Design Space Investigation by RSMs Techniques in Aeronautical Metal Cutting Applications

none3A. DEL PRETE; A. DE VITIS; D. MAZZOTTADEL PRETE, Antonio; DE VITIS, ANTONIO ALBERTO; D., Mazzott

EXPERIMENTAL DEVELOPMENT OF RSM TECHNIQUES FORSURFACE QUALITY PREDICTION IN METAL CUTTING APPLICATIONS

The aim of this work is to analyze the influence of cutting conditions on surface roughness with slot end milling on AL7075-T6. The considered parameters are: cutting speed, feed, depth of cutting and mill radial engage. Response surface models based on experimental data obtained with physical tests have been developed, the authors have performed a consistent set of experimental tests based on design points selected within the four-dimensional design space. Each test has been repeated 3 times to ensure the stability of the collected statistical data. These welldistributed results has been subsequently used to create RS models through approximation techniques based on polynomial and neural network methods and to verify their reliability in terms of correct responses behaviour. The obtained results show that the most significant factors affecting the surface roughness are feed and speed

Design Space Investigation by RSMs Techniques in Aeronautical Metal Cutting Applications

A FEM model able to predict the cutting interactions between tool and workpiece (cutting forces and cutting edge temperature) for a typical aeronautical engine Nickel-alloy Inconel 718, has been used to perform a reduced number of FEM calculations indicate by a DOE, to evaluate the design space for process parameters. These well-distributed results can be subsequently used to create and evaluate the quality in terms of correct responses behaviour for the metamodels created through different approximation techniques (polynomial and neural network). The metamodels based on the best methodology (in terms of effectiveness of process behaviour prediction) has been used to optimize, through ASA (Adaptive Simulated Annealing) algorithms, the process parameters defined in a CAM part program block. The aim of the authors is to modify the Part Program operation parameters according to the constraints arising from the physical nature of the cutting process obtained by FEA

AIDS and COVID-19 are two diseases separated by a common lymphocytopenia

HIV and SARS-CoV-2 are responsible for two of the most dangerous and life-threatening infectious diseases of our times. To better analyze the difference in the immunological response elicited by the two infections, we compared the alterations in the lymphocyte subpopulations, measured by flow cytometry analysis (FCA) in both AIDS and COVID-19 patients, referred to our University Hospital. A total of 184 HIV infected patients were retrospectively examined and the results of FCA collected and compared to those obtained in 110 SARS-CoV-2 infected patients, examined during the COVID- 19 outbreak. We observed a comparable reduction in B cells in both diseases and a more severe reduction in the total amount of T cells in COVID-19 as compared to AIDS patients. The analysis of the T cells subpopulations indicates that there is a comparable reduction in the CD4+ cells count. Conversely, a remarkable difference between them is observed in the CD8+ counts. In AIDS patients the CD8+ cells are slightly higher than normal, while in COVID-19 patients the CD8+ cell count is markedly reduced. As a result, the CD4+/CD8+ ratios, is very low in AIDS and higher than normal in COVID-19 patients. The NK cells are reduced in both diseases, but SARS-CoV-2 infection causes a more severe reduction compared to HIV infection. In conclusion, both HIV and SARS-CoV-2 viruses induce major changes in the lymphocytes count, with remarkable similarities and differences between them. The total absolute numbers of T cells and, in particular of the CD8+ subpopulation, are lower in COVID-19 patients compared to AIDS ones, while the CD4+ are reduced in both at similar levels. These results indicate that the host immune system reacts differently to the two infection, but they are responsible of a comparable dropping effect on the serum levels of CD4+ T cell population. The meaning of the similarities and of the differences in terms of T cells activation and serum depletion are discussed. The knowledge on how the immune system reacts to these two infections will be useful to better define their mechanism of action and to design specific preventive and therapeutic approaches

Deconvolution of malignant pleural effusions immune landscape unravels a novel macrophage signature associated with worse clinical outcome in lung adenocarcinoma patients

Background: Immune checkpoint inhibitors are still unable to provide clinical benefit to the large majority of non-small cell lung cancer (NSCLC) patients. A deeper characterization of the tumor immune microenvironment (TIME) is expected to shed light on the mechanisms of cancer immune evasion and resistance to immunotherapy. Here, we exploited malignant pleural effusions (MPEs) from lung adenocarcinoma (LUAD) patients as a model system to decipher TIME in metastatic NSCLC. Methods: Mononuclear cells from MPEs (PEMC) and peripheral blood (PBMC), cell free pleural fluid and/or plasma were collected from a total of 24 LUAD patients and 12 healthy donors. Bulk-RNA sequencing was performed on total RNA extracted from PEMC and matched PBMC. The DEseq2 Bioconductor package was used to perform differential expression analysis and CIBERSORTx for the regression-based immune deconvolution of bulk gene expression data. Cytokinome analysis of cell-free pleural fluid and plasma samples was performed using a 48-Plex Assay panel. THP-1 monocytic cells were used to assess macrophage polarization. Survival analyses on NSCLC patients were performed using KM Plotter (LUAD, N=672; lung squamous cell carcinoma, N=271). Results: Transcriptomic analysis of immune cells and cytokinome analysis of soluble factors in the pleural fluid depicted MPEs as a metastatic niche in which all the components required for an effective antitumor response are present, but conscripted in a wound-healing, proinflammatory and tumor-supportive mode. The bioinformatic deconvolution analysis revealed an immune landscape dominated by myeloid subsets with the prevalence of monocytes, protumoral macrophages and activated mast cells. Focusing on macrophages we identified an MPEs-distinctive signature associated with worse clinical outcome in LUAD patients. Conclusions: Our study reports for the first time a wide characterization of MPEs LUAD microenvironment, highlighting the importance of specific components of the myeloid compartment and opens new perspectives for the rational design of new therapies for metastatic NSCLC