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Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (TKIs) have improved chronic myeloid leukemia (CML) patient survival markedly but fail to eradicate quiescent CML leukemia stem cells (LSCs). Thus, strategies targeting LSCs are required to induce long-term remission and achieve cure. Here, we investigated the ability of topoisomerase II (Top II) inhibitor etoposide (Eto) to target CML LSCs. Treatment with Eto combined with IM markedly induced apoptosis in primitive CML CD34 CD38 stem cells resistant to eradication by IM alone, but not in normal hematopoietic stem cells, CML and normal mature CD34 cells, and other leukemia and lymphoma cell lines. The interaction of IM and Eto significantly inhibited phosphorylation of PDK1, AKT, GSK3, S6, and ERK proteins; increased the expression of pro-apoptotic gene Bax; and decreased the expression of anti-apoptotic gene c-Myc in CML CD34 cells. Top II inhibitors treatment represents an attractive approach for targeting LSCs in CML patients undergoing TKIs monotherapy.

This paper investigates the effect of the field winding interturn short-circuit (FWISC) position on the rotor vibration properties in turbo generators. Different from the previous studies which focused on the influence of the short-circuit degree, this work pays much attention to the impact of the short-circuit position on the rotor unbalanced magnetic pull (UMP) properties and vibration characteristics. The theoretical UMP model is firstly deduced based on the analysis of the magnetic flux density (MFD) variation. Then, the finite element analysis (FEA) is performed to calculate the UMP data. Finally, the rotor vibrations are tested on a CS-5 prototype generator which has two poles and a rated capacity of 5 kVA. It is shown that the occurrence of FWISC will greatly increase the UMP as well as the rotor vibration. In addition to the short-circuit degree, the short-circuit position will also affect the UMP and vibration. The nearer the short-circuit position is to the big rotor teeth, the larger the UMP and vibration will be. The proposed study in this paper will be beneficial for the monitoring and diagnosis of FWISC faults.