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A commutation torque ripple suppression strategy for the brushless DC motor (BLDCM) with commutation time is proposed. First, a torque model considering back electromotive force (back‐EMF) variation is presented, and the cause of commutation torque ripple is analysed. The results show that the commutation torque ripple of BLDCM is inevitable even if the non‐commutation current remains steady. On this basis, the influence and quantitative relationships of non‐commutation current and commutation time on commutation torque ripple are studied. Furthermore, two impact factors are proposed to comprehensively consider their effects on commutation torque ripple. The three‐phase windings are modulated in the commutation process at individual duty cycles. The comprehensive optimisation index of commutation torque ripple for different working conditions is obtained by calculating the relative relationship of the impact factors. The optimisation index determines the proper modulation duty cycles. Therefore, the motor parameters and working conditions do not limit the strategy. Finally, the experimental results verify the correctness of the theoretical analysis and the feasibility of the proposed strategy. The proposed strategy can reduce the commutation torque ripple by 16.28% and 21.80% and shorten the commutation time by 50.00% and 36.67% at low speed and high speed, respectively, compared with the conventional strategy. [ABSTRACT FROM AUTHOR]

This study proposes a novel inter‐turn fault diagnosis method for a permanent magnet synchronous machine. Search coils are set on every stator tooth to measure the tooth fluxes. The high‐order harmonics produced by the inverter are adopted to diagnose the inter‐turn fault existence and locate the fault tooth. The fault severity coefficient is proposed on the basis of theoretical analysis and can identify the fault severity. A comparative[AQ ID=Q1] analysis of a traditional method based on co‐simulation shows that the proposed method is sensitive and that the fault severity coefficient is accurate, intuitive and independent of the operating condition of the motor. An experimental platform is set up, and it validates the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Although numerous studies on the impacts of climate change on biodiversity have been published, only a handful are focused on the intraspecific level or consider population‐level models (separate models per population). We endeavored to fill this knowledge gap relative to the Qinghai‐Tibetan plateau (QTP) by combining species distribution modeling (SDMs) with population genetics (i.e., population‐level models) and phylogenetic methods (i.e., phylogenetic tree reconstruction and phylogenetic diversity analyses). We applied our models to 11 endemic and widely distributed herpetofauna species inhabiting high elevations in the QTP. We aimed to determine the influence of environmental heterogeneity on species' responses to climate change, the magnitude of climate‐change impacts on intraspecific diversity, and the relationship between species range loss and intraspecific diversity losses under 2 shared socioeconomic pathways (SSP245 and SSP585) and 3 future periods (2050s, 2070s, and 2090s). The effects of global climatic change were more pronounced at the intraspecific level (22% of haplotypes lost and 36% of populations lost) than the morphospecies level in the SSP585 climate change scenario. Maintenance of genetic diversity was in general determined by a combination of factors including range changes, species genetic structure, and the part of the range predicted to be lost. This is owing to the fact that the loss and survival of populations were observed in species irrespective of the predicted range changes (contraction or expansion). In the southeast (mountainous regions), climate change had less of an effect on range size (>100% in 3 species) than in central and northern QTP plateau regions (range size <100% in all species). This may be attributed to environmental heterogeneity, which provided pockets of suitable climate in the southeast, whereas ecosystems in the north and central regions were homogeneous. Generally, our results imply that mountainous regions with high environmental heterogeneity and high genetic diversity may buffer the adverse impacts of climate change on species distribution and intraspecific diversity. Therefore, genetic structure and characteristics of the ecosystem may be crucial for conservation under climate change. [ABSTRACT FROM AUTHOR]

Aims To determine the induction effect of rifampicin on the activity of 4′-hydroxylase in poor metabolizers (PMs) with m[sub 1] mutation of S-mephenytoin 4′-hydroxylation and the relationship of the effect with gene dose. Methods Seven extensive metabolizers (EMs) of S-mephenytoin 4′-hydroxylation and five PMs with m[sub 1] mutation were chosen to take rifampicin 300 mg day[sup -1] orally for 22 days. Prior to and after rifampicin treatment, each subject was given racemic mephenytoin 100 mg. The 4′-hydroxymephenytoin (4′-OH-MP) excreted in the 0–24 h urine and mephenytoin S/R ratio in the 0–8 h urine were determined by h.p.l.c. and GC, respectively. Results In all EMs, the excretion of 4′-OH-MP in the 0–24 h urine was increased by 146.4±17.9%, 0–8 h urinary mephenytoin S/R ratio was decreased by 77.3±8.8%, the percentage increase in the 0–24 h excretion of 4′-OH-MP in those CYP2C19 homozygous (wt/wt) was greater than that in those heterozygous (wt/m[sub 1] and wt/m[sub 2] ) (203.9±42.5% vs 69.6±4.1%). 0–8 h urinary mephenytoin S/R ratio of those PMs with m[sub 1] mutation was decreased by 9.6%, the amount of 4′-OH-MP excreted in the 0–24 h urine was increased by 80.1±48.0%. Conclusions The activity of 4′-hydroxylase of PMs with m[sub 1] mutation of S-mephenytoin 4′-hydroxylation can be induced by rifampicin and the inducing effect of rifampicin on 4′-hydroxylase is gene dependent. [ABSTRACT FROM AUTHOR]

