Synthesis,Molecular Modeling and Biological Evaluation of Metabolically Stable Analogues of the Endogenous Fatty Acid Amide Palmitoylethanolamide

Palmitoylethanolamide (PEA) belongs to the class of N-acylethanolamine and is an endogenous lipid potentially useful in a wide range of therapeutic areas; products containing PEA are licensed for use in humans as a nutraceutical, a food supplement, or food for medical purposes for its analgesic and anti-inflammatory properties demonstrating efficacy and tolerability. However, the exogenously administered PEA is rapidly inactivated; in this process, fatty acid amide hydrolase (FAAH) plays a key role both in hepatic metabolism and in intracellular degradation. So, the aim of the present study was the design and synthesis of PEA analogues that are more resistant to FAAH-mediated hydrolysis. A small library of PEA analogues was designed and tested by molecular docking and density functional theory calculations to find the more stable analogue. The computational investigation identified RePEA as the best candidate in terms of both synthetic accessibility and metabolic stability to FAAH-mediated hydrolysis. The selected compound was synthesized and assayed ex vivo to monitor FAAH-mediated hydrolysis and to confirm its anti-inflammatory properties. ¹H-NMR spectroscopy performed on membrane samples containing FAAH in integral membrane protein demonstrated that RePEA is not processed by FAAH, in contrast with PEA. Moreover, RePEA retains PEA’s ability to inhibit LPS-induced cytokine release in both murine N9 microglial cells and human PMA-THP-1 cells.     

High-Energy Physics on the Grid: the ATLAS and CMS Experience

In this paper we present the experience of the ATLAS and CMS High-Energy Physics (HEP) experiments at the Large Hadron Collider (LHC) with the LCG/EGEE Grid infrastructure. The activity developed around the following two main lines: large-scale physics and detector simulations and end-user analysis. The LCG/EGEE Grid infrastructure offers a large amount of computing and storage resources and is growing very rapidly. It provides the natural environment for large-scale physics and detector simulations. Also, the analysis of these detector simulation data (and in the near future of the reconstructed data from physics collisions) requires efficient end-users access to Grid resources. In this paper, the main findings and lessons learned in terms of performance, robustness and scalability of the whole system are discussed in detail.     

The Rovereto Emotion and Cooperation Corpus: a new resource to investigate cooperation and emotions

The Rovereto Emotion and Cooperation Corpus (RECC) is a new resource collected to investigate the relationship between cooperation and emotions in an interactive setting. Previous attempts at collecting corpora to study emotions have shown that this data are often quite difficult to classify and analyse, and coding schemes to analyse emotions are often found not to be reliable. We collected a corpus of task-oriented (MapTask-style) dialogues in Italian, in which the segments of emotional interest are identified using psycho-physiological indexes (Heart Rate and Galvanic Skin Conductance) which are highly reliable. We then annotated these segments in accordance with novel multimodal annotation schemes for cooperation (in terms of effort) and facial expressions (an indicator of emotional state). High agreement was obtained among coders on all the features. The RECC corpus is to our knowledge the first resource with psycho-physiological data aligned with verbal and nonverbal behaviour data.     

Implementation of a real option in a sustainable supply chain: an empirical study of alkaline battery recycling

Green supply chain management (GSCM) has emerged as a key approach for enterprises seeking to become environmentally sustainable. This paper aims to evaluate and describe the advantages of a GSCM approach by analysing practices and performance consequences in the battery recycling sector. It seeks to integrate works in supply chain management (SCM), environmental management, performance management and real option (RO) theory into one framework. In particular, life cycle assessment (LCA) is applied to evaluate the environmental impact of a battery recycling plant project, and life cycle costing (LCC) is applied to evaluate its economic impact. Firms, also understanding the relevance of GSCM, have often avoided applying the green principles because of the elevated costs that such management involved. Such costs could also seem superior to the potential advantages since standard performance measurement systems are internally and business focused; for these reasons, we consider all the possible value deriving also by uncertainty associated to a green project using the RO theory. This work is one of the few and pioneering efforts to investigate GSCM practices in the battery recycling sector.     

Bio-PEPA: A framework for the modelling and analysis of biological systems

In this work we present Bio-PEPA, a process algebra for the modelling and the analysis of biochemical networks. It is a modification of PEPA, originally defined for the performance analysis of computer systems, in order to handle some features of biological models, such as stoichiometry and the use of general kinetic laws. Bio-PEPA may be seen as an intermediate, formal, compositional representation of biological systems, on which different kinds of analyses can be carried out. Bio-PEPA is enriched with some notions of equivalence. Specifically, the isomorphism and strong bisimulation for PEPA have been considered and extended to our language. Finally, we show the translation of a biological model into the new language and we report some analysis results.     

