Analysis of Natural and Engineered Amyloid Aggregates by Spectroscopic and Scattering Techniques

The increasing knowledge about natural functional fibrils has triggered the interest in synthetic or engineered fibrils. Naturally occurring amyloid fibrils (functional and pathogenic) have been analyzed for many years at different structural levels. Engineered fibrils are structurally similar to natural fibrils and the main sub-structural feature of amyloids is characterized by cross-beta structure stabilizing the fibril formation. However, a number of peculiarities exist comparing natural and engineered fibrils that may affect their analysis, especially in spectroscopic and scattering methods. For this reason, several methods that are commonly used for natural fibril analysis are presented and particularities for their application in the characterization of engineered fibrils are described. In addition, the understanding about structure–function relation of fibrils studied in the different research areas may mutually improve when using the same analytical approaches for natural and engineered fibril

Determination of specific and non-specific protein-protein interactions for beta-lactoglobulin by analytical ultracentrifugation and membrane osmometry experiments

Protein-protein interactions are essential for the understanding of biological processes. Specific protein aggregation is an important aspect for many biological systems. In particular, electrostatic interactions play the key role for protein-protein interactions, as many amino acids have pH-dependent charge states. Moreover, protein dissociation is directly related to the solution pH, ionic strength, temperature and protein concentration. The subtle interplay between different specific and non-specific interactions is demonstrated for beta-lactoglobulin (BLG) with a focus on low salt concentrations, thus mimicking technically relevant processing conditions. BLG is a well-characterized model system, proven to attain its monomer-dimer equilibrium strongly dependent upon the pH of the solution. In this manuscript, we present a unique combination of analytical ultracentrifugation and membrane osmometry experiments, which quantifies specific and non-specific interactions, i.e. in terms of the dimer dissociation constants and the second osmotic virial coefficient, at pH 3 and 7 and sodium chloride concentrations of 10 mM and 100 mM. This provides direct insight to protein-protein interactions for a system with a concentration-dependent monomer-dimer equilibrium. Moreover, using a coarse-grained extended DLVO model in combination with molecular dynamics simulations, we quantify non-specific monomer-monomer, monomer-dimer and dimer-dimer interactions as well as the binding free energy of BLG dimerization from theoretical calculations. The experimentally determined interactions are shown to be mainly governed by electrostatic interactions and further agree with free energy calculations. Our experimental protocol aims to determine non-specific and specific interactions for a dynamically interacting system and provides an understanding of protein-protein interactions for BLG at low salt concentrations

Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

Molecular tumour pathology - and tumour genetic

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

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

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