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Remanufacturing represents one of the most promising strategies for promoting circular economy (CE) principles and achieving economic and environmental sustainability goals. The implementation of Industry 4.0 (I4.0) enabling technologies such as cloud computing and the Internet of Things in the classical remanufacturing process provides the opportunity to define a new approach called Cloud Remanufacturing, which realises a distributed system in which remanufacturing resources, located at different geographic sites, are shared and managed in a centralised environment. This paper aims to introduce the new concept of Cloud Remanufacturing by proposing a framework to explain its logic and characterise its main features. Furthermore, the mathematical relationships for evaluating the costs and the times for completing the remanufacturing process enhanced by I4.0 technologies will be developed, and, relying on them, the model will be tested for 2 scenarios involving different extended areas. In detail, the problem of activity scheduling in Cloud Remanufacturing will be addressed using two metaheuristic approaches. The results show the effectiveness and theoretical applicability of the model, even if a comparison with a real case study is not possible due to the lack of a real centrally managed remanufacturing distributed system.

Maintenance represents a critical aspect of manufacturing systems. Its optimization may lead companies to save costs related to production losses and can extend the whole lifecycle of assets or components. This paper aims at proposing a methodology for evaluating the behavior of systems for maintenance purpose by means of analysis carried out on real vibration data collected in the work environment. To this purpose, a digital twin approach has been developed and the statistical method of the control charts has been integrated to conduct the analysis about the vibration data. The methodology has been applied to a real case study in order to analyze the behavior of an electric motor used in the industrial sector and the results show that the method is effective in predicting possible failures that can lead to apply preventive maintenance actions.

Additive Manufacturing (AM) is increasingly adopted into manufacturing context mainly due its capabilities to produce very complex components in a more cost-effective way. Today more than ever, the environmental sustainability is an aspect not to be neglected. The aim of the research was to evaluate the potentials of AM technologies in terms of environmental sustainability by exploiting the Life Cycle Assessment (LCA) methodology. This study investigates the environmental impacts of the Selective Laser Sintering (SLS) and compared them with those deriving from the injection moulding process. In this study, the LCA has been applied to a section of the product life cycle, the so-called from cradle to gate approach. The LCA is a well-established quantitative method, governed by ISO 14040’s, for modelling the life cycle of a product and assessing its environmental impacts; it considers all the resources, e.g. energy and material, taken by each individual phase. The standardized steps of the LCA have been carried out using the software OPEN LCA® . A multi-scenario analysis has been conducted in order to assess the role of the production volume, the parts’ geometrical complexity in determining the environmental impacts. Since AM seems to have further technology development, a future scenario has been also implemented by improving some process parameters.

Purpose: ATTRACTION-2 trial assessed the role of Nivolumab as a new standard treatment for Asian patients with pretreated metastatic gastric cancer (mGC). The aim of this analysis was to evaluate the safety and efficacy of Nivolumab in a real-life Western population, considering the lack of evidence to date. Patients and Methods: Patients progressed after ≥2 chemotherapy regimens and able to receive Nivolumab (3 mg/kg q14) were eligible for the analysis. Results: 16 patients received Nivolumab as third (81.3%) or fourth line (18.7%) from September 2017 to July 2019. The safety was in line with the literature and only one patient discontinued treatment due to persistent hematological toxicity. Overall response rate and disease control rate were 18.7% and 31.2%, respectively. Median duration of response was 5 months. With a median follow-up of 21 months, median OS was 6 months (7, 21 and 22 months in the responders) and median PFS 3 months. PD-L1 and microsatellite status were retrospectively collected in 12 patients. All the major responders were MSI, although no statistically significant difference in OS or PFS was observed according to molecular analysis. Conclusion: Nivolumab is feasible and effective in Western patients with mGC. Further investigation is urgently needed also in non-Asians.

The mitochondrial Human Proteome Project aims at understanding the function of the mitochondrial proteome and its crosstalk with the proteome of other organelles. Being able to choose a suitable and validated enrichment protocol of functional mitochondria, based on the specific needs of the downstream proteomics analysis, would greatly help the researchers in the field. Mitochondrial fractions from ten model cell lines were prepared using three enrichment protocols and analyzed on seven different LC-MS/MS platforms. All data were processed using neXtProt as reference database. The data are available for the Human Proteome Project purposes through the ProteomeXchange Consortium with the identifier PXD007053. The processed datasets were analysed using a suite of R routines to perform a statistical analysis and to retrieve subcellular and sub-mitochondrial localizations. Although the overall number of identified total and mitochondrial proteins was not significantly dependent on the enrichment protocol, specific line to line differences were observed. Moreover, the protein lists were mapped to a network representing the functional mitochondrial proteome, encompassing mitochondrial proteins and their first interactors. More than 80% of the identified proteins resulted nodes of this network but with a different ability in co-isolating mitochondria-associated structures for each enrichment protocol/cell line pair.

