3,391 research outputs found

    A corpus-based study of vocabulary distribution in the finance register

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    Session 1: Text typology (E 131)As far as is known to date, no attempts have been made to comprehensively describe the vocabulary in the finance register in terms of its lexical density, range, and frequency by financial sectors, text types, modes of communication, and geographical locations around the world. This corpus-based study aims at investigating vocabulary distribution in the finance register. Authentic texts of the finance register from 20 companies in sectors of banks, financial services, insurance, and real estate (Industry Classification Benchmark, 2011) were …postprin

    Seismic responses of civil structures under magnetorheological-device direct control

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    This paper presents an efficient control strategy for magnetorheological (MR) dampers embedded in building structures to mitigate quake-induced vibrations. In this work, MR dampers are used as semi-active devices, taking the advantages of the fail-safe operation and low power requirement. By using a static hysteresis model for the MR damper, a suitable controller is proposed here for direct control of the supply currents of the MR dampers using feedback linearization. The dampers are configured in a differential mode to counteract the force-offset problem from the use of a single damper. The effectiveness of the proposed technique is verified in simulation by using a ten-storey building model subject to quake-like excitations

    Hemodynamic Measurement Using Four-Dimensional Phase-Contrast MRI: Quantification of Hemodynamic Parameters and Clinical Applications

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    Recent improvements have been made to the use of time-resolved, three-dimensional phase-contrast (PC) magnetic resonance imaging (MRI), which is also named four-dimensional (4D) PC-MRI or 4D flow MRI, in the investigation of spatial and temporal variations in hemodynamic features in cardiovascular blood flow. The present article reviews the principle and analytical procedures of 4D PC-MRI. Various fluid dynamic biomarkers for possible clinical usage are also described, including wall shear stress, turbulent kinetic energy, and relative pressure. Lastly, this article provides an overview of the clinical applications of 4D PC-MRI in various cardiovascular regions.113Ysciescopuskc

    Polymorphisms of CR1, CLU and PICALM confer susceptibility of Alzheimer's disease in a southern Chinese population

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    In this case-controlled study, we tested susceptible genetic variants for Alzheimer's disease (AD) in CR1, CLU and PICALM from genome-wide association studies (GWAS) in a southern Chinese population. Eight hundred twelve participants consisting of 462 late-onset Alzheimer's disease (LOAD) patients and 350 nondemented control subjects were recruited. We found by multivariate logistic regression analysis, that single nucleotide polymorphisms (SNPs) in CR1 (rs6656401 adjusted allelic p = 0.035; adjusted genotypic p = 0.043) and CLU (rs2279590 adjusted allelic p = 0.035; adjusted genotypic p = 0.006; rs11136000 adjusted allelic p = 0.038; adjusted genotypic p = 0.009) were significantly different between LOAD patients and nondemented controls. For PICALM, LOAD association was found only in the APOE ε4 (-) subgroup (rs3851179 adjusted allelic p = 0.028; adjusted genotypic p = 0.013). Our findings showed evidence of CR1, CLU, and PICALM and LOAD susceptibility in an independent southern Chinese population, which provides additional evidence for LOAD association apart from prior genome-wide association studies in Caucasian populations. © 2012 Elsevier Inc.postprin

    Macroscopic nucleation phenomena in continuum media with long-range interactions

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    Nucleation, commonly associated with discontinuous transformations between metastable and stable phases, is crucial in fields as diverse as atmospheric science and nanoscale electronics. Traditionally, it is considered a microscopic process (at most nano-meter), implying the formation of a microscopic nucleus of the stable phase. Here we show for the first time, that considering long-range interactions mediated by elastic distortions, nucleation can be a macroscopic process, with the size of the critical nucleus proportional to the total system size. This provides a new concept of "macroscopic barrier-crossing nucleation". We demonstrate the effect in molecular dynamics simulations of a model spin-crossover system with two molecular states of different sizes, causing elastic distortions.Comment: 12 pages, 4 figures. Supplementary information accompanies this paper at http://www.nature.com/scientificreport

    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 π-π 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

    Cost effectiveness of stapled haemorrhoidopexy and traditional excisional surgery for the treatment of haemorrhoidal disease

