Marking Estimation of Petri Nets With Silent Transitions

In this paper, we deal with the problem of estimating the marking of a labeled Petri net system based on the observation of transitions labels. In particular, we assume that a certain number of transitions are labeled with the empty string , while unique labels taken from a given alphabet are assigned to each of the other transitions. Transitions labeled with the empty string are called silent because their firing cannot be observed. Under some technical assumptions on the structure of the unobservable subnet, we formally prove that the set of markings consistent with the observed word can be represented by a linear system with a fixed structure that does not depend on the length of the observed word.     

On Nonparametric Residual Variance Estimation

In this paper, the problem of residual variance estimation is examined. The problem is analyzed in a general setting which covers non-additive heteroscedastic noise under non-iid sampling. To address the estimation problem, we suggest a method based on nearest neighbor graphs and we discuss its convergence properties under the assumption of a Hölder continuous regression function. The universality of the estimator makes it an ideal tool in problems with only little prior knowledge available.     

Nitrate estimation in the denitrifying post-filtration unit of a municipal wastewater treatment plant: the Viikinm?ki case

In this work we present and discuss the design of an array of soft-sensors to estimate the nitrate concentration in the denitrifying post-filtration unit at the Viikinm?ki wastewater treatment plant in Helsinki (Finland). The developed sensors aim at supporting the existing hardware analyzers by providing a reliable back-up system in case of malfunction of the instruments. In the attempt to design easy to implement and interpretable sensors, computationally light linear models have been considered. However, due to the intrinsic nonlinearity of the process, also nonlinear but still computationally affordable models have been considered for comparison. The experimental results demonstrate the potential of the developed soft-sensors and the possibility for an on-line implementation in the plant's control system as alternative monitoring devices.     

Inhibition of colon adenocarcinoma cell proliferation by flavonols is linked to a G2/M cell cycle block and reduction in cyclin D1 expression

The moderate consumption of red wine has been proposed to reduce the incidence of colorectal cancer. Its anti-cancer action my in part be mediated by the actions of polyphenols on colon cancer epithelial cells. We show that a red wine phenolic (50 μg/ml) extract devoid of anthocyanins (removed to reflect polyphenol bioavailability to the large intestine) and the major red wine flavonols quercetin, myricetin, laricitrin and syringetin (50 μM) are capable of inhibiting the proliferation of colorectal epithelial adenocarcinoma cells. This anti-proliferative activity was partly mediated by the direct cytotoxic actions of flavonols and also their ability to cause a significant cell cycle blockage in G2/M. The anti-proliferative effects induced by flavonols were preceded, in most cases, by a strong and significant reduction of cyclooxygenase-2 (COX-2) and cyclin D1 expression. These results indicate that the observed inverse correlation between colon cancer and a moderate red wine intake may be partly mediated by the actions of red wine flavonols on the growth of cancer cells.     

Optimal control of continuous-time switched affine systems

This paper deals with optimal control of switched piecewise affine autonomous systems, where the objective is to minimize a performance index over an infinite time horizon. We assume that the switching sequence has a finite length, and that the decision variables are the switching instants and the sequence of operating modes. We present two different approaches for solving such an optimal control problem. The first approach iterates between a procedure that finds an optimal switching sequence of modes, and a procedure that finds the optimal switching instants. The second approach is inspired by dynamic programming and identifies the regions of the state space where an optimal mode switch should occur, therefore providing a state feedback control law.     

Pharmacokinetic study of praziquantel administered alone and in combination with cimetidine in a single-day therapeutic regimen

A brief therapeutic regimen of praziquantel, reduced to a single day, has been effective for treatment of neurocysticercosis. To study its pharmacokinetic characteristics, levels of praziquantel in plasma were determined for eight healthy volunteers after the administration of three oral doses of 25 mg/kg of body weight given at 2-h intervals, alone and with the simultaneous administration of cimetidine. Each volunteer received both regimens in a randomized crossover design. Blood samples were taken during a period of 12 h, and praziquantel concentration was measured by high-performance liquid chromatography. Levels of praziquantel in plasma remained above 300 ng/ml during a period of 12 h; they increased 100% when cimetidine was jointly administered. Compared with other regimens, the high levels obtained and the longer duration of action seem to be advantageous in prolonging the exposure of the parasites to the drug and support previous clinical experience showing that the treatment of neurocysticercosis with praziquantel can be reduced from 2 weeks to 1 day with the drug still retaining its cysticidal properties. Moreover, simultaneous administration of praziquantel and cimetidine could improve further the efficacy of the single-day therapy for cysticercosis and other parasitic diseases, such as schistosomiasis.     

Effect of process parameters on the quality of aluminium alloy Al5Si deposits in wire and arc additive manufacturing using a cold metal transfer process

A 3D print device using a cold metal transfer arc welding station to melt a metallic filler wire is developed to build aluminium part by optimising the process parameters. First tests achieved using standard pre-recorded process parameters allow to study the effect of the travel speed and the average welding power on the geometrical characteristics of mono-layer deposits and on walls built by layers superposition. Finally, a parametric study of the effect of each process parameter controlling the shape of the arc current or voltage and the filler wire feeding is carried out in order to try to improve the geometrical regularity of the deposits, and to better understand the effect of each parameter on the melting of the filler wire, its transfer on the support plate, and the geometry of the formed bead.     

Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation

HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents.