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  • 1
    Publication Date: 2011-03-30
    Description: In human disorders, the genotype-phenotype relationships are often complex and influenced by genetic and/or environmental factors. Wilson disease (WD) is a monogenic disorder caused by mutations in the copper-transporting P-type ATPase ATP7B. WD shows significant phenotypic diversity even in patients carrying identical mutations; the basis for such diverse manifestations is unknown. We demonstrate that the 2623A/G polymorphism (producing the Gly875→Arg substitution in the A-domain of ATP7B) drastically alters the intracellular properties of ATP7B, whereas copper reverses the effects. Under basal conditions, the common Gly875 variant of ATP7B is targeted to the trans-Golgi network (TGN) and transports copper into the TGN lumen. In contrast, the Arg875 variant is located in the endoplasmic reticulum (ER) and does not deliver copper to the TGN. Elevated copper corrects the ATP7B-Arg875 phenotype. Addition of only 0.5–5 μM copper triggers the exit of ATP7B-Arg875 from the ER and restores copper delivery to the TGN. Analysis of the recombinant A-domains by NMR suggests that the ER retention of ATP7B-Arg875 is attributable to increased unfolding of the Arg875-containing A-domain. Copper is not required for the folding of ATP7B-Arg875 during biosynthesis, but it stabilizes protein and stimulates its activity. A chemotherapeutical drug, cisplatin, that mimics a copper-bound state of ATP7B also corrects the “disease-like” phenotype of ATP7B-Arg875 and promotes its TGN targeting and transport function. We conclude that in populations harboring the Arg875 polymorphism, the levels of bioavailable copper may play a vital role in the manifestations of WD.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
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    American Institute of Physics (AIP)
    Publication Date: 2015-05-12
    Description: Momentum transport in collisional magnetized plasmas due to gradients in the heat flux, a “heat flux viscosity,” is demonstrated. Even though no net particle flux is associated with a heat flux, in a plasma there can still be momentum transport owing to the velocity dependence of the Coulomb collision frequency, analogous to the thermal force. This heat-flux viscosity may play an important role in numerous plasma environments, in particular, in strongly driven high-energy-density plasma, where strong heat flux can dominate over ordinary plasma flows. The heat flux viscosity can influence the dynamics of the magnetic field in plasmas through the generalized Ohm's law and may therefore play an important role as a dissipation mechanism allowing magnetic field line reconnection. The heat flux viscosity is calculated directly using the finite-difference method of Epperlein and Haines [Phys. Fluids 29 , 1029 (1986)], which is shown to be more accurate than Braginskii's method [S. I. Braginskii, Rev. Plasma Phys. 1 , 205 (1965)], and confirmed with one-dimensional collisional particle-in-cell simulations. The resulting transport coefficients are tabulated for ease of application.
    Print ISSN: 1070-664X
    Electronic ISSN: 1089-7674
    Topics: Physics
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  • 3
    Publication Date: 2015-04-26
    Description: IMI 834 Titanium alloy is a near alpha (hcp) titanium alloy used for high temperature applications with the service temperature up to 600?C. Generally, this alloy is widely used in gas turbine engine applications such as low pressure compressor discs. For these applications, good fatigue and creep properties are required, which have been noticed better in a bimodal microstructure, containing 15-20% volume fraction of primary alpha grains (? p ) and remaining bcc beta (?) grains transformed secondary alpha laths (? s ). The bimodal microstructure is achieved during processing of IMI 834 in the high temperature ?+? region. The major issue of bimodal IMI 834 during utilization is its poor dwell fatigue life time caused by textured macrozones. Textured macrozone is the spatial accumulation of similar oriented grains in the microstructure generated during hot processing in the high temperature ?+? region. Textured macrozone can be mitigated by controlling the hot def...
    Print ISSN: 1757-8981
    Electronic ISSN: 1757-899X
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 4
    Publication Date: 2016-03-25
    Description: We show that a resonant magnetic perturbation applied to the boundary of an ideal plasma screw-pinch equilibrium with nested surfaces can penetrate inside the resonant surface and into the core. The response is significantly amplified with increasing plasma pressure. We present a rigorous verification of nonlinear equilibrium codes against linear theory, showing excellent agreement.
    Print ISSN: 1070-664X
    Electronic ISSN: 1089-7674
    Topics: Physics
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  • 5
    Publication Date: 2019
    Description: Abstract The Magnetospheric Multiscale (MMS) mission has given us unprecedented access to high cadence particle and field data of magnetic reconnection at Earth's magnetopause. MMS first passed very near an X‐line on 16 October 2015, the Burch event, and has since observed multiple X‐line crossings. Subsequent 3D particle‐in‐cell (PIC) modeling efforts of and comparison with the Burch event have revealed a host of novel physical insights concerning magnetic reconnection, turbulence induced particle mixing, and secondary instabilities. In this study, we employ the Gkeyll simulation framework to study the Burch event with different classes of extended, multi‐fluid magnetohydrodynamics (MHD), including models that incorporate important kinetic effects, such as the electron pressure tensor, with physics‐based closure relations designed to capture linear Landau damping. Such fluid modeling approaches are able to capture different levels of kinetic physics in global simulations and are generally less costly than fully kinetic PIC. We focus on the additional physics one can capture with increasing levels of fluid closure refinement via comparison with MMS data and existing PIC simulations. In particular, we find that the ten‐moment model well captures the agyrotropic structure of the pressure tensor in the vicinity of the X‐line and the magnitude of anisotropic electron heating observed in MMS and PIC simulations. However, the ten‐moment model has difficulty resolving the lower hybrid drift instability, which has been observed to plays a fundamental role in heating and mixing electrons in the current layer.
