Condition monitoring of insulated gate bipolar transistor (IGBT) modules is an effective way to improve the transient performance and reliability of modular multilevel converters (MMC). This article ...proposes a novel bond wire failure monitoring method for the multichip IGBT modules in the MMC half-bridge submodule (SM) structure. The collector voltage undershoot V CA(np) of the complementary IGBT switch is measured during the turn- off switching transition of the controlled IGBT switch. V CA(np) is sensitive to the induced voltage over the stray inductance of the IGBT bond wires and provides high sensitivity as a health indicator. The non-intrusive measurement technique is demonstrated using a half-bridge circuit during the turn- off transition of the controlled IGBT, while its complementary switch (i.e., the device under test) is in the off state. Theoretical analysis and experimental results show that the parametric drift due to wire bonding failures can be effectively monitored with high specific relative sensitivity and granularity. To ensure its effectiveness in practical applications, the influence of load current, SM capacitor voltage, and junction temperature is discussed. In addition, a readout circuit is designed featuring the integrated desaturation detection and voltage peak detection, which offers both the short-term overcurrent fault protection and long-term bond wire aging monitoring functions.
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•The coercivity as high as 738.1 ± 81.0 Oe is achieved in Alnico ribbons.•Some rod-like second phases are precipitated at grain boundaries.•The α1 and α2 distribute alternately like a ...maze.•The microstructure and domain structure model is built up.•The pinning mechanism contributes to the excellent hard magnetic properties.
Al-Ni-Co alloy has been widely applied in various industrial fields due to its excellent thermal and magnetic stability. In this paper, new Al-Ni-Co ribbons are prepared by simple processes combining melt-spinning with annealing, and their phase transition, microstructure and magnetic properties are studied. The results show that after as-spun ribbons are annealed, the grain size of ribbons increases from 1.1 ± 0.3 μm to 4.8 ± 0.8 μm, but still much smaller than that of the bulk Al-Ni-Co alloy manufactured by traditional technologies. In addition, some rod-like Al70Co20Ni10-type, Al9Co2-type and Fe2Nb-type phases are precipitated at grain boundaries; simultaneously, the distinct spinodal decomposition microstructure with periodic ingredient variation is thoroughly formed in all grains by the reaction of α → α1 + α2. Furthermore, the α1 and α2 distribute alternately like a maze, the Fe-Co-rich α1 phase holds 35.9–47.3 vol%, while the Al-Ni-rich α2 phase occupies the rest. Finally, the coercivity of annealed ribbons can reach to 485.3 ± 76.6 Oe. If the annealed ribbons are further aged at 560 °C, their Hc even increases to 738.1 ± 81.0 Oe. The coercivity mechanism is discussed by the combination of microstructure and domain structure.
Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase ...Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation.
High-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo.
We identified a small molecular inhibitor, "MNPC," that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo.
Thus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.
Objective
We aimed to investigate the association between the 5A/6A promoter polymorphism in the matrix metalloproteinase 3 (MMP3) gene and in-stent restenosis (ISR) in a regional Chinese population.
...Methods
A total of 818 patients who underwent primary implantation of drug-eluting stents were enrolled and received a 6-month follow-up angiography and DNA genotyping of the 5A/6A polymorphism.
Results
ISR was found in 36.9% of all patients (302 ISR vs. 516 no ISR). The genotype proportion of 6A6A was significantly increased in ISRs (74.2% ISR vs. 66.8% no ISR), whereas the allele frequency of 5A was significantly decreased in ISR patients (25.8%) compared with controls who did not undergo ISR (33.1%).
Conclusions
Our data indicate that the MMP3 6A6A genotype is a genetic susceptibility factor for ISR after coronary stent placement, but the 5A allele can lower the risk for patients within 6 months after stenting. Therefore, genotyping 5A/6A in the MMP3 promoter is suggested for patients who undergo coronary stent implantation.
Blood stasis syndromes (BSSs) are closely related to the occurrence and development of tumors, although the mechanism is still unclear. This study was aimed at exploring the effect and mechanism ...underlying different BSSs on tumor growth and metastasis. We established four BSS mouse models bred with breast cancer: qi deficiency and blood stasis (QDBS), cold coagulation blood stasis (CCBS), heat toxin and blood stasis (HTBS), and qi stagnation and blood stasis (QSBS). The results showed that microcirculation in the lower limb, abdominal wall, and tumor in situ decreased by varying degrees in the BSS groups. In addition, BSS promoted tumor growth and lung metastasis. The ratio of regulatory T cells in the tumor microenvironment was downregulated. Moreover, hypoxia-inducible factor 1-α, Wnt1, β-catenin, vascular endothelial growth factor, and Cyclin D1 levels increased in the tumors of BSS mice. In conclusion, BSS not only promoted the formation of a hypoxic and immunosuppressive microenvironment but also promoted the neovascularization.
