A method to generate first passage times for a class of stochastic processes is proposed. It does not require construction of the trajectories as usually needed in simulation studies, but is based on an integral equation whose unknown quantity is the probability density function of the studied first passage times and on the application of the hazard rate method. The proposed procedure is particularly efficient in the case of the Ornstein-Uhlenbeck process, which is important for modeling spiking neuronal activity.

With the aim to describe the interaction between a couple of neurons a stochastic model is proposed and formalized. In such a model, maintaining statements of the Leaky Integrate-and-Fire framework, we include a random component in the synaptic current, whose role is to modify the equilibrium point of the membrane potential of one of the two neurons and when a spike of the other one occurs it is turned on. The initial and after spike reset positions do not allow to identify the inter-spike intervals with the corresponding first passage times. However, we are able to apply some well-known results for the first passage time problem for the Ornstein-Uhlenbeck process in order to obtain (i) an approximation of the probability density function of the interspike intervals in one-way-type interaction and (ii) an approximation of the tail of the probability density function of the inter-spike intervals in the mutual interaction. Such an approximation is admissible for small instantaneous firing rates of both neurons.

Given a simple undirected graph G and a positive integer s, the maximum vertex coverage problem (MVC) is the problem of finding a set U of s vertices of G such that the number of edges having at least one endpoint in U is as large as possible. The problem is NP-hard even in bipartite graphs, as shown in two recent papers [N. Apollonio and B. Simeone, Discrete Appl. Math., 165 (2014), pp. 37-48; G. Joret and A. Vetta, Reducing the Rank of a Matroid, preprint, arXiv: 1211.4853v1 [cs.DS], 2012]. By exploiting the structure of the fractional optimal solutions of a linear programming formulation for the maximum coverage problem, we provide a 4/5-approximation algorithm for the problem. The algorithm immediately extends to the weighted version of MVC.

Objective: To provide a frame to estimate the systemic impact (side/adverse events) of (novel) therapeutic targets by taking into consideration drugs potential on the numerous districts involved in rheumatoid arthritis (RA) from the inflammatory and immune response to the gut-intestinal (GI) microbiome. Methods: We curated the collection of molecules from high-throughput screens of diverse (multi-omic) biochemical origin, experimentally associated to RA. Starting from such collection we generated RA-related protein-protein interaction (PPI) networks (interactomes) based on experimental PPI data. Pharmacological treatment simulation, topological and functional analyses were further run to gain insight into the proteins most affected by therapy and by multi-omic modeling. Results: Simulation on the administration of MTX results in the activation of expected (apoptosis) and adverse (nitrogenous metabolism alteration) effects. Growth factor receptor-bound protein 2 (GRB2) and Interleukin-1 Receptor Associated Kinase-4 (IRAK4, already an RA target) emerge as relevant nodes. The former controls the activation of inflammatory, proliferative and degenerative pathways in host and pathogens. The latter controls immune alterations and blocks innate response to pathogens. Conclusions: This multi-omic map properly recollects in a single analytical picture known, yet complex, information like the adverse/side effects of MTX, and provides a reliable platform for in silico hypothesis testing or recommendation on novel therapies. These results can support the development of RA translational research in the design of validation experiments and clinical trials, as such we identify GRB2 as a robust potential new target for RA for its ability to control both synovial degeneracy and dysbiosis, and, conversely, warn on the usage of IRAK4-inhibitors recently promoted, as this involves potential adverse effects in the form of impaired innate response to pathogens.

In this paper we deal with a semilinear hyperbolic chemotaxis model in one space dimension evolving on a network, with suitable transmission conditions at nodes. This framework is motivated by tissue-engineering scaffolds used for improving wound healing. We introduce a numerical scheme, which guarantees global mass densities conservation. Moreover our scheme is able to yield a correct approximation of the effects of the source term at equilibrium. Several numerical tests are presented to show the behavior of solutions and to discuss the stability and the accuracy of our approximation.

