507 research outputs found

    Introduction

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    NWOClassics and Classical Civilizatio

    Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate

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    The protozoan Trypanosoma brucei has a functional pteridine reductase (TbPTR1), an NADPH-dependent short-chain reductase that participates in the salvage of pterins, which are essential for parasite growth. PTR1 displays broad-spectrum activity with pterins and folates, provides a metabolic bypass for inhibition of the trypanosomatid dihydrofolate reductase and therefore compromises the use of antifolates for treatment of trypanosomiasis. Catalytic properties of recombinant TbPTR1 and inhibition by the archetypal antifolate methotrexate have been characterized and the crystal structure of the ternary complex with cofactor NADP(+) and the inhibitor determined at 2.2 Å resolution. This enzyme shares 50% amino acid sequence identity with Leishmania major PTR1 (LmPTR1) and comparisons show that the architecture of the cofactor binding site, and the catalytic centre are highly conserved, as are most interactions with the inhibitor. However, specific amino acid differences, in particular the placement of Trp221 at the side of the active site, and adjustment of the β6-α6 loop and α6 helix at one side of the substrate-binding cleft significantly reduce the size of the substrate binding site of TbPTR1 and alter the chemical properties compared with LmPTR1. A reactive Cys168, within the active site cleft, in conjunction with the C-terminus carboxyl group and His267 of a partner subunit forms a triad similar to the catalytic component of cysteine proteases. TbPTR1 therefore offers novel structural features to exploit in the search for inhibitors of therapeutic value against African trypanosomiasis

    Dynamical modelling of the elliptical galaxy NGC 2974

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    In this paper we analyse the relations between a previously described oblate Jaffe model for an ellipsoidal galaxy and the observed quantities for NGC 2974, and obtain the length and velocity scales for a relevant elliptical galaxy model. We then derive the finite total mass of the model from these scales, and finally find a good fit of an isotropic oblate Jaffe model by using the Gauss-Hermite fit parameters and the observed ellipticity of the galaxy NGC 2974. The model is also used to predict the total luminous mass of NGC 2974, assuming that the influence of dark matter in this galaxy on the image, ellipticity and Gauss-Hermite fit parameters of this galaxy is negligible within the central region, of radius 0.5Re.0.5R_{\rm e}.Comment: 7 figure

    Galactic-Centre Gamma Rays in CMSSM Dark Matter Scenarios

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    We study the production of gamma rays via LSP annihilations in the core of the Galaxy as a possible experimental signature of the constrained minimal supersymmetric extension of the Standard Model (CMSSM), in which supersymmetry-breaking parameters are assumed to be universal at the GUT scale, assuming also that the LSP is the lightest neutralino chi. The part of the CMSSM parameter space that is compatible with the measured astrophysical density of cold dark matter is known to include a stau_1 - chi coannihilation strip, a focus-point strip where chi has an enhanced Higgsino component, and a funnel at large tanb where the annihilation rate is enhanced by the poles of nearby heavy MSSM Higgs bosons, A/H. We calculate the total annihilation rates, the fractions of annihilations into different Standard Model final states and the resulting fluxes of gamma rays for CMSSM scenarios along these strips. We observe that typical annihilation rates are much smaller in the coannihilation strip for tanb = 10 than along the focus-point strip or for tanb = 55, and that the annihilation branching ratios differ greatly between the different dark matter strips. Whereas the current Fermi-LAT data are not sensitive to any of the CMSSM scenarios studied, and the calculated gamma-ray fluxes are probably unobservably low along the coannihilation strip for tanb = 10, we find that substantial portions of the focus-point strips and rapid-annihilation funnel regions could be pressured by several more years of Fermi-LAT data, if understanding of the astrophysical background and/or systematic uncertainties can be improved in parallel.Comment: 33 pages, 12 figures, comments and references added, version to appear in JCA

    Monte Carlo Methods for Estimating Interfacial Free Energies and Line Tensions

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    Excess contributions to the free energy due to interfaces occur for many problems encountered in the statistical physics of condensed matter when coexistence between different phases is possible (e.g. wetting phenomena, nucleation, crystal growth, etc.). This article reviews two methods to estimate both interfacial free energies and line tensions by Monte Carlo simulations of simple models, (e.g. the Ising model, a symmetrical binary Lennard-Jones fluid exhibiting a miscibility gap, and a simple Lennard-Jones fluid). One method is based on thermodynamic integration. This method is useful to study flat and inclined interfaces for Ising lattices, allowing also the estimation of line tensions of three-phase contact lines, when the interfaces meet walls (where "surface fields" may act). A generalization to off-lattice systems is described as well. The second method is based on the sampling of the order parameter distribution of the system throughout the two-phase coexistence region of the model. Both the interface free energies of flat interfaces and of (spherical or cylindrical) droplets (or bubbles) can be estimated, including also systems with walls, where sphere-cap shaped wall-attached droplets occur. The curvature-dependence of the interfacial free energy is discussed, and estimates for the line tensions are compared to results from the thermodynamic integration method. Basic limitations of all these methods are critically discussed, and an outlook on other approaches is given

    Rotating Black Branes in the presence of nonlinear electromagnetic field

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    In this paper, we consider a class of gravity whose action represents itself as a sum of the usual Einstein-Hilbert action with cosmological constant and an U(1)U(1) gauge field for which the action is given by a power of the Maxwell invariant. We present a class of the rotating black branes with Ricci flat horizon and show that the presented solutions may be interpreted as black brane solutions with two event horizons, extreme black hole and naked singularity provided the parameters of the solutions are chosen suitably. We investigate the properties of the solutions and find that for the special values of the nonlinear parameter, the solutions are not asymptotically anti-deSitter. At last, we obtain the conserved quantities of the rotating black branes and find that the nonlinear source effects on the electric field, the behavior of spacetime, type of singularity and other quantities.Comment: 7 pages, 5 figures, to appear in EPJ

    Dynamical stability of infinite homogeneous self-gravitating systems: application of the Nyquist method

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    We complete classical investigations concerning the dynamical stability of an infinite homogeneous gaseous medium described by the Euler-Poisson system or an infinite homogeneous stellar system described by the Vlasov-Poisson system (Jeans problem). To determine the stability of an infinite homogeneous stellar system with respect to a perturbation of wavenumber k, we apply the Nyquist method. We first consider the case of single-humped distributions and show that, for infinite homogeneous systems, the onset of instability is the same in a stellar system and in the corresponding barotropic gas, contrary to the case of inhomogeneous systems. We show that this result is true for any symmetric single-humped velocity distribution, not only for the Maxwellian. If we specialize on isothermal and polytropic distributions, analytical expressions for the growth rate, damping rate and pulsation period of the perturbation can be given. Then, we consider the Vlasov stability of symmetric and asymmetric double-humped distributions (two-stream stellar systems) and determine the stability diagrams depending on the degree of asymmetry. We compare these results with the Euler stability of two self-gravitating gaseous streams. Finally, we determine the corresponding stability diagrams in the case of plasmas and compare the results with self-gravitating systems

    Can forest management based on natural disturbances maintain ecological resilience?

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    Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance
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