10 research outputs found
Designed, highly expressing, thermostable dengue virus 2 envelope protein dimers elicit quaternary epitope antibodies
Dengue virus (DENV) is a worldwide health burden, and a safe vaccine is needed. Neutralizing antibodies bind to quaternary epitopes on DENV envelope (E) protein homodimers. However, recombinantly expressed soluble E proteins are monomers under vaccination conditions and do not present these quaternary epitopes, partly explaining their limited success as vaccine antigens. Using molecular modeling, we found DENV2 E protein mutations that induce dimerization at low concentrations (\u3c100 pM) and enhance production yield by more than 50-fold. Cross-dimer epitope antibodies bind to the stabilized dimers, and a crystal structure resembles the wild-type (WT) E protein bound to a dimer epitope antibody. Mice immunized with the stabilized dimers developed antibodies that bind to E dimers and not monomers and elicited higher levels of DENV2-neutralizing antibodies compared to mice immunized with WT E antigen. Our findings demonstrate the feasibility of using structure-based design to produce subunit vaccines for dengue and other flaviviruses
Designed, highly expressing, thermostable dengue virus 2 envelope protein dimers elicit quaternary epitope antibodies
Dengue virus (DENV) is a worldwide health burden, and a safe vaccine is needed. Neutralizing antibodies bind to quaternary epitopes on DENV envelope (E) protein homodimers. However, recombinantly expressed soluble E proteins are monomers under vaccination conditions and do not present these quaternary epitopes, partly explaining their limited success as vaccine antigens. Using molecular modeling, we found DENV2 E protein mutations that induce dimerization at low concentrations (\u3c100 pM) and enhance production yield by more than 50-fold. Cross-dimer epitope antibodies bind to the stabilized dimers, and a crystal structure resembles the wild-type (WT) E protein bound to a dimer epitope antibody. Mice immunized with the stabilized dimers developed antibodies that bind to E dimers and not monomers and elicited higher levels of DENV2-neutralizing antibodies compared to mice immunized with WT E antigen. Our findings demonstrate the feasibility of using structure-based design to produce subunit vaccines for dengue and other flaviviruses
Disposition of Flavonoids via Enteric Recycling: Enzyme Stability Affects Characterization of Prunetin Glucuronidation across Species, Organs, and UGT Isoforms
Comparison of runaway electron generation parameters in small, medium-sized and large tokamaks - A survey of experiments in COMPASS, TCV, ASDEX-Upgrade and JET
This paper presents a survey of the experiments on runaway electrons (RE) carried out recently in frames of EUROFusion Consortium in different tokamaks: COMPASS, ASDEX-Upgrade, TCV and JET. Massive gas injection (MGI) has been used in different scenarios for RE generation in small and medium-sized tokamaks to elaborate the most efficient and reliable ones for future RE experiments. New data on RE generated at disruptions in COMPASS and ASDEX-Upgrade was collected and added to the JET database. Different accessible parameters of disruptions, such as current quench rate, conversion rate of plasma current into runaways, etc have been analysed for each tokamak and compared to JET data. It was shown, that tokamaks with larger geometrical sizes provide the wider limits for spatial and temporal variation of plasma parameters during disruptions, thus extending the parameter space for RE generation. The second part of experiments was dedicated to study of RE generation in stationary discharges in COMPASS, TCV and JET. Injection of Ne/Ar have been used to mock-up the JET MGI runaway suppression experiments. Secondary RE avalanching was identified and quantified for the first time in the TCV tokamak in RE generating discharges after massive Ne injection. Simulations of the primary RE generation and secondary avalanching dynamics in stationary discharges has demonstrated that RE current fraction created via avalanching could achieve up to 70-75% of the total plasma current in TCV. Relaxations which are reminiscent the phenomena associated to the kinetic instability driven by RE have been detected in RE discharges in TCV. Macroscopic parameters of RE dominating discharges in TCV before and after onset of the instability fit well to the empirical instability criterion, which was established in the early tokamaks and examined by results of recent numerical simulations
Real-time-capable prediction of temperature and density profiles in a tokamak using RAPTOR and a first-principle-based transport model
1488siThe RAPTOR code is a control-oriented core plasma profile simulator with various applications in control design and verification, discharge optimization and real-time plasma simulation. To date, RAPTOR was capable of simulating the evolution of poloidal flux and electron temperature using empirical transport models, and required the user to input assumptions on the other profiles and plasma parameters. We present an extension of the code to simulate the temperature evolution of both ions and electrons, as well as the particle density transport. A proof-of-principle neural-network emulation of the quasilinear gyrokinetic QuaLiKiz transport model is coupled to RAPTOR for the calculation of first-principle-based heat and particle turbulent transport. These extended capabilities are demonstrated in a simulation of a JET discharge. The multi-channel simulation requires ∼0.2 s to simulate 1 second of a JET plasma, corresponding to ∼20 energy confinement times, while predicting experimental profiles within the limits of the transport model. The transport model requires no external inputs except for the boundary condition at the top of the H-mode pedestal. This marks the first time that simultaneous, accurate predictions of T e, T i and n e have been obtained using a first-principle-based transport code that can run in faster-than-real-time for present-day tokamaks.reservedmixedRedondo J.; Meyer H.; Eich Th.; Beurskens M.; Coda S.; Hakola A.; Martin P.; Adamek J.; Agostini M.; Aguiam D.; Ahn J.; Aho-Mantila L.; Akers R.; Albanese R.; Aledda R.; Alessi E.; Allan S.; Alves D.; Ambrosino R.; Amicucci L.; Anand H.; Anastassiou G.; Andrebe Y.; Angioni C.; Apruzzese G.; Ariola M.; Arnichand H.; Arter W.; Baciero A.; Barnes M.; Barrera L.; Behn R.; Bencze A.; Bernardo J.; Bernert M.; Bettini P.; Bilkova P.; Bin W.; Birkenmeier G.; Bizarro J.P.S.; Blanchard P.; Blanken T.; Bluteau M.; Bobkov V.; Bogar O.; Bohm P.; Bolzonella T.; Boncagni L.; Botrugno A.; Bottereau C.; Bouquey F.; Bourdelle C.; Bremond S.; Brezinsek S.; Brida D.; Brochard F.; Buchanan J.; Bufferand H.; Buratti P.; Cahyna P.; Calabro G.; Camenen Y.; Caniello R.; Cannas B.; Canton A.; 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A locked mode indicator for disruption prediction on JET and ASDEX upgrade