Fibroblast protein profile analysis highlights the role of oxidative stress and vitamin K recycling in the pathogenesis of pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a genetic disorder associated to mutations in the ABCC6 gene; however, the pathogenetic mechanisms leading to elastic fibre calcifications and to clinical manifestations are still unknown. Dermal fibroblasts, directly involved in the production of the extracellular milieu, have been isolated from healthy subjects and from patients affected by PXE, cultured in vitro and characterized for their ability to produce reactive oxygen species, for structural and functional properties of their cell membranes, for changes in their protein profile. Data demonstrate that oxidative stress has profound and endurable consequences on PXE fibroblast phenotype being responsible for: reduced levels of global DNA methylation, increased amount of carbonylated proteins and of lipid peroxidation products, altered structural properties of cell membranes, modified protein expression. Data shed new light on the pathogenetic pathways in PXE, by identifying a network of proteins affecting elastic fibre calcification through inefficient vitamin K recycling, and highlight the role of differentially expressed proteins as targets for validating the efficacy of future therapeutic strategies aiming to delay and/or revert the pathologic phenotype of PXE fibroblasts. Moreover, data open new perspectives for investigating PXE-like phenotypes in the absence of ABCC6 mutations.     

Performance evaluation of a region growing procedure for mammographic breast lesion identification

At present, mammography is the most effective examination for an early diagnosis of breast cancer. Nevertheless, the detection of cancer signs in mammograms is a difficult procedure owing to the great number of non-pathological structures which are also present in the image. Recent statistics show that in current breast cancer screenings 10%-25% of the tumors are missed by the radiologists. For this reason, a lot of research is currently being done to develop systems for Computer Aided Detection (CADe). Probably, some causes of the false-negative screening examinations are that tumoral masses have varying dimension and irregular shape, their borders are often ill-defined and their contrast is very low, thus making difficult the discrimination from parenchymal structures. Therefore, in a CADe system a preliminary segmentation procedure has to be implemented in order to separate the mass from the background tissue. In this way, various characteristics of the segmented mass can be evaluated and used in a classification step to discriminate benign and malignant cases. In this paper, we describe an effective algorithm for massive lesions segmentation based on a region-growing technique and we provide full details the performance evaluation procedure used in this specific context.     

Integrating web service and semantic dialogue model for user models interoperability on the web

Nowadays there is a great number of Web information systems that build a model of the user and adapt their services according to the needs and preferences maintained by the user model (UM). One of the most challenging issues of this scenario is the possibility to enable different systems to cooperate in order to exchange the available information about a user. Our aim is to create rich (and scalable) communication protocols and infrastructures to enable consumers and providers of UM data to interact. Our solution for dealing with such an issue is to exploit Web standards for interoperability (i.e. Semantic Web and Web Services) for implementing simple atomic communication, and a dialogue model for implementing enhanced communication capabilities. In particular, two systems can start a semantics-enhanced Dialogue Game as a form of negotiation to clarify the meaning of the requested concepts when a shared knowledge model does not exist, and to approximate the response when the exact one is not available. We propose a distributed semantic conversation framework based on the Sesame semantic environment for the exchange of user model knowledge on the Web. Systems have to expose their user model data as a Web Service, and to exploit a public dialogue knowledge base to start the dialogue. The main advantage of the approach is to allow systems to deal with difficult situations by starting an appropriate dialogue game instead of stopping the communication as in the traditional “all-or-nothing” Web Service approach. On the basis of a preliminary evaluation, the approach has shown an improvement of the adaptation results provided by the systems we tested.     

The evaluation of a social adaptive website for cultural events

In this paper, we present an evaluation of a social adaptive website in the domain of cultural events, iCITY DSA, which provides information about cultural resources and events that promote the cultural heritage in the city of Turin. Using this evaluation, our objective was to investigate the actual usage of a social adaptive website, in an effort to discover the real behavior of users, the unforeseen correlations among user actions and the consequent interactive behavior, the accuracy of both system and social recommendations and their impact on the users themselves, and the role of tagging in the user modeling process. The major contributions of the paper are manifold: insights into user interactions with social adaptive systems; guidelines for future designs; evaluation of the tagging activity and tag meanings in relation to the application domain and thus their impact on the representation of the user model; and a demonstration of how a combination and interplay of evaluation methodologies (e.g., quantitative and qualitative) can enhance our comprehension of evaluation data.