Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

A Framework for Using Web Services to Enhance QoS for Content Delivery

An integrated approach to quality of service for content delivery using Web services includes quality definitions, user contracts, and fault monitoring.     

Assessment of interatomic parameters for the reproduction of borosilicate glass structures via DFT-GIPAW calculations

Borates and borosilicates are potential candidates for the design and development of glass formulations with important industrial and technological applications. A major challenge that retards the pace of development of borate/borosilicate based glasses using predictive modeling is the lack of reliable computational models to predict the structure-property relationships in these glasses over a wide compositional space. A major hindrance in this pursuit has been the complexity of boron-oxygen bonding due to which it has been difficult to develop adequate B–O interatomic potentials. In this article, we have evaluated the performance of three B–O interatomic potential models recently developed by Bauchy et al [J. Non-Cryst. Solids, 2018, 498, 294–304], Du et al [J. Am. Ceram. Soc. https://doi.org/10.1111/jace.16082 ] and Edèn et al [Phys. Chem. Chem. Phys., 2018, 20, 8192–8209] aiming to reproduce the short-to-medium range structures of sodium borosilicate glasses in the system 25 Na₂O x B₂O₃ (75 − x) SiO₂ (x = 0-75 mol%). To evaluate the different force fields, we have computed at the density functional theory level the NMR parameters of ¹¹B, ²³Na, and ²⁹Si of the models generated with the three potentials and the simulated MAS NMR spectra compared with the experimental counterparts. It was observed that the rigid ionic models proposed by Bauchy and Du can both reliably reproduce the partitioning between BO₃ and BO₄ species of the investigated glasses, along with the local environment around sodium in the glass structure. However, they do not accurately reproduce the second coordination sphere of silicon ions and the Si–O–T (T = Si, B) and B-O-T distribution angles in the investigated compositional space which strongly affect the NMR parameters and final spectral shape. On the other hand, the core-shell parameterization model proposed by Edén underestimates the fraction of BO₄ species of the glass with composition 25Na₂O 18.4B₂O₃ 56.6SiO₂ but can accurately reproduce the shape of the ¹¹B and ²⁹Si MAS-NMR spectra of the glasses investigations due to the narrower B–O–T and Si-O-T bond angle distributions. Finally, the effect of the number of boron atoms (also distinguishing the BO₃ and BO₄ units) in the second coordination sphere of the network former cations on the NMR parameters have been evaluated.     

Advanced control in factory automation: a survey

This paper provides a survey of the main advanced control techniques currently adopted in factory automation. In particular, it focuses on five classes of control approaches, namely: model-based control, control based on computational intelligence, adaptive control, discrete event systems-based control and finally event-triggered and self-triggered control. A particular focus is put on the most significant and recent contributions in these areas with attention to their application in the factory automation domain. Finally, open issues, challenges and the requirements of further research efforts for each class are pointed out.     

Real time identification of discrete event systems using Petri nets

The paper defines the identification problem for Discrete Event Systems (DES) as the problem of inferring a Petri Net () model using the observation of the events and the available output vectors, that correspond to the markings of the measurable places. Two cases are studied considering different levels of the system knowledge. In the first case the place and transition sets are assumed known. Hence, an integer linear programming problem is defined in order to determine a modelling the DES. In the second case the transition and place sets are assumed unknown and only an upper bound of the number of places is given. Hence, the identification problem is solved by an identification algorithm that observes in real time the occurred events and the corresponding output vectors. The integer linear programming problem is defined at each observation so that the can be recursively identified. Some results and examples characterize the identified systems and show the flexibility and simplicity of the proposed technique. Moreover, an application to the synthesis of supervisory control of systems via monitor places is proposed.     

Identification of the unobservable behaviour of industrial automation systems by Petri nets

This paper addresses the problem of identifying the model of the unobservable behaviour of discrete event systems in the industrial automation sector. Assuming that the fault-free system structure and dynamics are known, the paper proposes an algorithm that monitors the system on-line, storing the occurred observable event sequence and the corresponding reached states. At each event observation, the algorithm checks whether some unobservable events have occurred on the basis of the knowledge of the Petri net (PN) modelling the nominal system behaviour and the knowledge of the current PN marking. By defining and solving some integer linear programming problems, the algorithm decides whether it is necessary to introduce some unobservable (silent) transitions in the PN model and provides a PN structure that is consistent with the observed event string. A case study describing an industrial automation system shows the efficiency and the applicability of the proposed algorithm.     

The role of antioxidant supplement in immune system,neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile

This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS) play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects.     

The impact of ICT on intermodal transportation systems: A modelling approach by Petri nets

The paper addresses the issues of modelling and managing Intermodal Transportation Systems (ITS) at the operational level, considering the impact of the new Information and Communication Technologies (ICT). ITS are regarded as discrete event systems and are modelled in a timed Petri net framework. In order to show the efficiency of the ITS modelling and controlling technique, the case study of the ferry terminal of Trieste (Italy) is considered. The results show that the approach can be employed to verify the potential of ICT for efficient real time management of ITS, and their impact on the ITS infrastructures.     

On-line fault detection in discrete event systems by Petri nets and integer linear programming

The paper addresses the fault detection problem for discrete event systems in a Petri Net (PN) framework. Assuming that the structure of the PN model and the initial marking are known, faults are modelled by unobservable transitions. Moreover, we assume that there may be additional unobservable transitions associated with the system legal behaviour and that the marking reached after the firing of any transition is unknown. The proposed diagnoser works on-line: it waits for the firing of an observable transition and employs an algorithm based on the definition and solution of some integer linear programming problems to decide whether the system behaviour is normal or exhibits some possible faults. The results characterize the properties that the PN modelling the system fault behaviour has to fulfill in order to reduce the on-line computational effort.     

A hierarchical optimization technique for the strategic design of distribution networks

The paper addresses the optimal design of the last supply chain branch, i.e., the Distribution Network (DN), starting from manufacturers till the retailers. It considers a distributed system composed of different stages connected by material links labeled with suitable performance indices. A hierarchical procedure employing direct graph (digraph) modeling, mixed integer linear programming, and the Analytic Hierarchy Process (AHP) is presented to select the optimal DN configuration. More in detail, a first-level DN optimization problem taking into account the definition and evaluation of the distribution chain performance provides a set of Pareto optimal solutions defined by digraph modeling. A second level DN optimization using the AHP method selects, on the basis of further criteria, the DN configuration from the Pareto face alternatives. To show the method effectiveness, the optimization model is applied to a case study describing an Italian regional healthcare drug DN. The problem solution by the proposed design method allows improving the DN flexibility and performance.