An optimized, automatic TMS in operations in Roma Tiburtina and Monfalcone stations

Abstract A remarkable number of works on automatic train dispatching have recently appeared in the scientific literature, many of which also exploiting some exact or heuristic optimization. Despite of this blooming, very few automatic dispatching systems are actually in operations in main line or mass transit networks, mostly devoted to simple tasks in small lines. In this work we describe a recent implementation of a real time dispatching system monitoring and controlling trains in two large stations, namely Roma Tiburtina and Monfalcone. The system exploits optimization in order to take and implement crucial dispatching decisions. In particular, the algorithm finds suitable routes and schedules for the movements of trains in the station, so as to minimize costs and delays. The resulting trains movement is conflictfree, and respects safety and specific traffic rules. Also, it computes, exploits and provides accurate traffic forecast information based on the trains and railway real time status. A heuristic and an exact optimization algorithm, the latter based on Mixed Integer Linear Programming, are developed and run independently to introduce redundancy and increase safety. Computational experience on real-life instances shows that both methods are able to provide either good or optimal solutions in very short time (less than a second). A first release of the system is in operation since February 2014; the final release is scheduled to be operational by December 2014

Terahertz underdamped vibrational motion governs protein-ligand binding in solution

Low-frequency collective vibrational modes in proteins have been proposed as being responsible for efficiently directing biochemical reactions and biological energy transport. However, evidence of the existence of delocalized vibrational modes is scarce and proof of their involvement in biological function absent. Here we apply extremely sensitive femtosecond optical Kerr-effect spectroscopy to study the depolarized Raman spectra of lysozyme and its complex with the inhibitor triacetylchitotriose in solution. Underdamped delocalized vibrational modes in the terahertz frequency domain are identified and shown to blue-shift and strengthen upon inhibitor binding. This demonstrates that the ligand-binding coordinate in proteins is underdamped and not simply solvent-controlled as previously assumed. The presence of such underdamped delocalized modes in proteins may have significant implications for the understanding of the efficiency of ligand binding and protein–molecule interactions, and has wider implications for biochemical reactivity and biological function

Looking at NB-IoT over LEO Satellite Systems: Design and Evaluation of a Service-Oriented Solution

The adoption of the NB-IoT technology in satellite communications intends to boost Internet of Things services beyond the boundaries imposed by the current terrestrial infrastructures. Apart from link-level studies in the scientific literature and preliminary 3GPP technical reports, the overall debate is still open. To provide a further step forward in this direction, the work presented herein pursues a novel service-oriented methodology to design an effective solution, meticulously stitched around application requirements and technological constraints. To this end, it conducts link-level and system-level investigations to tune physical transmissions, satellite constellation, and protocol architecture, while ensuring the expected system behavior. To offer a real smart agriculture service operating in Europe, the resulting solution exploits 24 Low Earth Orbit satellites, grouped into 8 different orbits, moving at an altitude of 500 km. The configured protocol stack supports the transmission of tens of bytes generated at the application layer, by also counteracting the issues introduced by the satellite link. Since each satellite has the whole protocol stack on-board, terminals can transmit data without the need for the feeder link. This ensures communication latencies ranging from 16 minutes to 75 minutes, depending on the served number of terminals and the physical transmission settings. Moreover, the usage of the Early Data Transmission scheme reduces communication latencies up to 40%. These results pave the way towards the deployment of an effective proof-of-concept, which drastically reduces the time-to-market imposed by the current state of the art

Solvent contribution to the stability of a physical gel characterized by quasi-elastic neutron scattering

The dynamics of a physical gel, namely the Low Molecular Mass Organic Gelator {\textit Methyl-4,6-O-benzylidene-$\alpha$ -D-mannopyranoside ($\alpha$-manno)} in water and toluene are probed by neutron scattering. Using high gelator concentrations, we were able to determine, on a timescale from a few ps to 1 ns, the number of solvent molecules that are immobilised by the rigid network formed by the gelators. We found that only few toluene molecules per gelator participate to the network which is formed by hydrogen bonding between the gelators' sugar moieties. In water, however, the interactions leading to the gel formations are weaker, involving dipolar, hydrophobic or $\pi-\pi$ interactions and hydrogen bonds are formed between the gelators and the surrounding water. Therefore, around 10 to 14 water molecules per gelator are immobilised by the presence of the network. This study shows that neutron scattering can give valuable information about the behaviour of solvent confined in a molecular gel.Comment: Langmuir (2015

Water Dynamics at Protein Interfaces: Ultrafast Optical Kerr Effect Study

The behavior of water molecules surrounding a protein can have an important bearing on its structure and function. Consequently, a great deal of attention has been focused on changes in the relaxation dynamics of water when it is located at the protein surface. Here we use the ultrafast optical Kerr effect to study the H-bond structure and dynamics of aqueous solutions of proteins. Measurements are made for three proteins as a function of concentration. We find that the water dynamics in the first solvation layer of the proteins are slowed by up to a factor of 8 in comparison to those in bulk water. The most marked slowdown was observed for the most hydrophilic protein studied, bovine serum albumin, whereas the most hydrophobic protein, trypsin, had a slightly smaller effect. The terahertz Raman spectra of these protein solutions resemble those of pure water up to 5 wt % of protein, above which a new feature appears at 80 cm–1, which is assigned to a bending of the protein amide chain

Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial)

Background and Purpose—Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay. Methods—According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends. Results—We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60–1.08; P=0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (P=0.07). Conclusions—Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01881152

Cause specific mortality in an Italian pool of asbestos workers cohorts

Background Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers.Methods Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period.Results The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter.Conclusions Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time

Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy

Background: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos. Methods: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution. Results: Mortality was significantly increased for ‘All Causes’ and ‘All Malignant Neoplasm (MN)’, in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%. Conclusions: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studie

Italian pool of asbestos workers cohorts: asbestos related mortality by industrial sector and cumulative exposure

Objective. Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers. Methods. Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period. Results. The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most als

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor