Design, synthesis and biological evaluation of substituted naphthalene diimides as anticancer agents

It has been proved that naphthalene diimide (NDI) derivatives display anticancer properties as intercalators and G-quadruplex-binding ligands, leading to DNA damage, senescence and down-regulation of oncogene expression. This thesis deals with the design and synthesis of disubstituted and tetrasubstituted NDI derivatives endowed with anticancer activity, interacting with DNA together with other targets implicated in cancer development. Disubstituted NDI compounds have been designed with the aim to provide potential multitarget directed ligands (MTDLs), in order to create molecules able to simultaneously interact with some of the different targets involved in this pathology. The most active compound, displayed antiproliferative activity in submicromolar range, especially against colon and prostate cancer cell lines, the ability to bind duplex and quadruplex DNA, to inhibit Taq polymerase and telomerase, to trigger caspase activation by a possible oxidative mechanism, to downregulate ERK 2 protein and to inhibit ERKs phosphorylation, without acting directly on microtubules and tubuline. Tetrasubstituted NDI compounds have been designed as G-quadruplex-binding ligands endowed with anticancer activity. In order to improve the cellular uptake of the lead compound, the N-methylpiperazine moiety have been replaced with different aromatic systems and methoxypropyl groups. The most interesting compound was 1d, which was able to interact with the G-quadruplexes both telomeric and in HSP90 promoter region, and it has been co-crystallized with the human telomeric G-quadruplex, to directly verify its ability to bind this kind of structure, and also to investigate its binding mode. All the morpholino substituted compounds show antiproliferative activity in submicromolar values mainly in pancreatic and lung cancer cell lines, and they show an improved biological profile in comparison with that of the lead compound. In conclusion, both these studies, may represent a promising starting point for the development of new interesting molecules useful for the treatment of cancer, underlining the versatility of the NDI scaffold.

Design and optimization of components and processes for plasma sources in advanced material treatments

The research activities described in the present thesis have been oriented to the design and development of components and technological processes aimed at optimizing the performance of plasma sources in advanced in material treatments. Consumables components for high definition plasma arc cutting (PAC) torches were studied and developed. Experimental activities have in particular focussed on the modifications of the emissive insert with respect to the standard electrode configuration, which comprises a press fit hafnium insert in a copper body holder, to improve its durability. Based on a deep analysis of both the scientific and patent literature, different solutions were proposed and tested. First, the behaviour of Hf cathodes when operating at high current levels (250A) in oxidizing atmosphere has been experimentally investigated optimizing, with respect to expected service life, the initial shape of the electrode emissive surface. Moreover, the microstructural modifications of the Hf insert in PAC electrodes were experimentally investigated during first cycles, in order to understand those phenomena occurring on and under the Hf emissive surface and involved in the electrode erosion process. Thereafter, the research activity focussed on producing, characterizing and testing prototypes of composite inserts, combining powders of a high thermal conductibility (Cu, Ag) and high thermionic emissivity (Hf, Zr) materials The complexity of the thermal plasma torch environment required and integrated approach also involving physical modelling. Accordingly, a detailed line-by-line method was developed to compute the net emission coefficient of Ar plasmas at temperatures ranging from 3000 K to 25000 K and pressure ranging from 50 kPa to 200 kPa, for optically thin and partially autoabsorbed plasmas. Finally, prototypal electrodes were studied and realized for a newly developed plasma source, based on the plasma needle concept and devoted to the generation of atmospheric pressure non-thermal plasmas for biomedical applications.

Ahmedabad | Laboratorio di architettura moderna Il National Institute of Design (1961-68) fra contatti internazionali ed echi della tradizione

Oggetto della ricerca è lo studio del National Institute of Design (NID), progettato da Gautam Sarabhai e sua sorella Gira, ad Ahmedabad, assunta a paradigma del nuovo corso della politica che il Primo Ministro Nehru espresse nei primi decenni del governo postcoloniale. Obiettivo della tesi è di analizzare il fenomeno che unisce modernità e tradizione in architettura. La modernità indiana, infatti, nacque e si sviluppò con i caratteri di un Giano bifronte: da un lato, la politica del Primo Ministro Nehru favorì lo sviluppo dell’industria e della scienza; dall’altro, la visione di Gandhi mirava alla riscoperta del locale, delle tradizioni e dell’artigianato. Questi orientamenti influenzarono l’architettura postcoloniale. Negli anni ‘50 e ’60 Ahmedabad divenne la culla dell’architettura moderna indiana. Kanvinde, i Sarabhai, Correa, Doshi, Raje trovarono qui le condizioni per costruire la propria identità come progettisti e come intellettuali. I motori che resero possibile questo fermento furono principalmente due: una committenza di imprenditori illuminati, desiderosi di modernizzare la città; la presenza ad Ahmedabad, a partire dal 1951, dei maestri dell’architettura moderna, tra cui i più noti furono Le Corbusier e Kahn, invitati da quella stessa committenza, per la quale realizzarono edifici di notevole rilevanza. Ad Ahmedabad si confrontarono con forza entrambe le visioni dell’India moderna. Lo sforzo maggiore degli architetti indiani si espresse nel tentativo di conciliare i due aspetti, quelli che derivavano dalle influenze internazionali e quelli che provenivano dallo spirito della tradizione. Il progetto del NID è uno dei migliori esempi di questo esercizio di sintesi. Esso recupera nella composizione spaziale la lezione di Wright, Le Corbusier, Kahn, Eames ibridandola con elementi della tradizione indiana. Nell’uso sapiente della struttura modulare e a padiglione, della griglia ordinatrice a base quadrata, dell’integrazione costante fra spazi aperti, natura e architettura affiorano nell’edificio del NID echi di una cultura millenaria.