The composition and structure of the Yarlung Zangbo Suture Zone (YZSZ) provide important constraints on long‐standing disputes about the evolution of the Neo‐Tethys Ocean and continental collision. The Permian tectonic blocks (mainly composed of limestones and volcanic rocks) are widely distributed in the YZSZ. There are still different understandings about the origin of these blocks and their relationship with the evolution of the Neo‐Tethys Ocean. Here, we report the first reliable palaeomagnetic results of the Permian tectonic blocks in the Gyanyima and Mayum areas, the western segment of the YZSZ. Fossil records and our new zircon U–Pb results provide 254–252 Ma and 249 ± 2 Ma age constraints for the strata in the Gyanyima and Mayum sections, respectively. A total of 109 specimens were subjected to stepwise thermal demagnetizations. Among them, 83 specimens yielded interpretable results. After removing a recent geomagnetic field direction at low to intermediate temperature ranges, characteristic remanent magnetization (ChRM) directions can be isolated from the upper Permian–lower Triassic Gyanyima Formation (Fm). Unblocking temperature spectra of the ChRM indicate magnetite and haematite as the main carriers in the basalt and limestone/andesitic‐basalt samples, respectively. The ChRM passed the fold tests and a reversal test at 95% confidence level, indicating that it is most likely a primary remanence. The tilt‐corrected mean direction for 14 sites is D = 18.0°, I = −14.4°, k = 20.5, and α95 = 9.0°, which corresponds to a palaeolatitude of 7.3°S and a palaeopole at 48.3°N, 233.3°E with A95 = 8.1°. Combining the rock assemblage, palaeomagnetic, palaeontological, and geochronologic data, we conclude that these blocks were most likely seamounts formed in the low‐latitude area of the Neo‐Tethys Ocean. The palaeolatitude and origin of these blocks indicate that the evolution of the Neo‐Tethys Ocean was a complex process interspersed with the development of a series of seamounts and microblocks. [ABSTRACT FROM AUTHOR]

The PI3K‐AKT signaling pathway regulates cell survival, proliferation, and migration. An abnormal activation of PI3K plays an important role in cancer development. Here, we identify TRAF6 as a potent E3 ubiquitin ligase for the PI3K catalytic subunit PIK3CA (p110α). TRAF6 interacts with PIK3CA and promotes its nonproteolytic polyubiquitination under serum stimulation. TRAF6 ubiquitinates both individual and regulatory subunit‐bound PIK3CA but does not ubiquitinate the regulatory subunit of PI3K. The examination of TRAF6 mRNA expression revealed its upregulation in multiple human malignancies. We demonstrate that overexpression of TRAF6 greatly enhances PI3K activation, leading to an increase in AKT phosphorylation and cell growth. We conclude that TRAF6 is a novel PIK3CA regulator whose deregulated overexpression represents a mechanism for PI3K overactivation in tumors. [ABSTRACT FROM AUTHOR]

Naturalized plants play pivotal roles in local plant biodiversity and ecological functions; however, the drivers of naturalization remain poorly understood at a fine scale. Thus, understanding the processes of the development and dominance of alien plants in local natural habitats is of paramount importance. In the present study, we report for the first time the naturalization of Cydonia oblonga in China based on community structure and population dynamics at a fine scale. We conducted a comprehensive survey of the species through field community investigations, interviews, and a literature review. Cydonia oblonga is an ancient fruit tree with a long introduction history of over 4500 years worldwide and a cultivation history of over 2500 years in China. We analyzed C. oblonga community structure using the spatiotemporal substitution method and quantitatively analyzed population dynamics using a static life table, survivorship curve, and time series model to explore the naturalization processes. The following results were obtained. (i) The community comprised 31 coexisting vascular plant species (16 woody and 15 herbaceous species) belonging to 28 genera in 20 families. Rosaceae and Asteraceae were the two most dominant families. (ii) All individuals in the shrub layer as well as the C. oblonga population exhibited a roughly inverted J‐shaped basal diameter distribution. A complete age structure was noted, and the survival curve was classified as Deevey type II. According to time series analysis, the population is estimated to increase in the future, specifically of medium and large individuals. (iii) Religious exchange, potent resource competitiveness, and similarity with the native habitat may be the major drivers of the introduction and successful naturalization of C. oblonga. These results suggest that alien species closely related to native ones are more likely to invade, naturalize, and dominate communities in local habitats. [ABSTRACT FROM AUTHOR]

Influenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is high. It is important to develop broad‐spectrum influenza antivirals to be ready for any possible vaccine shortcomings. Anti‐influenza drugs are available but they are far from ideal. Arguably, an ideal antiviral should target conserved viral domains and be virucidal, that is, irreversibly inhibit viral infectivity. Here, a new class of broad‐spectrum anti‐influenza macromolecules is described that meets these criteria and display exceedingly low toxicity. These compounds are based on a cyclodextrin core modified on its primary face with long hydrophobic linkers terminated either in 6'sialyl‐N‐acetyllactosamine (6'SLN) or in 3'SLN. SLN enables nanomolar inhibition of the viruses while the hydrophobic linkers confer irreversibility to the inhibition. The combination of these two properties allows for efficacy in vitro against several human or avian influenza strains, as well as against a 2009 pandemic influenza strain ex vivo. Importantly, it is shown that, in mice, one of the compounds provides therapeutic efficacy when administered 24 h post‐infection allowing 90% survival as opposed to no survival for the placebo and oseltamivir. [ABSTRACT FROM AUTHOR]

Aims The study was designed to investigate whether genetically determined CYP2C19 activity affects the metabolism of fluoxetine in healthy subjects. Methods A single oral dose of fluoxetine (40 mg) was administrated successively to 14 healthy young men with high (extensive metabolizers, n=8) and low (poor metabolizers, n = 6) CYP2C19 activity. Blood samples were collected for 5–7 half-lives and fluoxetine, and norfluoxetine were determined by reversed-phase high performance liquid chromatography. Results Poor metabolizers (PMs) showed a mean 46% increase in fluoxetine peak plasma concentrations (Cmax, P < 0.001), 128% increase in area under the concentration vs time curve (AUC(0,∞), P < 0.001), 113% increase in terminal elimination half-life (t½) (P < 0.001), and 55% decrease in CLo (P < 0.001) compared with extensive metabolizers (EMs). Mean ± (s.d) norfluoxetine AUC(0,192 h) was significantly lower in PMs than that in EMs (1343 ± 277 vs 2935 ± 311, P < 0.001). Mean fluoxetine Cmax and AUC(0,∞) in wild-type homozygotes (CYP2C19*1/CYP2C19*1) were significantly lower than that in PMs (22.4 ± 3.9 vs 36.7 ± 8.9, P < 0.001; 732 ± 42 vs 2152 ± 492, P < 0.001, respectively). Mean oral clearance in individuals with the wild type homozygous genotype was significantly higher than that in heterozygotes and that in PMs (54.7 ± 3.4 vs 36.0 ± 8.7, P < 0.01; 54.7 ± 3.4 vs 20.6 ± 6.2, P < 0.001, respectively). Mean norfluoxetine AUC(0,192 h) in PMs was significantly lower than that in wild type homozygotes (1343 ± 277 vs 3163 ± 121, P < 0.05) and that in heterozygotes (1343 ± 277 vs 2706 ± 273, P < 0.001), respectively. Conclusions The results indicated that CYP2C19 appears to play a major role in the metabolism of fluoxetine, and in particular its N-demethylation among Chinese healthy subjects. [ABSTRACT FROM AUTHOR]

Monilinia fructicola is the most widely distributed species among the Monilinia genus in the world, and causes blossom blight, twig canker, and fruit rot on Rosaceae fruits. To date, studies on genomics and pathogenicity are limited in M. fructicola. In this study, we identified a redox‐related gene, MfOfd1, which was significantly up‐regulated at 1 hr after inoculation of M. fructicola on peach fruits. We used the clustered regulatory inter‐spaced short palindromic repeats (CRISPR)/Cas9 system combined with homologous recombination to determine the function of the MfOfd1 gene. The results showed that the sporulation of knockdown transformants was reduced by 53% to 83%. The knockdown transformants showed increased sensitivity to H2O2 and decreased virulence on peach fruits compared to the wild‐type isolate Bmpc7. It was found that H2O2 could stimulate the expression of MfOfd1 in the wild‐type isolate. The transformants were also more sensitive to exogenous osmotic stress, such as glycerol, d‐sorbitol, and NaCl, and to dicarboximide fungicides (iprodione and dimethachlon). These results indicate that the MfOfd1 gene plays an important role in M. fructicola in sporulation, oxidative response, osmotic stress tolerance, and virulence. [ABSTRACT FROM AUTHOR]

