169 research outputs found

    Diagnostic suite used for magnetohydrodynamics equilibrium reconstruction on the PEGASUS

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    Neurofibromin Deficiency Induces Endothelial Cell Proliferation and Retinal Neovascularization

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    Purpose: Neurofibromatosis type 1 (NF1) is the result of inherited mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin. Eye manifestations are common in NF1 with recent reports describing a vascular dysplasia in the retina and choroid. Common features of NF1 retinopathy include tortuous and dilated feeder vessels that terminate in capillary tufts, increased endothelial permeability, and neovascularization. Given the retinal vascular phenotype observed in persons with NF1, we hypothesize that preserving neurofibromin may be a novel strategy to control pathologic retinal neovascularization. Methods: Nf1 expression in human endothelial cells (EC) was reduced using small hairpin (sh) RNA and EC proliferation, migration, and capacity to form vessel-like networks were assessed in response to VEGF and hypoxia. Wild-type (WT), Nf1 heterozygous (Nf1+/-), and Nf1flox/+;Tie2cre pups were subjected to hyperoxia/hypoxia using the oxygen-induced retinopathy model. Retinas were analyzed quantitatively for extent of retinal vessel dropout, neovascularization, and capillary branching. Results: Neurofibromin expression was suppressed in response to VEGF, which corresponded with activation of Mek-Erk and PI3-K-Akt signaling. Neurofibromin-deficient EC exhibited enhanced proliferation and network formation in response to VEGF and hypoxia via an Akt-dependent mechanism. In response to hyperoxia/hypoxia, Nf1+/- retinas exhibited increased vessel dropout and neovascularization when compared with WT retinas. Neovascularization was similar between Nf1+/- and Nf1flox/+;Tie2cre retinas, but capillary drop out in Nf1flox/+;Tie2cre retinas was significantly reduced when compared with Nf1+/- retinas. Conclusions: These data suggest that neurofibromin expression is essential for controlling endothelial cell proliferation and retinal neovascularization and therapies targeting neurofibromin-deficient EC may be beneficial

    Three-dimensional distortions of the tokamak plasma boundary: boundary displacements in the presence of saturated MHD instabilities

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    The three-dimensional plasma boundary displacement induced by long-lasting core magnetohydrodynamic (MHD) instabilities has been measured in JET, MAST and NSTX. Only saturated instabilities are considered here since transient rapidly growing modes which degrade confinement and act as potential triggers for disruptions bring more fundamental concerns than boundary displacements. The measured displacements are usually small, although in extreme cases in MAST when the rotation braking is strong, a significant global displacement can be observed. The instability most likely to saturate and exist for many energy confinement times whilst distorting the boundary of ITER is the saturated internal kink, or helical core, which can be found in plasmas with a wide region of low magnetic shear such as the hybrid scenario. This mode can lead to non-negligible boundary displacements. Nonetheless, the boundary displacement resultant from core MHD instabilities in ITER is predicted to be less than ±1.5% of the minor radius, well within tolerable limits for heat loads to plasma-facing components
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