The complement anaphylatoxin C5a has a pathogenetic role in endotoxin-induced lung inflammatory injury by regulating phagocytic cell migration and activation. Endotoxin and C5a activate the enzyme sphingosine kinase (Sphk) 1 to generate the signaling lipid sphingosine-1-phosphate (S1P), a critical regulator of phagocyte function. We assessed the function of Sphk1 and S1P in experimental lung inflammatory injury and determined their roles in anaphylatoxin receptor signaling and on the expression of the two C5a receptors, C5aR (CD88) and C5L2, on phagocytes. We report that Sphk1 gene deficient (Sphk1−/−) mice had augmented lung inflammatory response to endotoxin compared to wild type mice. Sphk1 was required for C5a-mediated reduction in cytokine and chemokine production by macrophages. Moreover, neutrophils from Sphk1−/− mice failed to upregulate the anaphylatoxin receptor C5L2 in response to LPS. Exogenous S1P restored C5L2 cell surface expression of Sphk1−/− mouse neutrophils to wild type levels but had no effect on cell surface expression of the other anaphylatoxin receptor, CD88. These results provide the first genetic evidence of the crucial role of Sphk1 in regulating the balance between expression of CD88 and C5L2 in phagocytes. S1P-mediated up-regulation of C5L2 is a novel therapeutic target for mitigating endotoxin-induced lung inflammatory injury.
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AbstractDrilling underbalanced is often expected to prevent formation damage, avoid lost circulation, and increase rate of penetration. However, it is also risky and may lead to borehole collapse due to lack of positive support provided by the borehole mud. Hence, its feasibility should be evaluated thoroughly through an accurate evaluation of in-situ stresses and a realistic estimation of formation rock mechanical properties. These two entities combined with the proposed borehole trajectory and mud weight design play an important role in avoiding borehole instability problems and achieving the field objectives.A study was conducted in San Joaquin field in Eastern Venezuela, to evaluate the feasibility of drilling underbalanced in highly depleted sands inter-layered with normally pressured shales. Data required for the study was obtained from five wells in the field (pressures, daily drilling reports, wireline logs, leak off tests and rock mechanical tests).A geo-stress model was developed, including pore pressure model, minimum and maximum horizontal stresses, and overburden stress. The in-situ horizontal stress directions were estimated from caliper logs, image logs and other field data. Formation rock mechanical properties were obtained using a program which utilizes the log data from the field and estimates the more representative static mechanical properties, which were then calibrated with the lab results. The combined geo-stress and mechanical properties models were calibrated with respect to drilling induced fractures and breakouts observed on the image logs. The calibrated models were used to estimate the required mud weights for drilling under various degrees of underbalance. Instabilities (breakouts) associated with each degree of underbalance were also quantified. The required mud weights to avoid shear and tensile failures, or the expected breakouts for a given mud weight, can be estimated from the generated contour plots for any borehole azimuth and inclination in the field.The results of the study were successfully implemented in the field, resulting in cost benefits of $1MM over five wells. Lost circulation was significantly avoided, and improvements in drilling rate as well as savings in rig days were achieved.The outcome of the study is expected to provide guidelines for underbalanced drilling for future wells in the area.
The light curve and spectra of Nova Centauri 1995 (V888 Cen) are analysed. The spectra were obtained a few days post‐maximum. The nova is found to be a very fast nova, declining by 2 mag within about 5±2 d of maximum. The light curve shows strong oscillations in the transition region, of peak‐to‐peak amplitude about 1.5 mag and period 12–15 d. The light curve of Nova Centauri resembles closely that of Nova Aquilae 1918 (V603 Aql).
The early blue and red spectra obtained at Mt John show broad emission lines, many with P Cygni profiles. The absorption lines are found in two velocity systems at about −1765 and −3010 km s−1, in respectively the principal and diffuse‐enhanced stages of spectral development, as defined by McLaughlin. Nova Centauri has many Fe ii lines in emission, indicating that it is a member of the Williams Fe ii class of classical novae.
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