Il ruolo delle architetture di controllo nella progettazione e sviluppo di applicazioni web: Un confronto fra event-loop e control-loop utilizzando il linguaggio dart e linguaggi agent-oriented

Quando si parla di architetture di controllo in ambito Web, il Modello ad Eventi è indubbiamente quello più diffuso e adottato. L’asincronicità e l’elevata interazione con l’utente sono caratteristiche tipiche delle Web Applications, ed un architettura ad eventi, grazie all’adozione del suo tipico ciclo di controllo chiamato Event Loop, fornisce un'astrazione semplice ma sufficientemente espressiva per soddisfare tali requisiti. La crescita di Internet e delle tecnologie ad esso associate, assieme alle recenti conquiste in ambito di CPU multi-core, ha fornito terreno fertile per lo sviluppo di Web Applications sempre più complesse. Questo aumento di complessità ha portato però alla luce alcuni limiti del modello ad eventi, ancora oggi non del tutto risolti. Con questo lavoro si intende proporre un differente approccio a questa tipologia di problemi, che superi i limiti riscontrati nel modello ad eventi proponendo un architettura diversa, nata in ambito di IA ma che sta guadagno popolarità anche nel general-purpose: il Modello ad Agenti. Le architetture ad agenti adottano un ciclo di controllo simile all’Event Loop del modello ad eventi, ma con alcune profonde differenze: il Control Loop. Lo scopo di questa tesi sarà dunque approfondire le due tipologie di architetture evidenziandone le differenze, mostrando cosa significa affrontare un progetto e lo sviluppo di una Web Applications avendo tecnologie diverse con differenti cicli di controllo, mettendo in luce pregi e difetti dei due approcci.

Agent-based simulation for renewable energy incentive design

In this thesis, we propose a novel approach to model the diffusion of residential PV systems. For this purpose, we use an agent-based model where agents are the families living in the area of interest. The case study is the Emilia-Romagna Regional Energy plan, which aims to increase the produc- tion of electricity from renewable energy. So, we study the microdata from the Survey on Household Income and Wealth (SHIW) provided by Bank of Italy in order to obtain the characteristics of families living in Emilia-Romagna. These data have allowed us to artificial generate families and reproduce the socio-economic aspects of the region. The families generated by means of a software are placed on the virtual world by associating them with the buildings. These buildings are acquired by analysing the vector data of regional buildings made available by the region. Each year, the model determines the level of diffusion by simulating the installed capacity. The adoption behaviour is influenced by social interactions, household’s economic situation, the environmental benefits arising from the adoption and the payback period of the investment.

Modelling and simulating in systems biology: an approach based on multi-agent systems

Systems Biology is an innovative way of doing biology recently raised in bio-informatics contexts, characterised by the study of biological systems as complex systems with a strong focus on the system level and on the interaction dimension. In other words, the objective is to understand biological systems as a whole, putting on the foreground not only the study of the individual parts as standalone parts, but also of their interaction and of the global properties that emerge at the system level by means of the interaction among the parts. This thesis focuses on the adoption of multi-agent systems (MAS) as a suitable paradigm for Systems Biology, for developing models and simulation of complex biological systems. Multi-agent system have been recently introduced in informatics context as a suitabe paradigm for modelling and engineering complex systems. Roughly speaking, a MAS can be conceived as a set of autonomous and interacting entities, called agents, situated in some kind of nvironment, where they fruitfully interact and coordinate so as to obtain a coherent global system behaviour. The claim of this work is that the general properties of MAS make them an effective approach for modelling and building simulations of complex biological systems, following the methodological principles identified by Systems Biology. In particular, the thesis focuses on cell populations as biological systems. In order to support the claim, the thesis introduces and describes (i) a MAS-based model conceived for modelling the dynamics of systems of cells interacting inside cell environment called niches. (ii) a computational tool, developed for implementing the models and executing the simulations. The tool is meant to work as a kind of virtual laboratory, on top of which kinds of virtual experiments can be performed, characterised by the definition and execution of specific models implemented as MASs, so as to support the validation, falsification and improvement of the models through the observation and analysis of the simulations. A hematopoietic stem cell system is taken as reference case study for formulating a specific model and executing virtual experiments.

Self-management di malattie croniche in sistemi di mobile Health: sviluppo di un modello agent-based per casi di diabete

L'obiettivo della tesi è proporre e motivare l'adozione di un modello computazionale Agent-Based nell'ambito del Self-Management di malattie croniche in un sistema di mobile Health. Viene quindi affrontata in maniera approfondita la tematica del mobile Health, settore in grande espansione che vede l'introduzione massiccia dei dispositivi mobili (smartphone, tablet, PDA) in ambito sanitario, e quella del Self-Managment di malattie croniche, un processo di cura caratterizzato dalla partecipazione autonoma del paziente stesso, fornendo una panoramica dei vari approcci computazionali sviluppati. Successivamente vengono presentate le peculiarità dei modelli computazionali risultati dalle ricerche in letteratura strumenti innovati nell'ambito. Nel caso di studio viene adottata la tecnica di modellazione Agent-Based per sviluppare un modello a supporto di malati cronici affetti da diabete mellito di tipo 1. Con la successiva implementazione sulla piattaforma di simulazione MASON, vengono eseguiti diversi esperimenti per dimostrare la fattibilità dell’approccio adottato nell'ambito del Self-Management di malattie croniche.

ADME pharmacogenetics: investigation of the pharmacokinetics of the antiretroviral agent lopinavir coformulated with ritonavir

An ADME (absorption, distribution, metabolism and excretion)-pharmacogenetics association study may identify functional variants relevant to the pharmacokinetics of lopinavir co-formulated with ritonavir (LPV/r), a first-line anti-HIV agent.

Disabling c-Myc in childhood medulloblastoma and atypical teratoid/rhabdoid tumor cells by the potent G-quadruplex interactive agent S2T1-6OTD

We investigated here the effects of S2T1-6OTD, a novel telomestatin derivative that is synthesized to target G-quadruplex-forming DNA sequences, on a representative panel of human medulloblastoma (MB) and atypical teratoid/rhabdoid (AT/RT) childhood brain cancer cell lines. S2T1-6OTD proved to be a potent c-Myc inhibitor through its high-affinity physical interaction with the G-quadruplex structure in the c-Myc promoter. Treatment with S2T1-6OTD reduced the mRNA and protein expressions of c-Myc and hTERT, which is transcriptionally regulated by c-Myc, and decreased the activities of both genes. In remarkable contrast to control cells, short-term (72-hour) treatment with S2T1-6OTD resulted in a dose- and time-dependent antiproliferative effect in all MB and AT/RT brain tumor cell lines tested (IC(50), 0.25-0.39 micromol/L). Under conditions where inhibition of both proliferation and c-Myc activity was observed, S2T1-6OTD treatment decreased the protein expression of the cell cycle activator cyclin-dependent kinase 2 and induced cell cycle arrest. Long-term treatment (5 weeks) with nontoxic concentrations of S2T1-6OTD resulted in a time-dependent (mainly c-Myc-dependent) telomere shortening. This was accompanied by cell growth arrest starting on day 28 followed by cell senescence and induction of apoptosis on day 35 in all of the five cell lines investigated. On in vivo animal testing, S2T1-6OTD may well represent a novel therapeutic strategy for childhood brain tumors.

Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors

Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents.

Pain and swelling after periapical surgery related to the hemostatic agent used: anesthetic solution with vasoconstrictor or aluminum chloride

To assess pain and swelling in the first 7 days after periapical surgery and their relationship with the agent used for bleeding control.

Squirrel Monkeys (Saimiri sciureus) Infected with the Agent of Bovine Spongiform Encephalopathy Develop Tau Pathology

Squirrel monkeys (Saimiri sciureus) were infected experimentally with the agent of classical bovine spongiform encephalopathy (BSE). Two to four years later, six of the monkeys developed alterations in interactive behaviour and cognition and other neurological signs typical of transmissible spongiform encephalopathy (TSE). At necropsy examination, the brains from all of the monkeys showed pathological changes similar to those described in variant Creutzfeldt-Jakob disease (vCJD) of man, except that the squirrel monkey brains contained no PrP-amyloid plaques typical of that disease. Constant neuropathological features included spongiform degeneration, gliosis, deposition of abnormal prion protein (PrP(TSE)) and many deposits of abnormally phosphorylated tau protein (p-Tau) in several areas of the cerebrum and cerebellum. Western blots showed large amounts of proteinase K-resistant prion protein in the central nervous system. The striking absence of PrP plaques (prominent in brains of cynomolgus macaques [Macaca fascicularis] with experimentally-induced BSE and vCJD and in human patients with vCJD) reinforces the conclusion that the host plays a major role in determining the neuropathology of TSEs. Results of this study suggest that p-Tau, found in the brains of all BSE-infected monkeys, might play a role in the pathogenesis of TSEs. Whether p-Tau contributes to development of disease or appears as a secondary change late in the course of illness remains to be determined.

The vascular-disrupting agent combretastatin impairs splitting and sprouting forms of physiological angiogenesis

Vascular-disrupting agents like combretastatin (CA-4-P), used to attenuate tumor blood flow in vivo, exert anti-mitotic and anti-migratory effects on endothelial cells in vitro. We tested whether anti-vascular or anti-angiogenic effects of CA-4-P are evident with physiological angiogenesis in skeletal muscle (EDL) due to sustained hyperemia (intraluminal splitting) and chronic muscle overload (abluminal sprouting).

Evaluation of cell death mechanisms induced by the vascular disrupting agent OXi4503 during a phase I clinical trial

OXi4503 is a tubulin-binding vascular disrupting agent that has recently completed a Cancer Research UK-sponsored phase I trial. Preclinical studies demonstrated early drug-induced apoptosis in tumour endothelial cells at 1-3 h and secondary tumour cell necrosis between 6 and 72 h.