Chandra X-Ray Spectroscopy Of The Very Early O Supergiant HD 93129A: Constraints On Wind Shocks And The Mass-Loss Rate

We present an analysis of both the resolved X-ray emission-line profiles and the broad-band X-ray spectrum of the O-2 If* star HD 93129A, measured with the Chandra High Energy Transmission Grating Spectrometer ( HETGS). This star is among the earliest and most massive stars in the Galaxy, and provides a test of the embedded wind-shock scenario in a very dense and powerful wind. A major new result is that continuum absorption by the dense wind is the primary cause of the hardness of the observed X-ray spectrum, while intrinsically hard emission from colliding wind shocks contributes less than 10 per cent of the X-ray flux. We find results consistent with the predictions of numerical simulations of the line-driving instability, including line broadening indicating an onset radius of X-ray emission of several tenths of R-*. Helium-like forbidden-to-intercombination line ratios are consistent with this onset radius, and inconsistent with being formed in a wind-collision interface with the star\u27s closest visual companion at a distance of 100 au. The broad-band X-ray spectrum is fitted with a dominant emission temperature of just kT = 0.6 keV along with significant wind absorption. The broad-band wind absorption and the line profiles provide two independent measurements of the wind mass-loss rate:. M = 5.2(-1.5)(+1.8) x 10(-6) and 6.8(-2.2)(+2.8) x 10(-6) M-circle dot yr(-1), respectively. This is the first consistent modelling of the X-ray line-profile shapes and broad-band X-ray spectral energy distribution in a massive star, and represents a reduction of a factor of 3-4 compared to the standard H alpha mass-loss rate that assumes a smooth wind

Enhanced inflammatory responses to toll-like receptor 2/4 stimulation in type 1 diabetic coronary artery endothelial cells: the effect of insulin

<p>Abstract</p> <p>Background</p> <p>Endothelial inflammatory responses mediated by Toll-like receptors (TLRs), particularly TLR2 and TLR4, play an important role in atherogenesis. While Type 1 diabetes (T1D) promotes the development and progression of atherosclerosis, the effect of T1D on TLR2/4-mediated inflammatory responses in coronary artery endothelial cells (CAECs) remains unclear.</p> <p>Methods</p> <p>We tested the hypothesis that diabetic CAECs have enhanced inflammatory responses to TLR2/4 stimulation. Non-diabetic and diabetic CAECs were treated with TLR2 agonist peptidoglycan and TLR4 agonist lipopolysaccharide. The expression of ICAM-1, IL-6 and IL-8 were analyzed by real-time PCR, immunoblotting and ELISA, and NF-κB activation by immunoblotting and immunostaining. In additional experiments, insulin was added before TLR stimulation to determine whether insulin deficiency alone is responsible for the alteration of TLR2/4-mediated inflammatory responses.</p> <p>Results</p> <p>Stimulation of TLR2 or TLR4 induced NF-κB activation, and the expression of ICAM-1, IL-6 and IL-8. Interestingly, the expression of inflammatory mediators was significantly enhanced in diabetic cells. The enhanced inflammatory responses correlated with augmented NF-κB activation in the absence of a change in TLR2 or TLR4 protein levels. Further, pretreatment of diabetic cells with insulin failed to suppress the enhanced inflammatory responses.</p> <p>Conclusions</p> <p>Diabetic CAECs have enhanced inflammatory responses to stimulation of TLR2 or TLR4, and insulin alone is insufficient to correct the hyper-inflammatory responses. The mechanism underlying the enhanced inflammatory responses appears to be augmentation of pro-inflammatory signaling, rather than up-regulation of levels of TLR2 and TLR4. These findings suggest that diabetic CAECs adopt a hyper-inflammatory phenotype and that this endothelial phenotypic change may predispose coronary artery to atherogenesis.</p

Group IIa secretory phospholipase expression correlates with group IIa secretory phospholipase inhibition–mediated cell death in K-ras mutant lung cancer cells

ObjectiveThere are currently no targeted therapies against lung tumors with oncogenic K-ras mutations that are found in 25% to -40% of lung cancers and are characterized by their resistance to epidermal growth factor receptor inhibitors. The isozyme group IIa secretory phospholipase A2 (sPLA2IIa) is a potential biomarker and regulator of lung cancer cell invasion; however, the relationship between K-ras mutations and sPLA2IIa has yet to be investigated. We hypothesize that sPLA2IIa modulates lung cancer cell growth in K-ras mutant cells and that sPLA2IIa expression in human lung tumors is increased in K-ras mutant tumors.MethodsBaseline sPLA2IIa expression in K-ras mutant lung cancer cell lines (A549, SW1573, H358, H2009) was assessed. Cells were treated with a specific sPLA2IIa inhibitor and evaluated for apoptosis and cell viability. Nuclear factor kappa-b (NF-κB) and extracellular signal-regulated kinase 1/2 activity were detected by Western blot. Human tumor samples were evaluated for sPLA2IIa mRNA expression by quantitative reverse-transcription polymerase chain reaction.ResultsCytotoxicity of sPLA2IIa inhibition correlates with sPLA2IIa expression. Apoptosis in response to sPLA2 inhibition parallels attenuation in NF-κB activity. In addition, sPLA2IIa expression in human tumors correlates with squamous cell pathology and increasing stage of K-ras mutant lung tumors.ConclusionsBaseline sPLA2IIa expression predicts response to sPLA2IIa inhibition in some K-ras mutant lung cancer cells. This finding is independent of p53 mutation status. Furthermore, squamous tumors and advanced-stage K-ras mutant tumors express more sPLA2IIa. These data support a role for sPLA2IIa as a potential global therapeutic target in the treatment of lung cancer