Design and implementation of a novel multi-constellation FPGA-based dual frequency GNSS receiver for space applications

The PhD activity described in the document is part of the Microsatellite and Microsystem Laboratory of the II Faculty of Engineering, University of Bologna. The main objective is the design and development of a GNSS receiver for the orbit determination of microsatellites in low earth orbit. The development starts from the electronic design and goes up to the implementation of the navigation algorithms, covering all the aspects that are involved in this type of applications. The use of GPS receivers for orbit determination is a consolidated application used in many space missions, but the development of the new GNSS system within few years, such as the European Galileo, the Chinese COMPASS and the Russian modernized GLONASS, proposes new challenges and offers new opportunities to increase the orbit determination performances. The evaluation of improvements coming from the new systems together with the implementation of a receiver that is compatible with at least one of the new systems, are the main activities of the PhD. The activities can be divided in three section: receiver requirements definition and prototype implementation, design and analysis of the GNSS signal tracking algorithms, and design and analysis of the navigation algorithms. The receiver prototype is based on a Virtex FPGA by Xilinx, and includes a PowerPC processor. The architecture follows the software defined radio paradigm, so most of signal processing is performed in software while only what is strictly necessary is done in hardware. The tracking algorithms are implemented as a combination of Phase Locked Loop and Frequency Locked Loop for the carrier, and Delay Locked Loop with variable bandwidth for the code. The navigation algorithm is based on the extended Kalman filter and includes an accurate LEO orbit model.

Design, development and first evaluation of a client/server system for managing and querying linguistic corpora

This thesis is concerned with the role played by software tools in the analysis and dissemination of linguistic corpora and their contribution to a more widespread adoption of corpora in different fields. Chapter 1 contains an overview of some of the most relevant corpus analysis tools available today, presenting their most interesting features and some of their drawbacks. Chapter 2 begins with an explanation of the reasons why none of the available tools appear to satisfy the requirements of the user community and then continues with technical overview of the current status of the new system developed as part of this work. This presentation is followed by highlights of features that make the system appealing to users and corpus builders (i.e. scholars willing to make their corpora available to the public). The chapter concludes with an indication of future directions for the projects and information on the current availability of the software. Chapter 3 describes the design of an experiment devised to evaluate the usability of the new system in comparison to another corpus tool. Usage of the tool was tested in the context of a documentation task performed on a real assignment during a translation class in a master's degree course. In chapter 4 the findings of the experiment are presented on two levels of analysis: firstly a discussion on how participants interacted with and evaluated the two corpus tools in terms of interface and interaction design, usability and perceived ease of use. Then an analysis follows of how users interacted with corpora to complete the task and what kind of queries they submitted. Finally, some general conclusions are drawn and areas for future work are outlined.

I doveri e le responsabilità contabili nella corporate governance delle società di capitali

La costruzione di un modello efficiente di corporate governance deve offrire una disciplina adeguata dei doveri contabili. Ciò nonostante, gli ordinamenti giuridici configurano i doveri di contabilità in modo incompleto, giacché l’inadempimento di questi non comporta una sanzione diretta per il soggetto inadempiente. Come informazione sulla situazione economica e finanziaria della società, esiste un interesse pubblico nella contabilità, e questa può servire come base di giudizio a soggetti interni ed esterni all’impresa, nell’adozione delle sue scelte. Disporre di un’informazione falsa o inesatta al riguardo può comportare un danno ingiustificato alla società stessa, ai soci o ai terzi, che potranno esercitare le azioni precise per il risarcimento del danno cagionato. Per evitare la produzione di questi danni, da una prospettiva preventiva, la corporate governance delle società di capitali può prevedere dei meccanismi di controllo che riducano il rischio di offrire un’informazione sbagliata. Questi controlli potranno essere esercitati da soggetti interni o esterni (revisori legali) alla struttura della società, ed avranno una configurazione diversa a seconda che le società adottino una struttura monistica o dualistica di governance. Questo ci colloca di fronte ad una eventuale situazione di concorrenza delle colpe, giacché i diversi soggetti che intervengono nel processo d’elaborazione dell’informazione contabile versano la sua attuazione sullo stesso documento: il bilancio. Risulta dunque cruciale determinare il contributo effettivo di ciascuno per analizzare il suo grado di responsabilità nella produzione del danno.