The SIMBIO-SYS (Spectrometer and Imaging for MPO BepiColombo Integrated Observatory SYStem) is a complex instrument suite part of the scientific payload of the Mercury Planetary Orbiter for the ...BepiColombo mission, the last of the cornerstone missions of the European Space Agency (ESA) Horizon + science program.
The SIMBIO-SYS instrument will provide all the science imaging capability of the BepiColombo MPO spacecraft. It consists of three channels: the STereo imaging Channel (STC), with a broad spectral band in the 400-950 nm range and medium spatial resolution (at best 58 m/px), that will provide Digital Terrain Model of the entire surface of the planet with an accuracy better than 80 m; the High Resolution Imaging Channel (HRIC), with broad spectral bands in the 400-900 nm range and high spatial resolution (at best 6 m/px), that will provide high-resolution images of about 20% of the surface, and the Visible and near-Infrared Hyperspectral Imaging channel (VIHI), with high spectral resolution (6 nm at finest) in the 400-2000 nm range and spatial resolution reaching 120 m/px, it will provide global coverage at 480 m/px with the spectral information, assuming the first orbit around Mercury with periherm at 480 km from the surface. SIMBIO-SYS will provide high-resolution images, the Digital Terrain Model of the entire surface, and the surface composition using a wide spectral range, as for instance detecting sulphides or material derived by sulphur and carbon oxidation, at resolutions and coverage higher than the MESSENGER mission with a full co-alignment of the three channels. All the data that will be acquired will allow to cover a wide range of scientific objectives, from the surface processes and cartography up to the internal structure, contributing to the libration experiment, and the surface-exosphere interaction. The global 3D and spectral mapping will allow to study the morphology and the composition of any surface feature. In this work, we describe the on-ground calibrations and the results obtained, providing an important overview of the instrument performances. The calibrations have been performed at channel and at system levels, utilizing specific setup in most of the cases realized for SIMBIO-SYS. In the case of the stereo camera (STC), it has been necessary to have a validation of the new stereo concept adopted, based on the push-frame. This work describes also the results of the Near-Earth Commissioning Phase performed few weeks after the Launch (20 October 2018). According to the calibration results and the first commissioning the three channels are working very well.
Abstract
On 2022 September 26, the DART spacecraft will impact the surface of Dimorphos, the ∼160 m size satellite of the binary near-Earth asteroid (NEA) (65803) Didymos. What will be observed on ...the surfaces of both asteroids and at the DART impact site is largely unknown, beyond the details of Didymos revealed by previous Arecibo and Goldstone radar observations. We present here the expected DART and LICIACube observations of the Didymos system and discuss the planned mapping strategies. By searching similar geological features and processes identified on other NEAs, we constrain the impact conditions that DART might encounter at Dimorphos, assessing both the asteroid’s surface and interior structure.
Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib, targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor, are currently under clinical investigation in ...breast cancer (BC) patients. We have previously demonstrated the anti-tumor efficacy of these anti-PI3K/AKT-inibitors in combination with anti-microtubule drugs in human BC cell lines, through a complete cytoskeleton disorganization. In this work, we generated ex-vivo three-dimensional (3D) cultures from human BC as a model to test drug efficacy and to identify new molecular biomarkers for selection of BC patients suitable for anti-PI3K/AKT-inibitors treatment. We have established 3D cultures from 25/27 human BC samples, in which the ability of growth in vitro replicates the clinical and biological aggressiveness of the original tumors. According to the results of next generation sequencing analysis, a direct correlation was found between PI3KA mutations and the sensitivity in 3D models in vitro to taselisib and ipatasertib alone and combined with anti-microtubule agents. Moreover, mutations in HER and MAPK families related genes, including EGFR, KRAS and BRAF, were found in resistant samples, suggesting their potential role as negative predictive factors of response to these agents. Thus, we demonstrated that ex vivo 3D cultures from human BC patients allow a rapid and efficient drug screening for chemotherapies and targeted agents in genetically selected patients and represent an innovative model to identify new biomarkers of drug resistance.
•PI3K/AKT inhibitors exert synergistic antitumor activity with anti-microtubule drugs in breast cancer ex vivo 3D-cultures.•The presence of PI3K-alpha subunit mutation correlates with sensitivity in 3D models in vitro to taselisib and ipatasertib alone and combined with anti-microtubule agents.•Breast cancer ex vivo 3D-cultures represent an innovative model for an efficient drug and biomarkers screening.
Metastatic colorectal cancer (mCRC) patients tend to have modest benefits from molecularly driven therapeutics. Patient-derived tumor organoids (PDTOs) represent an unmatched model to elucidate tumor ...resistance to therapy, due to their high capacity to resemble tumor characteristics.
We used viable tumor tissue from two cohorts of patients with mCRC, naïve or refractory to treatment, respectively, for generating PDTOs. The derived models were subjected to a 6-day drug screening assay (DSA) with a comprehensive pipeline of chemotherapy and targeted drugs against almost all the actionable mCRC molecular drivers. For the second cohort DSA data were matched with those from PDTO genotyping.
A total of 40 PDTOs included in the two cohorts were derived from mCRC primary tumors or metastases. The first cohort included 31 PDTOs derived from patients treated in front line. For this cohort, DSA results were matched with patient responses. Moreover, RAS/BRAF mutational status was matched with DSA cetuximab response. Ten out of 12 (83.3%) RAS wild-type PDTOs responded to cetuximab, while all the mutant PDTOs, 8 out of 8 (100%), were resistant. For the second cohort (chemorefractory patients), we used part of tumor tissue for genotyping. Four out of nine DSA/genotyping data resulted applicable in the clinic. Two RAS-mutant mCRC patients have been treated with FOLFOX–bevacizumab and mitomycin–capecitabine in third line, respectively, based on DSA results, obtaining disease control. One patient was treated with nivolumab–second mitochondrial-derived activator of caspases mimetic (phase I trial) due to high tumor mutational burden at genotyping, experiencing stable disease. In one case, the presence of BRCA2 mutation correlated with DSA sensitivity to olaparib; however, the patient could not receive the therapy.
Using CRC as a model, we have designed and validated a clinically applicable methodology to potentially inform clinical decisions with functional data. Undoubtedly, further larger analyses are needed to improve methodology success rates and propose suitable treatment strategies for mCRC patients.
•CRC is a heterogeneous disease and mechanism of tumor resistance to drugs occurs, impairing treatment success.•PDTOs resemble three-dimensional tumor characteristics.•PDTOs provide information for functionally informed therapeutic decisions.
Primary pleural squamous cell carcinoma is exceedingly rare. Diagnosis is challenging because of the rarity of the neoplasm, the possibility of secondary involvement of the pleura by metastatic ...squamous cell carcinoma and the fact that cytology may be interpreted as squamoid malignant mesothelioma. A cell‐block or a core‐biopsy is necessary to perform immunohistochemical tests and confirm the squamous nature of the tumour and exclude a malignant mesothelioma. This is crucial for appropriate clinical management of the patient.
PDF
