Disseminazioni in reti peer-to-peer attraverso algoritmi di gossip a due fasi

Gli algoritmi di gossip sono utilizzati per la disseminazione di messaggi in una rete peer-to-peer. La tesi tratta lo sviluppo, l'implementazione e l'analisi di quattro nuovi algoritmi di gossip "a due fasi". Gli algoritmi sono stati sviluppati e testati con il simulatore LUNES per poi essere analizzati in vari confronti con gli algoritmi classici dell'ambito, ovvero Fixed Probability e Conditional Broadcast. Le prove sono state effettuate su varie tipologie di grafi, ovvero Random, Scale-free, Small-world e K-Regular.

Determinazione e analisi del rischio sismico e idrogeologico nelle reti di distribuzione acqua

In questo elaborato si è focalizzata l’attenzione sulla determinazione del rischio simico e idrogeologico per una rete di distribuzione acqua. Partendo dalle caratteristiche di ogni singolo elemento si sono valutati la vulnerabilità, l’esposizione e la pericolosità per ogni condotta. In conclusione si è analizzato il rischio al fine di individuare quegli elementi maggiormente compromessi su cui concentrare l’attenzione per possibili interventi futuri.

Facile double-functionalization of designed ankyrin repeat proteins using click and thiol chemistries

Click chemistry is a powerful technology for the functionalization of therapeutic proteins with effector moieties, because of its potential for bio-orthogonal, regio-selective, and high-yielding conjugation under mild conditions. Designed Ankyrin Repeat Proteins (DARPins), a novel class of highly stable binding proteins, are particularly well suited for the introduction of clickable methionine surrogates such as azidohomoalanine (Aha) or homopropargylglycine (Hpg), since the DARPin scaffold can be made methionine-free by an M34L mutation in the N-cap which fully maintains the biophysical properties of the protein. A single N-terminal azidohomoalanine, replacing the initiator Met, is incorporated in high yield, and allows preparation of "clickable" DARPins at about 30 mg per liter E. coli culture, fully retaining stability, specificity, and affinity. For a second modification, we introduced a cysteine at the C-terminus. Such DARPins could be conveniently site-specifically linked to two moieties, polyethylene glycol (PEG) to the N-terminus and the fluorophore Alexa488 to the C-terminus. We present a DARPin selected against the epithelial cell adhesion molecule (EpCAM) with excellent properties for tumor targeting as an example. We used these doubly modified molecules to measure binding kinetics on tumor cells and found that PEGylation has no effect on dissociation rate, but slightly decreases the association rate and the maximal number of cell-bound DARPins, fully consistent with our previous model of PEG action obtained in vitro. Our data demonstrate the benefit of click chemistry for site-specific modification of binding proteins like DARPins to conveniently add several functional moieties simultaneously for various biomedical applications.

Governance of Massive Multiauthor Collaboration – Linux, Wikipedia, and Other Networks: Governed by Bilateral Contracts, Partnerships, or Something in Between?

Open collaborative projects are moving to the foreground of knowledge production. Some online user communities develop into longterm projects that generate a highly valuable and at the same time freely accessible output. Traditional copyright law that is organized around the idea of a single creative entity is not well equipped to accommodate the needs of these forms of collaboration. In order to enable a peculiar network-type of interaction participants instead draw on public licensing models that determine the freedoms to use individual contributions. With the help of these access rules the operational logic of the project can be implemented successfully. However, as the case of the Wikipedia GFDL-CC license transition demonstrates, the adaptation of access rules in networks to new circumstances raises collective action problems and suffers from pitfalls caused by the fact that public licensing is grounded in individual copyright. Legal governance of open collaboration projects is a largely unexplored field. The article argues that the license steward of a public license assumes the position of a fiduciary of the knowledge commons generated under the license regime. Ultimately, the governance of decentralized networks translates into a composite of organizational and contractual elements. It is concluded that the production of global knowledge commons relies on rules of transnational private law.

Increasing the Antitumor Effect of an EpCAM-Targeting Fusion Toxin by Facile Click PEGylation

Fusion toxins used for cancer-related therapy have demonstrated short circulation half-lives, which impairs tumor localization and, hence, efficacy. Here, we demonstrate that the pharmacokinetics of a fusion toxin composed of a designed ankyrin repeat protein (DARPin) and domain I–truncated Pseudomonas Exotoxin A (PE40/ETA″) can be significantly improved by facile bioorthogonal conjugation with a polyethylene glycol (PEG) polymer at a unique position. Fusion of the anti-EpCAM DARPin Ec1 to ETA″ and expression in methionine-auxotrophic E. coli enabled introduction of the nonnatural amino acid azidohomoalanine (Aha) at position 1 for strain-promoted click PEGylation. PEGylated Ec1-ETA″ was characterized by detailed biochemical analysis, and its potential for tumor targeting was assessed using carcinoma cell lines of various histotypes in vitro, and subcutaneous and orthotopic tumor xenografts in vivo. The mild click reaction resulted in a well-defined mono-PEGylated product, which could be readily purified to homogeneity. Despite an increased hydrodynamic radius resulting from the polymer, the fusion toxin demonstrated high EpCAM-binding activity and retained cytotoxicity in the femtomolar range. Pharmacologic analysis in mice unveiled an almost 6-fold increase in the elimination half-life (14 vs. 82 minutes) and a more than 7-fold increase in the area under the curve (AUC) compared with non-PEGylated Ec1-ETA″, which directly translated in increased and longer-lasting effects on established tumor xenografts. Our data underline the great potential of combining the inherent advantages of the DARPin format with bioorthogonal click chemistry to overcome the limitations of engineering fusion toxins with enhanced efficacy for cancer-related therapy.

Liquid-Crystalline Dendrimers Designed by Click Chemistry

Liquid-crystalline dendrimers have been prepared from second-generation Percec-type poly(benzyl ether) dendrons or second-generation poly(aryl ester) dendrons carrying cyanobiphenyl mesogens. The Janus dendrimer, which combines the two types of dendromesogens, has also been synthesized. Those compounds have been prepared under copper-catalyzed azide–alkyne cycloaddition conditions. The mesomorphic properties have been studied by thermal analysis (POM, DSC) and small-angle X-ray scattering. Smectic A, nematic, and columnar phases have been observed depending on the dendritic building blocks. The click reaction has proven to be a powerful and elegant synthetic tool for the design of complex dendritic liquid-crystalline architectures.

Aplicación de representación gráfica de datos y/o señales en entorno GNU/LINUX

El contenido de este PFC supone el desarrollo de una aplicación gráfica en el entorno GNU/LINUX. La aplicación debe representar en la pantalla gráficos procedentes de una fuente externa (un fichero, una tarjeta de adquisición de datos, otra aplicación, etc.) Debe permitir las siguientes funcionalidades: Representar la señal uniendo puntos o marcándolos como símbolos. Debe gestionar de forma adecuada el zoom. Debe permitir exportar la gráfica a formatos SVG y PDF. Debe permitir mostrar varias señales superpuestas para poder compararlas. Opcionalmente debe permitir arrastrar y soltar (“drag and drop”). ABSTRACT The content of the thesis is the development of a graphical application in GNU / Linux environment. The application must render graphics on the screen from an external source (a file, a data acquisition card, other applications, etc..) It must allow the following functionality: Joining dots represent the signal or marking them as symbols. Must properly manage the zoom. Allow export the graph to SVG and PDF formats. Allow display multiple signals superimposed for comparison. Optionally should allow drag and drop.