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Brushless Direct Current (BLDC) motors have seen significant improvements across various electrical applications. The growing focus on motor design research highlights the BLDC motor’s superior efficiency compared to traditional motors, which consume more power. BLDC motors are compact, lightweight, energy-efficient, and easy to control, making them ideal for modern applications. This study aims to enhance BLDC motor design and performance by employing the Taguchi method, Response Surface Methodology (RSM), and Finite Element Method (FEM) for multi-stage optimization. A 26-watt BLDC electric fan motor is the reference model for this study. The Taguchi method helps identify optimization points, guiding further enhancements in the second stage. The study proposes a design with improved output power, torque, and efficiency. The final design achieves a 15% higher energy efficiency than the reference model, with a 10 W increase in output power and a 0.032 Nm increase in maximum torque. The FEM analysis using JMAG software v 21.2 validates the proposed design, which shows improved configurations compared to the reference model, demonstrating the efficiency of the optimization techniques for BLDC motor design.

Smoker patients with non-small cell lung cancer (NSCLC) have poorer prognosis and survival than those without smoking history. However, the mechanisms underlying the low response rate of those patients to EGFR tyrosine kinase inhibitors (TKIs) are not well understood. Here we report that exposure to cigarette smoke extract enhances glycolysis and attenuates AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR; this in turn reduces the sensitivity of NSCLC cells with wild-type EGFR (EGFR WT ) to EGFR TKI by repressing expression of liver kinase B1 (LKB1), a master kinase of the AMPK subfamily, via CpG island methylation. In addition, LKB1 expression is correlated positively with sensitivity to TKI in patients with NSCLC. Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFR WT and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFR WT .

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are used to treat BRCA-mutated (BRCAm) cancer patients; however, resistance has been observed. Therefore, biomarkers to indicate PARPi resistance and combination therapy to overcome that are urgently needed. We identified a high prevalence of activated FGF receptor 3 (FGFR3) in BRCAm triple-negative breast cancer (TNBC) cells with intrinsic and acquired PARPi resistance. FGFR3 phosphorylated PARP1 at tyrosine 158 (Y158) to recruit BRG1 and prolong chromatin-loaded MRE11, thus promoting homologous recombination (HR) to enhance PARPi resistance. FGFR inhibition prolonged PARP trapping and synergized with PARPi in vitro and in vivo. High-level PARP1 Y158 phosphorylation (p-Y158) positively correlated with PARPi resistance in TNBC patient-derived xenograft models, and in PARPi-resistant TNBC patient tumors. These findings reveal that PARP1 p-Y158 facilitates BRG1-mediated HR to resolve the PARP-DNA complex, and PARP1 p-Y158 may indicate PARPi resistance that can be relieved by combining FGFR inhibitors (FGFRis) with PARPis. In summary, we show that FGFRi restores PARP trapping and PARPi antitumor efficacy in PARPi-resistant breast cancer by decreasing HR through the PARP1 p-Y158/BRG1/MER11 axis, suggesting that PARP1 p-Y158 is a biomarker for PARPi resistance that can be overcome by combining FGFRis with PARPis.

Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist-induced arachidonic acid (AA) release for prostaglandin (PG) synthesis during inflammation triggered by tumor necrosis factor-α (TNF-α). However, the mechanisms underlying TNF-α-induced cPLA2 expression in human lung epithelial cells (HPAEpiCs) were not completely understood. We demonstrated that TNF-α induced cPLA2 mRNA and protein expression, promoter activity, and PGE2 secretion in HPAEpiCs. These responses induced by TNF-α were inhibited by pretreatment with the inhibitor of MEK1/2 (PD98059), p38 MAPK (SB202190), JNK1/2 (SP600125), or AP-1 (Tanshinone IIA) and transfection with siRNA of TNFR1, p42, p38, JNK2, c-Jun, c-Fos, or ATF2. We showed that TNF-α markedly stimulated p42/p44 MAPK, p38 MAPK, and JNK1/2 phosphorylation which were attenuated by their respective inhibitors. In addition, TNF-α also stimulated c-Jun and ATF2 phosphorylation which were inhibited by pretreatment with SP600125 and SB202190, respectively, but not PD98059. Furthermore, TNF-α-induced cPLA2 promoter activity was abrogated by transfection with the point-mutated AP-1 cPLA2 construct. Finally, we showed that TNF-α time-dependently induced p300/c-Fos/c-Jun/ATF2 complex formation in HPAEpiCs. On the other hand, TNF-α induced in vivo binding of c-Jun, c-Fos, ATF2, and p300 to the cPLA2 promoter in these cells. In an in vivo study, we found that TNF-α induced leukocyte count in BAL fluid of mice and cPLA2 mRNA levels in lung tissues via MAPKs and AP-1. Taken together, these results demonstrated that TNF-α-induced cPLA2 expression was mediated through p38 MAPK- and JNK1/2-dependent p300/c-Fos/c-Jun/ATF2 complex formation in HPAEpiCs.

To find new molecular targets for triple negative breast cancer (TNBC), we analyzed a large-scale drug screening dataset based on breast cancer subtypes. We discovered that BDP-9066, a specific MRCK inhibitor (MRCKi), may be an effective drug against TNBC. After confirming the efficacy and specificity of BDP-9066 against TNBC and , we further analyzed the underlying mechanism of specific activity of BDP-9066 against TNBC. Comparing the transcriptome of BDP-9066-sensitive and -resistant cells, the activation of the focal adhesion and YAP/TAZ pathway were found to play an important role in the sensitive cells. Furthermore, YAP/TAZ is indeed repressed by BDP-9066 in the sensitive cells, and active form of YAP suppresses the effects of BDP-9066. YAP/TAZ expression and activity are high in TNBC, especially the Claudin-low subtype, consistent with the expression of focal adhesion-related genes. Interestingly, NF-κB functions downstream of YAP/TAZ in TNBC cells and is suppressed by BDP-9066. Furthermore, the PI3 kinase pathway adversely affected the effects of BDP-9066 and that alpelisib, a PI3 kinase inhibitor, synergistically increased the effects of BDP-9066, in mutant TNBC cells. Taken together, we have shown for the first time that MRCKi can be new drugs against TNBC, particularly the Claudin-low subtype.

The tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have been widely used for non-small cell lung cancer (NSCLC) patients, but the development of acquired resistance remains a therapeutic hurdle. The reduction of glucose uptake has been implicated in the anti-tumor activity of EGFR TKIs. In this study, the upregulation of the active sodium/glucose co-transporter 1 (SGLT1) was found to confer the development of acquired EGFR TKI resistance and was correlated with the poorer clinical outcome of the NSCLC patients who received EGFR TKI treatment. Blockade of SGLT1 overcame this resistance in vitro and in vivo by reducing glucose uptake in NSCLC cells. Mechanistically, SGLT1 protein was stabilized through the interaction with PKCδ-phosphorylated (Thr678) EGFR in the TKI-resistant cells. Our findings revealed that PKCδ/EGFR axis-dependent SGLT1 upregulation was a critical mechanism underlying the acquired resistance to EGFR TKIs. We suggest co-targeting PKCδ/SGLT1 as a potential strategy to improve the therapeutic efficacy of EGFR TKIs in NSCLC patients.

Commonly, electrical energy is generated by using non-renewable energy such as natural gas, coal, and oil. As electrical energy is a basic asset for the development of a region, its utilization is increasing every year, which causes the existence of non-renewable energy to decrease every year. This issue is becoming a serious concern all over the world, which encourages every country to harness energy from renewable energy. Wind energy is a promising candidate for generating electricity today. In wind turbine generation, a three-phase generator is usually used. Along with the rapid development of power electronic devices and efforts to improve generator performances, the use of a multiphase system is considered important for harnessing energy from the wind more efficiently. In this study, a five-phase system is proposed to upgrade the output power and power density of the most qualified AFPMG in the previous study. The Taguchi optimization method is employed to obtain the lowest total harmonic distortion (THD) of the on-load voltage waveform. In addition to the Taguchi method, an Artificial Neural Network (ANN) is also employed to compare the results from the Taguchi method and the results are proven to have an excellent relationship. The data processed for Taguchi and ANN methods are strongly helped by using the finite element method from the Ansys Maxwell software. The performances of the proposed five-phase axial flux permanent magnet generator (FP-AFPMG) show good improvement, especially in THD, ripple torque, and ripple in the rectified voltage.

