Hubert Curien Pluridisciplinary Institute

Background: Colorectal cancer is one of the leading and most lethal neoplasms. Standard chemotherapy is ineffective, especially in metastatic cancer, and does not target cancer stem cells. A promising approach to improve cancer treatment is the combination therapy of standard cytostatic drugs with natural compounds. Several plant-derived compounds have been proven to possess anticancer properties, including the induction of apoptosis and inhibition of cancer invasion. This study was focused on investigating in vitro the combination of camptothecin (CPT) with celastrol (CEL) or resveratrol (RSV) as a potential strategy to target metastatic (LOVO) and stem-like (LOVO/DX) colon cancer cells. Methods: The genotoxic effects that drive cancer cells into death-inducing pathways and the ability to inhibit the migratory properties of cancer cells were evaluated. The γH2AX+ assay and Fast-Halo Assay (FHA) were used to evaluate genotoxic effects, the annexin-V apoptosis assay to rate the level of apoptosis, and the scratch test to assess antimigratory capacity. Results: The results showed that both combinations CPT-CEL and CPT-RSV improve general genotoxicity of CPT alone on metastatic cells and CSCs. However, the assessment of specific double-stranded breaks (DSBs) indicated a better efficacy of the CPT-CEL combination on LOVO cells and CPT-RSV in LOVO/DX cells. Interestingly, the combinations CPT-CEL and CPT-RSV did not improve the pro-apoptotic effect of CPT alone, with both LOVO and LOVO/DX cells suggesting activation of different cell death mechanisms. Furthermore, it was found that the combinations of CPT-CEL and CPT-RSV improve the inhibitory effect of camptothecin on cell migration. Conclusions: These findings suggest the potential utility of combining camptothecin with celastrol or resveratrol in the treatment of colon cancer, including more aggressive forms of the disease. So far, no studies evaluating the effects of combinations of these compounds have been published in the available medical databases.

The Jiangmen Underground Neutrino Observatory (JUNO), the first multi-kton liquid scintillator detector, which is under construction in China, will have a unique potential to perform a real-time measurement of solar neutrinos well below the few MeV threshold typical of Water Cherenkov detectors. JUNO's large target mass and excellent energy resolution are prerequisites for reaching unprecedented levels of precision. In this paper, we provide estimation of the JUNO sensitivity to 7Be, pep, and CNO solar neutrinos that can be obtained via a spectral analysis above the 0.45 MeV threshold. This study is performed assuming different scenarios of the liquid scintillator radiopurity, ranging from the most optimistic one corresponding to the radiopurity levels obtained by the Borexino experiment, up to the minimum requirements needed to perform the neutrino mass ordering determination with reactor antineutrinos — the main goal of JUNO. Our study shows that in most scenarios, JUNO will be able to improve the current best measurements on 7Be, pep, and CNO solar neutrino fluxes. We also perform a study on the JUNO capability to detect periodical time variations in the solar neutrino flux, such as the day-night modulation induced by neutrino flavor regeneration in Earth, and the modulations induced by temperature changes driven by helioseismic waves.

The Cherenkov Telescope Array and the KM3NeT neutrino telescopes are major upcoming facilities in the fields of $\gamma$-ray and neutrino astronomy, respectively. Possible simultaneous production of $\gamma$ rays and neutrinos in astrophysical accelerators of cosmic-ray nuclei motivates a combination of their data. We assess the potential of a combined analysis of CTA and KM3NeT data to determine the contribution of hadronic emission processes in known Galactic $\gamma$-ray emitters, comparing this result to the cases of two separate analyses. In doing so, we demonstrate the capability of Gammapy, an open-source software package for the analysis of $\gamma$-ray data, to also process data from neutrino telescopes. For a selection of prototypical $\gamma$-ray sources within our Galaxy, we obtain models for primary proton and electron spectra in the hadronic and leptonic emission scenario, respectively, by fitting published $\gamma$-ray spectra. Using these models and instrument response functions for both detectors, we employ the Gammapy package to generate pseudo data sets, where we assume 200 hours of CTA observations and 10 years of KM3NeT detector operation. We then apply a three-dimensional binned likelihood analysis to these data sets, separately for each instrument and jointly for both. We find that the largest benefit of the combined analysis lies in the possibility of a consistent modelling of the $\gamma$-ray and neutrino emission. Assuming a purely leptonic scenario as input, we obtain, for the most favourable source, an average expected 68% credible interval that constrains the contribution of hadronic processes to the observed $\gamma$-ray emission to below 15%.

