Maintenance resources optimization applied to a manufacturing system

This paper presents an availability optimization of an engineering system assembled in a series configuration, with redundancy of units and corrective maintenance resources as optimization parameters. The aim is to reach maximum availability, considering as constraints installation and corrective maintenance costs, weight and volume. The optimization method uses a Genetic Algorithm based on biological concepts of species evolution. It is a robust method, as it does not converge to a local optimum. It does not require the use of differential calculus, thus facilitating computational implementation. Results indicate that the methodology is suitable to solve a wide range of engineering design problems involving allocation of redundancies and maintenance resources.     

Harnessing Multiple Folding Mechanisms in Soft Periodic Structures for Tunable Control of Elastic Waves

Mechanical instabilities in periodic porous elastic structures may lead to the formation of homogeneous patterns, opening avenues for a wide range of applications that are related to the geometry of the system. This study focuses on an elastomeric porous structure comprising a triangular array of circular holes, and shows that by controlling the loading direction, multiple pattern transformations can be induced by buckling. Interestingly, these different pattern transformations can be exploited to design materials with highly tunable properties. In particular, these results indicate that they can be effectively used to tune the propagation of elastic waves in phononic crystals, enhancing the tunability of the dynamic response of the system. Using a combination of finite element simulations and experiments, a proof‐of‐concept of the novel material is demonstrated. Since the proposed mechanism is induced by elastic instability, it is reversible, repeatable, and scale‐independent, opening avenues for the design of highly tunable materials and devices over a wide range of length scales.     

A New Human Platelet Lysate for Mesenchymal Stem Cell Production Compliant with Good Manufacturing Practice Conditions Preserves the Chemical Characteristics and Biological Activity of Lyo-Secretome Isolated by Ultrafiltration

Recently, we proposed a Good Manufacturing Practice (GMP)-compliant production process for freeze-dried mesenchymal stem cell (MSC)-secretome (lyo-secretome): after serum starvation, the cell supernatant was collected, and the secretome was concentrated by ultrafiltration and freeze-dried, obtaining a standardized ready-to-use and stable powder. In this work, we modified the type of human platelet lysate (HPL) used as an MSC culture supplement during the lyo-secretome production process: the aim was to verify whether this change had an impact on product quality and also whether this new procedure could be validated according to GMP, proving the process robustness. MSCs were cultured with two HPLs: the standard previously validated one (HPL-E) and the new one (HPL-S). From the same pool of platelets, two batches of HPL were obtained: HPL-E (by repeated freezing and thawing cycles) and HPL-S (by adding Ca-gluconate to form a clot and its subsequent mechanical wringing). Bone marrow MSCs from three donors were separately cultured with the two HPLs until the third passage and then employed to produce lyo-secretome. The following indicators were selected to evaluate the process performance: (i) the lyo-secretome quantitative composition (in lipids and proteins), (ii) the EVs size distribution, and (iii) anti-elastase and (iv) immunomodulant activity as potency tests. The new HPL supplementation for MSCs culture induced only a few minimal changes in protein/lipid content and EVs size distribution; despite this, it did not significantly influence biological activity. The donor intrinsic MSCs variability in secretome secretion instead strongly affected the quality of the finished product and could be mitigated by concentrating the final product to reach a determined protein (and lipid) concentration. In conclusion, the modification of the type of HPL in the MSCs culture during lyo-secretome production induces only minimal changes in the composition but not in the potency, and therefore, the new procedure can be validated according to GMP.     

Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP,TNF-α, and IL-6

Amyloidosis is a heterogeneous group of protein deposition diseases associated with the presence of amyloid fibrils in tissues. Analogs of insulin that are used for treating diabetic patients (including regular insulin) can form amyloid fibrils, both in vitro and in vivo as reported in patients. The main purpose of this study was the induction of localized insulin-generated amyloidosis and the observation of silymarin effects on this process. In order to obtain amyloid structures, regular insulin was incubated at 37 °C for 24 h. Congo red absorbance and transmission electron microscopy images validated the formation of amyloid fibrils. Those fibrils were then injected subcutaneously into rats once per day for 6, 12 or 18 consecutive days in the presence or absence of silymarin, and caused development of firm waxy masses. These masses were excised and stained with Hematoxylin and Eosin, Congo red and Thioflavin S. Histological examination showed adipose cells and connective tissue in which amyloid deposition was visible. Amyloids decreased in the presence of silymarin, and the same effect was observed when silymarin was added to normal insulin and injected subsequently. Furthermore, plasma concentrations of MMP2, TNF-α, and IL-6 inflammatory factors were measured, and their gene expression was locally assessed in the masses by immunohistochemistry. All three factors increased in the amyloidosis state, while silymarin had an attenuating effect on their plasma levels and gene expression. In conclusion, we believe that silymarin could be effective in counteracting insulin-generated local amyloidosis.     

Conditional neural sequence learners for generating drums’ rhythms

Neural Computing and Applications - Machine learning has shown a successful component of methods for automatic music composition. Considering music as a sequence of events with multiple complex...