Objective: To explore the role of Na þ /H þ exchanger regulatory factor 1 (NHERF1) in autosomal-dominant polycystic kidney disease (ADPKD). Methods: NHERF1 and b-catenin protein were detected by immunohistochemistry and Western blotting of kidney tissue samples from patients with ADPKD and controls (normal kidney tissue [>5 cm from the foci] collected from patients undergoing unilateral nephrectomy for kidney cancer). NHERF1 and b-catenin protein and mRNA were quantified by Western blot and real-time fluorescent quantitative polymerase chain reaction, respectively, in kidney tissue samples from Han:SPRD (þ/þ) and (cy/þ) rats. The effects of human recombinant NHERF1 on proliferation and cell cycle of ADPKD cyst-lining epithelial cells (WT9-12) were evaluated by MTT assay and flow cytometry, respectively. Results: Levels of NHERF1 protein and mRNA were significantly lower, and b-catenin levels significantly higher, in patients with ADPKD and Han:SPRD (cy/þ) rats, compared with control subjects and (þ/þ) rats, respectively. Exogenous recombinant NHERF1 significantly inhibited proliferation of WT9-12 cells and increased the proportion of cells in G 0 /G 1 phase. Conclusions: ADPKD is associated with a decrease in NHERF1 protein and mRNA levels. Supplementing exogenous NHERF1 inhibited the proliferation of WT9-12 cells.
To reduce the manufacturing cost of integrated circuits, the size of the silicon wafer has become larger, with the diameter increasing from 200 to 450 mm. The large diameter silicon wafer poses challenges to the manufacturing process, as its surface profile is more difficult to control and the planarization process is harder to optimize in mass production. Based on different types of contact, gap adjustment and convex pad dressing methods were proposed in this paper to control the pressure distribution on the wafer, which further influenced the wafer profile. Pressure distributions with different gap values and different pad profiles were explained with contact mechanics and verified by simulations. The simulation results show that a negative gap value and a convex pad profile contribute to the improvement of the pressure uniformity on the wafer. Both methods were then applied in the double-sided planarization (DSP) process of 300 mm silicon wafers. The results from the test run of the DSP process show that wafer flatness is improved with a negative gap value. This indicates that gap adjustment is an effective approach for wafer profile control. In the subsequent mass production of the DSP process, silicon wafers with a global flatness of 120 nm and a site flatness of 21.7 nm were obtained.
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