A83-01 inhibits TGF-β-induced upregulation of Wnt3 and epithelial to mesenchymal transition in HER2-overexpressing breast cancer cells

PurposeThe aim of this study is to investigate the mechanisms of interactions between TGF-β and Wnt/β-catenin pathways that induce and regulate EMT and promote breast cancer cells to become resistant to treatment.MethodsThe effect of TGF-β on Wnt/β-catenin signaling pathway was examined by using a human Wnt/β-catenin-regulated cDNA plate array and western blot analysis. The interaction of Twist at promoter of Wnt3 was examined by chromatin immunoprecipitation (ChIP) assay. Secreted Wnt3 level was determined by ELISA assay.ResultsHER2-overexpressing breast cancer cells treated with TGF-β have a reduced response to trastuzumab and exhibited EMT-like phenotype. The TGF-β-induced EMT in HER2-cells was concordant with upregulation of Wnt3 and β-catenin pathways. The TGF-β-induced induction of Wnt3 during EMT was found to be Smad3-dependent. ChIP analysis identified occupancy of Twist at promoter region of Wnt3. Knock-down of Twist by shRNA confirmed the significance of Twist in response to TGF-β regulating Wnt3 during EMT. Subsequently, TGF-β-induced matrix metalloproteinases, MMP1, MMP7, MMP9, MMP26, Vascular endothelial growth factors (VEGF), and activation of Wnt/β-catenin signaling were repressed by the shRNA treatment. TGF-βR1 ALK5 kinase inhibitor, A83-01 can effectively prevent the TGF-β-induced Twist and Wnt3. Co-treating A83-01 and trastuzumab inhibited TGF-β-induced cell invasion significantly in both trastuzumab responsive and resistant cells.ConclusionsOur data demonstrated an important interdependence between TGF-β and Wnt/β-catenin pathways inducing EMT in HER2-overexpressing breast cancer cells. Twist served as a linkage between the two pathways during TGF-β-induced EMT. A83-01 could inhibit the TGF-β-initiated pathway interactions and enhance HER2-cells response to trastuzumab treatment

A New Hunting Control Method for Permanent Magnet Hysteresis Motors

Hunting is a flutter associated with the synchronous speed that gives rise to the gyro drifting errors and may cause objectionable time-displacement errors in video head wheel drives and other precision scanning systems. In this paper, dynamic characteristics of permanent Magnet hysteresis motors are presented and hunting is explained. New damping techniques have been developed using optimized eigenvalues calculation. They are calculated from LQR optimization method. In this damping method, a distinct reduction in hunting has been archived. Furthermore field oriented control result of motor is presented that have good effect on Hunting. Nearest agreement between simulated and measurement results shows the accuracy of motor model. Comparison between this paper results and other measured damping methods result are shown its success

Using Modular Pole for Multi-Objective Design Optimization of a Linear Permanent Magnet Synchronous Motor by Particle Swarm Optimization (PSO)

In this paper particle swarm optimization (PSO) is used for a design optimization of a linear permanent magnet synchronous motor (LPMSM) considering ultra low thrust force ripples, low magnet consumption, improved efficiency and thrust. The influence of PM material is discussed, too and the modular poles are proposed to achieve the best characteristic. PM dimensions and material, air gap and motor width are chosen as design variables. Finally 2-D finite element analyses validate the optimization results

Multi-Objective Design Optimization of a Linear Brushless Permanent Magnet Motor Using Particle Swarm Optimization (PSO)

In this paper a brushless permanent magnet motor is designed considering minimum thrust ripple and maximum thrust density (the ratio of the thrust to permanent magnet volumes). Particle Swarm Optimization (PSO) is used as optimization method. Finite element analysis (FEA) is carried out base on the optimized and conventional geometric dimensions of the motor. The results of the FEA deal to the significant improvement of the all objective functions

Parameter Identification of a Brushless Resolver Using Charge Response of Stator Current

Because of temperature independence, high resolution and noiseless outputs, brushless resolvers are widely used in high precision control systems. In this paper, at first dynamic performance characteristics of brushless resolver, considering parameters identification are presented. Then a mathematical model based on d-q axis theory is given. This model can be used for studying the dynamic behavior of the resolver and steady state model is obtained by using dynamic model. The main object of this paper is to present an approach to identify electrical and mechanical parameters of a brushless resolver based on DC charge excitation and weight, pulley and belt method, respectively. Finally, the model of resolver based on the obtained parameters is simulated. Experimental results approve the validity of proposed method

Dynamic Performance Prediction of Brushless Resolver

A mathematical model based on d-q axis theory and dynamic performance characteristic of brushless resolvers is discussed in this paper. The impact of rotor eccentricity on the accuracy of position in precise applications is investigated. In particular, the model takes the stator currents of brushless resolver into account. The proposed model is used to compute the dynamic and steady state equivalent circuit of resolvers. Finally, simulation results are presented. The validity and usefulness of the proposed method are thoroughly verified with experiments