2,873 research outputs found

    Strongly indefinite functionals and multiple solutions of elliptic systems

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    We study existence and multiplicity of solutions of the elliptic system (GRAPHICS) where Omega subset of R-N; Ngreater than or equal to3, is a smooth bounded domain and His an element ofC(1) ((Omega) over barx R-2, R). We assume that the nonlinear term (GRAPHICS) where p is an element of (1, 2*), 2* := 2N/(N-2), and q is an element of (1,infinity). So some supercritical systems are included. Nontrivial solutions are obtained. When H(x, u, v) is even in (u, v), we show that the system possesses a sequence of solutions associated with a sequence of positive energies (resp. negative energies) going toward infinity (resp. zero) if p>2 (resp. p<2). All results are proved using variational methods. Some new critical point theorems for strongly indefinite functionals are proved.35572973298

    Adherence to the Atrial Fibrillation Better Care (ABC) pathway and the risk of major outcomes in patients with atrial fibrillation:A post-hoc analysis from the prospective GLORIA-AF Registry

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    BackgroundThe 'Atrial fibrillation Better Care' (ABC) pathway has been proposed to streamline a more holistic or integrated care approach to atrial fibrillation (AF) management. We aimed to analyse the impact of adherence to the ABC pathway on the risk of major adverse outcomes in a contemporary prospective global cohort of patients with AF.MethodsPatients enrolled Phase II and III of the GLORIA-AF Registry with complete data on ABC pathway adherence and follow-up were included in this post-hoc analysis between November 2011 and December 2014 for Phase II, and between January 2014 and December 2016 for Phase III. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Multivariable Cox-regression and delay of event (DoE) analyses were used to evaluate the association between adherence to the ABC pathway and the risk of outcomes.FindingsWe included 24,608 patients in this analysis (mean age: 70.2 (10.3) years, 10,938 (44.4%) females). Adherence to the ABC pathway was associated with a significant risk reduction for the primary outcome, with greatest magnitude observed for full ABC pathway adherence (adjusted Hazard Ratio [aHR] 0.54, 95% Confidence Interval [CI]: 0.44-0.67, p InterpretationAdherence to the ABC pathway in patients with AF was associated with a reduced risk of major adverse events, including mortality, thromboembolism and MACE. This underlines the importance of using the ABC pathway in the clinical care of patients with AF.FundingThis study was funded by Boehringer Ingelheim

    Postnatal expression of myostain (MSTN) and myogenin (MYoG) genes in Hu sheep of China

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    The study of candidate genes is an important tool to identify genes associated with economic traits. Skeletal muscle development is an important physiological process in meat animals, and it directly affects meat production. The expression of myostain (MSTN) and myogenin (MYoG) genes in longissimus dorsi, during the early growth stage of Hu sheep, was studied by semi-quantitative Reverse transcription polymerase chain reaction (RT-PCR). The results demonstrate that age and gender were playing a very important role in the expression of sheep muscle. MSTN and MYOG genes showed similar variation pattern for the male and female. The expression level of the MSTN and MYoG genes all showed a positive correlation with live weight, carcass weight and meat percentage, but only showed a significant relationship with meat percentage. MSTN gene showed an extreme significant positive relationship with MYoG.Key words: Sheep, myostain (MSTN), myogenin (MYoG), gene expression, muscle trait

    Alisertib, an Aurora kinase A inhibitor, induces apoptosis and autophagy but inhibits epithelial to mesenchymal transition in human epithelial ovarian cancer cells.

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    Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects, and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear. This study investigated the effects of ALS on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT), and the underlying mechanisms in human epithelial ovarian cancer SKOV3 and OVCAR4 cells. Our docking study showed that ALS, MLN8054, and VX-680 preferentially bound to AURKA over AURKB via hydrogen bond formation, charge interaction, and &pi;-&pi; stacking. ALS had potent growth-inhibitory, proapoptotic, proautophagic, and EMT-inhibitory effects on SKOV3 and OVCAR4 cells. ALS arrested SKOV3 and OVCAR4 cells in G2/M phase and induced mitochondria-mediated apoptosis and autophagy in both SKOV3 and OVCAR4 cell lines in a concentration-dependent manner. ALS suppressed phosphatidylinositol 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways but activated 5\u27-AMP-dependent kinase, as indicated by their altered phosphorylation, contributing to the proautophagic activity of ALS. Modulation of autophagy altered basal and ALS-induced apoptosis in SKOV3 and OVCAR4 cells. Further, ALS suppressed the EMT-like phenotype in both cell lines by restoring the balance between E-cadherin and N-cadherin. ALS downregulated sirtuin 1 and pre-B cell colony enhancing factor (PBEF/visfatin) expression levels and inhibited phosphorylation of AURKA in both cell lines. These findings indicate that ALS blocks the cell cycle by G2/M phase arrest and promotes cellular apoptosis and autophagy, but inhibits EMT via phosphatidylinositol 3-kinase/Akt/mTOR-mediated and sirtuin 1-mediated pathways in human epithelial ovarian cancer cells. Further studies are warranted to validate the efficacy and safety of ALS in the treatment of ovarian cancer
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