The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression

The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. Mutation of Trp39, Tyr69 and Tyr88, which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. In conclusion, the N-terminus of hGLP-1R regulates receptor trafficking and maturation. Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression

Modelling of JET hybrid scenarios with GLF23 transport model: E × B shear stabilization of anomalous transport

The E&nbsp;×&nbsp;B shear stabilization of anomalous transport in JET hybrid discharges is studied via self-consistent predictive modelling of electron and ion temperature, ion density and toroidal rotation velocity performed with the GLF23 model. The E&nbsp;×&nbsp;B shear stabilization factor (parameter α E in the GLF23 model) is adjusted to predict accurately the four simulated quantities under different experimental conditions, and the uncertainty in α E determined by 15% deviation between simulated and measured quantities is estimated. A correlation of α E with toroidal rotation velocity and E&nbsp;×&nbsp;B shearing rate is found in the low density plasmas, suggesting that the turbulence quench rule may be more complicated than assumed in the GLF23 model with constant α E . For the selected discharges the best predictive accuracy is obtained by using weak/no E&nbsp;×&nbsp;B shear stabilization (i.e. α E&nbsp;≈&nbsp;0) at low toroidal angular frequency (Ω&nbsp;&lt;&nbsp;60&nbsp;krad&nbsp;s −1 ), even in the scenarios with the current overshoot, and α E&nbsp;=&nbsp;0.9 at high frequency (Ω&nbsp;&gt;&nbsp;100&nbsp;krad&nbsp;s −1 ). Interestingly, a weak E&nbsp;×&nbsp; B shear stabilization of anomalous transport is found in the medium density strongly rotating discharge. An importance of linear β e stabilization in this discharge is estimated and compared to the low density discharge with equally high β e . The toroidal rotation velocity is well predicted here by assuming that the momentum diffusion coefficient is a fraction of thermal ion diffusivity. Taking into account the α E and Prandtl number with their uncertainties determined in the modelling of JET hybrid discharges, the performance of ITER hybrid scenario with optimized heat mix (33&nbsp;MW of NBI and 20&nbsp;MW of ECCD) is estimated showing the importance of toroidal rotation for achieving Q &nbsp;&gt;&nbsp;5.</p

Integrated core–SOL–divertor modelling for ITER including impurity: effect of tungsten on fusion performance in H-mode and hybrid scenario

The compatibility of two operational constraints—operation above the L–H power threshold and at low power to divertor—is examined for ITER long pulse H-mode and hybrid scenarios in integrated core–scrape off layer (SOL)–divertor modelling including impurities (intrinsic Be, He, W and seeded Ne). The core thermal, particle and momentum transport is simulated with the GLF23 transport model tested in the self-consistent simulations of temperatures, density and toroidal rotation velocity in JET hybrid discharges and extrapolated to ITER. The beneficial effect of toroidal rotation velocity on fusion gain is shown. The sensitivity studies with respect to operational (separatrix and pedestal density, Ne gas puff) and unknown physics (W convective velocity and perpendicular diffusion in SOL as well as W prompt re-deposition) parameters are performed to determine their influence on the operational window and fusion gain.</p