Both endothelium-dependent and endothelium-independent vasodilation is significantly impaired in patients with stable COPD. Airflow obstruction and systemic inflammation may increase the risk of cardiovascular disease in patients with COPD.

SUMMARY We present 2-D numerical simulations of convergence at a hyperextended passive margin with exhumed subcontinental mantle. We consider viscoelasto-plastic deformation, heat transfer and thermomechanical coupling by shear heating and associated thermal softening due to temperature dependent viscosity. The simulations show subduction initiation for convergence velocities of 2 cm yr−1, initial Moho temperatures of 525 °C and maximal deviatoric stresses of ca. 800 MPa, around the Moho, prior to localization. Subduction initiates in the region with thinned continental crust and is controlled by a thermally activated ductile shear zone in the mantle lithosphere. The shear zone temperature can be predicted with a recently published analytical expression. The criterion for subduction initiation is a temperature difference of at least 225 °C between predicted temperature and initial Moho temperature. The modelled forced subduction broadly agrees with geological data and reconstructions of subduction during closure of the Piemont-Liguria basin, caused by convergence of the European and Adriatic plates during the Alpine orogeny.

The generation of ductile shear zones is essential for the formation of tectonic plate boundaries, such as subduction or strike-slip zones. However, the primary mechanism of ductile strain localization is still contentious. We study here the spontaneous generation of ductile shear zones by thermal softening using thermo-mechanical numerical simulations for linear and power-law viscous flow in one-dimension (1D), 2D and 3D. All models are velocity-driven. The 1D model exhibits bulk simple shear whereas the 2D and 3D models exhibit bulk pure shear.The initial conditions include a small temperature perturbation in otherwise homogeneous material. We use a series of 1D simulations to determine a new analytical formula which predicts the temperature evolution inside the shear zone. This temperature prediction requires knowledge of only the boundary velocity, flow law and thermal parameters, but no a priori information about the shear zone itself, such as thickness, stress and strain rate. The prediction is valid for 1D, 2D and 3D shear zones in bulk pure and simple shear. The results show that shear heating dominates over conductive cooling if the relative temperature increase is > 50 • C.The temperature variation induced by the shear zone is nearly one order of magnitude wider than the corresponding finite strain variation so that no significant temperature variation occurs between shear zone and wall rock. Applying typical flow laws for lithospheric rocks shows that shear zone generation by thermal softening occurs for typical plate tectonic velocities of few cm.yr −1 or strain rates between 10 −16 and 10 −14 s −1 . Shear stresses larger than 200 MPa can already cause strain localization. The results indicate that thermal softening is a feasible mechanism for spontaneous ductile shear zone generation in the lithosphere and may be one of the primary mechanisms of lithospheric strain localization.The spontaneous generation of shear zones in ductile rocks is fundamental 2 for the formation of tectonic plate boundaries, such as subduction and strike slip 3 zones, or the generation of tectonic nappes during orogenic wedge formation. 4 We refer here to spontaneous generation of a shear zone when the fundamen-5 tal shear zone parameters, such as thickness, shear stress and strain rate, are not 6 a priori prescribed by the natural or model configuration. We refer to ductile 7 deformation when the deformation behaviour is described mathematically by a 8 relation between stress and strain rate, such as by flow laws for diffusion, dislo-9 cation or Peierls creep (i.e. low temperature plasticity). The conversion of dis-10 sipative work into heat, the related local temperature increase and the associated 11 decrease of temperature dependent rock viscosities has frequently been suggested 12 as a cause of spontaneous strain localization and shear zone formation in the litho-13 2 sphere (Yuen et al., 1978; Regenauer-Lieb and Yuen, 1998; Leloup et al., 1999; 14 Kaus and Podladchikov, 2006; Takeuchi and Fialko, 2012; Thielmann ...

Receptor function is traditionally controlled from the orthosteric binding site of G-protein coupled receptors. Here, we show that the functional activity and signalling of human dopamine D2 and D3 receptor...