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    Objective Our objective was to compare the cost effectiveness of stapled haemorrhoidopexy (SH) and traditional haemorrhoidectomy (TH) in the treatment of grade II–IV haemorrhoidal disease from the perspective of the UK national health service. Methods An economic evaluation was conducted alongside an open, two-arm, parallel-group, pragmatic, multicentre, randomised controlled trial conducted in several hospitals in the UK. Patients were randomised into either SH or TH surgery between January 2011 and August 2014 and were followed up for 24 months. Intervention and subsequent resource use data were collected using case review forms and questionnaires. Benefits were collected using the EQ-5D-3L (EuroQoL—five dimensions—three levels) instrument. The primary economic outcome was incremental cost measured in pounds (£), year 2016 values, relative to the incremental benefit, which was estimated using quality-adjusted life-years (QALYs). Cost and benefits accrued in the second year were discounted at 3.5%. The base-case analysis was based on imputed data. Uncertainty was explored using univariate sensitivity analyses. Results Participants (n = 777) were randomised to SH (n = 389) or TH (n = 388). The mean cost of SH was £337 (95% confidence interval [CI] 251–423) higher than that of TH and the mean QALYs were −0.070 (95% CI −0.127 to −0.011) lower than for TH. The base-case cost-utility analysis indicated that SH has zero probability of being cost effective at both the £20,000 and the £30,000 threshold. Results from the sensitivity analyses were similar to those from the base-case analysis. Conclusions The evidence suggests that, on average, the total mean costs over the 24-month follow-up period were significantly higher for the SH arm than for the TH arm. The QALYs were also, on average, significantly lower for the SH arm. These results were supported by the sensitivity analyses. Therefore, in terms of cost effectiveness, TH is a superior surgical treatment for the management of grade II–IV haemorrhoids when compared with SH

    Interactions in vivo between the Vif protein of HIV-1 and the precursor (Pr55GAG) of the virion nucleocapsid proteins

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    The abnormality of viral core structure seen in vif-defective HIV-1 grown in PBMCs has suggested a role for Vif in viral morphogenesis. Using an in vivo mammalian two-hybrid assay, the interaction between Vif and the precursor (Pr55GAG) of the virion nucleocapsid proteins has been analysed. This revealed the amino-terminal (aa 1–22) and central (aa 70–100) regions of Vif to be essential for its interaction with Pr55GAG, but deletion of the carboxy-terminal (aa 158–192) region of the protein had only a minor effect on its interaction. Initial deletion studies carried out on Pr55GAG showed that a 35-amino-acid region of the protein bridging the MA(p17)–CA(p24) junction was essential for its ability to interact with Vif. Site-directed mutagenesis of a conserved tryptophan (Trp21) near the amino terminus of Vif showed it to be important for the interaction with Pr55GAG. By contrast, mutagenesis of the highly conserved YLAL residues forming part of the BC-box motif, shown to be important in Vif promoting degradation of APOBEC3G/3F, had little or no effect on the Vif–Pr55GAG interaction

    Safety of a new extensively hydrolysed formula in children with cow's milk protein allergy: a double blind crossover study

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    BACKGROUND: Formulae for infants with cow's milk protein allergy (CMA) should be based on extensively hydrolysed protein. 'Extensively' however is not strictly defined. Differences in molecular weight and peptide chain length may affect its clinical outcome. We studied the safety of a new extensively hydrolysed casein based formula (Frisolac Allergycare(®): FAC) for children with IgE mediated CMA. METHODS: Thirty children, aged 1.5 – 14.8 years old (median 4.9 years) with persistent CMA were enrolled in this double-blind reference product (Nutramigen(®): NUT) controlled crossover study. All had positive skin prick tests (SPT) and IgE mediated allergy, showing immediate reactions after ingestion of small amounts of milk. Twenty-five children also had positive radio allergen sorbent tests (RAST) to cow's milk. Formulae provided consisted of 80% elementary formula in combination with 20% reference or test product. Crossover periods lasted for two weeks. From both products molecular weight (MALDI-TOF method and HPLC) and peptide chain length distribution (adapted Edman degradation) were determined. RESULTS: Maximum molecular weights of NUT and FAC are 2.1 and 2.56 kDa, respectively. The contribution of free amino acids and small peptides <0.5 kDa is 46% for FAC and 53% for NUT. About 50% of the protein fraction of both products consists of peptides longer than four amino acids. Three children did not complete the study. The other children all tolerated FAC very well; no adverse reactions were reported. CONCLUSIONS: The new extensively hydrolysed casein-based formula (FAC) can safely be used in children with IgE mediated cow's milk allergy

    Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

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    Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation
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