Deciphering cellular states of innate tumor drug responses

BACKGROUND: The molecular mechanisms underlying innate tumor drug resistance, a major obstacle to successful cancer therapy, remain poorly understood. In colorectal cancer (CRC), molecular studies have focused on drug-selected tumor cell lines or individual candidate genes using samples derived from patients already treated with drugs, so that very little data are available prior to drug treatment. RESULTS: Transcriptional profiles of clinical samples collected from CRC patients prior to their exposure to a combined chemotherapy of folinic acid, 5-fluorouracil and irinotecan were established using microarrays. Vigilant experimental design, power simulations and robust statistics were used to restrain the rates of false negative and false positive hybridizations, allowing successful discrimination between drug resistance and sensitivity states with restricted sampling. A list of 679 genes was established that intrinsically differentiates, for the first time prior to drug exposure, subsequently diagnosed chemo-sensitive and resistant patients. Independent biological validation performed through quantitative PCR confirmed the expression pattern on two additional patients. Careful annotation of interconnected functional networks provided a unique representation of the cellular states underlying drug responses. CONCLUSION: Molecular interaction networks are described that provide a solid foundation on which to anchor working hypotheses about mechanisms underlying in vivo innate tumor drug responses. These broad-spectrum cellular signatures represent a starting point from which by-pass chemotherapy schemes, targeting simultaneously several of the molecular mechanisms involved, may be developed for critical therapeutic intervention in CRC patients. The demonstrated power of this research strategy makes it generally applicable to other physiological and pathological situations

A new 3MW ECRH system at 105 GHz for WEST

The aim of the WEST experiments is to master long plasma pulses (1000s) and expose ITER-like tungsten wall to deposited heat fluxes up to 10 MW/m$^2$. To increase the margin to reach the H-Mode and to control W-impurities in the plasma, the installation of an upgraded ECRH heating system, with a gyrotron performance of 1MW/1000s per unit, is planned in 2023. With the modifications of Tore Supra to WEST, simulations at a magnetic field B$_0$∼3.7T and a central density n$_{e0}$∼6 × 10$^{19}$ m$^{−3}$ show that the optimal frequency for central absorption is 105 GHz. For this purpose, a 105 GHz/1MW gyrotron (TH1511) has been designed at KIT in 2021, based on the technological design of the 140 GHz/1.5 MW (TH1507U) gyrotron for W7-X. Currently, three units are under fabrication at THALES. In the first phase of the project, some of the previous Tore Supra Electron Cyclotron (EC) system components will be re-installed and re-used whenever possible. This paper describes the studies performed to adapt the new ECRH system to 105 GHz and the status of the modifications necessary to re-start the system with a challenging schedule

Multi-physics modeling and Au-Ni/Rh coating assessment for ITER ion cyclotron resonance heating radio-frequency sliding contacts

ITER is a large scale fusion experimental device under construction in Cadarache (France) intended to prove the viability of fusion as an energy source. Ion Cyclotron Resonance Heating (ICRH) system is one of the three heating systems which will supply total heating power of 20 MW (40-55 MHz) up to one hour of operation. Radio-Frequency (RF) contacts are integrated within the antennas for assembly and operation considerations, which will face extremely harsh service conditions, including neutron irradiation, heavy electrical loads (RF current reaches up to 2 kA with a linear current density of 4.8 kA/m) and high thermal loads. Based on the thermal analysis, the contact resistance is expected to be lower than 7 mΩ to keep the maximum temperature on the louvers lower than 250°C. Few weeks of vacuum (~10 -5 Pa) baking at 250°C for outgassing is expected before each plasma experimental campaign, under which the RF contact materials' mechanical properties change and diffusion phenomena between different materials are inevitable. CuCrZr and 316L are proper base materials for ITER RF contact louvers and conductors respectively. In order to improve the RF contact's wear and corrosion resistivity as well as to reduce the contact resistance, Au-Ni and Rh functional layers could be electroplated on CuCrZr and 316L accordingly. The application of the Au-Ni/Rh coating pairs is assessed through the thermal ageing and diffusion tests. Wear and electrical contact performances of the Au-Ni/Rh pairs are deeply studied on a dedicated tribometer operated at ITER relevant conditions

Radiofrequency and mechanical tests of silver coated CuCrZr contacts for the ITER ion cyclotron antenna

The ITER Ion Cyclotron Resonance Heating (ICRH) system is designed to couple to the plasma 20 MW of RF power from two antennas in the 40–55 MHz frequency range during long pulses of up to 3600 s and under various plasma conditions with Edge Localized Modes. Radio-Frequency (RF) contacts are integrated within the ITER ICRH launcher in order to ensure the RF current continuity and ease the mechanical assembly by allowing the free thermal expansion of the Removable Vacuum Transmission Line coaxial conductors during RF operations or during 250 °C baking phases. A material study has been carried out to determine which materials and associated coatings are relevant for RF contacts application in ITER. In parallel, RF tests have been performed with a new prototype of Multi-Contact® LA-CUT/0,25/0 contacts made of silver-coated CuCrZr louvers. During these tests on a RF vacuum resonator, currents between 1.2 kA and 1.3 kA peak have been reached a few tens of times in steady-state conditions without any visible damage on the louvers. A final 62 MHz pulse ending in a 300 s flat top at 1.9 kA resulted in severe damage to the contact. In addition, a test bed which performs sliding test cycles has been built in order to reproduce the wear of the contact prototype after 30 000 sliding cycles on a 3 mm stroke at 175 °C under vacuum. The silver coating of the louvers is removed after approximately a hundred cycles whilst, to the contrary, damage to the CuCrZr louvers is relatively low

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

La perception de la couleur

MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Odontologie (341722110) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Actes de l'école d'été européenne : Sciences, société, environnement

National audienceL'initiative de lancer cette école d'été européenne a été prise par des chercheurs en sciences sociales de l'Université Pierre Mendès France. Les communications sont regroupées autour de trois thèmes : la construction de la notion d'environnement, la connaissance de l'environnement, et sa gestion. Deux objectifs étaient affichés au départ : renforcer la capacité des sciences humaines et sociales à prendre leur véritable place au sein des programmes interdisciplinaires sur l'environnement, et développer une formation longue et intensive qui soit aussi le moyen de favoriser les échanges et réseaux européens dans le domaine de l'environnement

Actes de l'école d'été européenne : Sciences, société, environnement

National audienceL'initiative de lancer cette école d'été européenne a été prise par des chercheurs en sciences sociales de l'Université Pierre Mendès France. Les communications sont regroupées autour de trois thèmes : la construction de la notion d'environnement, la connaissance de l'environnement, et sa gestion. Deux objectifs étaient affichés au départ : renforcer la capacité des sciences humaines et sociales à prendre leur véritable place au sein des programmes interdisciplinaires sur l'environnement, et développer une formation longue et intensive qui soit aussi le moyen de favoriser les échanges et réseaux européens dans le domaine de l'environnement

Operational domain for the new 3MW/1000s ECRH System on WEST

International audienc