16,439 research outputs found

    Development of an antibody fragment that stabilizes GPCR/G-protein complexes.

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    Single-particle cryo-electron microscopy (cryo-EM) has recently enabled high-resolution structure determination of numerous biological macromolecular complexes. Despite this progress, the application of high-resolution cryo-EM to G protein coupled receptors (GPCRs) in complex with heterotrimeric G proteins remains challenging, owning to both the relative small size and the limited stability of these assemblies. Here we describe the development of antibody fragments that bind and stabilize GPCR-G protein complexes for the application of high-resolution cryo-EM. One antibody in particular, mAb16, stabilizes GPCR/G-protein complexes by recognizing an interface between Gα and Gβγ subunits in the heterotrimer, and confers resistance to GTPγS-triggered dissociation. The unique recognition mode of this antibody makes it possible to transfer its binding and stabilizing effect to other G-protein subtypes through minimal protein engineering. This antibody fragment is thus a broadly applicable tool for structural studies of GPCR/G-protein complexes

    The conceptualisation and measurement of DSM-5 Internet Gaming Disorder: the development of the IGD-20 Test

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    Background: Over the last decade, there has been growing concern about ‘gaming addiction’ and its widely documented detrimental impacts on a minority of individuals that play excessively. The latest (fifth) edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included nine criteria for the potential diagnosis of Internet Gaming Disorder (IGD) and noted that it was a condition that warranted further empirical study. Aim: The main aim of this study was to develop a valid and reliable standardised psychometrically robust tool in addition to providing empirically supported cut-off points. Methods: A sample of 1003 gamers (85.2% males; mean age 26 years) from 57 different countries were recruited via online gaming forums. Validity was assessed by confirmatory factor analysis (CFA), criterion-related validity, and concurrent validity. Latent profile analysis was also carried to distinguish disordered gamers from non-disordered gamers. Sensitivity and specificity analyses were performed to determine an empirical cut-off for the test. Results: The CFA confirmed the viability of IGD-20 Test with a six-factor structure (salience, mood modification, tolerance, withdrawal, conflict and relapse) for the assessment of IGD according to the nine criteria from DSM-5. The IGD-20 Test proved to be valid and reliable. According to the latent profile analysis, 5.3% of the total participants were classed as disordered gamers. Additionally, an optimal empirical cut-off of 71 points (out of 100) seemed to be adequate according to the sensitivity and specificity analyses carried

    Electric-field-induced alignment of electrically neutral disk-like particles: modelling and calculation

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    This work reveals a torque from electric field to electrically neutral flakes that are suspended in a higher electrical conductive matrix. The torque tends to rotate the particles toward an orientation with its long axis parallel to the electric current flow. The alignment enables the anisotropic properties of tiny particles to integrate together and generate desirable macroscale anisotropic properties. The torque was obtained from thermodynamic calculation of electric current free energy at various microstructure configurations. It is significant even when the electrical potential gradient becomes as low as 100 v/m. The changes of electrical, electroplastic and thermal properties during particles alignment were discussed

    Stochastic Gravity: Theory and Applications

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    Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

    Interaction imaging with amplitude-dependence force spectroscopy

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    Knowledge of surface forces is the key to understanding a large number of processes in fields ranging from physics to material science and biology. The most common method to study surfaces is dynamic atomic force microscopy (AFM). Dynamic AFM has been enormously successful in imaging surface topography, even to atomic resolution, but the force between the AFM tip and the surface remains unknown during imaging. Here, we present a new approach that combines high accuracy force measurements and high resolution scanning. The method, called amplitude-dependence force spectroscopy (ADFS) is based on the amplitude-dependence of the cantilever's response near resonance and allows for separate determination of both conservative and dissipative tip-surface interactions. We use ADFS to quantitatively study and map the nano-mechanical interaction between the AFM tip and heterogeneous polymer surfaces. ADFS is compatible with commercial atomic force microscopes and we anticipate its wide-spread use in taking AFM toward quantitative microscopy

    Quantum fluctuations in high field magnetization of 2D square lattice J1-J2 antiferromagnets

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    The J1-J2 square lattice Heisenberg model with spin S=1/2 has three phases with long-range magnetic order and two unconventionally ordered phases depending on the ratio of exchange constants. It describes a number of recently found layered vanadium oxide compounds. A simple means of investigating the ground state is the study of the magnetization curve and high-field susceptibility. We discuss these quantities by using the spin-wave theory and the exact diagonalization in the whole J1-J2 plane. We compare both results and find good overall agreement in the sectors of the phase diagram with magnetic order. Close to the disordered regions the magnetization curve shows strong deviations from the classical linear behaviour caused by large quantum fluctuations and spin-wave approximation breaks down. On the FM side (J1<0) where one approaches the quantum gapless spin nematic ground state this region is surprisingly large. We find that inclusion of second order spin-wave corrections does not lead to fundamental improvement. Quantum corrections to the tilting angle of the ordered moments are also calculated. They may have both signs, contrary to the always negative first order quantum corrections to the magnetization. Finally we investigate the effect of the interlayer coupling and find that the quasi-2D picture remains valid up to |J_\perp/J1| ~ 0.3.Comment: 13 pages, 6figure

    Rubber Impact on 3D Textile Composites

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    A low velocity impact study of aircraft tire rubber on 3D textile-reinforced composite plates was performed experimentally and numerically. In contrast to regular unidirectional composite laminates, no delaminations occur in such a 3D textile composite. Yarn decohesions, matrix cracks and yarn ruptures have been identified as the major damage mechanisms under impact load. An increase in the number of 3D warp yarns is proposed to improve the impact damage resistance. The characteristic of a rubber impact is the high amount of elastic energy stored in the impactor during impact, which was more than 90% of the initial kinetic energy. This large geometrical deformation of the rubber during impact leads to a less localised loading of the target structure and poses great challenges for the numerical modelling. A hyperelastic Mooney-Rivlin constitutive law was used in Abaqus/Explicit based on a step-by-step validation with static rubber compression tests and low velocity impact tests on aluminium plates. Simulation models of the textile weave were developed on the meso- and macro-scale. The final correlation between impact simulation results on 3D textile-reinforced composite plates and impact test data was promising, highlighting the potential of such numerical simulation tools
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