Grouping complex systems: a weighted network comparative analysis

In this study, the authors compare two inter-municipal commuting networks (MCN) pertaining to the Italian islands of Sardinia and Sicily, by approaching their characterization through a weighted network analysis. They develop on the results obtained for the MCN of Sardinia (De Montis et al. 2007) and attempt to use network analysis as a mean of detection of similarities or dissimilarities between the systems at hand

Modeling commuting systems through a complex network analysis: a study of the Italian islands of Sardinia and Sicily

This study analyzes the inter-municipal commuting systems of the Italian islands of Sardinia and Sicily, employing weighted network analysis technique. Based on the results obtained for the Sardinian commuting network, the network analysis is used to identify similarities and dissimilarities between the two systems

Dynamic Max-Consensus and Size Estimation of Anonymous Multi-Agent Networks

In this paper we propose a novel consensus protocol for discrete-time multi-agent systems (MAS), which solves the dynamic consensus problem on the max value, i.e., the dynamic max-consensus problem. In the dynamic max-consensus problem to each agent is fed a an exogenous reference signal, the objective of each agent is to estimate the instantaneous and time-varying value of the maximum among the signals fed to the network, by exploiting only local and anonymous interactions among the agents. The absolute and relative tracking error of the proposed distributed control protocol is theoretically characterized and is shown to be bounded and by tuning its parameters it is possible to trade-off convergence time for steady-state error. The dynamic Max-consensus algorithm is then applied to solve the distributed size estimation problem in a dynamic setting where the size of the network is time-varying during the execution of the estimation algorithm. Numerical simulations are provided to corroborate the theoretical analysis

Ontologies for Quantified Self: a Semantic Approach

The spreading of devices and applications that allow people to collect personal information opens new opportunities for user modeling (UM). In this new scenario UM together with personal informatics (PI) can offer a new way for self-monitoring that can provide the users with a sophisticated mirror of their behavior, attitudes and habits and their consequences on their life, on the environment and on contexts in which they live in. These new forms of self-reflection and self-knowledge can trigger and motivate the behavior change. In this paper we describe the first step in this direction, focusing on opportunities offered by semantic web ontologies for data integration and reasoning over data for recommendation purposes

Discovery of novel endocannabinoid level modulators by modification of old analgesic drugs

Fatty acid amide hydrolase (FAAH) is a serine hydrolase that catalyzes the deactivating hydrolysis of the fatty acid ethanolamide family of signaling lipids, which includes anandamide (AEA), an endogenous ligand for cannabinoid receptors. Endogenous FAAH substrates such as AEA serve key regulatory functions in the body and have been implicated in a variety of pathological conditions including pain, inflammation, sleep disorders, anxiety, depression, and vascular hypertension, and there has been an increasing interest in the development of inhibitors of this enzyme. Different structural classes of FAAH inhibitors have been reported including alpha-ketoheterocycles, (thio)hydantoins, piperidine/piperazine ureas, and carbamate derivatives. When tested, these compounds have been shown to be efficacious in models of inflammatory, visceral, and in some cases neuropathic pain without producing the central effects seen with directly acting cannabinoid receptor agonists. An intriguing aspect of FAAH inhibition is that some currently marketed nonsteroidal anti-inflammatory drugs (NSAIDs) have also been shown to be weak inhibitors of FAAH, but can be used as a template for the design of more potent compounds. However, structure–activity relationships of analogues of clinically used NSAIDs with respect to FAAH inhibition have been examined scarcely in the literature. These findings led us to design and synthesis of new series of FAAH inhibitors derivable from conjugation of heterocyclic structures with NSAIDs as profens, fenamates, and new their correlate molecules. In this keynote we report on the synthetic pathways to transform old analgesic drugs into FAAH inhibitors and SAR studies on the new inhibitor series

Synthesis and carbonic anhydrase I, II, IX and XII inhibitory activity of sulfamates incorporating piperazinyl-ureido moieties

A series of sulfamates were synthesized using as lead compound SLC-0111, a sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor in Phase I clinical trials. The new derivatives incorporated ureido moieties as spacers between the benzene sulfamate fragment which binds the zinc ion from the active site, and the tail of the inhibitor, but the urea moieties were part of a substituted piperazine ring system. The derivatives (and some of their phenol precursors) were tested for the inhibition of the cytosolic, hCA I and II (off target isoforms) and the trans-membrane, tumor-associated hCA IX and XII enzymes (anticancer drug targets). Generally hCA I was not effectively inhibited, whereas many low nanomolar inhibitors were evidenced against hCA II (KIs in the range of 1.0–94.4 nM), IX (KIs in the range of 0.91–36.9 nM), and XII (KIs in the range of 1.0–84.5 nM). The best substitution fragments at the piperazine ring included the following moieties: 3-methylphenyl, 2,3-dimethylphenyl, 4-methoxyphenyl, 6-arylpyrimidine-2-yl

Synthesis of Sulfonamides Incorporating Piperidinyl-Hydrazidoureido and Piperidinyl-Hydrazidothioureido Moieties and Their Carbonic Anhydrase I, II, IX and XII Inhibitory Activity

Here we report a small library of hydrazinocarbonyl-ureido and thioureido benzenesulfonamide derivatives, designed and synthesized as potent and selective human carbonic anhydrase inhibitors (hCAIs). The synthesized compounds were evaluated against isoforms hCA I, II, IX and XII using acetazolamide (AAZ) as standard inhibitor. Several urea and thiourea derivatives showed inhibitory activity at low nanomolar levels with selectivity against the cytosolic hCA II isoform, as well as the transmembrane, tumor-associated enzymes hCA IX and XII. The thiourea derivatives showed enhanced potency as compared to urea analogues. Additionally, eight compounds 5g, 5m, 5o, 5q, 6l, 6j, 6o and 6u were selected for docking analysis on isoform I, II, IX, XII to illustrate the potential interaction with the enzyme to better understand the activity against the different isoforms

Accessibility in commuting systems network based performance indicators

The aim of this paper is to contribute to the discussion on accessibility by adopting complex network analysis as a base for constructing accessibility indicators. In this case, a contribution is offered in construction of two groups of indicators: travel cost and gravity based indexes. A case study is proposed on the level of accessibility of two towns of commuters in the island of Sardinia, Italy

Molecular Basis for Non-Covalent, Non-Competitive FAAH Inhibition

Fatty acid amide hydrolase (FAAH) plays a key role in the control of cannabinoid signaling and it represents a promising therapeutic strategy for the treatment of a wide range of diseases, including neuropathic pain and chronic inflammation. Starting from kinetics experiments carried out in our previous work for the most potent inhibitor 2-amino-3-chloropyridine amide (TPA14), we have investigated its non-competitive mechanism of action using molecular dynamics, thermodynamic integration and QM-MM/GBSA calculations. The computational studies highlighted the impact of mutations on the receptor binding pockets and elucidated the molecular basis of the non-competitive inhibition mechanism of TPA14, which prevents the endocannabinoid anandamide (AEA) from reaching its pro-active conformation. Our study provides a rationale for the design of non-competitive potent FAAH inhibitors for the treatment of neuropathic pain and chronic inflammation