Oxygen diffusion and crack growth for a nickel-based superalloy under fatigue-oxidation conditions

Advanced microscopy characterisation and numerical modelling have been carried out to investigate oxygen diffusion and crack growth in a nickel-based superalloy under fatigue-oxidation conditions. Penetration of oxygen into the material and the associated internal oxidation, which leads to material embrittlement and failure, have been found from Focused Ion Beam (FIB) examinations. Applied fatigue loading tends to enhance the extent of internal oxidation for temperatures at 750°C and above. Using a submodelling technique, finite element analyses of oxygen penetration at grain level have been carried out to quantify the fatigue-oxidation damage and calibrate the diffusion parameters based on the measurements of maximum depth of internal oxidation. The grain microstructure was considered explicitly in the finite element model, where the grain boundary was taken as the primary path for oxygen diffusion. A sequentially coupled mechanical-diffusion analysis was adopted to account for the effects of deformation on diffusion during fatigue loading, for which the material constitutive behaviour was described by a crystal plasticity model at grain level. Prediction of oxidation-assisted crack growth has also been carried out at elevated temperature from the finite 2 element analyses of oxygen diffusion near a fatigue crack tip. A failure curve for crack growth has been constructed based on the consideration of both oxygen concentration and accumulated inelastic strain near the crack tip. The predictions from the fatigue-oxidation failure curve compared well with the experimental results for triangular and dwell loading waveforms, with significant improvement achieved over those predicted from the viscoplastic model alone

In vivo expression of innate immunity markers in patients with mycobacterium tuberculosis infection

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs), Coronin-1 and Sp110 are essential factors for the containment of <it>Mycobacterium tuberculosis </it>infection. The purpose of this study was to investigate the <it>in vivo </it>expression of these molecules at different stages of the infection and uncover possible relationships between these markers and the state of the disease.</p> <p>Methods</p> <p>Twenty-two patients with active tuberculosis, 15 close contacts of subjects with latent disease, 17 close contacts of subjects negative for mycobacterium antigens and 10 healthy, unrelated to patients, subjects were studied. Quantitative mRNA expression of Coronin-1, Sp110, TLRs-1,-2,-4 and -6 was analysed in total blood cells <it>vs </it>an endogenous house-keeping gene.</p> <p>Results</p> <p>The mRNA expression of Coronin-1, Sp110 and TLR-2 was significantly higher in patients with active tuberculosis and subjects with latent disease compared to the uninfected ones. Positive linear correlation for the expression of those factors was only found in the infected populations.</p> <p>Conclusions</p> <p>Our results suggest that the up-regulation of Coronin-1 and Sp110, through a pathway that also includes TLR-2 up-regulation may be involved in the process of tuberculous infection in humans. However, further studies are needed, in order to elucidate whether the selective upregulation of these factors in the infected patients could serve as a specific molecular marker of tuberculosis.</p

Static and dynamic mechanics of the murine lung after intratracheal bleomycin

<p>Abstract</p> <p>Background</p> <p>Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure.</p> <p>Methods</p> <p>Single intratracheal injections of saline (50 μL) or bleomycin (2 mg/Kg in 50 μL saline) were administered to C57BL/6 (<it>n </it>= 40) and Balb/c (<it>n </it>= 32) mice. Injury/fibrosis score, tissue volume density (TVD), collagen content, airway resistance (<it>R_N</it>), tissue damping (<it>G</it>) and elastance coefficient (<it>H</it>), hysteresivity (<it>η</it>), and area of pressure-volume curve (PV-A) were determined after 7 and 21 days (inflammation and fibrosis stage, respectively). Statistical hypothesis testing was performed using one-way ANOVA with LSD <it>post hoc </it>tests.</p> <p>Results</p> <p>Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and <it>G </it>and <it>H </it>non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. <it>G </it>and <it>H</it>, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, <it>H </it>and <it>G </it>was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls.</p> <p>Conclusions</p> <p>Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.</p

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection

The use of various methods for the study of metal pollution in marine sediments, the case of Euvoikos Gulf, Greece

This study presents the results on heavy metal (Mn, Fe, Cu, Zn) analyses of sediments taken from Euvoikos Gulf, Greece, which is a semi-enclosed system receiving pollution loads from several urban and industrial sources and is affected by a strong tidal current. A sequential extraction schema and two single-step methods were used for the determination of trace metals. The data of the 1997 period are compared with data from previous studies carried out in the authors&apos; laboratory in the area (1980, 1993) using various analytical techniques, in an attempt to evaluate both the evolution of pollution in the area and the effectiveness of analytical methods. It has been confirmed that a significant part of the pollution load remains in coastal localities in the vicinity of the land based pollution sources, whereas there are also some more remote sites where small polluted particles are transported, deposited and accumulated. The sedimentology regime of the area affects the concentration of metals in a rather complex way depending also on its content of carbonates, organic C and clay minerals. The study of sediment cores has indicated elevated metal concentrations in recent surface sediments. On the other hand, some environmentally positive trends were also observed (i.e. the reduction of mobile metals). A systematic monitoring is needed in the marine environment coupled with some reduction in pollution inputs and integrated management on the coastal zone because the overall hydrological characteristics of the area favour its rapid self-restoration. © 2002 Elsevier Science Ltd. All rights reserved