic Functionalism to maintain its claim of universal applicability to any sign system for communication it needs to incorporate in its premisses the notions and definitions proposed here. The thesis begins by a brief general introduction to semiotics. This is followed by a discussion of what constitutes scientific theories in relation to semiotics (including linguistics). The relevant aspects of Axiomatic Functionalism are then discussed, after which certain original theoretical notions are introduced. These include: “mnemonic economy" (with its many manifestations including "mnemonic/pictorial motivation"), the "general organising principle" ("systemic principle"), "principle of coinage" (a mechanism for generating signa), and "signum-family”. Having established the necessary theoretical background, the author proceeds to describe various graphic “signum-systems" discussing their important features and establishing the types of signum they consist of and, consequently, the types of system they are, their complexity and the "plerology” (grammar) of each system, where present. The systems discussed include various systems used in books on plants; a system used in a book on "lace knitting"; a system used in working models; a system used in providing information about paintings in the "Classics of World Art" series of books; and a system used in the "Automobile Association" handbooks. Further Axiomatic Functionalist theoretical notions, directly relevant to the systems described thereafter, are then introduced. This is followed by a description of three systems: two computer "languages", the "Hexadecimal notation" and the "binary code", and the "Library of Congress classification system". A final brief "Epilogue" concludes the thesis

    Exact two-dimensionalization of low-magnetic-Reynolds-number flows subject to a strong magnetic field

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    We investigate the behavior of flows, including turbulent flows, driven by a horizontal body-force and subject to a vertical magnetic field, with the following question in mind: for very strong applied magnetic field, is the flow mostly two-dimensional, with remaining weak three-dimensional fluctuations, or does it become exactly 2D, with no dependence along the vertical? We restrict attention to low-magnetic-Reynolds number (Rm) flow. Because liquid metals have low magnetic Prandtl number, such low-RmRm flows can have a kinetic Reynolds number as large as one million and therefore be strongly turbulent. We first focus on the quasi-static approximation, i.e. the asymptotic limit of vanishing magnetic Reynolds number Rm << 1: we prove that the flow becomes exactly 2D asymptotically in time, regardless of the initial condition and provided the interaction parameter N is larger than a threshold value. We call this property absolute two-dimensionalization: the attractor of the system is necessarily a (possibly turbulent) 2D flow. We then consider the full-magnetohydrodynamic equations and we prove that, for low enough Rm and large enough N, the flow becomes exactly two-dimensional in the long-time limit provided the initial vertically-dependent perturbations are infinitesimal. We call this phenomenon linear two-dimensionalization: the (possibly turbulent) 2D flow is an attractor of the dynamics, but it is not necessarily the only attractor of the system. Some 3D attractors may also exist and be attained for strong enough initial 3D perturbations. These results shed some light on the existence of a dissipative anomaly for magnetohydrodynamic flows subject to a strong external magnetic field

    The Decay of Wall Bounded MHD Turbulence at Low RM

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    We have developed a new spectral method to simulate flows with very fine boundary layers present. We apply it to calculate the evolution of freely decaying MHD turbulence between isolating walls. By comparison them with results obtained in fully periodic domain we quantify the influence of the channel walls on the character of freely decaying MHD turbulence

    IL-4 receptor alpha is an important modulator of IL-4 and IL-13 receptor binding: implications for the development of therapeutic targets

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    IL-4 is a key cytokine associated with allergy and asthma. Induction of cell signaling by IL-4 involves interaction with its cognate receptors, a complex of IL-4Ralpha with either the common gamma-chain or the IL-13R chain alpha1 (IL-13Ralpha1). We found that IL-4 bound to the extracellular domain of IL-4Ralpha (soluble human (sh)IL-4Ralpha) with high affinity and specificity. In contrast with the sequential mechanism of binding and stabilization afforded by IL-4Ralpha to the binding of IL-13 to IL-13Ralpha1, neither common gamma-chain nor IL-13Ralpha1 contributed significantly to the stabilization of the IL-4:IL-4Ralpha complex. Based on the different mechanisms of binding and stabilization of the IL-4R and IL-13R complexes, we compared the effects of shIL-4Ralpha and an IL-4 double mutein (R121D/Y124D, IL-4R antagonist) on IL-4- and IL-13-mediated responses. Whereas IL-4R antagonist blocked responses to both cytokines, shIL-4Ralpha only blocked IL-4. However, shIL-4Ralpha stabilized and augmented IL-13-mediated STAT6 activation and eotaxin production by primary human bronchial fibroblasts at suboptimal doses of IL-13. These data demonstrate that IL-4Ralpha plays a key role in the binding affinity of both IL-13R and IL-4R complexes. Under certain conditions, shIL-4Ralpha has the potential to stabilize binding IL-13 to its receptor to augment IL-13-mediated responses. Thus, complete understanding of the binding interactions between IL-4 and IL-13 and their cognate receptors may facilitate development of novel treatments for asthma that selectively target these cytokines without unpredicted or detrimental side effects.</p

