A Fast Procedure for the Design of Composite Stiffened Panels

This paper describes the analysis and the minimum weight optimisation of a fuselage composite stiffened panel made from carbon/epoxy material and stiffened by five omega stringers. The panel investigated inside the European project MAAXIMUS is studied using a fast tool, which relies on a semi-analytical procedure for the analysis and on genetic algorithms for the optimisation. The semi-analytical approach is used to compute the buckling load and to study the post-buckling response. Different design variables are considered during the optimisation, such as the stacking sequences of the skin and the stiffener, the geometry and the cross-section of the stiffener. The comparison between finite element and fast tool results reveals the ability of the formulation to predict the buckling load and the post-buckling response of the panel. The reduced CPU time necessary for the analysis and the optimisation makes the procedure an attractive strategy to improve the effectiveness of the preliminary design phases

Exact Refined Buckling Solutions for Laminated Plates Under Uniaxial and Biaxial Loads

This paper presents a unified Lévy-type solution procedure for the buckling analysis of both thin and thick composite plates under biaxial loads. The plates are simply-supported at two opposite edges, while the two remaining sides are subjected to any combination of simply-supported, clamped and free conditions. The problem is formulated in the context of a variable-kinematic approach, offering the advantage of automatically handling theories of various order. Both layerwise and equivalent single layer theories are considered. The governing equilibrium equations are derived analytically from the Principle of Virtual Displacements (PVD), and are solved exactly referring to the Lévy-type procedure. The accuracy of the predictions is demonstrated by comparison with results available in literature, including exact 3D solutions. A comprehensive set of benchmark results is provided for plates subjected to different loading and boundary conditions and characterized by various width-to-thickness ratios

Optimization of Non-Symmetric Composite Panels Using Fast Analysis Techniques

A semi-analytical approach is presented for the optimization of laminated panels with nonsymmetric lay-ups, and with the possibility of introducing requirements on the buckling load, the postbuckling response and the eigenfrequencies. The design strategy relies on the combined use of semi-analytical techniques for the structural analysis and genetic algorithms for the optimization. The structural analysis is performed with a highly efficient code based on thin plate theory, where the problem is formulated in terms of Airy stress function and out of plane displacement, expanded using trigonometric series. The solution of two distinct eigenvalue problems is performed to determine eigenfrequencies and buckling load, while an arc-length method is adopted for the postbuckling computation. The genetic algorithm is implemented by using proper alphabet cardinalities to handle different steps for the angles of orientation, while specific mutation operators are used to guarantee good reliability of the optimization. To show the potentialities of the proposed optimization toolbox, two examples are presented regarding the design of balanced non-symmetric laminates subjected to linear and nonlinear constraints. The accuracy of the analytical predictions is demonstrated by comparison with finite element results

Development and Applications of a Virtual Hybrid Platform for Multiscale Analysis of Advanced Structures of Aircraft (DEVISU)

This paper outlines the main findings of the project “DEvelopment and applications of a VIrtual hybrid platform for multiscale analysis of advanced StructUres of aircraft” (DEVISU), which deals with failure of composite structures and noise/vibration reduction, along with investigation of new materials for aerospace applications

Remodelling of biological parameters during human ageing: evidence for complex regulation in longevity and in type 2 diabetes.

Factor structure analyses have revealed the presence of specific biological system markers in healthy humans and diseases. However, this type of approach in very old persons and in type 2 diabetes (T2DM) is lacking. A total sample of 2,137 Italians consisted of two groups: 1,604 healthy and 533 with T2DM. Age (years) was categorized as adults (≤65), old (66-85), oldest old (>85-98) and centenarians (≥99). Specific biomarkers of routine haematological and biochemical testing were tested across each age group. Exploratory factorial analysis (EFA) by principal component method with Varimax rotation was used to identify factors including related variables. Structural equation modelling (SEM) was applied to confirm factor solutions for each age group. EFA and SEM identified specific factor structures according to age in both groups. An age-associated reduction of factor structure was observed from adults to oldest old in the healthy group (explained variance 60.4% vs 50.3%) and from adults to old in the T2DM group (explained variance 57.4% vs 44.2%). Centenarians showed three-factor structure similar to those of adults (explained variance 58.4%). The inflammatory component became the major factor in old group and was the first one in T2DM. SEM analysis in healthy subjects suggested that the glucose levels had an important role in the oldest old. Factorial structure change during healthy ageing was associated with a decrease in complexity but showed an increase in variability and inflammation. Structural relationship changes observed in healthy subjects appeared earlier in diabetic patients and later in centenarians

PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients

Background: The PD-1/PD-L1 axis has recently emerged as an immune checkpoint that controls antitumor immune responses also in hematological malignancies. However, the use of anti-PD-L1/PD-1 antibodies in multiple myeloma (MM) patients still remains debated, at least in part because of discordant literature data on PD-L1/PD-1 expression by MM cells and bone marrow (BM) microenvironment cells. The unmet need to identify patients which could benefit from this therapeutic approach prompts us to evaluate the BM expression profile of PD-L1/PD-1 axis across the different stages of the monoclonal gammopathies. Methods: The PD-L1/PD-1 axis was evaluated by flow cytometry in the BM samples of a total cohort of 141 patients with monoclonal gammopathies including 24 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), 38 patients with smoldering MM (SMM), and 79 patients with active MM, including either newly diagnosed or relapsed-refractory patients. Then, data were correlated with the main immunological and clinical features of the patients. Results: First, we did not find any significant difference between MM and SMM patients in terms of PD-L1/PD-1 expression, on both BM myeloid (CD14+) and lymphoid subsets. On the other hand, PD-L1 expression by CD138+ MM cells was higher in both SMM and MM as compared to MGUS patients. Second, the analysis on the total cohort of MM and SMM patients revealed that PD-L1 is expressed at higher level in CD14+CD16+ non-classical monocytes compared with classical CD14+CD16− cells, independently from the stage of disease. Moreover, PD-L1 expression on CD14+ cells was inversely correlated with BM serum levels of the anti-tumoral cytokine, IL-27. Interestingly, relapsed MM patients showed an inverted CD4+/CD8+ ratio along with high levels of pro-tumoral IL-6 and a positive correlation between Í14+PD-L1+ and Í8+PD-1+ cells as compared to both SMM and newly diagnosed MM patients suggesting a highly compromised immune-compartment with low amount of CD4+ effector cells. Conclusions: Our data indicate that SMM and active MM patients share a similar PD-L1/PD-1 BM immune profile, suggesting that SMM patients could be an interesting target for PD-L1/PD-1 inhibition therapy, in light of their less compromised and more responsive immune-compartment

Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

Immune parameters identify Italian centenarians with a longer five-year survival independent of their health and functional status.

Centenarians are rare and exceptional individuals characterized by a peculiar phenotype. They are the best ex- ample of healthy aging in humans as most of them have escaped or substantially delayed the onset of major age-related diseases. Within this scenario, the purpose of the present work was to understand if immune status is associated with survival and health status in centenarians. To this aim, 116 centenarians were concomitantly characterized for their immunological, health and functional status, and followed-up for five-year survival. On the basis of previous knowledge we focused on a core of fundamental and basic immune parameters (number of leukocytes, monocytes, total lymphocytes, CD3+ T lymphocytes, CD4+ helper T lymphocytes, CD8+ cytotoxic T lymphocytes, CD19+ B lymphocytes and plasma levels of IgM), and the most important findings can be sum- marized as follows: i. a hierarchical cluster analysis was able to define Cluster1 (88 centenarians) and Cluster2 (28 centenarians) characterized by low and high values of all these immune parameters, respectively; ii. cente- narians of Cluster2 showed a statistically longer five-year survival and more favorable values of other important immune (naïve, activated/memory and effector/memory T cells) and metabolic (glycemia, insulin and HOMA-IR) parameters, in accord with previous observations that centenarians have a peculiar immune profile, a preserved insulin pathway and a lower incidence of type 2 diabetes; and iii. unexpectedly, parameters related to frailty, as well as functional and cognitive status, did not show any significant correlation with the immune clustering, de- spite being capable per se of predicting survival. In conclusion, high values of basic immunological parameters and important T cell subsets correlate with five-year survival in centenarians, independent of other phenotypic characteristics. This unexpected biological scenario is compatible with the general hypothesis that in centenarians a progressive disconnection and loss of biological coherence among the different functions of the body occur, where survival/mortality result from the failure of any of these domains which apparently follow an independent age-related trajectory