Novel developments of atropisomeric organic molecules. Design of atropisomeric drugs, fluorescent compounds and investigation of reaction mechanisms.

In recent years, the study of restricted rotation bonds in organic compounds has aroused increasing interest. The reason is that this characteristic can lead to obtaining new properties in organic compounds. In this research thesis, an intense investigation was carried out using DFT calculations and experimental evaluation of the barriers to rotational energies, in order to discover new properties deriving from the restricted rotation bonds. Research has been developed in various fields of organic chemistry, ranging from drugs (the atropisomeric atorvastatin in Chapter 3) to luminescent compounds (aryls amino borane in Chapter 4). Furthermore, an organocatalytic central to axial conversion mechanism was investigated through DFT calculations, finding out interesting outcomes (Chapter 5). Finally, a project in collaboration with Dr. Farran and Prof. Vanthuyne of the Aix-Marseille University was done to investigate the interactions in transition states of rotational barriers.

Supervised and weakly supervised counting-by-segmentation: the fluorescent microscopy use case

This thesis focuses on automating the time-consuming task of manually counting activated neurons in fluorescent microscopy images, which is used to study the mechanisms underlying torpor. The traditional method of manual annotation can introduce bias and delay the outcome of experiments, so the author investigates a deep-learning-based procedure to automatize this task. The author explores two of the main convolutional-neural-network (CNNs) state-of-the-art architectures: UNet and ResUnet family model, and uses a counting-by-segmentation strategy to provide a justification of the objects considered during the counting process. The author also explores a weakly-supervised learning strategy that exploits only dot annotations. The author quantifies the advantages in terms of data reduction and counting performance boost obtainable with a transfer-learning approach and, specifically, a fine-tuning procedure. The author released the dataset used for the supervised use case and all the pre-training models, and designed a web application to share both the counting process pipeline developed in this work and the models pre-trained on the dataset analyzed in this work.

Considerations on indirect adhesive restorations at the material and tooth interfaces

Objective: Lithium-silicate (LiSi) ceramic is nowadays widely used in dentistry. However, for the longevity of LiSi indirect restorations, it is important to pretreat the material and the dental substrate adequately. However, is not certain how the simplification of the manufacturing and conditioning procedures influences the bonding performances of LiSi ceramic restorations. Accordingly, the aims of this thesis were to investigate the effect of: 1) different LiSi ceramic surface decontamination procedures on the shear bond strength (SBS) to resin composite; 2) different types of lithium-disilicate (LiDi) (pressed vs CAD-CAM) on SBS to resin composite; 3) an experimental metal salt-based zirconium oxynitrate etchant [ZrO(NO3)2] on bonding performances to dentin. Materials and Methods: SBS test was used to investigate the influence of different cleaning protocols applied, or different processing techniques (CAD or PRESS) on the bond strength to composite resin. The third study tackled the interface between restorative materials and dentin, and investigated the microtensile bond strength test (µTBS), nanoleakage expression analysis (NL), gelatin zymography and in situ zymography of dentin conditioned with an experimental metal salt-based zirconium oxynitrate etchant [ZrO(NO3)2]. Results: MEP showed comparable bond strength to the double HP etching and higher compared to other groups. BS of press LiSi to composite was higher than that of CAD/CAM LiSi. ZON pretreatment increased bond strength to dentin when used with a universal adhesive, and inhibited dentinal endogenous enzymes. Conclusions: While simplification of the LiSi conditioning and cleaning procedures seems to yield bond strength comparable to the traditional procedures, it could be recommended in the clinical practice. However, pressed LiSi still seems to perform better in terms of bond strength compared to the CAD/CAM LiSi. Further, the novel ZON etchant seems to perform better compared to the traditional phosphoric dentin etching.