122 research outputs found

    Methodology for the numerical prediction of pollutant formation in gas turbine combustors and associated validation experiments

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    International audienceFor aircraft engine manufacturers the formation of pollutants such as NOx or soot particles is an important issue because the regulations on pollutant emissions are becoming increasingly stringent. In order to comply with these regulations, new concepts of gas turbine combustors must be developed with the help of simulation tools. In this paper we present two different strategies, proposed by ONERA and DLR respectively, to simulate soot or NOx formation in combustors. The first one is based on simple chemistry models allowing significant effort to be spent on the LES description of the flow, while the second one is based on more accurate, but also more expensive, models for soot chemistry and physics. Combustion experiments dedicated to the validation of these strategies are described next: The first one, performed at DLR, was operated at a semi-technical scale and aimed at very accurate and comprehensive information on soot formation and oxidation under well-defined experimental conditions; the second one, characterized at ONERA, was aimed at reproducing the severe conditions encountered in realistic gas turbine combustors. In the third part of the paper the results of combustion simulations are compared to those of the validation experiments. It is shown that a fine description of the physics and chemistry involved in the pollutant formation is necessary but not sufficient to obtain quantitative predictions of pollutant formation. An accurate calculation of the turbulent reactive flow interacting with pollutant formation and influencing dilution, oxidation and transport is also required: when the temperature field is correctly reproduced, as is the case of the ONERA simulation of the DLR combustor, the prediction of soot formation is quite satisfactory while difficulty in reproducing the temperature field in the TLC combustor leads to overestimations of NOx and soot concentrations.Pour les constructeurs de moteurs d’avion, la formation de polluants comme les NOx ou les particules de suies est une question importante car la rĂ©glementation sur les Ă©missions polluantes est de plus en plus sĂ©vĂšre. Pour respecter cette rĂ©glementation, de nouveaux concepts de foyers de turbine Ă  gaz doivent ĂȘtre dĂ©veloppĂ©s avec l’aide d’outils de simulation. Dans cet article, nous prĂ©sentons deux stratĂ©gies diffĂ©rentes proposĂ©es par l’ONERA et le DLR pour simuler la formation des suies et des NOx dans les chambres de combustion. La premiĂšre est basĂ©e sur des modĂšles chimiques simples permettant de faire porter l’effort de calcul sur la description LES de l’écoulement, tandis que la seconde est basĂ©e sur des modĂšles physico-chimiques de formation des suies plus prĂ©cis mais aussi plus coĂ»teux en temps de calcul. Des expĂ©riences de combustion conçues pour la validation de ces stratĂ©gies sont ensuite dĂ©crites : La premiĂšre, rĂ©alisĂ©e au DLR, reproduit la combustion Ă  une Ă©chelle semi-industrielle et a pour but de donner une information trĂšs prĂ©cise et complĂšte sur les mĂ©canismes de formation des suies et leur oxydation dans des conditions expĂ©rimentales parfaitement maĂźtrisĂ©es ; la seconde, rĂ©alisĂ©e Ă  l’ONERA, a pour but de reproduire de façon rĂ©aliste les conditions sĂ©vĂšres rencontrĂ©es dans les foyers de turbine Ă  gaz industrielles. Dans la troisiĂšme partie du papier, les rĂ©sultats des simulations de combustion sont comparĂ©s Ă  ceux des expĂ©riences de validation. Il est dĂ©montrĂ© que la description prĂ©cise de la physique et de la chimie intervenant dans la formation des polluants est nĂ©cessaire mais non suffisante pour simuler correctement les quantitĂ©s de polluants formĂ©s. Un calcul prĂ©cis de l’écoulement turbulent rĂ©actif interagissant avec les mĂ©canismes de formation, de dilution, d’oxydation et de transport des polluants est Ă©galement nĂ©cessaire : Lorsque le champ de tempĂ©rature est correctement reproduit comme c’est le cas pour la simulation ONERA du foyer DLR, la simulation de la formation des suies est assez satisfaisante, alors qu’une difficultĂ© pour reproduire le champ de tempĂ©rature dans le foyer TLC conduit Ă  une surestimation des concentrations de NOx et de suies

    Mcl‐1 targeting strategies unlock the proapoptotic potential of TRAIL in melanoma cells

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    TNF‐related apoptosis‐inducing ligand (TRAIL) induces apoptosis selectively in cancer cells. For melanoma, the targeting of TRAIL signaling appears highly attractive, due to pronounced TRAIL receptor expression in tumor tissue. However, mechanisms of TRAIL resistance observed in melanoma cells may limit its clinical use. The Bcl‐2 family members are critical regulators of cell‐intrinsic apoptotic pathways. Thus, the antiapoptotic Bcl‐2 protein myeloid cell leukemia 1 (Mcl‐1) is overexpressed in many tumor types and was linked to chemotherapy resistance in melanoma. In this study, we evaluated the involvement of antiapoptotic Bcl‐2 proteins (Bcl‐2, Bcl‐xL, Bcl‐w, Mcl‐1, Bcl‐A1, and Bcl‐B) in TRAIL resistance. They were targeted by small interfering RNA‐mediated silencing in TRAIL‐sensitive (A‐375, Mel‐HO) and in TRAIL‐resistant melanoma cell lines (Mel‐2a, MeWo). This highlighted Mcl‐1 as the most efficient target to overcome TRAIL resistance. In this context, we investigated the effects of Mcl‐1‐targeting microRNAs as well as the Mcl‐1‐selective inhibitor S63845. Both miR‐193b and S63845 resulted in significant enhancement of TRAIL‐induced apoptosis, associated with decreased cell viability. Apoptosis induction was mediated by caspase‐3 processing as well as by Bax and Bak activation, indicating the critical involvement of intrinsic apoptosis pathways. These data may indicate a high relevance of Mcl‐1 targeting also in melanoma therapy. Furthermore, the data may suggest to consider the use of the tumor suppressor miR‐193b as a strategy for countering TRAIL resistance in melanoma