BACKGROUND INFORMATION: Up-regulated Gene clone 7 (URG7) is an ER resident protein, whose expression is upregulated in the presence of hepatitis B virus X antigen (HBxAg) during HBV infection. In virus-infected hepatocytes, URG7 shows an anti-apoptotic activity due to the PI3K/AKT signaling activation, does not seem to have tumorigenic properties, but it appears to promote the development and progression of fibrosis. However, the molecular mechanisms underlying URG7 activity remain largely unknown. RESULTS: To shed light on URG7 activity, we first analyzed its interactome in HepG2 transfected cells: this analysis suggests that URG7 could have a role in affecting protein synthesis, folding and promoting proteins degradation. Moreover, keeping into account its subcellular localization in the ER and that several viral infections give rise to ER stress, a panel of experiments was performed to evaluate a putative role of URG7 in ER stress. Our main results demonstrate that in ER stressed cells URG7 is able to modulate the expression of Unfolded Protein Response (UPR) markers toward survival outcomes, upregulating GRP78 protein and downregulating the pro-apoptotic protein CHOP. Furthermore, URG7 reduces the ER stress by decreasing the amount of unfolded proteins, by increasing both the total protein ubiquitination and the AKT activation and reducing caspase 3 activation. CONCLUSIONS: All together these data suggest that URG7 plays a pivotal role as a reliever of ER stress-induced apoptosis. SIGNIFICANCE: This is the first characterization of URG7 activity under ER stress conditions. The results presented here will help to hypothesize new strategies to counteract the antiapoptotic activity of URG7 in the context of the viral infection. This article is protected by copyright. All rights reserved.

Performance-enhancing drugs (PEDs) gained wide popularity not only among sportsmen but also among specific subsets of population, such as adolescents. Apart from their claimed effects on athletic performance, they are very appealing due to the body shaping effect exerted on fat mass and fat-free mass. Besides the ‘‘underestimated’’ massive misuse of PEDs, the short- as well as long-term consequences of such habits remain largely unrecognized. They have been strictly associated with serious adverse effects, but molecular mechanisms are yet to be elucidated. Here, we analyze the current understanding of the molecular effects of supraphysiological doses of doping agents in healthy biological systems, at genomic and proteomic levels, in order to define the molecular sensors of organ/tissue impairment, determined by their misuse. The focus is put on the anabolic androgenic steroids (AASs), specifically testosterone (T) and its most potent derivative dihydrotestosterone (DHT), and on the peptide hormones, specifically the growth hormone (GH) and the insulin-like growth factor-1 (IGF-1). A map of molecular targets is defined and the risk incidence for human health is taken into account.

Background The effects of sex and oral contraceptives (OCs) on blood metabolites have been scarcely studied. Considering the widespread use of OCs and the fact that protocol designs for clinical trials emphasise the use of contraception for women of childbearing potential, we examined if OCs and sex affect the serum levels of the physiologically relevant amino acids, carnitine and acylcarnitines, using metabolomics approaches. Methods Thirty-five healthy adult men and 67 women aged between 20 and 47 years were enrolled. They were drug free with the exception of women taking cyclic format OCs that contained ethinylestradiol and different progestins. OC-free women were analysed during the first ten days of their menstrual cycles, and amino acids, free carnitine and acylcarnitines were measured using HPLC or LC/MS/MS. Results The serum levels of alanine, serine, aspartic acid, arginine and taurine were not significantly different among the analysed groups. Men had significantly higher leucine, isoleucine, methionine, phenylalanine, asparagine, glutamine + glutamate, and histidine than women who did not use OCs, while tryptophan was significantly lower in men. OC use significantly decreased the levels of glycine, proline, glutamine + glutamate, lysine, hydroxyproline and ornitine when compared with non-user women. The level of free carnitine was higher in men than in women; in addition, OC use further reduced the levels of carnitine in women although the reduction is not significant. Total esterified carnitines were higher in untreated women when compared with that of men and OC users. Globally, the effect of OCs and sex was specific for the individual esterified carnitine. The observed metabolic changes were not attributable to renal or hepatic functions or to differences in body weight. Conclusion The assessed parameters were specifically influenced by sex, highlighting the need to have reference values for women and men. The major novelty of this study is the demonstration that OCs specifically change the profiles of serum amino acids and carnitine, which suggests that OC users and non-users should be represented in clinical trials.