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The effect of rapid laser irradiation on the optical properties of mature soot particles is investigated by performing wavelength-resolved extinction measurements in the visible spectral region. In particular, the spectral behavior of the absorption properties is explored during laser irradiation, at the peak of the incandescence signal (prompt LII) and few nanoseconds after the peak, and finally when particles have reached an equilibrium condition with the surrounding gas. A significant variation of the absorption coefficient of the laser-irradiated soot particles compared to that of the pristine ones is observed already at the LII peak. Such variation keeps evolving with time until it reaches a final permanent value. Results are presented in relation to the laser fluence used for irradiation and discussed with the aim of stressing the need of knowing the entity of the modification of soot absorption properties during laser irradiation for a correct interpretation of LII data.

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We report a new 1-6 self-immolative, traceless crosslinker derived from the natural product gallic acid. The linker acts through a pH-dependent mechanism for drug release. This 5-(hydroxymethyl)pyrogallol orthoester derivative (HMPO) was stable for 24 hours at pH values of 7.4 and 6.6 and in plasma, releasing molecules bound to the hydroxymethyl moiety under acid-dependent stimuli at pH 5.5. The linker was non-toxic and was used for the conjugation of Doxorubicin (Doxo) or Combretastatin A4 with Cetuximab. The ADCs formed showed their pH responsivity reducing cell viability of A431 and A549 cancer cells better than Cetuximab alone.

Natural Killer Group 2D (NKG2D) is a homo-dimeric transmembrane protein which is typically expressed on the surface of natural killer (NK) cells, natural killer T (NKT) cells, gamma delta T (γδT) cells, activated CD8 positive T-cells and activated macrophages. Bispecific molecules, capable of bridging NKG2D with a target protein expressed on the surface of tumor cells, may be used to redirect the cytotoxic activity of NK-cells towards antigen-positive malignant T-cells. In this work, we report the discovery of a novel NKG2D small molecule binder [KsubD/sub=(410±60) nM], isolated from a DNA-Encoded Chemical Library (DEL). The discovery of small organic NKG2D ligands may facilitate the generation of fully synthetic bispecific adaptors, which may serve as an alternative to bispecific antibody products and which may benefit from better tumor targeting properties.

It is here reported a fully sustainable and generally applicable protocol for the regioselective hydroformylation of terminal alkenes, using cheap commercially available catalysts and ligands, in mild reaction conditions (70 °C, 9 bar, 40 min). The process can take advantages from both micellar catalysis and microwave irradiation to obtain the linear aldehydes as the major or sole regioisomers in good to high yields. The substrate scope is largely explored as well as the application of hydroformylation in tandem with intramolecular hemiacetalization thus demonstrating the compatibility with a broad variety of functional groups. The reaction is efficient even in large scale and the catalyst and micellar water phase can be reused at least 5 times without any impact in reaction yields. The efficiency and sustainability of this protocol is strictly related to the in situ transformation of the aldehyde into the corresponding Bertagnini's salt that precipitates in the reaction mixture avoiding organic solvent mediated purification steps to obtain the final aldehydes as pure compounds.

Despite the development of new targeted and immune therapies, the prognosis of metastatic melanoma remains bleak. Therefore, it is critical to better understand the mechanisms controlling advanced melanoma to develop more effective treatment regimens. Hedgehog/GLI (HH/GLI) signaling inhibitors targeting the central pathway transducer Smoothened (SMO) have shown to be clinical efficacious in skin cancer; however, several mechanisms of non-canonical HH/GLI pathway activation limit their efficacy. Here, we identify a novel SOX2-BRD4 transcriptional complex driving the expression of GLI1, the final effector of the HH/GLI pathway, providing a novel mechanism of non-canonical SMO-independent activation of HH/GLI signaling in melanoma. Consistently, we find a positive correlation between the expression of GLI1 and SOX2 in human melanoma samples and cell lines. Further, we show that combined targeting of canonical HH/GLI pathway with the SMO inhibitor MRT-92 and of the SOX2-BRD4 complex using a potent Proteolysis Targeted Chimeras (PROTACs)-derived BRD4 degrader (MZ1), yields a synergistic anti-proliferative effect in melanoma cells independently of their BRAF, NRAS, and NF1 mutational status, with complete abrogation of GLI1 expression. Combination of MRT-92 and MZ1 strongly potentiates the antitumor effect of either drug as single agents in an orthotopic melanoma model. Together, our data provide evidence of a novel mechanism of non-canonical activation of GLI1 by the SOX2-BRD4 transcriptional complex, and describe the efficacy of a new combinatorial treatment for a subset of melanomas with an active SOX2-BRD4-GLI1 axis.

FAP-targeted radiopharmaceuticals represent a breakthrough in cancer imaging and a viable option for therapeutic applications. OncoFAP, an ultra-high affinity ligand of FAP, has been recently discovered and clinically validated for PET imaging procedures in patients with solid malignancies. While more and more clinical validation is becoming available, the need for scalable and robust procedures for the preparation of this new class of radiopharmaceuticals continues to increase. In this article, we present the development of automated radiolabelling procedures with FASTlab 2 for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging and therapy. A new series of [68Ga]Ga-OncoFAP, [177Lu]Lu-OncoFAP and [18F]AlF-OncoFAP was produced with high-yields. Chemical and biochemical characterization after radiolabelling confirmed excellent stability, retention of high affinity for FAP and absence of radiolysis by-products. The in vivo biodistribution of [18F]AlF-OncoFAP-NOTA, a candidate for PET imaging procedures in patients, was assessed in mice bearing FAP-positive solid tumours. The product showed rapid accumulation in solid tumours, with an average of 6.6% ID/g one hour after systemic administration and excellent tumour-to-healthy organs ratio. We have established methodologies to efficiently produce an OncoFAP-based radiotheranostic pair in which [68Ga]Ga-OncoFAP-DOTAGA is used as a companion diagnostic of the targeted therapeutic agent [177Lu]Lu-OncoFAP-DOTAGA Objectives: We have developed simple, quick, safe and robust synthetic procedures for the preparation of theranostic OncoFAP-compounds based on Gallium-68, Lutetium-177 and Alluminium-Fluoride-18 using the commercially available FASTlab 2 synthesis module.