    Assessment and implications of the supply of Semibalanus balanoides (L.) larvae to shores in Fife, East Scotland

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    Investigations into the supply, settlement and recruitment of the barnacle Semibalanus balanoides (L.) to shores in Fife, East Scotland were undertaken over three consecutive years (2004 – 2006). Several designs of a passive larval trap, based on earlier published designs, were employed to quantify the delivery (supply) of cyprids to the substratum. Pump samples from the water column were collected to provide a measure of intertidal cyprid concentration. Cyprid concentration was found to exhibit both spatial and temporal variation, but was also found to be significantly correlated with cyprid supply, as quantified by the traps. In some years, pump and trap samples suggested that cyprid abundance in the intertidal was mediated by wind-driven processes. An artificial substratum was used to quantify cyprid settlement, allowing investigations into the supply-settlement relationship. Supply and settlement were found to be two very distinct biological phases. Supply describes the flux of larvae to the substratum. Settlement provides a measure of the amount of larvae that decide to settle on the substratum, as initial attachment for barnacle larvae is not permanent. Whilst supply saturation is unfeasible, daily saturation of the substratum by settlers was observed at many sites along the Fife coast. Levels of settlement saturation were found to vary both temporally, between years, and spatially, over scales of km. Varying levels of the desperation of larvae to settle, mediated by dwindling energy reserves, was thought to explain some of this variation. The supply data also provided some evidence of the possible movement of cyprids along the Fife coast from Fife Ness to Tentsmuir. However, wind-induced transport may also play a dominant role on the Fife coast. A comparison of supply and recruitment of larvae into adult populations revealed that both pre- and post-settlement events may influence recruitment. The relative importance of these factors was shown to be density-dependent. Negative intraspecific interactions were only seen in denser aggregations of adults. In less crowded aggregations, recruitment reflected initial patterns of larval supply

    Linking actions to outcomes : the role of the posterior pedunculopontine tegmental nucleus in instrumental learning

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    Located in the mesopontine tegmentum, the pedunculopontine tegmental nucleus (PPTg) is comprised principally of glutamatergic, cholinergic and GABAergic neurons. In addition to being fully integrated into basal ganglia, PPTg projects to thalamus and motor output sites in the brainstem. Previous studies have shown a range of behavioural changes after PPTg manipulation. Prominent amongst these is an apparent deficit in the ability to learn the consequences of actions. PPTg is divisible into a posterior component (pPPTg) in receipt of rapid polymodal sensory input and projecting into VTA/SNc dopamine neurons and an anterior component (aPPTg) in receipt of basal ganglia outflow and projecting into SNc and lower brainstem structures. The research described here assesses the role of the pPPTg in instrumental learning. Using a contingency degradation paradigm, it was shown that inactivation of the pPPTg (by muscimol microinfusion) specifically blocked the updating of associations between actions and outcomes, without the affecting the ability to re-execute previously learned instrumental actions. Selective bilateral destruction of pPPTg cholinergic neurons (with the fusion toxin diphtheria toxin – urotensin II [Dtx-UII]) resulted in >90% loss of pPPTg cholinergic neurons. These lesions produced no detectable changes on any measured aspect of an instrumental learning task consisting of various fixed and variable ratio schedules of reinforcement and extinction. Subsequent experiments found that the same selective cholinergic pPPTg lesions also produced no changes in the locomotor response to nicotine or rate of nicotine sensitisation. These results are the first to demonstrate a brainstem role in action-outcome learning. Results support the view that PPTg performs a ‘first pass’ analysis on incoming sensory data and interfaces salient aspects of this with appropriate basal ganglia and brainstem circuitry, with glutamatergic pPPTg projections sending an essential signal and cholinergic projections performing as part of a wider modulatory system
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