The Design of Effective Maintenance Outsourcing Contracts

Recent developments in maintenance planning and management demonstrate that the establishment of optimized maintenance policies may drastically improve the performance and reduce the operating cost of facilities. However maintenance activities are typically outside of the core business of production facilities, hence enterprises often fail to catch the opportunities that may originate by properly optimized management strategies. A strategic maintenance management should hence encompass the possibility of outsourcing maintenance activities to ensure the necessary perfomance of production systems, while allowing enterprises to concentrate their resources on their core activities. In order to be effectively undertaken an outsourcing strategy must be supported by a proper performance oriented contract. The present paper aims to provide an adequate methodology to address such issues and to define a framework for the definition of the relevant contract variables such as availability levels, penalty policies, rewards and service cost. The methodology here proposed is based upon the evaluation of the expected profit function of both the outsourcer and the provider, by performing a trade-off analysis on the basis of the transaction costs

Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms

Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX) model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed altered voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 μg/kg/infusion). To this aim, olfactory-bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)] schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behavior after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5-10 mg/kg), did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive-like state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats

Towards the implementation of circular economy in the water softening industry: A technical, economic and environmental analysis

To reduce the environmental impact of the industrial sectors, circular strategies should be implemented to purify the effluents and recover raw materials. In this context, a novel integrated methodological approach is proposed to identify the most suitable strategy to improve the sustainability of the water softening industry via the treatment and recycling of the produced wastewater. Different concentration technologies and energy supply systems are compared to find economically feasible and environmentally friendly treatment systems. The investigated chains present the same pre-treatment step (nanofiltration and crystallization) and different concentration technologies: Multi-Effect Distillation (MED), Membrane Distillation (MD) and the coupling of Reverse Osmosis and Membrane Distillation (RO-MD). In the case of electricity supplied by the grid, the MED and the RO-MD chain are economically competitive with the state of the art (Levelized Brine Cost (LBC) between 4 and 6$/m3, lower than the regenerant solution cost, equal to 8$/m3). Moreover, the specific CO2 emissions due to the energy required by the treatment processes (10.8 kgCO2/m3regenerant for the MED chain and 16.7kgCO2/m3regenerant for the RO-MD chain) are lower than those produced by the current system (19.7kgCO2/m3regenerant). Varying the feed flow rate, the MED-chain is more feasible at larger plant sizes for its lower energy demand, while the chain including RO-MD shows lower costs at smaller plant sizes for its lower investment costs. When a photovoltaic-battery system is coupled, both the MED-chain and RO-MD-chain show a CO2 emission reduction of more than 75% with respect to the state of the art. Furthermore, their LBC values are very competitive, especially if the plant is located in a region with high solar potential

Deficiency of histone variant macroH2A1.1 is associated with sexually dimorphic obesity in mice

Obesity has a major socio-economic health impact. There are profound sex differences in adipose tissue deposition and obesity-related conditions. The underlying mechanisms driving sexual dimorphism in obesity and its associated metabolic disorders remain unclear. Histone variant macroH2A1.1 is a candidate epigenetic mechanism linking environmental and dietary factors to obesity. Here, we used a mouse model genetically depleted of macroH2A1.1 to investigate its potential epigenetic role in sex dimorphic obesity, metabolic disturbances and gut dysbiosis. Whole body macroH2A1 knockout (KO) mice, generated with the Cre/loxP technology, and their control littermates were fed a high fat diet containing 60% of energy derived from fat. The diet was administered for three months starting from 10 to 12 weeks of age. We evaluated the progression in body weight, the food intake, and the tolerance to glucose by means of a glucose tolerance test. Gut microbiota composition, visceral adipose and liver tissue morphology were assessed. In addition, adipogenic gene expression patterns were evaluated in the visceral adipose tissue. Female KO mice for macroH2A1.1 had a more pronounced weight gain induced by high fat diet compared to their littermates, while the increase in body weight in male mice was similar in the two genotypes. Food intake was generally increased upon KO and decreased by high fat diet in both sexes, with the exception of KO females fed a high fat diet that displayed the same food intake of their littermates. In glucose tolerance tests, glucose levels were significantly elevated upon high fat diet in female KO compared to a standard diet, while this effect was absent in male KO. There were no differences in hepatic histology. Upon a high fat diet, in female adipocyte cross-sectional area was larger in KO compared to littermates: activation of proadipogenic genes (ACACB, AGT, ANGPT2, FASN, RETN, SLC2A4) and downregulation of antiadipogenic genes (AXIN1, E2F1, EGR2, JUN, SIRT1, SIRT2, UCP1, CCND1, CDKN1A, CDKN1B, EGR2) was detected. Gut microbiota profiling showed increase in Firmicutes and a decrease in Bacteroidetes in females, but not males, macroH2A1.1 KO mice. MacroH2A1.1 KO mice display sexual dimorphism in high fat diet-induced obesity and in gut dysbiosis, and may represent a useful model to investigate epigenetic and metabolic differences associated to the development of obesity-associated pathological conditions in males and female

Metal-Organic-Framework-based nanofiltration membranes for selective multi-cationic recovery from seawater and brines

Nanofiltration (NF) is gaining a role of increasing importance in Zero Liquid Discharge (ZLD)/Minimal Liquid Discharge (MLD) systems, enhancing the efficiency of downstream technologies to recover valuable minerals from seawater and brines. However, often the purity of the recovered minerals does not meet market specifications, making ZLD/MLD currently economically unfeasible. To such end, in this study, a novel positively charged NF membrane was developed to enhance magnesium and calcium selectivity. The membrane comprised: (i) an ultrafiltration substrate and (ii) an active layer that incorporated NH2-MIL-101(Al) and ZnO nanoparticles in a chitosan matrix. The influence of different loadings of NH2-MIL-101(Al) and ZnO on membrane structure, selectivity and water permeability was investigated. Initial filtration tests with single-salt solutions at 1000 ppm (NaCl, Na2SO4, MgCl2, CaCl2) showed that the membrane with 35%wt of ZnO presented the highest rejections of MgCl2 (90.10%) and CaCl2 (86.49%). Selectivity towards MgCl2 and CaCl2 was higher than those of commercial membranes (NF90 and NF270) and the positively charged membranes introduced in recent literature. The novel synthesized membrane in this work was also tested with synthetic seawater and brine at a trans-membrane pressure of 30 bar. Results highlighted the intriguing competitiveness of the novel membrane in terms of magnesium and calcium selectivity with NF90 and NF270 within the field of both seawater and brine valorization

Extracellular Vesicles in Biological Fluids. A Biomarker of Exposure to Cigarette Smoke and Treatment with Chemopreventive drugs

Extracellular vesicles (EVs) are released from cells and enter into body fluids thereby providing a toxicological mechanism of cell-cell communication. The present study aimed at assessing (a) the presence of EVs in mouse body fluids under physiological conditions, (b) the effect of exposure of mice to cigarette smoke for 8 weeks, and (c) modulation of smoke-related alterations by the nonsteroidal anti-inflammatory drug celecoxib, a selective cyclooxygenase-2 inhibitor. To this purpose, ICR (CD-1) mice were either unexposed or exposed to cigarette smoke, either treated or untreated with oral celecoxib. EVs, isolated from bronchoalveolar lavage fluid (BALF), blood serum, and urines, were analyzed by nanoparticle tracking analysis and flow cytometry. EVs baseline concentrations in BALF were remarkably high. Larger EVs were detected in urines. Smoking increased EVs concentrations but only in BALF. Celecoxib remarkably increased EVs concentrations in the blood serum of both male and female smoking mice. The concentration of EVs positive for EpCAM, a mediator of cell-cell adhesion in epithelia playing a role in tumorigenesis, was much higher in urines than in BALF, and celecoxib significantly decreased their concentration. Thus, the effects of smoke on EVs concentrations were well detectable in the extracellular environment of the respiratory tract, where they could behave as delivery carriers to target cells. Celecoxib exerted both protective mechanisms in the urinary tract and adverse systemic effects of likely hepatotoxic origin in smoke-exposed mice. Detection of EVs in body fluids may provide an early diagnostic tool and an end-point exploitable for preventive medicine strategies.

A methodology for assessing the impact of salinity gradient power generation in urban contexts

The paper proposes a methodology to assess the potential impact of salinity gradient power technology in urban contexts. The idea to employ such energy source in urban contexts derives from the observation that, among the energy districts outputs, low-salinity treated wastewater can be used to produce electricity if a suitable source of high salinity feed (seawater of a salt-works) is also available. The methodology uses the HOMER software for assessing the district’s electric energy production, consumption and exchange with the main grid. Then, starting from the total gross surface and the number of inhabitants of the district, some possible realistic scenarios characterized by different wastewater flow rate are defined. Finally, for each scenario the size and the yearly energy production of the salinity gradient power system are calculated thanks to a simulator carried out by the same authors. An application example, considering three different scenarios, shows that urban density plays a crucial role in the process and that the most promising realistic scenarios are those including treated wastewater and brine and unlimited seawater and brine. The economic feasibility of the salinity gradient power technology is evaluated by a comparison with classical renewable technologies such as photovoltaic and wind systems

Pseudo-dipeptide bearing α,α-difluoromethyl ketone moiety as electrophilic warhead with activity against coronaviruses

The synthesis of α-fluorinated methyl ketones has always been challenging. New methods based on the homologation chemistry via nucleophilic halocarbenoid transfer, carried out recently in our labs, allowed us to design and synthesize a target-directed dipeptidyl α,α-difluoromethyl ketone (DFMK) 8 as a potential antiviral agent with activity against human coronaviruses. The ability of the newly synthesized compound to inhibit viral replication was evaluated by a viral cytopathic effect (CPE)-based assay performed on MCR5 cells infected with one of the four human coronaviruses associated with respiratory distress, i.e., hCoV-229E, showing antiproliferative activity in the micromolar range (EC50 = 12.9 ± 1.22 µM), with a very low cytotoxicity profile (CC50 = 170 ± 3.79 µM, 307 ± 11.63 µM, and 174 ± 7.6 µM for A549, human embryonic lung fibroblasts (HELFs), and MRC5 cells, respectively). Docking and molecular dynamics simulations studies indicated that 8 efficaciously binds to the intended target hCoV-229E main protease (Mpro). Moreover, due to the high similarity between hCoV-229E Mpro and SARS-CoV-2 Mpro, we also performed the in silico analysis towards the second target, which showed results comparable to those obtained for hCoV-229E Mpro and promising in terms of energy of binding and docking pose

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist/inverse agonist AM251 (0.5 mg/kg/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood

Metal-Organic-Framework-based nanofiltration membranes for selective multi-cationic recovery from seawater and brines

Nanofiltration (NF) is gaining a role of increasing importance in Zero Liquid Discharge (ZLD)/Minimal Liquid Discharge (MLD) systems, enhancing the efficiency of downstream technologies to recover valuable minerals from seawater and brines. However, often the purity of the recovered minerals does not meet market specifications, making ZLD/MLD currently economically unfeasible. To such end, in this study, a novel positively charged NF membrane was developed to enhance magnesium and calcium selectivity. The membrane comprised: (i) an ultrafiltration substrate and (ii) an active layer that incorporated NH2-MIL-101(Al) and ZnO nanoparticles in a chitosan matrix. The influence of different loadings of NH2-MIL-101(Al) and ZnO on membrane structure, selectivity and water permeability was investigated. Initial filtration tests with single-salt solutions at 1000 ppm (NaCl, Na2SO4, MgCl2, CaCl2) showed that the membrane with 35%wt of ZnO presented the highest rejections of MgCl2 (90.10%) and CaCl2 (86.49%). Selectivity towards MgCl2 and CaCl2 was higher than those of commercial membranes (NF90 and NF270) and the positively charged membranes introduced in recent literature. The novel synthesized membrane in this work was also tested with synthetic seawater and brine at a trans-membrane pressure of 30 bar. Results highlighted the intriguing competitiveness of the novel membrane in terms of magnesium and calcium selectivity with NF90 and NF270 within the field of both seawater and brine valorization.The authors would like to acknowledge that parts of the research activities were carried out within the framework of "Programma Operativo Nazionale Ricerca e Innovazione2014-2020 (CCI 2014IT16M2OP005), Fondo Sociale Europeo, Azione I.1 “Dottorati Innovativi con caratterizzazione Industriale”, Code: DOT204NJ79, CUP: B73D20005110001. J. López research was developed under the Margarita Salas postdoctoral fellowship from Ministerio de Universidades (MIU) and founded by the European Union-NextGenerationEU. Moreover, J.L. Cortina received support for the research through the “ICREA Academia” recognition for excellence in research funded by the Generalitat de Catalunya.Peer ReviewedPostprint (published version