Effective control of pulmonary vascular resistance with inhaled nitric oxide after cardiac operation

AbstractIncreased pulmonary vascular resistance may greatly complicate the perioperative management of cardiac surgical patients. Inhaled nitric oxide may be a promising new therapy to selectively lower pulmonary vascular resistance. The purpose of this study was to examine the effects of inhaled nitric oxide on pulmonary and systemic hemodynamics in cardiac surgical patients. Twenty patients (age 57 ± 6 years) were studied in the operating room after weaning from cardiopulmonary bypass. Mean pulmonary artery pressure, pulmonary vascular resistance, systemic vascular resistance, and mean aortic pressure were determined at four points of data collection: before nitric oxide, with 20 ppm nitric oxide, with 40 ppm nitric oxide, and after nitric oxide. Statistical analysis was by analysis of variance; significance was accepted for p < 0.05. Inhaled nitric oxide produced selective pulmonary vasorelaxation. Pulmonary vascular resistance was lowered from 343 ± 30 before nitric oxide to 233 ± 25 dynes · sec -1 · cm -5 with 20 ppm nitric oxide. Pulmonary vascular resistance was not further lowered by 40 ppm nitric oxide ( p < 0.05). Mean pulmonary arterial pressure was 29 ± 1 mm Hg before nitric oxide and was lowered to 22 ± 1 mm Hg by 20 ppm nitric oxide and 21 ± 1 mm Hg by 40 ppm nitric oxide ( p < 0.05). Both pulmonary vascular resistance and mean pulmonary arterial pressure returned to baseline after withdrawal of inhaled nitric oxide. Inhaled nitric oxide produced no changes in either systemic vascular resistance or mean aortic pressure. We conclude that nitric oxide may be used as an effective pulmonary vasodilator after cardiac operations. It may be particularly valuable for selectively lowering right ventricular afterload in patients with right ventricular dysfunction. (J THORAC CARDIOVASC SURG 1996;111:753-63

New observations of NGC 1624-2 reveal a complex magnetospheric structure and underlying surface magnetic geometry

NGC 1624-2 is the most strongly magnetized O-type star known. Previous spectroscopic observations of this object in the ultraviolet provided evidence that it hosts a large and dense circumstellar magnetosphere. Follow-up observations obtained with the \textit{Hubble Space Telescope} not only confirm that previous inference, but also suggest that NGC 1624-2's magnetosphere has a complex structure. Furthermore, an expanded spectropolarimetric time series shows a potential departure from a dipolar magnetic field geometry, which could mean that the strongest field detected at the surface of an O-type star is also topologically complex. This result raises important questions regarding the origin and evolution of magnetic fields in massive stars.Comment: 12 pages, 3 figures, accepted for publication by MNRAS (2020 December 1

Ultraviolet Line Profiles of Slowly Rotating Massive Star Winds Using the "Analytic Dynamical Magnetosphere" Formalism

Recent large-scale spectropolarimetric surveys have established that a small but significant percentage of massive stars host stable, surface dipolar magnetic fields with strengths on the order of kG. These fields channel the dense, radiatively driven stellar wind into circumstellar magnetospheres, whose density and velocity structure can be probed using ultraviolet (UV) spectroscopy of wind-sensitive resonance lines. Coupled with appropriate magnetosphere models, UV spectroscopy provides a valuable way to investigate the wind-field interaction, and can yield quantitative estimates of the wind parameters of magnetic massive stars. We report a systematic investigation of the formation of UV resonance lines in slowly rotating magnetic massive stars with dynamical magnetospheres. We pair the Analytic Dynamical Magnetosphere (ADM) formalism with a simplified radiative transfer technique to produce synthetic UV line profiles. Using a grid of models, we examine the effect of magnetosphere size, the line strength parameter, and the cooling parameter on the structure and modulation of the line profile. We find that magnetic massive stars uniquely exhibit redshifted absorption at most viewing angles and magnetosphere sizes, and that significant changes to the shape and variation of the line profile with varying line strengths can be explained by examining the individual wind components described in the ADM formalism. Finally, we show that the cooling parameter has a negligible effect on the line profiles.Comment: 16 pages, 15 figures, accepted to MNRA