Improved Current-Sharing Imbalance Control Model Based on Magnetic Ferrite Inductance and a Gate Drive Circuit

The dynamic and static imbalance of parallel current sharing has held the concern of researchers in view of the variation in multiple parasitic parameters on high-frequency parallel switching mode power supply (SMPS). The joint simulations and suppression experiments on the parallel current-sharing imbalance of various parasitic parameters are investigated on the improved dual-pulse detection circuit platform to determine the method of detecting the parallel current-sharing imbalance ratio using the sum of the differential magnetic flux. An improved model of current-sharing imbalance control is presented consisting of magnetic ferrite inductance and a gate drive circuit. The main concerns are the suppression performance of drain, gate, and source parasitic inductance, gate–source capacitance, driving time and voltage, gate resistance, and delayed forward/reverse driving signals on the ratio of parallel current-sharing imbalance, respectively. The improved model effectively reduces the parallel current-sharing imbalance ratio by more than 5% and 2–4.2%, compared with using a gate drive circuit alone and using magnetic ferrite inductance solely

The Herb-Drug Interaction of Clopidogrel and Xuesaitong Dispersible Tablet by Modulation of the Pharmacodynamics and Liver Carboxylesterase 1A Metabolism

Objective. Clopidogrel and Xuesaitong dispersible tablet (XST) have been clinically proven to be effective for treating cardiocerebrovascular disease. The present study was to investigate the herb-drug interaction of Clopidogrel and XST by modulation of the pharmacodynamics and liver Carboxylesterase 1A(CES1A) metabolism. Methods. 30 male SD rats were randomly divided into a control group (equal volumes of saline, 6 rats for mRNA analysis), a clopidogrel group (clopidogrel with dose 30 mg/kg), and a combination group (clopidogrel and XST, with dose 30 and 50 mg/kg respectively, each group continuous administration once daily for 30 days). The clopidogrel and combination group comprised 12 rats, with 6 designated for mRNA analysis and 6 for the pharmacokinetic study. The 2-bromo-3’-methoxyacetophenone- (MPB-) derivatized clopidogrel active thiol metabolite (CAMD) was measured by UHPLC-MS/MS for pharmacokinetics (n=6). The expression of CES1A mRNA was examined with real-time RT-PCR (n=6). Molecular simulation was used to investigate the inhibition effect of XST on the CES1A protein. The CAMD pharmacodynamics and CES1A metabolism were investigated to evaluated the herb-drug interaction. Results. Clopidogrel and XST coadministration appreciably increased the Cmax, AUC, and MRT of CAMD. However, the expression of CES1A mRNA was decreased accordingly. It also indicated that the bioactive components in XST had good interaction with the CES1A metabolism target by molecular simulation. The animal study indicated that clopidogrel and XST coadministration produced significant herb-drug interactions at active CAMD pharmacokinetic and CES1A metabolic enzyme aspect. Conclusion. 30-days dose of coadministration altered hepatic CES1A protein and resulted in reduced plasma levels of active CAMD. both the decreased CES1A mRNA expression and the inhibition on the protein were due to the combination of XST, which accordingly upregulated the pharmacokinetics of plasma active CAMD

Reversible metallization and carrier transport behavior of In2S3 under high pressure

The electrical transport properties of indium trisulfide (In2S3) under high pressure were investigated using the in situ Hall-effect and temperature dependent resistivity measurements. Resistivity, Hall coefficient, carrier concentration, and mobility were obtained at pressures up to 41.6 GPa. Pressure induced metallization of In2S3 occurred at approximately 6.8 GPa. This was determined by measuring temperature dependent resistivity. The metallization transition was also determined from compression electrical parameters, and the decompression electrical parameters indicated that the metallization was a reversible transition. The main cause of the sharp decline in resistivity was the increase in carrier concentration at 6.8 GPa. Superconductivity was not observed at the pressures (up to 32.5 GPa) and temperatures (100–300 K) used in the experiment

Ab Initio Studies on the Clathrate Hydrates of Some Nitrogen- and Sulfur-Containing Gases

Ab initio calculations are performed to investigate the host–guest interactions and multiple occupancies of some sulfur- (H₂S, CS₂) and nitrogen-containing (N₂, NO, and NH₃) molecules in dodecahedral, tetrakaidecahedral, and hexakaidecahedral water cages in this work. Five functionals in the framework of density functional theory are compared, and the M06-2X method appears to be the best to predict the binding energies as well as the geometries. Results show that N₂ and NO molecules are more stable in the 5¹²6⁴ cage, while NH₃ and H₂S prefer to stabilize in the 5¹²6² cage. This suggests that the sI hydrates of NH₃ and H₂S exhibit higher stability than the sII structures and that sII NO hydrate is more stable than sI NO hydrate. N₂ is found to be more stable in type II structure with single occupancy and to form type I hydrate with multiple occupancy, which is consistent with the experimental observations. As to the guest molecule CS₂, it may undergo severe structural deformation in the 5¹² and 5¹²6² cage. For multiple occupancies, the 5¹², 5¹²6², and 5¹²6⁴ water cages can trap up to two N₂ molecules, and the 5¹²6⁴ water cage can accommodate two H₂S molecules. This work is expected to provide new insight into the formation mechanism of clathrate hydrates for atmospherically important molecules

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk