L'Ottica di Euclide e la scienza della visione

La presente tesi concerne il trattato "Ottica" scritto da Euclide nel III secolo a.C. quando, nell'area del bacino del Mediterraneo, si verificò una rivoluzione scientifica che diede origine alla nascita della scienza moderna. Si colloca nel filone delle ricerche volte a ricostruire la verità storica ed il contenuto scientifico del pensiero dello scienziato ed a meglio illustrare i contributi dati, dalla scienza ellenistica, alla conoscenza del fenomeno visivo. Si sono presi in esame dunque il momento storico e la situazione economica, sociale e scientifica verificatasi nel III secolo a.C., in particolare ad Alessandria d'Egitto, dove l'incontro del pensiero greco con le culture preesistenti portò alla nascita del metodo scientifico moderno; si sono considerati il pensiero filosofico del tempo e le teorie scientifiche sviluppatesi, con particolare riguardo alla matematica ed alla scienza medica, fondata dal medico alessandrino Erofilo. Si è poi preso in esame il contenuto del trattato. L' "Ottica" è il primo trattato di ottica geometrica della storia e la prima teoria scientifica che si occupi della visione. È basato sul metodo ipotetico-deduttivo, su conoscenze di oftalmologia e sulla scienza matematica degli Elementi. È un modello geometrico di un processo fisiologico e riconferma la matematica quale strumento principe per la costruzione del sapere scientifico. Crea modelli utili per altre teorie scientifiche (ad es. l'astronomia) e per le arti figurative ed ha applicazioni tecnologiche (ad es. l'astrolabio e la diottra). È il testo di base della moderna ottica geometrica. Non si pone come una verità assoluta ma come un'ipotesi di lavoro. Si sono esaminati il difficile percorso storico e bibliografico dell'opera caratterizzato da incomprensioni e manomissioni nonché la ricerca filologica volta a ricostruire l'integrità del testo. Si ritenne infatti che la sua validità fosse inficiata da alcuni "errori", in realtà dovuti all'incomprensione dei concetti e del metodo euclidei ed alle successive manomissioni. Emerge come la scienza non abbia avuto un progresso costante, continuo, aprioristico e come sia incerta ed instabile la conservazione nel tempo del sapere scientifico. Appare inoltre evidente come la scienza sia un prodotto della cultura umana e pertanto come la conoscenza della storia sia una condizione fondante per il progresso scientifico

Missing data patterns in runners' careers: do they matter?

Predicting the future performance of young runners is an important research issue in experimental sports science and performance analysis. We analyse a data set with annual seasonal best performances of male middle distance runners for a period of 14 years and provide a modelling framework that accounts for both the fact that each runner has typically run in three distance events (800, 1500 and 5000 meters) and the presence of periods of no running activities. We propose a latent class matrix-variate state space model and we empirically demonstrate that accounting for missing data patterns in runners' careers improves the out of sample prediction of their performances over time. In particular, we demonstrate that for this analysis, the missing data patterns provide valuable information for the prediction of runner's performance

How Can Organisations and Business Models Lead to a More Sustainable Society? A Framework from a Systematic Review of the Industry 4.0

The concept of Industry 4.0 has been mainly addressed by the current literature from a technological perspective, overlooking the organisational and even ethical challenges related to this recent paradigm. In order to become ‘4.0 compliant’, an enterprise must adapt its organisation and business approaches, and these changes may lead to a significant impact on sustainability. Therefore, we performed a systematic literature review to investigate the most recent Industry 4.0 research streams by adopting a multi-perspective approach. This analysis led to collect insights on the key traits of an Enterprise 4.0: integration, decomposed hierarchy, flexibility, and autonomy. Each of these keywords involves work environments, business and organisational models, and educational approaches, which constitute the key traits of the novel framework proposed in this study

Auditory, Visual And Somatosensory Localization Of Piano Tones: A Preliminary Study

The paper presents an experiment in which subjects had to localize headphone-reproduced binaural piano tones while in front of a grand Disklavier instrument. Three experimental conditions were designed: when the fallboard was closed the localization was auditory only; when the fallboard was open the localization was auditory and visual, since the Disklavier’s actuated key could be seen moving down while the corresponding note was produced; when the listener actively played the note the localization was auditory, visual and somatosensory. In all conditions the tones were reproduced using binaural recordings previously acquired on the same instrument. Such tones were presented either transparently or by reversing the channels. Thirteen subjects participated in the experiment. Results suggest that if auditory localization associates the tone to the corresponding key, then the visual and somatosensory feedback refine the localization. Conversely, if auditory localization is confused then the visual and somatosensory channels cannot improve it. Further experimentation is needed to explain these results in relation with i) possible activation of the auditory precedence effect at least for some notes, and ii) potential locking of the sound source position that visual and/or somatosensory cues might cause when subjects observe a key moving down, or depress it

Synergistic inhibition of the Hedgehog pathway by newly designed Smo and Gli antagonists bearing the isoflavone scaffold

Aberrant activation of the Hedgehog (Hh) pathway is responsible for the onset and progression of several malignancies. Small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector Gli1 have thus emerged recently as valuable anticancer agents. Here, we have designed, synthesized, and tested new Hh inhibitors taking advantage by the highly versatile and privileged isoflavone scaffold. The introduction of specific substitutions on the isoflavone's ring B allowed the identification of molecules targeting preferentially Smo or Gli1. Biological assays coupled with molecular modeling corroborated the design strategy, and provided new insights into the mechanism of action of these molecules. The combined administration of two different isoflavones behaving as Smo and Gli antagonists, respectively, in primary medulloblastoma (MB) cells highlighted the synergistic effects of these agents, thus paving the way to further and innovative strategies for the pharmacological inhibition of Hh signaling

The Long March of Chinese Co-operatives: Towards Market Economy, Participation, and Sustainable Development

This is an Author Final Copy of a paper accepted for publication in Asia Pacific Business Review published by and copyright Taylor & Francis

Inhibition of Hedgehog-dependent tumors and cancer stem cells by a newly identified naturally occurring chemotype

Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the Hh signaling and is a validated target for the development of anticancer compounds, as underlined by the FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) for the treatment of basal cell carcinoma. However, Smo mutations that confer constitutive activity and drug resistance have emerged during treatment with Vismodegib. For this reason, the development of new effective Hh inhibitors represents a major challenge for cancer therapy. Natural products have always represented a unique source of lead structures in drug discovery, and in recent years have been used to modulate the Hh pathway at multiple levels. Here, starting from an in house library of natural compounds and their derivatives, we discovered novel chemotypes of Hh inhibitors by mean of virtual screening against the crystallographic structure of Smo. Hh functional based assay identified the chalcone derivative 12 as the most effective Hh inhibitor within the test set. The chalcone 12 binds the Smo receptor and promotes the displacement of Bodipy-Cyclopamine in both Smo WT and drug-resistant Smo mutant. Our molecule stands as a promising Smo antagonist able to specifically impair the growth of Hh-dependent tumor cells in vitro and in vivo and medulloblastoma stem-like cells and potentially overcome the associated drug resistance