Sintesi di nuovi derivati tri-componente per target photodynamic therapy della neoplasia prostatica

Therapies for the treatment of prostate cancer show several limitations, especially when the cancer metastasizes or acquires resistance to treatment. In addition, most of the therapies currently used entails the occurrence of serious side effects. A different therapeutic approach, more selective and less invasive with respect either to radio or to chemotherapy, is represented by the photodynamic therapy (PDT). The PDT is a treatment that makes use of photosensitive drugs: these agents are pharmacologically inactive until they are irradiated with light at an appropriate wavelength and in the presence of oxygen. The drug, activated by light, forms singlet oxygen, a highly reactive chemical species directly responsible for DNA damage, thus of cell death. In this thesis we present two synthetic strategies for the preparation of two new tri-component derivatives for photodynamic therapy of advanced prostate cancer, namely DRPDT1 and DRPDT2. Both derivatives are formed by three basic elements covalently bounded to each other: a specific ligand with high affinity for the androgen receptor, a suitably chosen spacer molecule and a photoactivated molecule. In particular, DRPDT2 differs from DRPDT1 from the nature of the AR ligand. In fact, in the case of DRPDT2 we used a synthetically engineered androgen receptor ligand able to photo-react even in the absence of oxygen, by delivering NO radical. The presence of this additional pharmacophore, together with the porphyrin, may ensure an additive/synergistic effect to the photo-stimulated therapy, which than may act both in the presence of oxygen and in hypoxic conditions. This approach represents the first example of multimodal photodynamic therapy for prostate cancer.

Beyond simple proton transfer processes: domino reactions between 4-substituted indoles and nitroethene as a new gateway to ergot alkaloids

The multimodal biology activity of ergot alkaloids is known by humankind since middle ages. Synthetically modified ergot alkaloids are used for the treatment of various medical conditions. Despite the great progress in organic syntheses, the total synthesis of ergot alkaloids remains a great challenge due to the complexity of their polycyclic structure with multiple stereogenic centres. This project has developed a new domino reaction between indoles bearing a Michael acceptor at the 4 position and nitroethene, leading to potential ergot alkaloid precursors in highly enantioenriched form. The reaction was optimised and applied to a large variety of substrate with good results. Even if unfortunately all attempts to further modify the obtained polycyclic structure failed, it was found a reaction able to produce the diastereoisomer of the polycyclic product in excellent yields. The compounds synthetized were characterized by NMR and ESIMS analysis confirming the structure and their enantiomeric excess was determined by chiral stationary phase HPLC. The mechanism of the reaction was evaluated by DFT calculations, showing the formation of a key bicoordinated nitronate intermediate, and fully accounting for the results observed with all substrates. The relative and absolute configuration of the adducts were determined by a combination of NMR, ECD and computational methods.

Interpretazione per i media: il caso particolare delle interviste sul podio della Formula 1

This dissertation analyses the live simultaneous interpretation from English into Italian of six 2013 Formula 1 World Championship podium interviews and focuses on four main aspects: how the interpreter handled the décalage at the end of the interview and during the turn-taking; if he used any marker to indicate that he was starting to translate a new turn of the source text; what he did when overlapped speech in the source texts occurred; what happened when the Italian commentators talked during the interpreter’s translation. In the first chapter a description mainly of what a Formula 1 podium interview is and what an interpreter translates during the Formula 1 weekends is present. In the second chapter a literature review on media interpreting, with particular attention put on Straniero Sergio’s paper on translating Formula 1 press-conferences (2003), and turn-taking is provided. In the third chapter the methodology used to obtain and process the video and audio files of source and target texts and to transcribe them is described. We concentrated primarily on Thibault’s multimodal text transcription techniques (2000) and on how they were used and adapted to fit the purposes of this dissertation. In the fourth chapter the results obtained through the analysis of the source and target texts are shown and described, focusing only on the objectives of the dissertation, without aiming to provide a qualitative evaluation of the interpretations. In the fifth and last chapter the conclusions and some final remarks are made, based on the results obtained during the analysis and the hope for a more in depth knowledge of Italian Formula 1 interpreter’s working conditions.

Typing your mind away. Comparing keylogged tasks with the Task Segment Framework

One of the main process features under study in Cognitive Translation & Interpreting Studies (CTIS) is the chronological unfolding of the tasks. The analyses of time spans in translation have been conceived in two ways: (1) studying those falling between text units of different sizes: words, phrases, sentences, and paragraphs; (2) setting arbitrary time span thresholds to explore where do they fall in the text, whether between text units or not. Writing disfluencies may lead to comprehensive insights into the cognitive activities involved in typing while translating. Indeed, long time spans are often taken as hints that cognitive resources have been subtracted from typing and devoted to other activities, such as planning, evaluating, etc. This exploratory, pilot study combined both approaches to seek potential general tendencies and contrasts in informants’ inferred mental processes when performing different writing tasks, through the analysis of their behaviors, as keylogged. The study tasks were retyping, monolingual free writing, translation, revision and a multimodal task—namely, monolingual text production based on an infographic leaflet. Task logs were chunked, and shorter time spans, including those within words, were analyzed following the Task Segment Framework (Muñoz & Apfelthaler, in press). Finally, time span analysis was combined with the analysis of the texts as to their lexical density, type-token ratio and word frequency. Several previous results were confirmed, and some others were surprising. Time spans in free writing were longer between paragraphs and sentences, possibly hinting at planning and, in translation, between clauses and words, suggesting more cognitive activities at these levels. On the other hand, the infographic was expected to facilitate the writing process, but most time spans were longer than in both free writing and translation. Results of the multimodal task and some other results suggest venues for further research.

Assessing the Environmental Performance of New Mobility

This report has two main goals. First to improve methodologies of new mobility services .Second identify the solution to improve new mobility in urban transportation to decrease energy loss and decline climate change. This report also compares energy use and greenhouse gasses (GHG) emission impact for new mobility and all transportation modes. Having focus on central estimates and a range of possible alternatives to enhance the result to advance environmental effects. This analysis and research help to identify the possible solutions to make new mobility more sustainable