Differential deposition of fibronectin by asthmatic bronchial epithelial cells

© 2015 the American Physiological Society. Altered ECM protein deposition is a feature in asthmatic airways. Fibronectin (Fn), an ECM protein produced by human bronchial epithelial cells (HBECs), is increased in asthmatic airways. This study investigated the regulation of Fn production in asthmatic or nonasthmatic HBECs and whether Fn modulated HBEC proliferation and inflammatory mediator secretion. The signaling pathways underlying transforming growth factor (TGF)-β1-regulated Fn production were examined using specific inhibitors for ERK, JNK, p38 MAPK, phosphatidylinositol 3 kinase, and activin-like kinase 5 (ALK5). Asthmatic HBECs deposited higher levels of Fn in the ECM than nonasthmatic cells under basal conditions, whereas cells from the two groups had similar levels of Fn mRNA and soluble Fn. TGF-β1 increased mRNA levels and ECM and soluble forms of Fn but decreased cell proliferation in both cells. The rate of increase in Fn mRNA was higher in nonasthmatic cells. However, the excessive amounts of ECM Fn deposited by asthmatic cells after TGF-β1 stimulation persisted compared with nonasthmatic cells. Inhibition of ALK5 completely prevented TGF- β1-induced Fn deposition. Importantly, ECM Fn increased HBEC proliferation and IL-6 release, decreased PGE2 secretion, but had no effect on VEGF release. Soluble Fn had no effect on cell proliferation and inflammatory mediator release. Asthmatic HBECs are intrinsically primed to produce more ECM Fn, which when deposited into the ECM, is capable of driving remodeling and inflammation. The increased airway Fn may be one of the key driving factors in the persistence of asthma and represents a novel, therapeutic target

Estimating time-varying effects for overdispersed recurrent events data with treatment switching

In the analysis of multivariate event times, frailty models assuming time-independent regression coefficients are often considered, mainly due to their mathematical convenience. In practice, regression coefficients are often time dependent and the temporal effects are of clinical interest. Motivated by a phase III clinical trial in multiple sclerosis, we develop a semiparametric frailty modelling approach to estimate time-varying effects for overdispersed recurrent events data with treatment switching. The proposed model incorporates the treatment switching time in the time-varying coefficients. Theoretical properties of the proposed model are established and an efficient expectation-maximization algorithm is derived to obtain the maximum likelihood estimates. Simulation studies evaluate the numerical performance of the proposed model under various temporal treatment effect curves. The ideas in this paper can also be used for time-varying coefficient frailty models without treatment switching as well as for alternative models when the proportional hazard assumption is violated. A multiple sclerosis dataset is analysed to illustrate our methodology

Free nitrous acid-based nitrifying sludge treatment in a two-sludge system enhances nutrient removal from low-carbon wastewater

© 2017 Elsevier Ltd A new method to enhance nutrient removal from low carbon-wastewater was developed. The method consists of a two-sludge system (i.e., an anaerobic-anoxic-oxic reactor coupled to a nitrifying reactor (N-SBR)) and a nitrifying-sludge treatment unit using free nitrous acid (FNA). Initially, 65.1 ± 2.9% in total nitrogen removal and 69.6 ± 3.4% in phosphate removal were obtained without nitrite accumulation. When 1/16 of the nitrifying sludge was daily treated with FNA at 1.1 mg N/L for 24 h, ∼28.5% of nitrite was accumulated in the N-SBR, and total nitrogen and phosphate removal increased to 72.4 ± 3.2% and 76.7 ± 2.9%, respectively. About 67.8% of nitrite was accumulated at 1.9 mg N/L FNA, resulting in 82.9 ± 3.8% in total nitrogen removal and 87.9 ± 3.5% in phosphate removal. Fluorescence in-situ hybridization analysis showed that FNA treatment reduced the abundance of nitrite oxidizing bacteria (NOB), especially that of Nitrospira sp

Effects of rapamycin on cultured hepatocyte proliferation and gene expression

Rapamycin, a potent immunosuppressive drug that disrupts normal signal‐transduction processes, inhibited hepatocyte proliferation without evidence of inherent cytotoxicity in rat hepatocytes cultured in conventional medium or in a medium enriched with epidermal growth factor. The antiproliferative effect was dose dependent, uninfluenced by the concentration of epidermal growth factor in the medium and long lasting after a brief exposure. The effect of rapamycin was unaltered by the concomitant presence of FK 506 in the medium, suggesting that different binding affinities of these two drugs or even a separate rapamycin binding site may exist. Hepatocytes harvested 12 and 24 hr after partial hepatectomy were progressively less responsive to the antiproliferative effect of rapamycin. The gene expression of transforming growth factor‐β was reduced under in vivo rapamycin treatment, but at the same time the gene expression of albumin and glyceraldehyde‐3‐phosphate dehydrogenase was unchanged or increased. The experiments confirm that rapamycin has inherent growth‐control qualities, and they strengthen the hypothesis that the recently defined immunophilin network is central to many aspects of cellular growth control. (HEPATOLOGY 1992;15:871–877). Copyright © 1992 American Association for the Study of Liver Disease

Lanthanum distribution and dielectric properties of intergrowth Bi₅ˍₓLaₓTiNbWO₁₅ ferroelectrics

Bi₅ˍₓLaₓTiNbWO₁₅ (x=0–1.50)ceramics prepared by conventional solid-state reaction were studied using x-ray diffraction(XRD),dielectric spectroscopy and Raman scattering techniques. The XRD analysis implied that single-phase intergrowth bismuth layered perovskite structure was obtained for all the samples and when x=0.75, the Bi³⁺ in (Bi₂O₂)²⁺ layer begins to be substituted by La³⁺. The dielectric spectra showed that, when Bi³⁺ in (Bi₂O₂)²⁺ is substituted, the Curie temperature becomes diffusive and the dielectricpermittivity at room temperature is increased in a wide frequency range. Especially when x=1.50, the dielectricpermittivity reaches its maximum of 270, nearly two times larger than that of the La3+ undoped sample. The Raman scattering experiments evidenced further that Bi³⁺ in (Bi₂O₂)²⁺ is substituted when x⩾0.75 and revealed the orthorhombic distortion of the octahedra is responsible for the increase of the dielectricpermittivity at x⩾1.25.This work was supported by the Ministry of Science and Technology of China through 973-Project under Grant No. 2002CB613307

Analytic study of Gauss-Bonnet holographic superconductors in Born-Infeld electrodynamics

Using Sturm-Liouville (SL) eigenvalue problem, we investigate several properties of holographic s-wave superconductors in Gauss-Bonnet gravity with Born-Infeld electrodynamics in the probe limit. Our analytic scheme has been found to be in good agreement with the numerical results. From our analysis it is quite evident that the scalar hair formation at low temperatures is indeed affected by both the Gauss-Bonnet as well as the Born-Infeld coupling parameters. We also compute the critical exponent associated with the condensation near the critical temperature. The value of the critical exponent thus obtained indeed suggests a universal mean field behavior.Comment: 9 pages, Latex, minor modifications, To appear in JHE