321 research outputs found

    Role of electrostatic interactions in amyloid beta-protein (Abeta) oligomer formation: A discrete molecular dynamics study

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    Pathological folding and oligomer formation of the amyloid beta-protein (Abeta) are widely perceived as central to Alzheimer's disease (AD). Experimental approaches to study Abeta self-assembly are problematic, because most relevant aggregates are quasi-stable and inhomogeneous. We apply a discrete molecular dynamics (DMD) approach combined with a four-bead protein model to study oligomer formation of the amyloid beta-protein (Abeta). We address the differences between the two most common Abeta alloforms, Abeta40 and Abeta42, which oligomerize differently in vitro. We study how the presence of electrostatic interactions (EIs) between pairs of charged amino acids affects Abeta40 and Abeta42 oligomer formation. Our results indicate that EIs promote formation of larger oligomers in both Abeta40 and Abeta42. The Abeta40 size distribution remains unimodal, whereas the Abeta42 distribution is trimodal, as observed experimentally. Abeta42 folded structure is characterized by a turn in the C-terminus that is not present in Abeta40. We show that the same C-terminal region is also responsible for the strongest intermolecular contacts in Abeta42 pentamers and larger oligomers. Our results suggest that this C-terminal region plays a key role in the formation of Abeta42 oligomers and the relative importance of this region increases in the presence of EIs. These results suggest that inhibitors targeting the C-terminal region of Abeta42 oligomers may be able to prevent oligomer formation or structurally modify the assemblies to reduce their toxicity.Comment: Accepted for publication at Biophysical Journa

    On the solutions of the Schrodinger equation with some molecular potentials: wave function ansatz

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    Making an ansatz to the wave function, the exact solutions of the DD% -dimensional radial Schrodinger equation with some molecular potentials like pseudoharmonic and modified Kratzer potentials are obtained. The restriction on the parameters of the given potential, δ\delta and η\eta are also given, where η\eta depends on a linear combination of the angular momentum quantum number \ell and the spatial dimensions DD and δ\delta is a parameter in the ansatz to the wave function. On inserting D=3, we find that the bound state eigensolutions recover their standard analytical forms in literature.Comment: 14 page

    Evolution of deformation and recrystallization textures in high-purity Ni and the Ni-5 at. pct W alloy

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    An attempt has been made to study the evolution of texture in high-purity Ni and Ni-5 at. pct W alloy prepared by the powder metallurgy route followed by heavy cold rolling (∼95 pct deformation) and recrystallization. The deformation textures of the two materials are of typical pure metal or Cu-type texture. Cube-oriented ({001} {100}) regions are present in the deformed state as long thin bands, elongated in the rolling direction (RD). These bands are characterized by a high orientation gradient inside, which is a result of the rotation of the cube-oriented cells around the RD toward the RD-rotated cube ({013} {100}). Low-temperature annealing produces a weak cube texture along with the {013} {100} component, with the latter being much stronger in high-purity Ni than in the Ni-W alloy. At higher temperatures, the cube texture is strengthened considerably in the Ni-W alloy; however, the cube volume fraction in high-purity Ni is significantly lower because of the retention of the {013} {100} component. The difference in the relative strengths of the cube, and the {013} {100} components in the two materials is evident from the beginning of recrystallization in which more {013} {100} -oriented grains than near cube grains form in high-purity Ni. The preferential nucleation of the near cube and the {013} {100} grains in these materials seems to be a result of the high orientation gradients associated with the cube bands that offer a favorable environment for early nucleation

    Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

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    An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic epep scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil

    A Search for Selectrons and Squarks at HERA

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    Data from electron-proton collisions at a center-of-mass energy of 300 GeV are used for a search for selectrons and squarks within the framework of the minimal supersymmetric model. The decays of selectrons and squarks into the lightest supersymmetric particle lead to final states with an electron and hadrons accompanied by large missing energy and transverse momentum. No signal is found and new bounds on the existence of these particles are derived. At 95% confidence level the excluded region extends to 65 GeV for selectron and squark masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure

    Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

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    Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25610-8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genomewide significant association

    Coherent π0 photoproduction on the deuteron up to 4 GeV

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    The differential cross section for 2H(γ,d)π0 has been measured at deuteron center-of-mass angles of 90° and 136°. This work reports the first data for this reaction above a photon energy of 1 GeV, and permits a test of the apparent constituent counting rule and reduced nuclear amplitude behavior as observed in elastic ed scattering. Measurements were performed up to a photon energy of 4.0 GeV, and are in good agreement with previous lower energy measurements. Overall, the data are inconsistent with both constituent-counting rule and reduced nuclear amplitude predictions
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