88 research outputs found

    Exploiting the potential of large eddy simulations (LES) for ducted fuel injection investigation in non-reacting conditions

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    The diesel combustion research is increasingly focused on ducted fuel injection (DFI), a promising concept to abate engine-out soot emissions in compression-ignition engines. A large set of experiments carried out in constant volume vessel and numerical simulations, at medium-low computational cost, showed that the duct adoption in front of the injector nozzle activates several soot mitigation mechanisms, leading to quasi-zero soot formation in several engine-like operating conditions. However, although the simplified CFD modelling so far played a crucial role for the preliminary understanding of DFI technology, a more accurate turbulence description approach, combined with a large set of numerical experiments for statistical purposes, is of paramount importance for a robust knowledge of the DFI physical behaviour. In this context, the present work exploits the potential of large eddy simulations (LES) to analyse the non-reacting spray of DFI configuration compared with the unconstrained spray. For this purpose, a previously developed spray model, calibrated and validated in the RANS framework against an extensive amount of experimental data related to both free spray and DFI, has been employed. The tests have been carried out considering a single-hole injector in an optical accessible constant volume vessel, properly replicated in the simulation environment. This high-fidelity simulation model has been adapted for LES, firstly selecting the best grid settings, and then carrying out several numerical experiments for both spray configurations until achieving a satisfying statistical convergence. With this aim, the number of independent samples for the averaging procedure has been increased exploiting the axial symmetry characteristics of the present case study. Thanks to this approach, a detailed description of the main DFI-enabled soot mitigation mechanisms has been achieved, shrinking the knowledge gap in the physical understanding of the impact of spray-duct interaction

    Experimental validation of a FSW model with an enhanced friction model: application to a threaded cylindrical pin tool

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    This work adopts a fast and accurate two-stage computational strategy for the analysis of FSW (Friction stir welding) processes using threaded cylindrical pin tools. The coupled thermo-mechanical problem is equipped with an enhanced friction model to include the effect of non-uniform pressure distribution under the pin shoulder. The overall numerical strategy is successfully validated by the experimental measurements provided by the industrial partner (Sapa). The verification of the numerical model using the experimental evidence is not only accomplished in terms of temperature evolution but also in terms of torque, longitudinal, transversal and vertical forces

    Microstructural evaluation of solid state welds obtained by means of flat rolling process

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    In extrusion operations based on the use of porthole dies, for the fabrication of tubes and hollow profiles ingeneral, material solid state welding takes place thanks to the very high pressure and temperature at whichthe material undergoes. Nevertheless, the most important aspect in this process still remains the quality of thewelds, also because the testing of extruded tubes is still today an un-regulated matter. A technique based onthe flat rolling process is applied in this paper, in combination with micrographic and macrographic analyses, toassess the quality of solid-state welds obtained using different process conditions. Flat rolling experimental testsexecuted on sandwiches made of two rectangular specimens in AA6060 and AA6082 aluminium alloys wereperformed. The specimens were characterized by different heights in order to consider different compressionratios that mean different interface pressure and effective stress distributions. All the tests were repeatedat different temperature. By verifying if, the material bonding took place or not, it was possible to identify thewelding limits conditions in terms of pressure and temperature. Particular attention was paid to the study of boththe macrostructure and microstructure of the rolled specimens in order to identify the influence of the processparameters on both the material weldability and the metallurgical weld quality.Keywords: Extrusion - Flat rolling - Solid state bonding - Aluminum alloys - Metallurgical analysi

    Experimental validation of an FSW model with an enhanced friction law: application to a threaded cylindrical pin tool

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    This work adopts a fast and accurate two-stage computational strategy for the analysis of FSW (Friction stir welding) processes using threaded cylindrical pin tools. The coupled thermo-mechanical problem is equipped with an enhanced friction model to include the effect of non-uniform pressure distribution under the pin shoulder. The overall numerical strategy is successfully validated by the experimental measurements provided by the industrial partner (Sapa). The verification of the numerical model using the experimental evidence is not only accomplished in terms of temperature evolution but also in terms of torque, longitudinal, transversal and vertical forces.Peer ReviewedPostprint (published version

    Sex and Gender Differences in Ischemic Heart Disease: Endocrine Vascular Disease Approach (EVA) Study Design

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    Improvements in ischemic heart disease (IHD) management have been unbalanced between sexes, with coronary microvascular dysfunction considered the likely underlying reason. The Endocrine Vascular disease Approach (EVA) is an observational study (Clinicaltrial.gov NCT02737982) aiming to assess sex and gender interactions between coronary circulation, sexual hormones, and platelet function. Consecutive patients with IHD undergoing coronary angiography will be recruited: (1) to assess sex and gender differences in angiographic reperfusion indexes; (2) to evaluate the effects of estrogen/androgen on sex-related differences in myocardial ischemia; (3) to investigate the platelet biology differences between men and women with IHD; (4) to verify sex- and gender-driven interplay between response to percutaneous coronary intervention, platelets, sex hormones, and myocardial damage at baseline and its impact on 12-month outcomes. The integration of sex and gender in this translational project on IHD will contribute to the identification of new targets for further innovative clinical interventions

    A Rapid and Sensitive Method for Measuring NAcetylglucosaminidase Activity in Cultured Cells

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    A rapid and sensitive method to quantitatively assess N-acetylglucosaminidase (NAG) activity in cultured cells is highly desirable for both basic research and clinical studies. NAG activity is deficient in cells from patients with Mucopolysaccharidosis type IIIB (MPS IIIB) due to mutations in NAGLU, the gene that encodes NAG. Currently available techniques for measuring NAG activity in patient-derived cell lines include chromogenic and fluorogenic assays and provide a biochemical method for the diagnosis of MPS IIIB. However, standard protocols require large amounts of cells, cell disruption by sonication or freeze-thawing, and normalization to the cellular protein content, resulting in an error-prone procedure that is material- and time-consuming and that produces highly variable results. Here we report a new procedure for measuring NAG activity in cultured cells. This procedure is based on the use of the fluorogenic NAG substrate, 4- Methylumbelliferyl-2-acetamido-2-deoxy-alpha-D-glucopyranoside (MUG), in a one-step cell assay that does not require cell disruption or post-assay normalization and that employs a low number of cells in 96-well plate format. We show that the NAG one-step cell assay greatly discriminates between wild-type and MPS IIIB patient-derived fibroblasts, thus providing a rapid method for the detection of deficiencies in NAG activity. We also show that the assay is sensitive to changes in NAG activity due to increases in NAGLU expression achieved by either overexpressing the transcription factor EB (TFEB), a master regulator of lysosomal function, or by inducing TFEB activation chemically. Because of its small format, rapidity, sensitivity and reproducibility, the NAG one-step cell assay is suitable for multiple procedures, including the high-throughput screening of chemical libraries to identify modulators of NAG expression, folding and activity, and the investigation of candidate molecules and constructs for applications in enzyme replacement therapy, gene therapy, and combination therapies

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

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    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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    In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field
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