numerical study of flutter stabilization in low pressure turbine rotor with intentional mistuning

Abstract Intentional mistuning concepts are used to mitigate the risk of flutter occurrence for compressor and turbine blades, as this design strategy represents one of the key aspects in nowadays turbomachinery aeroelastic design. In this paper, the effects of a mistuning pattern on LPT flutter stability are numerically investigated in order to highlight the differences with the classic tuned configuration. A LPT rotor is analysed with an intentional mistuning pattern composed by alternate blades with different additional masses at the blade tip, and the corresponding tuned configuration, consisting of the blisk (blade+disk) with identical blades. The first part of this work is devoted to the modal analysis for tuned and mistuned cases. Frequencies and mode shapes of the first bending mode family, obtained by FEM modal analysis in cyclic symmetry, are then used to perform CFD flutter analysis with moving blades. The results confirm the stabilizing effect of alternate mistuning pattern in contrast with the tuned system which denotes a strong flutter instability for a large range of negative nodal diameters. The numerically predicted flutter stabilization effect has been confirmed by measurements carried out during a tip timing experimental campaign performed within the Future EU project

Dexamethasone improves redox state in ataxia telangiectasia cells by promoting an NRF2-mediated antioxidant response

partially_open10noAtaxia telangiectasia (A-T) is a rare incurable neurodegenerative disease caused by biallelic mutations in the gene for ataxia-telangiectasia mutated (ATM). The lack of a functional ATM kinase leads to a pleiotropic phenotype, and oxidative stress is considered to have a crucial role in the complex physiopathology. Recently, steroids have been shown to reduce the neurological symptoms of the disease, although the molecular mechanism of this effect is largely unknown. In the present study, we have demonstrated that dexamethasone treatment of A-T lymphoblastoid cells increases the content of two of the most abundant antioxidants [glutathione (GSH) and NADPH] by up to 30%. Dexamethasone promoted the nuclear accumulation of the transcription factor nuclear factor (erythroid-derived 2)-like 2 to drive expression of antioxidant pathways involved in GSH synthesis and NADPH production. The latter effect was via glucose 6-phosphate dehydrogenase activation, as confirmed by increased enzyme activity and enhancement of the pentose phosphate pathway rate. This evidence indicates that glucocorticoids are able to potentiate antioxidant defenses to counteract oxidative stress in ataxia telangiectasia, and also reveals an unexpected role for dexamethasone in redox homeostasis and cellular antioxidant activity.openBiagiotti, Sara; Menotta, Michele; Orazi, Sara; Spapperi, Chiara; Brundu, Serena; Fraternale, Alessandra; Bianchi, Marzia; Rossi, Luigia; Chessa, Luciana; Magnani, MauroBiagiotti, Sara; Menotta, Michele; Orazi, Sara; Spapperi, Chiara; Brundu, Serena; Fraternale, Alessandra; Bianchi, Marzia; Rossi, Luigia; Chessa, Luciana; Magnani, Maur

Development of a Potential Gallium-68-Labelled Radiotracer Based on DOTA-Curcumin for Colon-Rectal Carcinoma: From Synthesis to In Vivo Studies

Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative (68Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. 68Ga-DOTA-C21 exhibits decent stability (57 \ub1 3% after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 \ub1 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of 68Ga-DOTA-C21 is 3.57 \ub1 0.3% of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 \ub1 0.2. High amount of activity (12.73 \ub1 1.9% ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 \ub1 3.3% ID/g), lungs (8.42 \ub1 0.8% ID/g), liver (5.81 \ub1 0.5% ID/g) and heart (4.70 \ub1 0.4% ID/g). Further studies are needed to understand the mechanism of accumulation and clearance; however, 68Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer