Automating the simulation of SME processes through a discrete event parametric model

At the factory level, the manufacturing system can be described as a group of processes governed by complex weaves of engineering strategies and technologies. Decision- making processes involve a lot of information, driven by managerial strategies, technological implications and layout constraints. Many factors affect decisions, and their combination must be carefully managed to determine the best solutions to optimize performances. In this way, advanced simulation tools could support the decisional process of many SMEs. The accessibility of these tools is limited by knowledge, cost, data availability and development time. These tools should be used to support strategic decisions rather than specific situations. In this paper, a novel approach is proposed that aims to facilitate the simulation of manufacturing processes by fast modelling and evaluation. The idea is to realize a model that is able to be automatically adapted to the user’s specific needs. The model must be characterized by a high degree of flexibility, configurability and adaptability in order to automatically simulate multiple/heterogeneous industrial scenarios. In this way, even a SME can easily access a complex tool, perform thorough analyses and be supported in taking strategic decisions. The parametric DES model is part of a greater software platform developed during COPERNICO EU funded project

PKM mechatronic clamping adaptive device

This study proposes a novel adaptive fixturing device based on active clamping systems for smart micropositioning of thin-walled precision parts. The modular architecture and the structure flexibility make the system suitable for various industrial applications. The proposed device is realized as a Parallel Kinematic Machine (PKM), opportunely sensorized and controlled, able to perform automatic error-free workpiece clamping procedures, drastically reducing the overall fixturing set-up time. The paper describes the kinematics and dynamics of this mechatronic system. A first campaign of experimental trails has been carried out on the prototype, obtaining promising results

Karbantartási műveletek tervezése Monte Carlo szimulációval: Planning maintenance events with Monte Carlo simulation

The competitive marketplace in the manufacturing industry forces companies not only to reduce life cycle cost but also to increase the reliability and maintainability performance of their production system. The maintenance of production equipment, therefore, has an increasing importance. The evaluation of different maintenance scenarios can only be performed effectively by simulation methods. In this paper, a methodology for maintenance evaluation is presented, including the machine decomposition, life data analysis, simulation process and life cycle cost calculation. Kivonat A kiélezett piaci verseny miatt a termelő vállalatok nem csupán berendezésiek életcikluskölt-ségének csökkentésére, de megbízhatósági és karbantarthatósági jellemzőinek javítására is kényszerülnek, ami miatt e berendezések karbantartásának helyes megtervezése kiemelt jelentőségű feladat. A különböző karbantartási stratégiák és ütemezések hatékony értékelésére kizárólag szimuláció segítségével van mód. E cikkben a karbantartás tervezésének egy módszertana kerül bemutatására, érintve az alkatrészfa létrehozását, az élettartam analízist, a szimulációt és az életciklusköltség számítását

A journey down to hell: new thermostable protein-tags for biotechnology at high temperatures

The specific labelling of proteins in recent years has made use of self-labelling proteins, such as the SNAP-tag® and the Halotag®. These enzymes, by their nature or suitably engineered, have the ability to specifically react with their respective substrates, but covalently retaining a part of them in the catalytic site upon reaction. This led to the synthesis of substrates conjugated with, e.g., fluorophores (proposing them as alternatives to fluorescent proteins), but also with others chemical groups, for numerous biotechnological applications. Recently, a mutant of the OGT from Saccharolobus solfataricus (H5) very stable to high temperatures and in the presence of physical and chemical denaturing agents has been proposed as a thermostable SNAP-tag® for in vivo and in vitro harsh reaction conditions. Here, we show two new thermostable OGTs from Thermotoga neapolitana and Pyrococcus furiosus, which, respectively, display a higher catalytic activity and thermostability respect to H5, proposing them as alternatives for in vivo studies in these extreme model organisms

Real-time performance of mechatronic PZT module using active vibration feedback control

This paper proposes an innovative mechatronic piezo-actuated module to control vibrations in modern machine tools. Vibrations represent one of the main issues that seriously compromise the quality of the workpiece. The active vibration control (AVC) device is composed of a host part integrated with sensors and actuators synchronized by a regulator; it is able to make a self-assessment and adjust to alterations in the environment. In particular, an innovative smart actuator has been designed and developed to satisfy machining requirements during active vibration control. This study presents the mechatronic model based on the kinematic and dynamic analysis of the AVC device. To ensure a real time performance, a H2-LQG controller has been developed and validated by simulations involving a machine tool, PZT actuator and controller models. The Hardware in the Loop (HIL) architecture is adopted to control and attenuate the vibrations. A set of experimental tests has been performed to validate the AVC module on a commercial machine tool. The feasibility of the real time vibration damping is demonstrated and the simulation accuracy is evaluate

Wastewater-based epidemiology for early warning of SARS-COV-2 circulation: A pilot study conducted in Sicily, Italy

There is increasing evidence of the use of wastewater-based epidemiology to integrate conventional monitoring assessing disease symptoms and signs of viruses in a specific territory. We present the results of SARS-CoV-2 environmental surveillance activity in wastewater samples collected between September 2020 and July 2021 in 9 wastewater treatment plants (WTPs) located in central and western Sicily, serving over 570,000 residents. The presence of SARS-CoV-2, determined in 206 wastewater samples using RT-qPCR assays, was correlated with the notified and geo-referenced cases on the areas served by the WTPs in the same study period. Overall, 51% of wastewater samples were positive. Samples were correlated with 33,807 SARS-CoV-2 cases, reported in 4 epidemic waves, with a cumulative prevalence of 5.9% among Sicilian residents. The results suggest that the daily prevalence of SARS-CoV-2 active cases was statistically significant and higher in areas with SARS-CoV-2 positive wastewater samples. According to these findings, the proposed method achieves a good sensitivity profile (78.3%) in areas with moderate or high viral circulation (≥133 cases/100,000 residents) and may represent a useful tool in the management of epidemics based on an environmental approach, although it is necessary to improve the accuracy of the process

Kinase and phosphatase engagement is dissociated between memory formation and extinction

Associative long-term memories (LTMs) support long-lasting behavioural changes resulting from sensory experiences. Retrieval of a stable LTM by means of a large number of conditioned stimulus (CS) alone presentations produces inhibition of the original memory through extinction. Currently, there are two opposing hypotheses to account for the neural mechanisms supporting extinction. The unlearning hypothesis posits that extinction affects the original memory trace by reverting the synaptic changes supporting LTM. On the contrary, the new learning hypothesis proposes that extinction is simply the formation of a new associative memory that inhibits the expression of the original one. We propose that detailed analysis of extinction-associated molecular mechanisms could help distinguish between these hypotheses. Here we will review experimental evidence regarding the role of protein kinases and phosphatases on LTM formation and extinction. Even though kinases and phosphatases regulate both memory processes, their participation appears to be dissociated. LTM formation recruits kinases, but is constrained by phosphatases. Memory extinction presents a more diverse molecular landscape, requiring phosphatases and some kinases, but also being constrained by kinase activity. Based on the available evidence, we propose a new theoretical model for memory extinction: a neuronal segregation of kinases and phosphatases supports a combination of time-dependent reversible inhibition of the original memory (CS-US), with establishment of a new associative memory trace (CS-noUS)

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia, A double-blind, randomised, placebo-controlled trial

Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. Methods: In this multicenter, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with Covid-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need of supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. Results: Overall, 112 of 151 (75.4%) patients in the pulse methylprednisolone arm and 111 of 150 (75.2%) in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups [15 days (95% confidence interval (CI), 13.0 to 17.0) and 16 days (95%CI, 13.8 to 18.2); hazard ratio (HR), 0.92; 95% CI 0.71-1.20; p=0.528]. No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to Intensive Care Unit with orotracheal intubation or death (20.0% versus 16.1%; HR, 1.26; 95%CI, 0.74-2.16; p=0.176), or overall mortality (10.0% versus 12.2%; HR, 0.83; 95%CI, 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. Conclusions: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia. Message of the study: Pulse glucocorticoid therapy is used for severe and/or life threatening immuno-inflammatory diseases. The addition of pulse glucocorticoid therapy to the standard low dose of dexamethasone scheme was not of benefit in patients with COVID-19 pneumonia