A systematic approach for product families formation in Reconfigurable Manufacturing Systems

The aim of this work is to establish a methodology for an effective working of Reconfigurable Manufacturing Systems (RMSs). These systems are the next step in manufacturing, allowing the production of any quantity of highly customised and complex products together with the benefits of mass production. In RMSs, products are grouped into families, each of which requires a system configuration. The system is configured to produce the first family of products. Once it is finished, the system is reconfigured in order to produce the second family, and so forth. Therefore, the effectiveness of a RMS depends on the formation of the best set of product families. Therefore, a methodology for grouping products into families, which takes into account the requirements of products in RMSs, is an issue of core importance. These requirements are modularity, commonality, compatibility, reusability, and product demand. The methodology starts by calculating, for each product requirement, a matrix that summarises the similarity between pairs of products. Then, through the use of the AHP methodology, a unique matrix that comprises the similarity values between products is obtained. The Average Linkage Clustering algorithm is applied to this matrix in order to obtain a dendogram that shows the diverse sets of product families that may be formed.     

Influence of Manufacturing and Ripening Conditions on the Survival of Enterobacteriaceae in Manchego Cheese

The effects of cooking temperature, time and temperature of brine-salting, and temperature of ripening on the behavior of Enterobacteriaceae in Manchego cheese were studied. Fifty lots of cheese from raw ewe's milk manufactured and ripened under different conditions were investigated throughout a 60-day ripening period. Differences in pH values due to temperature-dependent whey retention accounted for the effect of cooking temperature on coliform and fecal coliform counts. Temperature of brine-salting had no effect on Enterobacteriaceae counts, but a significant effect of salting time on Enterobacteriaceae and fecal coliform counts was detected. Ripening temperature was the manufacturing variable with greatest influence (P<.01) on Enterobacteriaceae and coliform counts during the whole curing period.     

Influence of cooking and drying processes at different temperatures on the nutritive value of the protein of mussels (Mytilus edulis)

The effect of steam cooking (96 degrees C for 15 minutes) and drying at two temperatures, 70 degrees C and 110 degrees C, on nutritive value of mussel protein was studied. The measurements were carried out by nitrogen balance techniques in growing rats, and the nutritional parameters studied were: CD, BV and NPU. The crude digestibility (CD) values were: 87 +/- 1 and 82 +/- 1, and the biological values (BV), 80 +/- 1 and 74 +/- 1 for raw mussels, dried at 70 degrees C and at 110 degrees C respectively. This implies a significant decrease in the protein nutritive values of the mussel dried at a higher temperature. Cooking prior to drying significantly improved the digestibility and the biological value of the mussel's protein. In effect, improvement was so great, that the different drying temperatures did not affect the previously cooked product in a different way; therefore, the CD (94 +/- 1 and 94 +/- 1) and the BV (90 +/- 1 and 90 +/- 2) were the same for the mussel's protein, cooked and dried at 70 degrees C or at 110 degrees C.     

Lack of PPCA expression only partially coincides with lysosomal storage in galactosialidosis mice: indirect evidence for spatial requirement of the catalytic rather than the protective function of PPCA

Protective protein/cathepsin A (PPCA) is a pleiotropic lysosomal enzyme that complexes with beta-galactosidase and neuraminidase, and possesses serine carboxypeptidase activity. Its deficiency in man results in the neurodegenerative lysosomal storage disorder galactosialidosis (GS). The mouse model of this disease resembles the human early onset phenotype and results in severe nephropathy and ataxia. To understand better the pathophysiology of the disease, we compared the occurrence of lysosomal PPCA mRNA and protein in normal adult mouse tissues with the incidence of lysosomal storage in PPCA(-/-) mice. PPCA expression was markedly variable among different tissues. Most sites that produced both mRNA and protein at high levels in normal mice showed extensive and overt storage in the knockout mice. However, this correlation was not consistent as some cells that normally expressed high levels of PPCA were unaffected in their storage capability in the PPCA(-/-) mice. In addition, some normally low expressing cells accumulated large amounts of undegraded products in the GS mouse. This apparent discrepancy may reflect a requirement for the catalytic rather than the protective function of PPCA and/or the presence of cell-specific substrates in certain cell types. A detailed map showing the cellular distribution of PPCA in nomal mouse tissues as well as the sites of lysosomal storage in deficient mice is critical for accurate assessment of the effects of therapeutic interventions.     

HIF-1α and Pro-Inflammatory Signaling Improves the Immunomodulatory Activity of MSC-Derived Extracellular Vesicles

Despite the strong evidence for the immunomodulatory activity of mesenchymal stromal cells (MSCs), clinical trials have so far failed to clearly show benefit, likely reflecting methodological shortcomings and lack of standardization. MSC-mediated tissue repair is commonly believed to occur in a paracrine manner, and it has been stated that extracellular vesicles (EVs) secreted by MSCs (EVMSC) are able to recapitulate the immunosuppressive properties of parental cells. As a next step, clinical trials to corroborate preclinical studies should be performed. However, effective dose in large mammals, including humans, is quite high and EVs industrial production is hindered by the proliferative senescence that affects MSCs during massive cell expansion. We generated a genetically modified MSC cell line overexpressing hypoxia-inducible factor 1-alpha and telomerase to increase the therapeutic potency of EVMSC and facilitate their large-scale production. We also developed a cytokine-based preconditioning culture medium to prime the immunomodulatory response of secreted EVs (EV_MSC-T-HIF^c). We tested the efficacy of this system in vitro and in a delayed-type hypersensitivity mouse model. MSC-T with an HIF-1α-GFP lentiviral vector (MSC-T-HIF) can be effectively expanded to obtain large amounts of EVs without major changes in cell phenotype and EVs composition. EV_MSC-T-HIF^c suppressed the proliferation of activated T-cells more effectively than did EVs from unmodified MSC in vitro, and significantly blunted the ear-swelling response in vivo by inhibiting cell infiltration and improving tissue integrity. We have developed a long-lived EV source that secretes high quantities of immunosuppressive EVs, facilitating a more standard and cost-effective therapeutic product.     

Low-Thermal-Conductivity Rare-Earth Zirconates for Potential Thermal-Barrier-Coating Applications

Rare-earth zirconates have been identified as a class of low-thermal-conductivity ceramics for possible use in thermal barrier coatings (TBCs) for gas-turbine engine applications. To document and compare the thermal conductivities of important rare-earth zirconates, we have measured the thermal conductivities of the following hot-pressed ceramics: (i) Gd₂Zr₂O₇ (pyrochlore phase), (ii) Gd₂Zr₂O₇ (fluorite phase), (iii) Gd_2.58Zr_1.57O₇ (fluorite phase), (iv) Nd₂Zr₂O₇ (pyrochlore phase), and (v) Sm₂Zr₂O₇ (pyrochlore phase). We have also measured the thermal conductivity of pressureless-sintered 7 wt% yttria-stabilized zirconia (7YSZ)—the commonly used composition in current TBCs. All rare-earth zirconates investigated here showed nearly identical thermal conductivities, all of which were ∼30% lower than the thermal conductivity of 7YSZ in the temperature range 25°–700°C. This finding is discussed qualitatively with reference to thermal-conductivity theory.