A practical protocol to emulate a reactor scenario on present machines, with application to the ASDEX Upgrade tokamak via predictive modeling

In this work, a novel practical strategy to emulate a reactor scenario on present tokamak experiments is presented. A recipe how to scale several relevant parameters from a hypothetical reactor scenario down to present devices is discussed. Equivalence between the energy flux channels is detailed, and the practical actuation scheme is presented. The application of the proposed protocol on the ASDEX Upgrade tokamak is shown foremost using the virtual flight simulator Fenix, with practical experiments planned for future campaigns

The modeling of a tokamak plasma discharge, from first principles to a flight simulator

A newly developed tool to simulate a tokamak full discharge is presented. The tokamak \u27flight simulator\u27 Fenix couples the tokamak control system with a fast and reduced plasma model, which is realistic enough to take into account several of the plasma non-linearities. A distinguishing feature of this modeling tool is that it only requires the pulse schedule (PS) as input to the simulator. The output is a virtual realization of the full discharge, whose time traces can then be used to judge if the PS satisfies control/physics goals or needs to be revised. This tool is envisioned for routine use in the control room before each pulse is performed, but can also be used off-line to correct PS in advance, or to develop and validate reduced models, control schemes for future machines like a commercial reactor, simulating realistic actuators and sensors behavior

Targeting a Versatile Actuator for EU-DEMO: Real Time Monitoring of Pellet Delivery to Facilitate Burn Control

Core particle fueling, an essential task in the European demonstration fusion power plant EU-DEMO, relies on adequate pellet injection. However, pellets are fragile objects, and their delivery efficiency can hardly be assumed to be unity. Exploring kinetic control of the EU-DEMO1 scenario indicates that such missed-out pellets do cause a considerable problem for keeping a burning plasma. Missed-out pellets can cause a severe drop of plasma density that in turn results in a potential drastic loss of burn power. Efforts are under way at the ASDEX Upgrade (AUG) tokamak aiming to provide real-time monitoring of pellet arrival and announcement of missed-out cases to the control systems. To further optimize the controllers, system identification experiments have been performed to identify the dynamic response of the system to the actuator

Bioisosteric analogs of MDMA: Improving the pharmacological profile?

3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is re-emerging in clinical settings as a candidate for the treatment of specific neuropsychiatric disorders (e.g. post-traumatic stress disorder) in combination with psychotherapy. MDMA is a psychoactive drug, typically regarded as an empathogen or entactogen, which leads to transporter-mediated monoamine release. Despite its therapeutic potential, MDMA can induce dose-, individual-, and context-dependent untoward effects outside safe settings. In this study, we investigated whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile. In vitro methods included radiotracer assays, transporter electrophysiology, bioluminescence resonance energy transfer and fluorescence-based assays, pooled human liver microsome/S9 fraction incubations, metabolic stability studies, isozyme mapping, and liquid chromatography coupled to high-resolution mass spectrometry. In silico methods included molecular docking. Compared with MDMA, all three MDMA bioisosteres (ODMA, TDMA, and SeDMA) showed similar pharmacological activity at human serotonin, dopamine, and norepinephrine transporters (hSERT, hDAT, and hNET, respectively) but decreased agonist activity at 5-HT2A/2B/2C receptors. Regarding their hepatic metabolism, they differed from MDMA, with N-demethylation being the only metabolic route shared, and without forming phase II metabolites. In addition, TDMA showed an enhanced intrinsic clearance in comparison to its congeners. Additional screening for their interaction with human organic cation transporters (hOCTs) and plasma membrane monoamine transporter (hPMAT) revealed a weaker interaction of the MDMA analogs with hOCT1, hOCT2, and hPMAT. Our findings suggest that these new MDMA bioisosteres might constitute appealing therapeutic alternatives to MDMA, sparing the primary pharmacological activity at hSERT, hDAT, and hNET, but displaying a reduced activity at 5-HT2A/2B/2C receptors and alternative hepatic metabolism. Whether these MDMA bioisosteres may pose lower risk alternatives to the clinically re-emerging MDMA warrants further studies