    Print ISSN: 2169-9380
    Electronic ISSN: 2169-9402
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
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    American Institute of Physics (AIP)
    Publication Date: 2015-06-23
    Description: This paper seeks to address a controversy regarding the applicability of the 3D nonlinear extended MHD code M3D [W. Park et al ., Phys. Plasmas 6 , 1796 (1999)] and similar codes to calculations of the electromagnetic interaction of a disrupting tokamak plasma with the surrounding vessel structures. M3D is applied to a simple test problem involving an external kink mode in an ideal cylindrical plasma, used also by the Disruption Simulation Code (DSC) as a model case for illustrating the nature of transient vessel currents during a major disruption. While comparison of the results with those of the DSC is complicated by effects arising from the higher dimensionality and complexity of M3D, we verify that M3D is capable of reproducing both the correct saturation behavior of the free boundary kink and the “Hiro” currents arising when the kink interacts with a conducting tile surface interior to the ideal wall.
    Print ISSN: 1070-664X
    Electronic ISSN: 1089-7674
    Topics: Physics
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  • 7
    Publication Date: 2015-10-17
    Description: Electron acceleration due to the electric field parallel to the background magnetic field during magnetic reconnection with no guide field is investigated by theory and two-dimensional electromagnetic particle-in-cell simulations, and compared with acceleration due to the electric field perpendicular to the magnetic field. The magnitude of the parallel electric potential shows dependence on the ratio of the plasma frequency to the electron cyclotron frequency as ( ω p e /Ω e ) −2 , and on the background plasma density as . In the Earth's magnetotail, the parameter ω p e /Ω e ∼9 and the background (lobe) density can be of the order of 0.01 cm −3 , and it is expected that the parallel electric potential is not large enough to accelerate electrons up to 100 keV. Therefore, we must consider the effect of the perpendicular electric field to account for electron energization in excess of 100 keV in the Earth's magnetotail. Trajectories for high energy electrons are traced in a simulation to demonstrate that acceleration due to the perpendicular electric field in the diffusion region is the dominant acceleration mechanism, rather than acceleration due to the parallel electric fields in the exhaust regions. For energetic electrons accelerated near the X-line due to the perpendicular electric field, pitch angle scattering converts the perpendicular momentum to the parallel momentum. On the other hand, for passing electrons that are mainly accelerated by the parallel electric field, pitch angle scattering converting the parallel momentum to the perpendicular momentum occurs. In this way, particle acceleration and pitch angle scattering will generate heated electrons in the exhaust regions.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 8
    Publication Date: 2016-08-10
    Description: An important problem in plasma physics is the lack of an accurate and complete description of Coulomb collisions in associated fluid models. To shed light on the problem, this Letter introduces an integral identity involving the multivariate Hermite tensor polynomials and presents a method for computing exact expressions for the fluid moments of the nonlinear Landau collision operator. The proposed methodology provides a systematic and rigorous means of extending the validity of fluid models that have an underlying inverse-square force particle dynamics to arbitrary collisionality and flow.
    Print ISSN: 1070-664X
    Electronic ISSN: 1089-7674
    Topics: Physics
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  • 9
    Publication Date: 2015-10-21
    Description: Author(s): J. Squire and A. Bhattacharjee We propose a new mechanism for a turbulent mean-field dynamo in which the magnetic fluctuations resulting from a small-scale dynamo drive the generation of large-scale magnetic fields. This is in stark contrast to the common idea that small-scale magnetic fields should be harmful to large-scale dyna… [Phys. Rev. Lett. 115, 175003] Published Tue Oct 20, 2015
    Keywords: Plasma and Beam Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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  • 10
    Publication Date: 2015-10-22
    Description: Author(s): A. Stanier, W. Daughton, L. Chacón, H. Karimabadi, J. Ng, Y.-M. Huang, A. Hakim, and A. Bhattacharjee To explain many natural magnetized plasma phenomena, it is crucial to understand how rates of collisionless magnetic reconnection scale in large magnetohydrodynamic (MHD) scale systems. Simulations of isolated current sheets conclude such rates are independent of system size and can be reproduced by… [Phys. Rev. Lett. 115, 175004] Published Wed Oct 21, 2015
    Keywords: Plasma and Beam Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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