MEMORIAL DE ATIVIDADES ACADÊMICAS SUZANI CASSIANI

We have performed a multiwavelength campaign on the high red-shift FSRQ PKS 0537-286 during October - November 2006 and February 2008. The automatic optical and near-infrared telescope (REM) and the Gamma-Ray Burst Optical and Near Infrared Detector (GROND) observed the source simultaneously to X-ray and hard X-ray satellite pointings with INTEGRAL/ISGRI, Swift/XRT and RXTE that allowed covering a wide range of energies. At X-ray energies no significant variability was found. The Swift/BAT light curve over two years of survey showed a constant flux level. We find a rather flat high energy spectrum and absorption at soft X-rays in excess to the Galactic value, as previously found in other FSRQ [10][13]. We propose that these features are the signature of bulk Comptonization of soft X-ray photons

Clonal fitness inferred from time-series modelling of single-cell cancer genomes

Progress in defining genomic fitness landscapes in cancer, especially those defined by copy number alterations (CNAs), has been impeded by lack of time-series single-cell sampling of polyclonal populations and temporal statistical models1-7. Here we generated 42,000 genomes from multi-year time-series single-cell whole-genome sequencing of breast epithelium and primary triple-negative breast cancer (TNBC) patient-derived xenografts (PDXs), revealing the nature of CNA-defined clonal fitness dynamics induced by TP53 mutation and cisplatin chemotherapy. Using a new Wright-Fisher population genetics model8,9 to infer clonal fitness, we found that TP53 mutation alters the fitness landscape, reproducibly distributing fitness over a larger number of clones associated with distinct CNAs. Furthermore, in TNBC PDX models with mutated TP53, inferred fitness coefficients from CNA-based genotypes accurately forecast experimentally enforced clonal competition dynamics. Drug treatment in three long-term serially passaged TNBC PDXs resulted in cisplatin-resistant clones emerging from low-fitness phylogenetic lineages in the untreated setting. Conversely, high-fitness clones from treatment-naive controls were eradicated, signalling an inversion of the fitness landscape. Finally, upon release of drug, selection pressure dynamics were reversed, indicating a fitness cost of treatment resistance. Together, our findings define clonal fitness linked to both CNA and therapeutic resistance in polyclonal tumours