IFN-γ and TNF-α synergize to inhibit CTGF expression in human lung endothelial cells.

Connective tissue growth factor (CTGF/CCN2) is an angiogenetic and profibrotic factor, acting downstream of TGF-β, involved in both airway- and vascular remodeling. While the T-helper 1 (Th1) cytokine interferon-gamma (IFN-γ) is well characterized as immune-modulatory and anti-fibrotic cytokine, the role of IFN-γ in lung endothelial cells (LEC) is less defined. Tumour necrosis factor alpha (TNF-α) is another mediator that drives vascular remodeling in inflammation by influencing CTGF expression. In the present study we investigated the influence of IFN-γ and TNF-α on CTGF expression in human LEC (HPMEC-ST1.6R) and the effect of CTGF knock down on human LEC. IFN-γ and TNF-α down-regulated CTGF in human LEC at the promoter-, transcriptional- and translational-level in a dose- and time-dependent manner. The inhibitory effect of IFN-γ on CTGF-expression could be almost completely compensated by the Jak inhibitor AG-490, showing the involvement of the Jak-Stat signaling pathway. Besides the inhibitory effect of IFN-γ and TNF-α alone on CTGF expression and LEC proliferation, these cytokines had an additive inhibitory effect on proliferation as well as on CTGF expression when administered together. To study the functional role of CTGF in LEC, endogenous CTGF expression was down-regulated by a lentiviral system. CTGF silencing in LEC by transduction of CTGF shRNA reduced cell proliferation, but did not influence the anti-proliferative effect of IFN-γ and TNF-α. In conclusion, our data demonstrated that CTGF was negatively regulated by IFN-γ in LEC in a Jak/Stat signaling pathway-dependent manner. In addition, an additive effect of IFN-γ and TNF-α on inhibition of CTGF expression and cell proliferation could be found. The inverse correlation between IFN-γ and CTGF expression in LEC could mean that screwing the Th2 response to a Th1 response with an additional IFN-γ production might be beneficial to avoid airway remodeling in asthma

Особенности налогообложения в розничной торговле

Объектом исследования является: ИП Хорева специализирующееся на розничной торговле изделиями из меха и кожи. Цель работы – анализ деятельности предприятия, определение основных показателей его экономической деятельности, расчет налогов, расчет и анализ налоговой нагрузки предприятия. В процессе исследования проводились: создание теоретической базы для анализа экономической деятельности предприятия, непосредственно анализ экономической деятельности, расчёт и анализ налоговой нагрузки предприятия. В результате исследования выработаны конкретные рекомендации по оптимизации экономической деятельности предприятия.The object of research is: IP Khoreva specializing in the retail sale of fur and leather products. The purpose of the work is the analysis of the enterprise, determining the main indicators of its economic activity, tax calculation, calculation and analysis of the tax burden of the enterprise. In the course of the research, the following was carried out: creation of a theoretical base for analysis of the economic activity of an enterprise, direct analysis of economic activity, calculation and analysis of the tax burden of the enterprise. As a result of the study, specific recommendations were developed to optimize the economic activity of the enterprise

A validation of Amazon Mechanical Turk for the collection of acceptability judgments in linguistic theory

Amazon’s Mechanical Turk (AMT) is a Web application that provides instant access to thousands of potential participants for survey-based psychology experiments, such as the acceptability judgment task used extensively in syntactic theory. Because AMT is a Web-based system, syntacticians may worry that the move out of the experimenter-controlled environment of the laboratory and onto the user-controlled environment of AMT could adversely affect the quality of the judgment data collected. This article reports a quantitative comparison of two identical acceptability judgment experiments, each with 176 participants (352 total): one conducted in the laboratory, and one conducted on AMT. Crucial indicators of data quality—such as participant rejection rates, statistical power, and the shape of the distributions of the judgments for each sentence type—are compared between the two samples. The results suggest that aside from slightly higher participant rejection rates, AMT data are almost indistinguishable from laboratory data

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum