A5011071577- Magnetic confinement fusion research
- Nuclear reactor physics and engineering
- Fusion materials and technologies
- Chronic Lymphocytic Leukemia Research
- Nuclear Materials and Properties
- Nuclear Engineering Thermal-Hydraulics
- Superconducting Materials and Applications
- PI3K/AKT/mTOR signaling in cancer
- Chronic Myeloid Leukemia Treatments
- Breastfeeding Practices and Influences
- Pancreatic and Hepatic Oncology Research
- Plasma Diagnostics and Applications
- Combustion and Detonation Processes
- Child Nutrition and Feeding Issues
- DNA Repair Mechanisms
- Ionosphere and magnetosphere dynamics
- Particle accelerators and beam dynamics
- Quinazolinone synthesis and applications
- Maternal Mental Health During Pregnancy and Postpartum
- Peptidase Inhibition and Analysis
- Patient-Provider Communication in Healthcare
- Viral Infectious Diseases and Gene Expression in Insects
- Fungal Plant Pathogen Control
- Protein Degradation and Inhibitors
- Risk and Safety Analysis
CEA Cadarache
2003-2025
Novartis (Switzerland)
2010-2024
Institut de Radioprotection et de Sûreté Nucléaire
2017-2023
Novartis Institutes for BioMedical Research
2012-2023
Novartis (China)
2023
Corium (United States)
2022
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2003-2021
Université Grenoble Alpes
2007-2012
Pathways Behavioral Services
2012
Sanofi (France)
2012
Abstract The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens 1–6 . Despite advances treatment immune checkpoint inhibitors 7–10 , there is an unmet need the of MSI cancers 11–14 Here we report structural, biochemical, cellular and pharmacological characterization clinical-stage inhibitor HRO761, which through innovative hit-finding lead-optimization strategy. HRO761 potent,...
The pan-phosphoinositide 3-kinase (PI3K) inhibitor BKM120 was found, at high concentrations, to cause cell death in various cellular systems, irrespective of their level PI3K addiction. Transcriptional and biochemical profiling studies were used identify the origin these unexpected apparently PI3K-independent effects. At 5- 10-fold, concentration needed half-maximally inhibit signaling. treatment caused changes expression mitotic genes induction a robust G(2)-M arrest. Tubulin polymerization...
Small Modular Reactors (SMRs) are receiving important attention due to the increasing demand for clean, reliable and cost-effective energy solutions. SMR designs incorporate compact features, inherent safety through passive cooling systems lower core inventories compared conventional power plants. Among different components of SMRs steam generators play a key role since they devoted heat transfer from primary secondary circuit. The use plate-type generator in an integral offers potential...
Real-time simultaneous control of several radially distributed magnetic and kinetic plasma parameters is being investigated on JET, in view developing integrated advanced tokamak scenarios. This paper describes the new model-based profile controller which has been implemented during 2006–2007 experimental campaigns. The aims to use combination heating current drive (H&CD) systems—and optionally poloidal field (PF) system—in an optimal way regulate evolution parameter profiles such as...
In order to simultaneously control the current and pressure profiles in high performance tokamak plasmas with internal transport barriers (ITB), a multi-variable model-based technique has been proposed. New algorithms using truncated singular value decomposition (TSVD) of linearized model operator retaining distributed nature system have implemented JET system. Their simplest versions applied density profile reversed shear three heating drive actuators (neutral beam injection, ion cyclotron...
This paper describes a new technique which has been implemented on the JET tokamak to investigate integrated real-time control of several plasma profiles simultaneously (such as current, temperature and pressure) reports results first experimental tests. The are handled through their projection suitable basis functions according Galerkin scheme. Their response three actuators (heating current drive powers injected in plasma) is linearized an experimentally deduced multi-input multi-output...
Antibody–drug conjugates (ADCs) are an established modality that allow for targeted delivery of a potent molecule, or payload, to desired site action. ADCs, wherein the payload is protein degrader, emerging area in field. Herein we describe our efforts delivering Bruton's tyrosine kinase (BTK) bifunctional degrader 1 via CD79b mAb (monoclonal antibody) where linked at ligase binding portion cleavable linker mAb. The resulting 3 and 4, exhibit vitro degradation cytotoxicity comparable with 1,...
The recent development of real-time measurements and control tools in JET has enhanced the reliability reproducibility relevant ITER scenarios. Diagnostics such as charge exchange, interfero-polarimetry, electron cyclotron emission have been upgraded for measurements. In addition, processes like magnetic equilibrium q profile reconstruction developed applied successfully experiments using model based techniques. Plasma operation against magnetohydrodynamic instabilities are also benefiting...
Abstract Background Solicited consultations constitute a substantial workload for infectious disease (ID) specialists in the hospital setting. The objectives of this survey were to describe requesting physicians' experiences regarding ID consultations. Methods A cross-sectional was conducted university-affiliated France 2009. All physicians eligible ( n = 530) and received self-administered questionnaire. main outcomes reasons request opinion. Secondary frequency declared adherence...
