The mitochondrial pool of Hsp90 and its mitochondrial paralogue, TRAP1, suppresses cell death and reprograms energy metabolism in cancer cells; therefore, Hsp90 and TRAP1 have been suggested as target proteins for anticancer drug development. Here, we report that the actual target protein in cancer cell mitochondria is TRAP1, and current Hsp90 inhibitors cannot effectively inactivate TRAP1 because of their insufficient accumulation in the mitochondria. To develop mitochondrial TRAP1 inhibitors, we determined the crystal structures of human TRAP1 complexed with Hsp90 inhibitors. The isopropyl amine of the Hsp90 inhibitor PU-H71 was replaced with the mitochondria-targeting moiety triphenylphosphonium to produce SMTIN-P01. SMTIN-P01 showed a different mode of action from the nontargeted PU-H71, as well as much improved cytotoxicity to cancer cells. In addition, we determined the structure of a TRAP1-adenylyl-imidodiphosphate (AMP-PNP) complex. On the basis of comparative analysis of TRAP1 structures, we propose a molecular mechanism of ATP hydrolysis that is crucial for chaperone function.
As MISRII/AMHRII is expressed in both granulosa and theca cells, this indicates that MIS/AMH, produced in the granulosa cells, is active in the theca cells as well. MIS/AMH is most likely actively involved not only in the autocrine and endocrine processes but also in the paracrine processes involving theca cells.
Steam Generator (SG) tube, as a barrier isolating the primary coolant system from the secondary side of nuclear power plants (NPP), must maintain the structural integrity for the public safety and their efficient power generation. So, SG tubes are subject to the periodic examination and the repairs if needed so that any defective tubes are not in service. Recently, corrosion related degradations were detected in the tubes of the domestic OPR-1000 NPP, as a form of axially oriented outer diameter stress corrosion cracking (ODSCC). According to the studies on the factors causing the heat fouling as well as developing corrosion cracking, densely scaled deposits on the secondary side of the SG tubes are mainly known to be problematic causing the adverse impacts against the soundness of the SG tubes [1]. Therefore, the processes of various cleaning methods efficiently to dissolve and remove the deposits have been applied as well as it is imperative to maintain the structural integrity of the tubes after exposing to the cleaning agent. So qualification test (QT) should be carried out to assess the perfection of the chemical cleaning and QT is to apply the processes and to do ECT. In this paper, the chemical cleaning processes to dissolve and remove the scaled deposits are introduced and results of ECT on the artificial crack specimens to determine the effectiveness of those processes are represented.
The eddy current testing performance directly affects the results of a steam generator tube integrity assessment because the integrity assessment of defected tubes is conducted based on eddy current testing results. This means that it may not be possible to accurately discriminate between adjacent flaws. This paper presents an investigation on the resolution of rotating pancake coils with multiple cracks and the effects on the structural integrity assessment of steam generator tubes.
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