La realizzazione di una Smart City è un processo molto complesso e di lungo periodo: è necessaria una profonda conoscenza della realtà locale, dei bisogni della collettività e dei singoli individui, delle criticità e dei servizi che devono essere gestiti e garantiti. I servizi di e-health sono un tassello fondamentale verso la realizzazione di una smart city dal punto di vista socio-sanitario. In questo contesto, il progetto e-SHS, non solo si occupa di servizi e-ealth, in particolare per soggetti fragili, ma propone strumenti innovativi per la loro inclusione sociale e l'incremento della solidarietà sociale. L'obiettivo principale di e-SHS è la realizzazione di un primo nucleo di una piattaforma per lo sviluppo di servizi personali e personalizzati basati sull'uso di tecnologie ICT innovative e non invasive nel settore della salute e della solidarietà sociale. Il centro del sistema è rappresentato dall'utente-paziente verso il quale sono definiti e sviluppati servizi di monitoraggio e supporto costante nella gestione della propria salute e del proprio stile di vita, al fine di migliorarne la qualità della vita ed aumentarne l'autonomia e l'indipendenza nelle attività quotidiane, sia in ambiente domestico che in ambienti esterni. Gli utenti verso i quali questo progetto si indirizza sono persone anziane, con problemi di riabilitazione motoria, con parametri vitali da tenere sotto controllo e con disturbi del sonno. Per la sperimentazione saranno coinvolti soggetti volontari. In particolare, e-SHS include servizi per: 1) il monitoraggio di parametri vitali degli utenti 2) il supporto all'esecuzione di attività riabilitative in ambiente domestico; 3) un supporto per monitorare le interazioni sociali degli utenti e migliorarne l'inclusione sociale nelle attività quotidiane; 4) lo sviluppo di reti di supporto sociale che coinvolgono pazienti, familiari, assistenti (i.e., caregivers), allo scopo di promuovere la continuità di assistenza socio-sanitaria in diversi ambienti. Le competenze presenti nel settore "ICT for health, care and well-being" negli 11 istituti del CNR partecipanti al progetto vanno ben oltre quelle che saranno utilizzate in questo progetto. In questo documento si intende presentare le principali attività di ricerca svolte nei singoli istituti ed attinenti al progetto e-SHS, cercando di evidenziare il filo conduttore che porterà alla definizione di un'unica architettura di sistema.

This paper focuses on two-tier city logistics systems for advanced management of urban freight activities and, in particular, on the first layer of such systems where freight is moved from distribution centers on the outskirts of the city to satellite platforms by urban vehicles, from where it will be distributed to customers by a different fleet of dedicated vehicles. We address the issue of planning the services of this first tier system, that is, select services, their routes and schedules, and determine the itineraries of the customer-demand flows through these facilities and services. We propose a general scheduled service network design modelling framework that captures the fundamental concepts related to the definition of urban-vehicle tactical plans within a two-tier distribution network. We examine several operational assumptions regarding the management of the urban-vehicle fleet and the flexibility associated with the delivery of goods, and show how the proposed modelling framework can evolve to represent an increasing level of detail. A discussion of algorithmic perspectives completes the paper.

In document image analysis the task of segmenting images of ancient printed documents in distinct elements is known to be a very complex problem. In general, these documents are of low quality and can present skew and degradations because of old printing or ink stains. To face these problems we will show and discuss the validity of the Mumford and Shah variational method, based on the ? convergence theory, along with its numerical handling. In particular, we segment and extract the interest regions, constituted by textual and non-textual blocks, from page images of ancient books, combining the variational approach with morphological operations. Study case is the first edition of 'Scienza Nuova' (1725) of Giambattista Vico.

In order to take into account the territory in which the outputs are in the market and the time-depending firms' strategies, the discrete Cournot duopoly game (with adaptive expectations, modeled by Kopel) is generalized through a non autonomous reaction-diffusion binary system of PDEs, with self and cross diffusion terms. Linear and nonlinear asymptotic $L^2$-stability, via the Lapunov Direct Method and a nonautonomous energy functional, are investigated.

One of the promising frontiers of bioengineering is the controlled release of a therapeutic drug from a vehicle across the skin (transdermal drug delivery). In order to study the complete process, a two-phase mathematical model describing the dynamics of a substance between two coupled media of different properties and dimensions is presented. A system of partial differential equations describes the diffusion and the binding/unbinding processes in both layers. Additional flux continuity at the interface and clearance conditions into systemic circulation are imposed. An eigenvalue problem with discontinuous coefficients is solved and an analytical solution is given in the form of an infinite series expansion. The model points out the role of the diffusion and reaction parameters, which control the complex transfer mechanism and the drug kinetics across the two layers. Drug masses are given and their dependence on the physical parameters is discussed.