Effects of Eltrombopag on In Vitro Macrophage Polarization in Pediatric Immune Thrombocytopenia

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug.     

Different Stages of Quiescence,Senescence, and Cell Stress Identified by Molecular Algorithm Based on the Expression of Ki67, RPS6, and Beta-Galactosidase Activity

During their life span, cells have two possible states: a non-cycling, quiescent state (G0) and a cycling, activated state. Cells may enter a reversible G0 state of quiescence or, alternatively, they may undergo an irreversible G0 state. The latter may be a physiological differentiation or, following a stress event, a senescent status. Discrimination among the several G0 states represents a significant investigation, since quiescence, differentiation, and senescence are progressive phenomena with intermediate transitional stages. We used the expression of Ki67, RPS6, and beta-galactosidase to identify healthy cells that progressively enter and leave quiescence through G0-entry, G0 and G0-alert states. We then evaluated how cells may enter senescence following a genotoxic stressful event. We identified an initial stress stage with the expression of beta-galactosidase and Ki67 proliferation marker. Cells may recover from stress events or become senescent passing through early and late senescence states. Discrimination between quiescence and senescence was based on the expression of RPS6, a marker of active protein synthesis that is present in senescent cells but absent in quiescent cells. Even taking into account that fixed G0 states do not exist, our molecular algorithm may represent a method for identifying turning points of G0 transitional states that continuously change.     

Challenges in supply chain redesign for the Circular Economy: a literature review and a multiple case study

Despite companies face several challenges when redesigning their supply chain for the Circular Economy, the literature lacks a systematisation of such challenges and of the ways to overcome them. Through a systematic literature review, this paper identifies and systematises 24 challenges that may hamper a supply chain redesign for the Circular Economy. Sixteen among these challenges are well known from research in related topics. On the contrary, the remaining eight are relatively new or take a different relevance within the Circular Economy context. A multiple case study in the household appliance supply chain is carried out, to explore how these challenges appear in practice and how companies may tackle them. The cases analysed involve actors at different supply chain levels, and findings suggest that a great degree of vertical integration by one actor in the supply chain is not a necessary condition for Circular Economy implementation. The empirical study, in conjunction with the literature analysis, leads to the development of a framework linking the challenges to specific levers that companies may pursue to overcome them. The framework can be seen as a reference for managers undertaking the path towards Circular Economy.     

POD-assisted strategies for structural topology optimization

We propose a new numerical tool for structural optimization design. To cut down the computational burden typical of the Solid Isotropic Material with Penalization (SIMP) method, we apply Proper Orthogonal Decomposition on SIMP snapshots computed on a fixed grid to construct a rough structure (predictor) which becomes the input of a SIMP procedure performed on an anisotropic adapted mesh (corrector). The benefit of the proposed design tool is to deliver smooth and sharp layouts which require a contained computational effort before moving to the 3D printing production phase.     

Trans-differentiation of human adipose-derived mesenchymal stem cells into cardiomyocyte-like cells on decellularized bovine myocardial extracellular matrix-based films

In this study, we aimed at fabricating decellularized bovine myocardial extracellular matrix-based films (dMEbF) for cardiac tissue engineering (CTE). The decellularization process was carried out utilizing four consecutive stages including hypotonic treatment, detergent treatment, enzymatic digestion and decontamination, respectively. In order to fabricate the dMEbF, dBM were digested with pepsin and gelation process was conducted. dMEbF were then crosslinked with N-hydroxysuccinimide/1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (NHS/EDC) to increase their durability. Nuclear contents of native BM and decellularized BM (dBM) tissues were determined with DNA content analysis and agarose-gel electrophoresis. Cell viability on dMEbF for 3rd, 7th, and 14th days was assessed by MTT assay. Cell attachment on dMEbF was also studied by scanning electron microscopy. Trans-differentiation capacity of human adipose-derived mesenchymal stem cells (hAMSCs) into cardiomyocyte-like cells on dMEbF were also evaluated by histochemical and immunohistochemical analyses. DNA contents for native and dBM were, respectively, found as 886.11?±?164.85 and 47.66?±?0.09?ng/mg dry weight, indicating a successful decellularization process. The results of glycosaminoglycan and hydroxyproline assay, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), performed in order to characterize the extracellular matrix (ECM) composition of native and dBM tissue, showed that the BM matrix was not damaged during the proposed method. Lastly, regarding the histological study, dMEbF not only mimics native ECM, but also induces the stem cells into cardiomyocyte-like cells phenotype which brings it the potential of use in CTE.     

Thermodynamic performance analysis of three solid oxide fuel cell and gas microturbine hybrid systems for application in auxiliary power units

In this study, three different configurations of a solid oxide fuel cell and gas microturbine hybrid system are evaluated for application in auxiliary power units. The first configuration is a common hybrid system in auxiliary power units, utilizing a fuel cell stack in the structure of the gas turbine cycle. The other configurations use two series and parallel fuel cell stacks in the structure of the gas turbine cycle. The main purpose of this research is thermodynamic analysis, evaluation of the performance of the proposed hybrid systems in similar conditions, and selection of an appropriate system in terms of efficiency, power generation, and entropy generation rate. In this study, the utilized fuel cells were subjected to electrochemical, thermodynamic, and thermal analyses and their working temperatures were calculated under various working conditions. Results indicate that the hybrid system with two series stacks had maximum power generation and efficiency compared with the other two cases. Moreover, the simple hybrid system and the system with two parallel stacks had relatively equal pure power generation and efficiency. According to the investigations, hybrid system with two series fuel cell stacks, which had 3424 and 1712 cells, respectively, can achieve the electrical efficiency of over 48%. A hybrid system with two parallel fuel cell stacks, in which each stack had 2568 cells, had the electrical efficiency of 46.3%. Findings suggested that maximum electrical efficiency occurred between the pressure ratios of 5–6 in the proposed hybrid systems.     

Effect of sand and clay fouling on the shear strength of railway ballast for different ballast gradations

Ballast contamination by fine materials such as sand and clay in railway track at arid regions is an important issue that causes track instability problems and settlement due to reduction of shear strength of ballast. In this paper, the results of direct shear box test conducted on clean ballast, sand-fouled ballast and clay-fouled ballast for different ballast gradations are reported and discussed. For this purpose, three different fouling amounts according to fouling index are added to clean ballast. Test results show that by increasing the fouling percentage, the ballast shear strength always decreases both for sand and clay fouled ballast. However, the amount of shear strength reduction is low at high normal stresses. Clay contamination has more adverse effect on the shear strength of ballast compared with sand contamination. Also, the results of tests for evaluation of gradation effect on shear strength of fouled ballast which are conducted on various gradations according to American Railway Engineering and Maintenance-of-Way Association, show that the maximum particle size as well as uniformity coefficient affect the shear strength of ballast. Also, an empirical equation is presented to observe the effect of ballast gradation on reduction of shear strength with regard to amount of fouling material and normal stress.