Galaxy cluster cosmology in KiDS, Planck, and Euclid surveys

In this Thesis, we present a series of works that encompass the fundamental steps of cosmological analyses based on galaxy clusters, spanning from mass calibration to deriving cosmological constraints through counts and clustering. Firstly, we focus on the 3D two-point correlation function (2PCF) of the galaxy cluster sample by Planck Collaboration XXVII (2016). The masses of these clusters are expected to be underestimated, as they are derived from a scaling relation calibrated through X-ray observations. We derived a mass bias which disagrees with simulation predictions, consistent with what derived by Planck Collaboration VI (2020). Furthermore, in this Thesis we analyse the cluster counts and 2PCF, respectively, of the photometric galaxy cluster sample developed by Maturi et al. (2019), based on the third data release of KiDS (KiDS-DR3, de Jong et al. 2017). We derived constraints on fundamental cosmological parameters which are consistent and competitive, in terms of uncertainties, with other state-of-the-art cosmological analyses. Then, we introduce a novel approach to establish galaxy colour-redshift relations for cluster weak-lensing analyses, regardless of the specific photometric bands in use. This method optimises the selection completeness of cluster background galaxies while maintaining a defined purity threshold. Based on the galaxy sample by Bisigello et al. (2020), we calibrated two colour selections, one relying on the ground-based griz bands, and the other including the griz and Euclid YJH bands. In addition, we present the preliminary work on the weak-lensing mass calibration of the clusters detected by Maturi et al. (in prep.) in the fourth data release of KiDS (KiDS-1000, Kuijken et al. 2019). This mass calibration will enable the cosmological analyses based on cluster counts and clustering, from which we expect remarkable improvements in the results compared to those derived in KiDS-DR3.

ABC transporters of the A subfamily: potential prognostic markers and candidates for antibody selection from phage-display libraries for therapeutic use in Ewing sarcoma

The prognostic value of ABC transporters in Ewing sarcoma is still poorly explored and controversial. We described for the first time the impact of various ABCs on Ewing sarcoma prognosis by assessment of their gene expression in two independent cohorts of patients. Unexpected associations with favourable outcomes were observed for two ABCs of the A-subfamily, ABCA6 and ABCA7, whereas no associations with the canonical multidrug ABC transporters were identified. The ABCs of the A-subfamily are involved in cholesterol/phospholipids transportation and efflux from cells. Our clinical data support the drug-efflux independent contribution to cancer progression of the ABCAs, which has been confirmed in PDX-derived cell lines. The impact of these ABCA transporters on tumor progression seems to be mediated by lowering intracellular cholesterol, supporting the role of these proteins in lipid transport. In addition, the gene expression of ABCA6 and ABCA7 is regulated by transcription factors which control lipid metabolism: ABCA6 was induced by the binding of FoxO1/FoxO3a to its promoter and repressed by IGF1R/Akt signaling, whereas the expression of ABCA7 was regulated by p53. The data point to ABCA6 and ABCA7 as potential prognostic markers in Ewing sarcoma and suggest the IGF1/ABCA/lipid axis as an intriguing therapeutic target. Agonist monoclonal antibodies towards ABCA6/7 or inhibitors of cholesterol biosynthesis, such as statins or aminobiphoshonates, may be investigated as therapeutic options in combination with chemotherapy. Considering that no monoclonal antibodies selectively targeting extracellular domains of ABCA6/7 are available, the second part of the project has been dedicated to the generation of human antibody phage-display libraries as tools for selecting monoclonal antibodies. A novel synthetic human antibody phage-display library has been designed, cloned and characterized. The library takes advantages of the high variability of a designed naïve repertoire to be a useful tool for isolating antibodies towards all potential antigens, including the ABCAs.