We discuss JUNO sensitivity to the annihilation of MeV dark matter in the galactic halo via detecting inverse beta decay reactions of electron anti-neutrinos resulting from the annihilation. We study possible backgrounds to the signature, including the reactor neutrinos, diffuse supernova neutrino background, charged- and neutral-current interactions of atmospheric neutrinos, backgrounds from muon-induced fast neutrons and cosmogenic isotopes. A fiducial volume cut, as well as the pulse shape discrimination and the muon veto are applied to suppress the above backgrounds. It is shown that JUNO sensitivity to the thermally averaged dark matter annihilation rate in 10 years of exposure would be significantly better than the present-day best limit set by Super-Kamiokande and would be comparable to that expected by Hyper-Kamiokande.

The main source of systematic uncertainty on neutrino cross-section measurements at the GeV scale originates from the poor knowledge of the initial flux. The goal of reducing this uncertainty to 1% can be achieved through the monitoring of charged leptons produced in association with neutrinos, by properly instrumenting the decay region of a conventional narrow-band neutrino beam. Large-angle muons and positrons from kaons are measured by a sampling calorimeter on the decay tunnel walls, while muon stations after the hadron dump can be used to monitor the neutrino component from pion decays. Furthermore, the narrow momentum width (<10%) of the beam provides a O (10%) measurement of the neutrino energy on an event-by-event basis, thanks to its correlation with the radial position of the interaction at the neutrino detector. The ENUBET project has been funded by the ERC in 2016 to prove the feasibility of such a monitored neutrino beam and, since 2019, ENUBET is also a CERN neutrino platform experiment (NP06/ENUBET). The breakthrough the project achieved is the design of a horn-less neutrino beamline that would allow for a 1% measurement of νe and νμ cross-sections in about 3 years of data taking at CERN-SPS, using ProtoDUNE as far detector.

Obesity is caused by a prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated3,4. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.

We measured the Coulomb dissociation of 16O into 4He and 12C within the FAIR Phase-0 program at GSI Helmholtzzentrum für Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section 16O(α,γ)12C, which is the time reversed reaction to 12C(α,γ)16O. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the R3B setup were necessary to cope with the high-intensity 16O beam. All tracking detectors were designed to let the unreacted 16O ions pass, while detecting the 12C and 4He.

In February and June 2020, the Fessenheim NPP respectively went through the shutdown of its first and second reactors. The question that now arises is whether the dismantling of the NPP will be significant in terms of water pollution and global warming. The PostAtomVie project consists in evaluating the environmental impacts during the last phase of the life of the Fessenheim NPP, in other words during the decommissioning phase of the plant in order to provide political decision-making assistance in terms of territorial environmental management and management of certain wastes. The system studied breaks down into three phases: dismantling, decontamination and demolition. It is understood that the technical operations of these three phases succeed one another, are often separated by upkeeping and maintenance phases and can be spread over periods ranging from 5 to 40 years, which implies a share of prospective modeling. The development of the database was the starting point for the modeling of the impacts. It brings together the different quantities of radioactive and conventional waste that will be handled during dismantling as well as the distances and transport of radioactive waste to their storage locations. The sources of the data used come from EDF (Electricité de France) reports, studies of previous dismantling. The data concerning waste comes from a report by ANDRA (National Agency for Radioactive Waste Management). The second point of the modeling is the evaluation, at each stage of the system, of the three most important impact categories: namely global warming, the use of non-renewable energy and the respiratory effects linked to compounds inorganic. The LCA calculation method used is Impact 2002+.