Design and Synthesis of Naphthalene Diimides Based Small Molecules as Anticancer Agents: Targeting the Polyamine Transporter, G-quadruplex Structures and HDAC

Cancer is a multifactorial disease characterized by a very complex etiology. Basing on its complex nature, a promising therapeutic strategy could be based by the “Multi-Target-Directed Ligand” (MTDL) approach, based on the assumption that a single molecule could hit several targets responsible for the pathology. Several agents acting on DNA are clinically used, but the severe deriving side effects limit their therapeutic application. G-quadruplex structures are DNA secondary structures located in key zones of human genome; targeting quadruplex structures could allow obtaining an anticancer therapy more free from side effects. In the last years it has been proved that epigenetic modulation can control the expression of human genes, playing a crucial role in carcinogenesis and, in particular, an abnormal expression of histone deacetylase enzymes are related to tumor onset and progression. This thesis deals with the design and synthesis of new naphthalene diimide (NDI) derivatives endowed with anticancer activity, interacting with DNA together with other targets implicated in cancer development, such as HDACs. NDI-polyamine and NDI-polyamine-hydroxamic acid conjugates have been designed with the aim to provide potential MTDLs, in order to create molecules able simultaneously to interact with different targets involved in this pathology, specifically the G-quadruplex structures and HDAC, and to exploit the polyamine transport system to get selectively into cancer cells. Macrocyclic NDIs have been designed with the aim to improve the quadruplex targeting profile of the disubstituted NDIs. These compounds proved the ability to induce a high and selective stabilization of the quadruplex structures, together with cytotoxic activities in the micromolar range. Finally, trisubstituted NDIs have been developed as G-quadruplex-binders, potentially effective against pancreatic adenocarcinoma. In conclusion, all 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.

Many-Core Architectures: Hardware-Software Optimization and Modeling Techniques

During the last few decades an unprecedented technological growth has been at the center of the embedded systems design paramount, with Moore’s Law being the leading factor of this trend. Today in fact an ever increasing number of cores can be integrated on the same die, marking the transition from state-of-the-art multi-core chips to the new many-core design paradigm. Despite the extraordinarily high computing power, the complexity of many-core chips opens the door to several challenges. As a result of the increased silicon density of modern Systems-on-a-Chip (SoC), the design space exploration needed to find the best design has exploded and hardware designers are in fact facing the problem of a huge design space. Virtual Platforms have always been used to enable hardware-software co-design, but today they are facing with the huge complexity of both hardware and software systems. In this thesis two different research works on Virtual Platforms are presented: the first one is intended for the hardware developer, to easily allow complex cycle accurate simulations of many-core SoCs. The second work exploits the parallel computing power of off-the-shelf General Purpose Graphics Processing Units (GPGPUs), with the goal of an increased simulation speed. The term Virtualization can be used in the context of many-core systems not only to refer to the aforementioned hardware emulation tools (Virtual Platforms), but also for two other main purposes: 1) to help the programmer to achieve the maximum possible performance of an application, by hiding the complexity of the underlying hardware. 2) to efficiently exploit the high parallel hardware of many-core chips in environments with multiple active Virtual Machines. This thesis is focused on virtualization techniques with the goal to mitigate, and overtake when possible, some of the challenges introduced by the many-core design paradigm.

L’espace urbain indien dans la littérature européenne au XXème siecle. Pour une perspective post-orientaliste.

L'affermarsi della teoria della « imaginative geography » di Edward Saïd (Orientalism, 1978), nell'arco degli ultimi trent'anni, ha imposto un orientamento prettamente sociopolitico, gramsciano e foucaultiano alla critica del testo, proponendo un'unica soluzione interpretativa per un corpus eterogeneo di testi (scientifici e artistici, antichi e moderni) accomunati dal fatto di « rappresentare l'Oriente ». La costruzione europea dello spazio orientale, dice Saïd, non rappresenta solo un misconoscimento dell'Altro, ma una sua rappresentazione tendenziosa e finalizzata a sostenere la macchina dell'imperialismo occidentale. In particolare, la rappresentazione « femminilizzata » della geografia orientale (come luogo dell'exploit del maschio bianco) preparebbe e accompagnerebbe l'impresa di assoggettamento politico e di sfruttamento economico dei paesi ad Est dell'Europa. Se Orientalism ha conosciuto fortune alterne dall'anno della sua apparizione, negli ultimi anni una vera e propria corrente anti-saidiana ha preso forza, soprattutto in ambito francese. Attraverso l'analisi di circa trenta opere francesi, belga, inglesi e italiane del Novecento, questa tesi cerca di visualizzare i limiti teorici della prospettiva saidiana rivolgendosi a un esame della rappresentazione dello spazio urbano indiano nella letteratura europea contemporanea. Nello specifico, uno studio delle nuove strutture e dei nuovi modelli della femminilizzazione dello spazio orientale indiano cercherà di completare – superandolo in direzione di un « post-orientalismo » – il riduzionismo della prospettiva saidiana.

Development of synthetic methods of silicon nanocrystals functionalized with photoactive molecules

The thesis is focused on the development of a method for the synthesis of silicon nanocrystals with different sizes, narrow size distribution, good optical properties and stability in air. The resulting silicon nanocrystals have been covalently functionalized with different chromophores with the aim to exploit the new electronic and chemical properties that emerge from the interaction between silicon nanocrystal surface and ligands. The purpose is to use these chromophores as light harvesting antennae, increasing the optical absorption of silicon nanocrystals. Functionalized silicon nanocrystals have been characterized with different analytical techniques leading to a good knowledge of optical properties of semiconductor quantum dots.