885 research outputs found
Environmental protection of titanium alloys in centrifugal compressors at 500°C in saline atmosphere
The use of the titanium alloy Ti-6246 (Ti–6Al–2Sn–4Zr–6Mo, wt-%) for gas turbine compressors allows an increase in working temperature and stress level. Under severe service conditions, the material experiences combined high temperature and high mechanical stress and, in saline atmospheres, stress corrosion cracking (SCC) can occur, leading to catastrophic mechanical failure. The present study was performed to evaluate the potential of several surface treatments to protect Ti-6246 alloy, after salt deposit, from hot salt SCC at temperatures ?500°C and 500 MPa static mechanical stress conditions. Shot peening, thermal oxidation and metal–ceramic coatings were investigated. Experimental results confirm the existence of brittle stress corrosion phenomena marked by a low residual elongation of test samples and the presence of oxides on the fracture surfaces. Both shot peening and metal–ceramic coatings increase the hot salt SCC resistance of the alloy. Times to rupture were improved by a factor of 3 for shot peening and by a factor of 10 for metal–ceramic coatings. Inversely, the time to rupture of preoxidised alloys has been halved compared with uncoated alloys. As well as these interesting quantitative results, structural studies of metal–ceramic coatings showed that they are mechanically and chemically compatible with the titanium alloy substructure and should work under severe thermomechanical stresses and aggressive atmospheres
Identification of N- and C-terminal corticotropin peptides in the Mr 80 000 form of neurophysin
AbstractThe 125I-labeled Mr 80 000 form of neurophysin has been purified from bovine neurohypophysi. Tryptic digests of this species were analyzed, prior to or after treatment with carboxypeptidase B, by high-pressure liquid chromatography followed by isoelectric focusing and the fragments compared with those generated by a similar treatment of reference bovine 1–39 adrenocorticotropin. The ACTH peptides 22–39 and 1–8, as well as the 1–7 derivative of the latter were identified by those two independent criteria. This provides chemical evidence supporting the hypothesis [8] that high Mr neurophysin may contain the sequence of ACTH
Red blood cell precursor mass as an independent determinant of serum erythropoietin level.
Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells
Epidemiological and nonclinical studies investigating effects of iron in carcinogenesis-A critical review
The efficacy and tolerability of intravenous (i.v.) iron in managing cancer-related anemia and iron deficiency has been clinically evaluated and reviewed recently. However, long-term data in cancer patients are not available; yet, long-term i.v. iron treatment in hemodialysis patients is not associated with increased cancer risk. This review summarizes epidemiological and nonclinical data on the role of iron in carcinogenesis. In humans, epidemiological data suggest correlations between certain cancers and increased iron exposure or iron overload. Nonclinical models that investigated whether iron can enhance carcinogenesis provide only limited evidence relevant for cancer patients since they were typically based on high iron doses as well as injection routes and iron formulations which are not used in the clinical setting. Nevertheless, in the absence of long-term outcome data from prospectively defined trials in i.v. iron-treated cancer patients, iron supplementation should be limited to periods of concomitant anti-tumor treatment
Direct Evidence of Multi-Bubble Sonoluminescence using Therapeutic Ultrasound and Microbubbles
The
intense conditions generated in the core of a collapsing bubble
have been the subject of intense scrutiny from fields as diverse as
marine biology and nuclear fusion. In particular, the phenomenon of
sonoluminescence, whereby a collapsing bubble emits light, has received
significant attention. Sonoluminescence has been associated predominantly
with millimeter-sized bubbles excited at low frequencies and under
conditions far removed from those associated with the use of ultrasound
in medicine. In this study, however, we demonstrate that sonoluminescence
is produced under medically relevant exposure conditions by microbubbles
commonly used as contrast agents for ultrasound imaging. This provides
a mechanistic explanation for the somewhat controversial reports of
“sonodynamic” therapy, in which light-sensitive drugs
have been shown to be activated by ultrasound-induced cavitation.
To illustrate this, we demonstrate the activation of a photodynamic
therapy agent using microbubbles and ultrasound. Since ultrasound
can be accurately focused at large tissue depths, this opens up the
potential for generating light at locations that cannot be reached
by external sources. This could be exploited both for diagnostic and
therapeutic applications, significantly increasing the range of applications
that are currently restricted by the limited penetration of light
in the tissue
Feed-back on the development of a small scale Contact Erosion Test in the laboratory (characteristic size ~ 30 cm)
To determine the hydraulic load requested to initiate contact erosion process, tests are performed with an apparatus called the “Contact Erosion Test”. This device originally results from research carried out by Grenoble University, Électricité de France and Compagnie Nationale du Rhône, at the scale of ~60 cm. It has been adapted to a smaller scale in geophyConsult laboratory to conduct tests on samples extracted from core drilling. The instrumentation was improved to enable a better control of the hydraulic loading and avoid biases. The test protocol was modified, especially to better constrain the soil density at the interface. From the first series of test, we drew conclusions on the test repeatability and on the influence of parameters of the soil state. Discrepancies with previous results obtained at the scale of ~60 cm were identified. Therefore, a new erosion test campaign was planned to confirm and determine the reasons for these differences
Azacytidine Enhances Regulatory T-Cells In Vivo and Prevents Experimental Xenogeneic Graft-Versus-Host Disease
Background
The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Tregs).
Objective
We investigated the impact of AZA on xenogeneic graft-versus-host disease (xGVHD) in a humanized murine model of transplantation, and described the impact of the drug on human T cells in vivo.
Methods
In order to induce xGVHD, human peripheral blood mononuclear cells (huPBMC) were administered intravenously in NOD-scid IL-2Rγnull (NSG) mice.
Results
AZA successfully improved both survival (p<0.0001) and xGVHD scores (p<0.0001). Further, AZA significantly decreased human T-cell proliferation as well as INF-γ and TNF-α serum levels, and reduced the expression of GRANZYME B and PERFORIN 1 by cytotoxic T cells. In addition, AZA administration significantly increased the function, proliferation and frequency of Tregs through demethylation of FOXP3i1 and higher secretion of IL-2 by conventional T cells due to IL2 gene promoter site 1 demethylation. Interestingly, among AZA-treated mice surviving the acute phase of xGVHD, there was an inverse correlation between the presence of Tregs and signs of chronic GVHD. Finally, Tregs harvested from the spleen of AZA-treated mice were suppressive and stable over time since they persisted at high frequency in secondary transplant experiments.
Conclusion
These findings emphasize a potential role for AZA as prevention or treatment of GVHD
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