Erythropoietin (EPO) plays an important role in erythropoiesis by its action in blocking apoptosis of progenitor cells and protects both photoreceptors and retinal ganglion cells from induced or inherited degeneration. A modified form of EPO, EPO-R76E has attenuated erythropoietic activity but is effective in inhibiting apoptosis, oxidative stress, and inflammation in several models of retinal degeneration. In this study, we used recombinant Adeno Associated Virus (AAV) to provide long-term sustained delivery of EPO-R76E and demonstrated its effects in a mouse model of dry-AMD in which retinal degeneration is induced by oxidative stress in the retinal pigment epithelial (RPE) cells. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific EPO expression. Retinal function was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress, which is implicated as a potential cause of Age-Related Macular Degeneration.
The displacement of monopile supporting offshore wind turbines needs to be strictly controlled, and the influence of local scour can not be ignored. Using p–y curves to simulate the pile–soil interaction and the finite difference method to calculate iteratively, a numerical frame for analysis of lateral loaded pile was discussed and then verified. On the basis of the field data from Dafeng Offshore Wind Farm in Jiangsu Province, the local scour characteristics of large diameter monopile were concluded, and a new method of considering scour effect applicable to large diameter monopile was put forward. The results show that, for scour of large diameter monopiles, there was no obvious scour pit, but local erosion and deposition. Under the test conditions, the displacement errors between the proposed and traditional method were 46.4%. By the proposed method, the p–y curves of monopile considering the scour effect were obtained through ABAQUS, and the deformation of large diameter monopile under scour was analyzed by the proposed frame. The results show that, with the increase of scour depth, the horizontal displacement of the pile head increases nonlinearly, the depth of rotation point moves downward, and both of the changes are related to the load level. Under the test conditions, the horizontal displacement of the pile head after scour could reach 1.4~3.6 times of that before scour. Finally, for different pile parameters, the pile head displacement was compared, and further, the susceptibility to scour was quantified by a proposed concept of scour sensitivity. The analysis indicates that increasing pile length is a more reasonable way than pile diameter and wall thickness to limit the scour effect on the displacement of large diameter pile.
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