This paper is devoted to the analysis and design of high performance permanent-magnet synchronous wind generators (PSWGs). A systematic and sequential methodology for the design of PMSGs is proposed with a high performance wind generator as a design model. Aiming at high induced voltage, low harmonic distortion as well as high generator efficiency, optimal generator parameters such as pole-arc to pole-pitch ratio and stator-slot-shoes dimension, etc. are determined with the proposed technique using Maxwell 2-D, Matlab software and the Taguchi method. The proposed double three-phase and six-phase winding configurations, which consist of six windings in the stator, can provide evenly distributed current for versatile applications regarding the voltage and current demands for practical consideration. Specifically, windings are connected in series to increase the output voltage at low wind speed, and in parallel during high wind speed to generate electricity even when either one winding fails, thereby enhancing the reliability as well. A PMSG is designed and implemented based on the proposed method. When the simulation is performed with a 6 Ω load, the output power for the double three-phase winding and six-phase winding are correspondingly 10.64 and 11.13 kW. In addition, 24 Ω load experiments show that the efficiencies of double three-phase winding and six-phase winding are 96.56% and 98.54%, respectively, verifying the proposed high performance operation.

Although hot-carrier-based photodetection using plasmonic effects has been widely investigated, photodetectors of this type with an external quantum efficiency (EQE) and an active area of mm remain out of reach even in the visible frequencies. In this work, a novel hot-electron-based, non-trench-type photodetector exploiting pure photoexcitation in a thin aluminum (Al) film and leaky plasmonic modes at and between its heterojunctions is proposed, analyzed, and experimentally demonstrated. Combining diffracted-order-resolved analytical analysis and numerical computations unravels the optical absorption mechanism of the innovative design. Leaky surface plasmon resonance (with leakage radiation into the air) produced by a propagating diffracted order and quasibound supermodes (with power leakage via coupled gap plasmon polariton and bound surface plasmon polariton modes) excited by evanescent diffracted orders are shown to significantly contribute to the absorptance in the preferred thin Al film where hot electrons are generated. At 638.9 nm and electric bias −0.9951 V, the measured per-unit-area responsivity, detectivity, and the external quantum efficiency reach 298.1444 μA/mW/mm , 4.3809 × 10 cm Hz /W, and 2.6878%, respectively, from an active area of 4.6457 × 10 mm . The performance is among the best of those previously reported operating at similar wavelengths and biases. The time constant is estimated to be about 1.673 μs from the current-voltage measurements. The physical insight into the innovative, experimentally demonstrated device could lay the groundwork for the practical use of low-voltage, metal-based photodetection.

In this paper, the design and performance analysis of a high-efficiency permanent-magnet synchronous wave generator (PSWG) are presented. A systematic approach for the design of the outer rotor was proposed as a prototype model. The magnetic field, magnetic circuit characteristics, electrical characteristics of the generator, and optimal design parameters such as the pole–arc ratio and shoe outer length were determined using the Taguchi method, finite-element analysis (FEA) software, and rotor skewing techniques. The proposed six series and six parallel-connection winding configurations can provide an evenly distributed current for practical applications. A PSWG was designed and fabricated according to the proposed methodology. According to the experimental results by implementing the optimized design, the efficiencies of the proposed PSWG which used 3.6 Ω load at 300 rpm is 86.32% and the efficiency error between simulation and experiment is less than 1.8%. It verifies the feasibility of the proposed method to PSWG and the structural reliability optimization design.