In this work cooled carbon nanoparticles are investigated with the aim of gaining knowledge on their properties. To this purpose, a double pulse experiment is employed consisting essentially of a modified Laser-Induced Incandescence (LII) approach. Before the conventional LII measurements, nanoparticles are additionally irradiated applying different laser fluences. The investigation is performed on carbon nanoparticles sampled from a rich premixed ethylene/air flame at two heights in order to compare the irradiation effects on young and mature particles. Two-color LII measurements are carried out on pristine and irradiated nanoparticles varying the LII laser fluence. In particular, the effects on the incandescence signal, temperature and concentration are investigated. Two phenomena are isolated, namely (1) a significant increase of the apparent particle volume fraction with the applied laser fluence; and (2) a noticeable increase of the LII signal depending on the laser irradiation fluence applied prior to LII. The effects are found to be stronger for young carbon nanoparticles compared to mature ones. These effects are discussed with the aim of understanding the phenomena occurring under laser irradiation and to suggest a possible role of the electrical properties of the particles under analysis.

Antitumor hydroxamates SAHA and Dacinostat have been linked to cetuximab and trastuzumab through a non-cleavable linker based on the p-mercaptobenzyl alcohol structure. These antibody drug conjugates (ADCs) were able to inhibit HDAC in several tumour cell lines. The cetuximab based ADCs block human lung adenocarcinoma cell proliferation, demonstrating that bioconjugation with antibodies is a suitable approach for targeted therapy based on hydroxamic acid-containing drugs. This work also shows that ADC-based delivery might be used to overcome the classical pharmacokinetic problems of hydroxamic acids.

Nel contesto dell'ottimizzazione energetico-ambientale dei sistemi di generazione locale di energia, in coerenza con il Piano triennale della Ricerca di Sistema Elettrico 2012-2014, il presente progetto prevede un approccio integrato di: i) attività di ricerca inquadrabili nell'area d'intervento "C1-Risparmio di energia elettrica", dedicate alla messa a punto di tecniche di monitoraggio/controllo dell'efficienza energetica nonchè allo sviluppo di un sistema di cogenerazione ad alta efficienza, e ii) attività di ricerca che riguardano la messa punto di tecniche di misura di inquinanti specifici dei combustibili derivanti da biomasse/rifiuti e dell'effetto della composizione dei combustibili sulla qualità delle emissioni, contestualizzate nell'area d'intervento denominata "B1.1 Energia elettrica da biomasse".

The formation of fuel/oxidizer mixture is of significant importance in combustion systems. Spectroscopic techniques suitable for the measurement of local equivalence ratio in laboratory and in practical combustion systems are currently under study. In the last two decades techniques involving spark spectroscopy have gained the attention of the combustion community. Typically the spark can be originated either by an electric discharge (i.e. engine spark plug) or by a focused laser pulse. Electrical spark emission spectroscopy is mainly restricted to the study of SI engines while Laser Induced Breakdown Spectroscopy (LIBS) is applied on many combustion systems. In principles, due to its simplicity, LIBS represents a very attractive measurement method for sensing the local equivalence ratio in every type of optically accessible combustion environment. In fact, a calibration curve linking the equivalence ratio to the ratio of two characteristic spectral lines of fuel and oxidizer can be easily obtained. However some problems arise when applying the technique to a practical system. Therefore a careful study of the behaviour of the LIBS measurements in a well known and controlled flame is required. In this work, LIBS measurements have been performed in a Bunsen type methane-air premixed flame. In order to evaluate the applicability of the LIBS technique for flames investigations, the spark behaviour and its effects on the flame have been analyzed by visualizations. It has been observed that the plasma is strongly influenced by the local thermodynamic conditions of the gas before the breakdown and every breakdown is followed by a shock wave that tends to disrupt the normal structure of the flame. Therefore, since the plasma characteristics strongly affect the measurements, a proper method for collecting in a single spectrum both plasma information and the characteristic spectral lines of fuel and oxidizer is required. To the same purpose the spectral resolution of the detection system has to be properly fixed. Moreover, the influence of laser parameters, such as the laser energy and the laser repetition rate, on the LIBS signals have also been investigated and optimized. Finally, LIBS equivalence ratio measurements at different locations in the flame have been performed and discussed.

In this work the applicability of the LIBS technique to the detection of carbonaceous particulate in a combustion environment is investigated. In particular, a comparison of the carbon atom concentration derived with LIBS and LIImeasurements is performed. .....................

Laser-Induced Incandescence (LII) technique is a powerful tool to measure concentration and size of soot particulate. In this work LII measurements are performed in different experimental conditions and compared with the ones derived by using a commercial aethalometer. .........................