The aim of this paper is to present a signal processing algorithm that, applied to the raw Locked Mode signal, allows us to obtain a disruption indicator in principle exploitable on different tokamaks. A common definition of such an indicator for different machines would facilitate the development of portable systems for disruption prediction, which is becoming of increasingly importance for the next tokamak generations. Moreover, the indicator allows us to overcome some intrinsic problems in the diagnostic system such as drift and offset. The behavior of the proposed indicator as disruption predictor, based on crossing optimized thresholds of the signal amplitude, has been analyzed using data of both JET and ASDEX Upgrade experiments. A thorough analysis of the disruption prediction performance shows how the indicator is able to recover some missed and tardy detections of the raw signal. Moreover, it intervenes and corrects premature or even wrong alarms due to, e.g., drifts and/or offsets
Real-time-capable prediction of temperature and density profiles in a tokamak using RAPTOR and a first-principle-based transport model
The RAPTOR code is a control-oriented core plasma profile simulator with various applications in control design and verification, discharge optimization and real-time plasma simulation. To date, RAPTOR was capable of simulating the evolution of poloidal flux and electron temperature using empirical transport models, and required the user to input assumptions on the other profiles and plasma parameters. We present an extension of the code to simulate the temperature evolution of both ions and electrons, as well as the particle density transport. A proof-of-principle neural-network emulation of the quasilinear gyrokinetic QuaLiKiz transport model is coupled to RAPTOR for the calculation of first-principle-based heat and particle turbulent transport. These extended capabilities are demonstrated in a simulation of a JET discharge. The multi-channel simulation requires ∼0.2 s to simulate 1 second of a JET plasma, corresponding to ∼20 energy confinement times, while predicting experimental profiles within the limits of the transport model. The transport model requires no external inputs except for the boundary condition at the top of the H-mode pedestal. This marks the first time that simultaneous, accurate predictions of Te, Tiand nehave been obtained using a first-principle-based transport code that can run in faster-than-real-time for present-day tokamaks
Runaway electron beam control
Post-disruption runaway electron (RE) beams in tokamaks with large current can cause deep melting of the vessel and are one of the major concerns for ITER operations. Consequently, a considerable effort is provided by the scientific community in order to test RE mitigation strategies. We present an overview of the results obtained at FTU and TCV controlling the current and position of RE beams to improve safety and repeatability of mitigation studies such as massive gas (MGI) and shattered pellet injections (SPI). We show that the proposed RE beam controller (REB-C) implemented at FTU and TCV is effective and that current reduction of the beam can be performed via the central solenoid reducing the energy of REs, providing an alternative/parallel mitigation strategy to MGI/SPI. Experimental results show that, meanwhile deuterium pellets injected on a fully formed RE beam are ablated but do not improve RE energy dissipation rate, heavy metals injected by a laser blow off system on low-density flat-top discharges with a high level of RE seeding seem to induce disruptions expelling REs. Instabilities during the RE beam plateau phase have shown to enhance losses of REs, expelled from the beam core. Then, with the aim of triggering instabilities to increase RE losses, an oscillating loop voltage has been tested on RE beam plateau phase at TCV revealing, for the first time, what seems to be a full conversion from runaway to ohmic current. We finally report progresses in the design of control strategies at JET in view of the incoming SPI mitigation experiments
Comparison of runaway electron generation parameters in small, medium-sized and large tokamaks - A survey of experiments in COMPASS, TCV, ASDEX-Upgrade and JET
This paper presents a survey of the experiments on runaway electrons (RE) carried out recently in frames of EUROFusion Consortium in different tokamaks: COMPASS, ASDEX-Upgrade, TCV and JET. Massive gas injection (MGI) has been used in different scenarios for RE generation in small and medium-sized tokamaks to elaborate the most efficient and reliable ones for future RE experiments. New data on RE generated at disruptions in COMPASS and ASDEX-Upgrade was collected and added to the JET database. Different accessible parameters of disruptions, such as current quench rate, conversion rate of plasma current into runaways, etc have been analysed for each tokamak and compared to JET data. It was shown, that tokamaks with larger geometrical sizes provide the wider limits for spatial and temporal variation of plasma parameters during disruptions, thus extending the parameter space for RE generation. The second part of experiments was dedicated to study of RE generation in stationary discharges in COMPASS, TCV and JET. Injection of Ne/Ar have been used to mock-up the JET MGI runaway suppression experiments. Secondary RE avalanching was identified and quantified for the first time in the TCV tokamak in RE generating discharges after massive Ne injection. Simulations of the primary RE generation and secondary avalanching dynamics in stationary discharges has demonstrated that RE current fraction created via avalanching could achieve up to 70-75% of the total plasma current in TCV. Relaxations which are reminiscent the phenomena associated to the kinetic instability driven by RE have been detected in RE discharges in TCV. Macroscopic parameters of RE dominating discharges in TCV before and after onset of the instability fit well to the empirical instability criterion, which was established in the early tokamaks and examined by results of recent numerical simulations