    Selective Induction of Apoptosis in Melanoma Cells by Tyrosinase Promoter-Controlled CD95 Ligand Overexpression

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    Induction of apoptosis has been demonstrated previously by overexpression of CD95 ligand (CD95L) in cultured human melanoma cells. For in vivo approaches based on CD95L, however, targeted expression is a prerequisite and tyrosinase promoters have been considered for selection. Luciferase reporter gene assays performed for a representative panel of melanoma cell lines characterized by strong (SK-Mel-19), moderate (SK-Mel-13, MeWo), weak (A-375), and missing expression (M-5) of endogenous tyrosinase revealed high tyrosinase promoter activities in SK-Mel-19, SK-Mel-13, and MeWo, but only weak activities in A-375 and M-5 as well as in non-melanoma cell lines. After transfection of a CMV promoter CD95L expression construct, melanoma cells were found highly sensitive, as compared with non-melanoma cells. By applying a tyrosinase promoter CD95L construct, apoptosis was selectively induced in SK-Mel-19, SK-Mel-13, MeWo as well as in A-375, which was characterized by high CD95 surface expression and high sensitivity to agonistic CD95 activation. M5 and non-melanoma cell lines remained uninfluenced. Also, resistance to agonistic CD95 activation seen in MeWo characterized by weak CD95 surface expression was overcome by overexpression of CD95L. Our investigations provide evidence that tyrosinase promoter CD95L constructs may be of value for selective induction of apoptosis in therapeutic strategies for melanoma

    How COVID-19 changed clinical research strategies: a global survey

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    Objective Clinical research has faced new challenges during the COVID-19 pandemic, leading to excessive operational demands affecting all stakeholders. We evaluated the impact of COVID-19 on clinical research strategies and compared different adaptations by regulatory bodies and academic research institutions in a global context, exploring what can be learned for possible future pandemics. Methods We conducted a cross-sectional online survey and identified and assessed different COVID-19-specific adaptation strategies used by academic research institutions and regulatory bodies. Results All 19 participating academic research institutions developed and followed similar strategies, including preventive measures, manpower recruitment, and prioritisation of COVID-19 projects. In contrast, measures for centralised management or coordination of COVID-19 projects, project preselection, and funding were handled differently amongst institutions. Regulatory bodies responded similarly to the pandemic by implementing fast-track authorisation procedures for COVID-19 projects and developing guidance documents. Quality and consistency of the information and advice provided was rated differently amongst institutions. Conclusion Both academic research institutions and regulatory bodies worldwide were able to cope with challenges during the COVID-19 pandemic by developing similar strategies. We identified some unique approaches to ensure fast and efficient responses to a pandemic. Ethical concerns should be addressed in any new decision-making process

    Random walks on activity-driven networks with attractiveness

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    Virtually all real-world networks are dynamical entities. In social networks, the propensity of nodes to engage in social interactions (activity) and their chances to be selected by active nodes (attractiveness) are heterogeneously distributed. Here, we present a time-varying network model where each node and the dynamical formation of ties are characterized by these two features. We study how these properties affect random-walk processes unfolding on the network when the time scales describing the process and the network evolution are comparable. We derive analytical solutions for the stationary state and the mean first-passage time of the process, and we study cases informed by empirical observations of social networks. Our work shows that previously disregarded properties of real social systems, such as heterogeneous distributions of activity and attractiveness as well as the correlations between them, substantially affect the dynamical process unfolding on the network

    Silencing of Mcl-1 overcomes resistance of melanoma cells against TRAIL-armed oncolytic adenovirus by enhancement of apoptosis

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    Arming of oncolytic viruses with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown as a viable approach to increase the antitumor efficacy in melanoma. However, melanoma cells may be partially or completely resistant to TRAIL or develop TRAIL resistance, thus counteracting the antitumor efficiency of TRAIL-armed oncolytic viruses. Recently, we found that TRAIL resistance in melanoma cells can be overcome by inhibition of antiapoptotic Bcl-2 protein myeloid cell leukemia 1 (Mcl-1). Here, we investigated whether the cytotoxicity of AdV-TRAIL, an oncolytic adenovirus, which expresses TRAIL after induction by doxycycline (Dox), can be improved in melanoma cells by silencing of Mcl-1. Two melanoma cell lines, the TRAIL-resistant MeWo and the TRAIL-sensitive Mel-HO were investigated. Treatment of both cell lines with AdV-TRAIL resulted in a decrease of cell viability, which was caused by an increase of apoptosis and necrosis. The proapoptotic effects were dependent on induction of TRAIL by Dox and were more pronounced in Mel-HO than in MeWo cells. SiRNA-mediated silencing of Mcl-1 resulted in a further significant decrease of cell viability and a further increase of apoptosis and necrosis in AdV-TRAIL-infected MeWo and Mel-HO cells. However, while in absolute terms, the effects were more pronounced in Mel-HO cells, in relative terms, they were stronger in MeWo cells. These results show that silencing of Mcl-1 represents a suitable approach to increase the cytotoxicity of a TRAIL-armed oncolytic adenovirus in melanoma cells.TU Berlin, Open-Access-Mittel – 202
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