329 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

    Identifying and understanding cognitive profiles in multiple sclerosis: a role for visuospatial memory functioning

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    BackgroundThe heterogeneous nature of cognitive impairment in people with multiple sclerosis (PwMS) hampers understanding of the underlying mechanisms and developing patient-tailored interventions. We aim to identify and classify cognitive profiles in PwMS, comparing these to cognitive status (preserved versus impaired).MethodsWe included 1213 PwMS (72% female, age 45.4 ± 10.7 years, 83% relapsing–remitting MS). Cognitive test scores were converted to Z-scores compared to healthy controls for the functions: attention, inhibition, information processing speed (IPS), verbal fluency and verbal/visuospatial memory. Concerning cognitive status, impaired cognition (CI) was defined as performing at Z ≤ − 1.5 SD on ≥ 2 functions. Cognitive profiles were constructed using latent profile analysis on all cognitive functions. Cognitive profiles or status was classified using gradient boosting decision trees, providing the importance of each feature (demographics, clinical, cognitive and psychological functioning) for the overall classification.ResultsSix profiles were identified, showing variations in overall performance and specific deficits (attention, inhibition, IPS, verbal fluency, verbal memory and visuospatial memory). Across the profiles, IPS was the most impaired function (%CI most preserved profile, Profile 1 = 22.4%; %CI most impaired profile, Profile 6 = 76.6%). Cognitive impairment varied from 11.8% in Profile 1 to 95.3% in Profile 6. Of all cognitive functions, visuospatial memory was most important in classifying profiles and IPS the least (area under the curve (AUC) = 0.910). For cognitive status, IPS was the most important classifier (AUC = 0.997).ConclusionsThis study demonstrated that cognitive heterogeneity in MS reflects a continuum of cognitive severity, distinguishable by distinct cognitive profiles, primarily explained by variations in visuospatial memory functioning.Health and self-regulatio

    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
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