The vast majority of breastfeeding mothers in Western countries have routine access to multimedia and Internet resources at home. aim this study was assess the effectiveness a CD-ROM-based intervention increasing rates breastfeeding. We conducted pre- post-intervention involving four control maternity units France. All were given program addressing various topics. primary outcome any 4 weeks assessed by follow-up telephone interview. secondary outcomes included duration, difficulties after...
In our laboratory we use cultured chicory (Cichorium intybus) explants as a model to investigate cell reactivation and somatic embryogenesis have produced 2 genotypes (K59, C15) sharing similar genetic background. K59 is responsive genotype (embryogenic) capable of undergoing complete i.e. de- re-differentiation leading (SE), whereas C15 non-responsive (non-embryogenic) unable undergo SE. Previous studies [1] showed that the β-D-glucosyl Yariv reagent (β-GlcY) specifically binds...
The Tore Supra facility is well suited to study ITER relevant topics such as the real-time control of plasma current and sustaining steady-state discharges. This work describes a tool that was recently developed implemented on in real time, by means direct knowledge suprathermal electron local emission profile, width lower hybrid power deposition profile. quantity can be considered some extent equivalent density profile case fully non-inductive system takes advantage an accurate hard x-ray...
The first electron temperature modulation experiments in plasmas characterized by strong and long-lasting ion internal transport barriers (ITB) have been performed JET using cyclotron resonance heating mode conversion scheme. ITB is shown to be a well localized narrow layer with low heat diffusivity, subcritical loss of stiffness. In addition, results from cold pulse propagation suggest second order transition process for formation.
The ITER hybrid scenario aims to exploit non-inductive current drive enable burn times in excess of 1000 s. To achieve this, and optimize fusion performance, requires high βN (the plasma pressure normalized a stability scaling) energy confinement equal or greater than that predicted for the baseline scenario. This paper discusses results from JET candidate scenario, where βN,MHD ⩽ 3.6 plasmas have been produced. Despite different initial phase, relevant parameters evolve rapidly towards...
Although a personally defined experience, successful breastfeeding is usually measured with regard to duration. This study investigated the determinants of maternal satisfaction experience for 907 mothers enrolled in prospective cohort study. Despite median duration (18 weeks) that fell short recommendations, 822 (90.6%) rated their as very or fairly satisfactory. Anticipated was determinant only women who actually breastfeed < 2 months; this subgroup mothers, rates ranged from 84.6%...
Abstract The RecQ DNA helicase WRN was identified as a synthetic lethal target in tumors with microsatellite instability (MSI) by several genetic screens. Despite recent advances the treatment of MSI immune checkpoint inhibitors, significant proportion patients still fails to respond or relapses after single agent anti-PD1 combination plus anti-CTLA4 treatments. We present biochemical, cellular and pharmacological characterization first potent selective inhibitor, HRO761. show that HRO761 is...
Predictive, time-dependent transport simulations with a semi-empirical plasma model have been used in closed-loop to control the q-profile and strength location of internal barrier (ITB). Five equations (Te, Ti, q, ne, vΦ) are solved, power levels lower hybrid current drive, NBI ICRH calculated feedback loop determined by controller matrix. The real-time (RTC) technique algorithms identical those implemented JET experiments (Laborde L. et al 2005 Plasma Phys. Control. Fusion 47 155 Moreau D....
A route to stationary MHD stable operation at high β N has been explored the Joint European Torus (JET) by optimizing current ramp-up, heating start time and waveform of neutral beam injection (NBI) power. In these scenarios ramp-up accompanied plasma pre-heat (or NBI started before flat-top) power up 22 MW applied during flat-top. discharges considered transient total ≈ 3.3 (during phase) 3 have achieved applying feedback control with in configurations monotonic or flat core safety factor...
Real time control of many plasma parameters will be an essential aspect in the development reliable high performance operation Next Step Tokamaks. The main prerequisites for any feedback scheme are precise real-time determination quantities to controlled, requiring top quality and highly diagnostics, availability robust algorithms. A new set real diagnostics was recently implemented on JET prove feasibility determining, with accuracy resolution, most important quantities. With regard...
Antibody-drug conjugates (ADCs) are an established modality which allows for targeted delivery of a potent molecule, or payload, to desired site action. ADCs, wherein the payload is protein degrader emerging area in field. Herein we describe our efforts delivering Bruton’s tyrosine kinase (BTK) bifunctional 1 via CD79b mAb where linked at ligase binding portion cleavable linker mAb. The resulting 3 and 4, exhibit vitro degradation cytotoxicity comparable ADC can achieve more sustained vivo...
The Tore Supra tokamak is well adapted to sustain long-duration noninductive discharges using the lower hybrid (LH) heating and current drive as main power source. In these conditions, LH deposition profile strongly linked density can be deduced from hard X-rays (HXRs) measurements which are produced by suprathermal electrons generated absorption of wave. powerful HXR diagnostics that present on has been recently connected real-time data network. availability in allowed development an ad hoc...