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Background : Autophagy describes the protective mechanism cells use to keep their interior “clean” and function optimal. Chronic obstructive pulmonary disease (COPD) is a progressive and life-threatening condition caused mainly by cigarette smoking. The role of autophagy in COPD remains controversial due to a lack of adequate measurements. Aim and objectives : We hypothesize that cigarette smoke exposure can impair autophagy in an in vitro model that mimics COPD. Methods : BEAS2B, a human lung epithelial cell line, were treated with cigarette smoke extracts (CSE) for 24 hours, media was replaced and the cells were incubated for another 24 hours. The formation of autophagosomes (AP) was assessed by the conversion of LC3B-I to LCE3B-II using Western blot and fluorescent microscopy. The flux of autophagy was investigated by measuring LC3B-II by CSE in the presence and absence of lysosomal inhibitor ammonium chloride and by the turnover of autophagy substrate protein p62. Autophagy initiation was measured by looking at phosphorylation of AMPK by Western blot. Lysosomal proteins LAMP1 and LAMP2 and the endosomal marker Rab7 were measured by Western blot. Results : CSE concentration-dependently increased the formation of autophagosomes as shown by increased LC3B-II and AP. Only high concentration of CSE (40%) impaired the flux of autophagy as shown by accumulation of p62. CSE (40%) decreased AMPK activity (>50%, p 75%) and LAMP1 protein levels but not Rab7. Conclusions : High levels of CSE can impair the autophagic flux in a bronchial epithelial cell line by possibly reducing AMPK activity and LAMP proteins. We propose that defective autophagy could play an important role in COPD pathogenesis.
Abstract In this project, we focus on the analysis of infrared observations of the clumps defined with the Galactic Census of High- and Medium-mass Protostars (ChaMP) (Barnes et al. 2011). We derive line of sight infrared extinction values, star counts and protostar candidates around the molecular gas emission obtained with the Mopra telescope. Then, we examine the correlation between radio and infrared properties of the clumps. For this stage of the project, we use the Vela-Carina and 2MASS catalogs to obtain a preliminary understanding of the final results. For the later stages, we will extract infrared photometry from our deep AAT near-IR and Spitzer 3.6 and 4.5 μm images. With the final deep photometry results, we will compile the properties of individual clusters.
Letters1 March 1994Special Problems in Treating TuberculosisPeter Barnes, MDPeter Barnes, MDUniversity of Southern California School of Medicine; Los Angeles, CA 90033Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-5-199403010-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Drs. Salomon, Perlman, and Goldstein present their experience with ofloxacin, ethambutol, and an aminoglycoside in HIV-infected patients with tuberculosis who developed hepatotoxicity while receiving standard antituberculous therapy. My limited experience with this combination therapy in patients with tuberculosis and without HIV infection also suggests that this regimen is adequate to keep the disease under control until the patient can tolerate more standard agents. We agree that additional evaluation of the microbiologic efficacy of this combination is needed.I disagree with Dr. Johnson that corticosteroids should be used liberally in patients with tuberculous pericarditis because of methodologic concerns in ...References1. Strang JI, Gibson DG, Mitchison DA, Girling DJ, Kakaza HH, Allen BW, et al. Controlled clinical trial of complete open surgical drainage and of prednisolone in treatment of tuberculous pericardial effusion in Transkei. Lancet. 1988; 2:759-64. Google Scholar2. Strang JI, Gibson DG, Nunn AJ, Kakaza HH, Girling DJ, Fox W. Controlled trial of prednisone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei. Lancet. 1987; 2:1418-22. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Southern California School of Medicine; Los Angeles, CA 90033 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1994Volume 120, Issue 5Page: 440-441KeywordsConfidence intervalsDeath ratesHIV infectionsTuberculosis ePublished: 15 August 2000 Issue Published: 1 March 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Under significant seismic loading conditions, the response of concentrically braced frames largely depends on the behaviour of the diagonal braces, which represent the key energy dissipating zones. Although the hysteretic response of steel braces under cyclic axial loading has been examined in previous studies, there is a need for further assessments that focus on quantifying failure. This paper describes the development of detailed finite-element models of hollow sections subjected to cyclic axial loading. The effects of initial imperfections and cyclic hardening are taken into consideration and the models are validated against data from 19 tests. A method to predict the fracture life of bracing members under cyclic loading is also described. Using the numerical models, parametric studies are undertaken to assess the influence of global and local slendernesses on the performance of the braces – both are found to affect the occurrence and severity of local buckling under cyclic loading, which causes high localised strains at the corner areas of sections, leading to fatigue fracture. A predictive equation addressing the coexisting influence of global slenderness and local slenderness on displacement ductility is presented. The observations in the current study are compared with conclusions from other experimental programmes, and the discrepancy between the findings is discussed.
We present $^{12}$CO, $^{13}$CO, and C$^{18}$O data as the next major release for the CHaMP project, an unbiased sample of Galactic molecular clouds in $l$ = 280$^{\circ}$-300$^{\circ}$. From a radiative transfer analysis, we self-consistently compute 3D cubes of optical depth, excitation temperature, and column density for $\sim$300 massive clumps, and update the $I_{\rm CO}$-dependent CO$\rightarrow$H$_2$ conversion law of Barnes et al (2015). For $N$ $\propto$ $I^p$, we find $p$ = 1.92$\pm$0.05 for the velocity-resolved conversion law aggregated over all clumps. A practical, integrated conversion law is $N_{\rm CO}$ = (4.0$\pm$0.3)$\times$10$^{19}$m$^{-2}$ $I_{\rm CO}^{1.27\pm0.02}$, confirming an overall 2$\times$ higher total molecular mass for Milky Way clouds, compared to the standard $X$ factor. We use these laws to compare the kinematics of clump interiors with their foreground $^{12}$CO envelopes, and find evidence that most clumps are not dynamically uniform: irregular portions seem to be either slowly accreting onto the interiors, or dispersing from them. We compute the spatially-resolved mass accretion/dispersal rate across all clumps, and map the local flow timescale. While these flows are not clearly correlated with clump structures, the inferred accretion rate is a statistically strong function of the local mass surface density $\Sigma$, suggesting near-exponential growth or loss of mass over effective timescales $\sim$30-50 Myr. At high enough $\Sigma$, accretion dominates, suggesting gravity plays an important role in both processes. If confirmed by numerical simulations, this sedimentation picture would support arguments for long clump lifetimes mediated by pressure confinement, with a terminal crescendo of star formation, suggesting a resolution to the 40-yr-old puzzle of the dynamical state of molecular clouds and their low star formation efficiency.
Elliptical hollow sections have been recently added to the family of hot-finished tubular sections, featuring square, rectangular and circular hollow sections. Their usage has attracted considerable interest from industry, and significant recent research towards the development of comprehensive structural design rules has been carried out. Investigations have been performed at both cross-section and member levels and in a range of structural configurations. On the basis of full-scale tests, non-linear numerical simulations and experience gained from studies on other tubular sections, design rules for elliptical hollow sections have been developed. This paper describes the background to and validation of these rules, which include, at cross-section level, a set of slenderness parameters and classification limits for compression and bending, shear resistance formualtions and an interaction curve for combined shear and bending. At member level, column buckling curves have been proposed in harmony with those for structural steel circular hollow sections.