Cervical spondylotic myelopathy (CSM) is the main cause of adult spinal cord dysfunction, mostly appearing in middle-aged and elderly patients. Currently, the diagnosis of this condition depends ...mainly on the available imaging tools such as X-ray, computed tomography and magnetic resonance imaging (MRI), of which MRI is the gold standard for clinical diagnosis. However, MRI data cannot clearly demonstrate the dynamic characteristics of CSM, and the overall process is far from cost-efficient. Therefore, this study proposes a new method using multiple gait parameters and shallow classifiers to dynamically detect the occurrence of CSM. In the present study, 45 patients with CSM and 45 age-matched asymptomatic healthy controls (HCs) were recruited, and a three-dimensional (3D) motion capture system was utilized to capture the locomotion data. Furthermore, 63 spatiotemporal, kinematic, and nonlinear parameters were extracted, including lower limb joint angles in the sagittal, coronal, and transverse planes. Then, the Shapley Additive exPlanations (SHAP) value was utilized for feature selection and reduction of the dimensionality of features, and five traditional shallow classifiers, including support vector machine (SVM), logistic regression (LR), k-nearest neighbor (KNN), decision tree (DT), and random forest (RF), were used to classify gait patterns between CSM patients and HCs. On the basis of the 10-fold cross-validation method, the highest average accuracy was achieved by SVM (95.56%). Our results demonstrated that the proposed method could effectively detect CSM and thus serve as an automated auxiliary tool for the clinical diagnosis of CSM.
To characterize the current state of emergency medicine (EM) and the requirements for advancing EM clinical practice, education and research in China.
An anonymous electronic survey was conducted by ...Chinese Society of Emergency Medicine during September to October 2021. The survey contained 30 questions divided into 2 sections: the current state of EM development and the requirements for EM growth.
722 hospitals were included, of 487 were Level III and 235 were Level II hospitals. We found that after 40 years of development, EM had established a mature disciplinary system and refined sub-specialties including critical care, cardiopulmonary resuscitation, toxicology, disaster and emergency rescue. In Level III hospitals, 70.8% of EDs were standardized training centers for EM residents, but master's degree program, Doctor Degree program and post-doctoral degree program was approved in only 37.8%, 8.4% and 2.9% of EDs respectively and postgraduate curriculum was available in 1/4 of EDs. Only 8% have national or provincial key laboratories. In addition to advance clinical practice, there was also a high demand to improve teaching and research capacities, mainly focusing on literature review, research design and delivery, paper writing, residency training.
EM has built a mature discipline system and refined sub-specialties in China. Teaching and research developed parallel with clinical practice. However, there was still a lack of EM master's and doctoral programs and research capacities need to be improved. More outstanding clinical and academic training should be provided to promote the rapid growth of EM in China.
Versicolols A and B (
1
and
2
), two rare prenylated isocoumarin derivatives, along with five known isocoumarins (
3
–
7
) were isolated from the fermentation products of an endophytic fungus
...Aspergillus versicolor
. Their structures were elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR techniques. Compounds
1
and
2
were evaluated for their cytotoxicity against five human tumor cell lines. The results showed that compounds
1
exhibited weak cytotoxicity against A549 and MCF7 cells with IC
50
values of 9.4 and 8.8 μm, and compound
2
exhibited weak cytotoxicity against SHSY5Y and MCF7 cells with IC
50
values of 8.2 and 6.8 μm, respectively.
Timely recognition of the characteristic electrocardiographic pattern of de Winter syndrome is important for providing immediate reperfusion therapy for acute anterior myocardial infarction. In this ...case, an electrocardiogram showed 1- to 3-mm upsloping ST-segment depression at the J point in leads V1 to V6, with loss of R wave progression in leads V1 to V4. Urgent angiography showed occlusion of the proximal left anterior descending coronary artery and 70% stenosis in the ostial first diagonal branch (Medina type 1.1.1.). For this bifurcation lesion, we successfully performed a modified jailed-balloon technique to protect the side branch during percutaneous coronary intervention stenting. Thereafter, thrombolysis in myocardial infarction 3 flow was restored in both branches. This modified jailed-balloon technique is safe and effective in stent placement for de Winter syndrome without any loss of side branches.