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.     

Post-transplant proteinuria associated with everolimus: Definition of main features with proteomics

Little is known on both the composition and mechanism(s) of proteinuria associated with the use of mTOR inhibitors, in particular of Everolimus (E). We characterized urinary proteins utilizing an integrated proteomics approach (quantitative essays, 2‐DE, MALDI‐TOF, Western blot) in 48 renal transplant recipients who were alternatively treated with E (n = 31) or with enteric coated mycophenolic acid (EC‐MPA) (n = 17). Twelve E patients (39%) developed high (>3 g/day) or intermediate proteinuria (1–3 g) compared to four (23%) of the EC‐MPA group. Urinary proteins (p<0.001), β2 microglobulin (p<0.001) and α1microglobulin (p<0.025) were higher in E than in EC‐MPA, appeared more rapidly and were inversely correlated with the day of treatment. Proteomics showed a marked increase of all urinary components in E and EC‐MPA patients, major changes involving typical components of glomerular damage (albumin, α1‐Zn glycoprotein, α2HS glycoprotein, leucin‐richα2‐glycoprotein) and specific bio‐markers for E (clusters of α1‐antitrypsin fragments and monoclonal λ chains). Finally, inter‐α‐trypsin‐inhibitor heavy chain H4 precursor was decreased in E and EC‐MPA urine compared to normal urine. In conclusion, E induced massive and generalized proteinuria of mixed glomerular and tubular origin that was correlated with the start of treatment and reached a nephrotic range in few cases. Specific urinary markers reflect renal alterations related to the transplant or specific alterations associated with the drug.     

Corrected ISICSoo class version

The Coster–Kronig enhancement factor calculation for _M3$M_3$ shell x-ray production cross sections was found to be incorrect in both ISICSoo class (Bati? et al. (2012) [1]) and isics program (Cipolla (2013) [2]). The affected functions of ISICSoo class have been corrected. The resulting X-ray production cross sections are modified by less than 15%, while ionization cross sections are unchanged.     

The Urokinase Receptor: A Multifunctional Receptor in Cancer Cell Biology. Therapeutic Implications

Proteolysis is a key event in several biological processes; proteolysis must be tightly controlled because its improper activation leads to dramatic consequences. Deregulation of proteolytic activity characterizes many pathological conditions, including cancer. The plasminogen activation (PA) system plays a key role in cancer; it includes the serine-protease urokinase-type plasminogen activator (uPA). uPA binds to a specific cellular receptor (uPAR), which concentrates proteolytic activity at the cell surface, thus supporting cell migration. However, a large body of evidence clearly showed uPAR involvement in the biology of cancer cell independently of the proteolytic activity of its ligand. In this review we will first describe this multifunctional molecule and then we will discuss how uPAR can sustain most of cancer hallmarks, which represent the biological capabilities acquired during the multistep cancer development. Finally, we will illustrate the main data available in the literature on uPAR as a cancer biomarker and a molecular target in anti-cancer therapy.     

Data Protection Comes of Age: The Data Protection Clauses in the European Constitutional Treaty

This article traces the evolution of the right to data protection in European law, with a particular focus on the inclusion of the right in the European Union Charter of Fundamental Rights and its proposed legal status under the new Constitutional Treaty. In particular, the discussion considers the legal impact of this 'constitutionalisation' of this area of legal protection. It is argued that this should be viewed as more than just a formal development in that entrenchment of the right may strengthen ground-level interpretation and implementation of data protection principles.     

Parameter identifiability of nonlinear systems: the role of initial conditions

Identifiability is a fundamental prerequisite for model identification; it concerns uniqueness of the model parameters determined from the input-output data, under ideal conditions of noise-free observations and error-free model structure. In the late 1980s concepts of differential algebra have been introduced in control and system theory. Recently, differential algebra tools have been applied to study the identifiability of dynamic systems described by polynomial equations. These methods all exploit the characteristic set of the differential ideal generated by the polynomials defining the system. In this paper, it will be shown that the identifiability test procedures based on differential algebra may fail for systems which are started at specific initial conditions and that this problem is strictly related to the accessibility of the system from the given initial conditions. In particular, when the system is not accessible from the given initial conditions, the ideal I having as generators the polynomials defining the dynamic system may not correctly describe the manifold of the solution. In this case a new ideal that includes all differential polynomials vanishing at the solution of the dynamic system started from the initial conditions should be calculated. An identifiability test is proposed which works, under certain technical hypothesis, also for systems with specific initial conditions.     

Incorporation of conjugated linoleic acid and vaccenic acid into lipids from rat tissues and plasma

The objective of this study was to determine the incorporation of conjugated linoleic acid (CLA) into triacylglycerols (TAG) and phospholipids (PL) of tissues and plasma, and to interpret the role of dietary‐derived vaccenic acid (VA) in increasing the tissue content of CLA (c9,t11) and the influence on the fatty acid profile. We fed five groups of rats semi‐purified diets with varying levels of CLA and VA: control butter with low CLA (c9,t11) and VA; control butter added 5% CLA (c9,t11); control butter added 5% Tonalin [equal amount of CLA (c9,t11) and CLA (t10,c12)]; control butter added 5% VA; butter with high CLA (c9,t11) and VA (H‐CLA), for 3 weeks. The highest incorporation of CLA (c9,t11) was found in adipose tissue, and the lowest was observed in liver. Low intake of CLA (c9,t11) combined with high intake of VA resulted in a higher incorporation of CLA (c9,t11) in tissues due to the conversion of VA to CLA (c9,t11), compared to feeding CLA (c9,t11) without VA. However, in enterocytes, the proportion of CLA (c9,t11) was low after feeding VA, indicating no or only a minor conversion of VA to CLA (c9,t11) in the intestine. The incorporation of CLA (t10,c12) into TAG from plasma and tissues was generally much lower than that of the CLA (c9,t11) isomer, except in the enterocyte TAG, which had similar proportions of the two isomers.     

Methods for detection of irradiation of spices

European Food Research and Technology - Three types of methods for the identification of irradiation of spices were tested as potential control methods. The methods were microbiological, combining...     

The use of a pharmacophore model for identification of novel ligands for the benzodiazepine binding site of the GABAA receptor

A Catalyst pharmacophore model has been developed for the benzodiazepine site within the GABA(A) receptor complex. The model is based on a pharmacophore model originally proposed by Cook and co-workers (Drug Des. Discovery 1995, 12, 193-248) and further developed by Kahnberg et al. (J. Med. Chem. 2002, 45, 4188-4201). The Catalyst pharmacophore model has been validated by using a series of flavonoids with varying affinities for the benzodiazepine receptor and has then been used as a search query in database searching with the aim of finding novel structures which have the possibility to be modified into novel lead compounds. Five of the hits from the database searching were purchased and their affinities for the benzodiazepine site of the GABA(A) receptor were determined. Two of the compounds displayed K(i) values below 10 microM. The substance showing highest potency in-vitro displayed an affinity of 121 nM making it an interesting compound for optimization. The false positive compounds (K(i) values >10 microM affinities) have been analysed in terms of conformational energy penalties and possibilities for hydrogen bond interactions. The analysis clearly demonstrates the need for post processing of Catalyst hits.