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Pathogenesis of chronic myeloid leukemia (CML) has mostly been studied with regard to the oncogenic roleof BCR/ABL fusion; however, recent disclosures have declared that the challenges with the treatment of CML patientswould not be resolved until the role of other aberrancies is ignored. Given the involvement of cyclin-dependent kinases(CDKs) in the pathogenesis of CML, the present study aimed to investigate the effects of a multi-CDK inhibitorAT7519 on BCR/ABL-harboring CML-derived K562 cells. Our results showed that AT7519 effectively reduced thesurvival of K562 and induced its anti-proliferative effect through the induction of G2/M arrest due to elevated p21and p27. The resulting data also revealed that either direct or indirect suppression of c-Myc using specific c-Mycinhibitor 10058-F4 and selective PI3K inhibitor CAL-101 resulted in a superior cytotoxicity, suggesting that theactivation of PI3K pathway could attenuate antileukemic effects of the inhibitor, at least partly, through a c-Mycdependent mechanism. To the best of our knowledge, to date, no study has addressed the effect of autophagy onCML cell response to AT7519, and, herein, we proposed for the first time that the suppression of autophagyboosted AT7519 cytotoxicity against K562. Overall, we suggested that selective CDK inhibitor AT7519 exertedantileukemic effect against CML cells and propose a novel therapeutic application for the inhibitor either as a singleagent or in combination with c-Myc and/or PI3K inhibitors.  相似文献   
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本研究结合两种常见的机制以提高系统吸收移动车辆或设备动能的能力. 该模型由两个独立的机制组成, 即圆管的膨胀和内胎的破碎, 通过内胎的摩擦、塑性变形和失效来耗散能量. 本研究调查24个在恒质量和恒体积两种不同设计控制下的案例以进行比较. 利用有限元模拟方法研究了模型的变形, 提取了耐撞性参数, 以反映机制的效率, 并对三种不同的内胎外形进行了参数化研究. 研究表明, 内环型和六角形管型模型由于经历了折叠、剪切和延性损伤三种不同的能量耗散系统, 吸收了更多的能量.  相似文献   
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The ac electrical data of the ZnO-Bi2O3 varistor system, in the frequency range 5 Hz to 13 MHz, when analyzed in the complex capacitance ( C *) plane, yields a distinct depressed semicircular relaxation having an average time constant on the order of 10−6 s. This trapping is attributed to the possible formation of ionized intrinsic/native defects. The decrease in the depression angle and average relaxation time, monitored as a function of the increasing sintering temperature (≥1100°C), indicated an improvement in the degree of uniformity in the loss-conductance and rapidity of response of the intrinsic trapping. The dependence of the ac parameters related to this trapping response obtained from the C * plane on the sintering temperature has been presented.  相似文献   
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In this paper, a numerical model using three-dimensional finite difference code FLAC3D is proposed for analysing the stability of an oil well drilled in four formations. Normalized Yielded Zone Area (NYZA, i.e., the ratio of surrounding yielded cross-sectional area to initial area of well) has been determined for different mud pressures. In each formation, by interpolating of obtained NYZA equal to one, the optimized mud pressure was determined using MATLAB software. Practical data including geomechanical parameters along with drilling data from one of Iranian oilfields, Mansouri-54 well have been utilized in this analysis. In situ stress was determined using stress polygon method and conducting hydraulic fracturing data in the field. Analytical solution using the Mogi–Coulomb and the Hoek–Brown failure criteria has been carried out and results are compared with the presented model. The results demonstrated that the NYZA and Hoek–Brown criteria might underestimate and overestimate the drilling mud pressure, respectively, and should be used cautiously. In the inclined section of the well, plastic zone showed more extension in the lower part than upper part of the well because of the high stress concentration.  相似文献   
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Thin films of tungsten oxide were prepared by anodic oxidation of 99.999% pure tungsten foils using an aqueous solution containing 0.4 M KNO3 and 0.04 M HNO3 as the electrolyte. Different films show different colours. The current-voltage characteristics are of the log I- V1/2 type. These characteristics can be interpreted in terms of the Poole—Frenkel type of conduction mechanism. The colours may be duo to the incorporation of H+ ions and the formation of HxWO3 during the anodizing process.  相似文献   
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The present study describes the inhibition of aluminium in 1N HNO3 with different concentrations of 1,2,4-triazole precursors ATD, BATD and DBATD using gravimetric method, potentiodynamic polarization studies (Tafel), electrochemical impedance spectroscopy (EIS), adsorption studies, surface morphological studies and quantum chemical calculations at 298 K. Polarization studies clearly showed that ATD, BATD and DBATD act as mixed type inhibitors. As the electron density around the inhibitor molecule increases due to substitution, the inhibition efficiency also increases correspondingly. Quantum chemical approach was used to calculate some electronic properties of the molecule to ascertain the correlation between inhibitive effect and molecular structure of the inhibitor. The corrosion inhibition efficiencies of these molecules and the global chemical reactivity relate to some parameters, such as E HOMO , E LUMO , gap energy (ΔE), electronegativity (χ), global hardness (η) and the fraction of electrons transferred from the inhibitor molecule to the metallic atom (DNDelta emph{N}). In addition, the local reactivity has been analysed through the Fukui function and condensed softness indices. Both the experimental and theoretical studies agree well in this regard and confirm that DBATD is a better inhibitor than BATD and ATD. The adsorption behaviours of molecules on the copper surface have been studied using molecular dynamics method and density functional theory. The order of inhibitory action is DBATD > BATD > ATD.  相似文献   
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Aspects of terrestrial microgrids and ship power systems are examined.The work exposes a variety of technical synergies from these two power systems to effectively advance their technologies.Understanding their overlap allows congruent efforts to target both systems;understanding their differences hinders conflict and redundancy in early-stage design.The paper concludes by highlighting how an understanding of both systems can reduce the investment in research resources.  相似文献   
30.
Given a polynomial P(s) = ansn + an?11Sn?1 + … -+ a1s + a0 which satisfies the Routh-Hurwitz criterion, a procedure is given for finding non-conservative upper bounds on the allowable variations of the coefficients such that the perturbed polynomial maintains the stability property.  相似文献   
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