Background and Purpose: Effective anti-respiratory syncytial virus (RSV) agents are still not available for clinical use. Current major targets are virus surface proteins, such as a fusion protein involved in viral entry, but agents effective after RSV infection is established are required. Here we have investigated the effects of late therapeutic intervention with a novel inhaled RSV polymerase inhibitor, PC786, on RSV infection in human airway epithelium.Experimental Approach: Air liquid interface-cultured bronchial or small airway epithelium was infected with RSVA2. PC786 was applied apically or basolaterally once daily following peak virus load on Day 3 post inoculation. Apical wash was collected daily for determination of viral burden by PCR and plaque assay (primary endpoints) and biomarker analyses. The effects were compared with those of ALS-8112, an anti-RSV nucleoside analogue, and GS-5806, a fusion-protein inhibitor, which were treated basolaterally.Key Results: Late intervention with GS-5806 did not show significant anti-viral effects, but PC786 produced potent, concentration-dependent inhibition of viral replication with viral load falling below detectable limits 3 days after treatment commenced in airway epithelium. These effects were superior to those of ALS-8112. PC786 showed inhibitory activities against RSV-induced increases of CCL5, IL-6, double-strand DNA and mucin. The effects of PC786 were also confirmed in small airway epithelium.Conclusion and Implications: Late therapeutic intervention with the RSV polymerase inhibitor, PC786, reduced the viral burden quickly in human airway epithelium. Thus, PC786 demonstrates the potential to be an effective therapeutic agent to treat active RSV infection. [ABSTRACT FROM AUTHOR]

Aims To investigate the distribution of CYP3A activity in the Chinese population, and to test for gender-related differences in CYP3A activity. Methods Using midazolam as a probe drug, CYP3A activity in 202 Chinese healthy subjects (104 men) was measured by plasma 1′-hydroxymidazolam:midazolam (1′-OH-MDZ:MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. The different phases of the menstrual cycle including preovulatory, ovulatory and luteal phases of 66 women phenotyped with midazolam were recorded. The concentrations of 1′-OH-MDZ and MDZ in plasma were measured by HPLC Results A 13-fold variation of CYP3A activity (log1′-OH-MDZ:MDZ: range -0.949–0.203) was shown. The CYP3A activity was normally distributed as indicated by the frequency distribution histogram, the probit plot and the Kolmogorov–Smirnov test (P > 0.05). The CYP3A activity of women was higher than that of men (median: -0.36 vs -0.43, P < 0.05; 95% CI for difference: -0.127, -0.012). There was a significant difference in CYP3A activity between the three phases of the menstrual cycle. The activity was highest in the preovulatory phase and decreased sequentially in the ovulatory and luteal phases (P < 0.05). Conclusions A normal distribution of CYP3A activity was observed in the Chinese population. The CYP3A activity is higher in female subjects than in males. CYP3A activity differed across the phases of the menstrual cycle. [ABSTRACT FROM AUTHOR]

Aims The present study was designed to define the kinetic behaviour of sertraline N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P450 involved in this metabolic pathway. Methods The kinetics of the formation of N-demethylsertraline were determined in human liver microsomes from six genotyped CYP2C19 extensive (EM) and three poor metabolisers (PM). Selective inhibitors of and specific monoclonal antibodies to various cytochrome P450 isoforms were also employed. Results The kinetics of N-demethylsertraline formation in all EM liver microsomes were fitted by a two-enzyme Michaelis-Menten equation, whereas the kinetics in all PM liver microsomes were best described by a single-enzyme Michaelis-Menten equation similar to the low-affinity component found in EM microsomes. Mean apparent K[sub m] values for the high-and low-affinity components were 1.9 and 88 μm and V [sub max] values were 33 and 554 pmol min[sup -1] mg[sup -1] protein, respectively, in the EM liver microsomes. Omeprazole (a CYP2C19 substrate) at high concentrations and sulphaphenazole (a selective inhibitor of CYP2C9) substantially inhibited N-demethylsertraline formation. Of five monoclonal antibodies to various cytochrome P450 forms tested, only anti-CYP2C8/9/19 had any inhibitory effect on this reaction. The inhibition of sertraline N-demethylation by anti-CYP2C8/9/19 was greater in EM livers than in PM livers at both low and high substrate concentrations. However, anti-CYP2C8/9/19 did not abolish the formation of N-demethylsertraline in the microsomes from any of the livers. Conclusions The polymorphic enzyme CYP2C19 catalyses the high-affinity N-demethylation of sertraline, while CYP2C9 is one of the low-affinity components of this metabolic pathway. [ABSTRACT FROM AUTHOR]