Epithelial calreticulin up-regulation promotes profibrotic responses and tubulointerstitial fibrosis development

Renal fibrosis is the common anatomical feature underlying the progression of chronic kidney disease, a leading cause of morbidity and mortality worldwide. In a previous study, we demonstrated that during development of renal fibrosis in a rat model of unilateral ureteric obstruction, calreticulin (CRT) is up-regulated in tubular epithelial cells (TECs). In the present study, we used in vitro and in vivo approaches to examine the role of CRT in TECs and its contribution to the progression of fibrosis. In cultured renal TECs, CRT overexpression induced acquisition of an altered, profibrotic cellular phenotype. Consistently, the opposite effects were observed for CRT knockdown. Subsequently, we confirmed that critical changes observed in vitro were also apparent in tubular cells in vivo in the animal model of unilateral ureteric obstruction. In agreement with these results, we demonstrate that substantial (50%) reduction in the expression of CRT reduced the development of tubulointerstitial fibrosis at a comparable level through regulation of inflammation, transcriptional activation, transforming growth factor b1eassociated effects, and apoptosis. In summary, our findings establish that CRT is critically involved in the molecular mechanisms that drive renal fibrosis progression and indicate that inhibition of CRT expression might be a therapeutic target for reduction of fibrosis and chronic kidney disease development

A novel test method for continuous nonlinear biaxial tensile deformation of sheet metals by bulging with stepped-dies

In this paper, a novel test method named bulging with stepped-dies is proposed to overcome the difficulty of traditional test methods in realizing continuous nonlinear loading paths from initial yield up to fracture on a sheet metal. To achieve this aim, the section shape of a stepped-die cavity is varied with increasing depth. During bulging with a stepped-die, the stress state at the pole of bulging area of the sheet changes continuously with the increase in bulging height, which results in a specific nonlinear loading path. A theoretical model is established to calculate the stress components at the pole based on the assumption that the bulged surface near the pole was approximated by a rotational ellipsoid. Bulging experiments with three different stepped-dies are performed by using ST16 steel sheet. Stress and strain paths up to fracture and equivalent stress-strain curves at the pole are analyzed and compared with the results of bulging with elliptical dies. It is shown that continuous nonlinear loading paths can be effectively realized through bulging with stepped-dies and the stress ratio at the pole changes from 0.5 up to 2.0 at most in one bulging experiment. The feasibility of the novel test method is validated successfully. And the experimental data obtained are useful to determine constitutive and forming limit models suitable for complex loading conditions

Modelling wake effects in large wind farms in complex terrain: the problem, the methods and the issues

Computational fluid dynamic (CFD) methods are used in this paper to predict the power production from entire wind farms in complex terrain and to shed some light into the wake flow patterns. Two full three-dimensional Navier–Stokes solvers for incompressible fluid flow, employing k − ϵ and k − ω turbulence closures, are used. The wind turbines are modeled as momentum absorbers by means of their thrust coefficient through the actuator disk approach. Alternative methods for estimating the reference wind speed in the calculation of the thrust are tested. The work presented in this paper is part of the work being undertaken within the UpWind Integrated Project that aims to develop the design tools for next generation of large wind turbines. In this part of UpWind, the performance of wind farm and wake models is being examined in complex terrain environment where there are few pre-existing relevant measurements. The focus of the work being carried out is to evaluate the performance of CFD models in large wind farm applications in complex terrain and to examine the development of the wakes in a complex terrain environment

High-efficiency forming processes for complex thin-walled titanium alloys components: State-of-the-art and Perspectives

Complex thin-walled titanium alloy components play a key role in the aircraft, aerospace and marine industries, offering the advantages of reduced weight and increased thermal resistance. The geometrical complexity, dimensional accuracy and in-service properties are essential to fulfill the high-performance standards required in new transportation systems, which brings new challenges to titanium alloy forming technologies. Traditional forming processes, such as superplastic forming or hot pressing, cannot meet all demands of modern applications due to their limited properties, low productivity and high cost. This has encouraged industry and research groups to develop novel high-efficiency forming processes. Hot Gas Pressure Forming (HGPF) and hot stamping-quenching technologies have been developed for the manufacture of tubular and panel components, and are believed to be the cut-edge processes guaranteeing dimensional accuracy, microstructure and mechanical properties. This article intends to provide a critical review of high-efficiency titanium alloy forming processes, concentrating on latest investigations of controlling dimensional accuracy, microstructure and properties. The advantages and limitations of individual forming process are comprehensively analyzed, through which, future research trends of high-efficiency forming are identified including trends in process integration, processing window design, full cycle and multi-objective optimization. This review aims to provide a guide for researchers and process designers on the manufacture of thin-walled titanium alloy components whilst achieving high dimensional accuracy and satisfying performance properties with high efficiency and low cost

Stability of an Exciton bound to an Ionized Donor in Quantum Dots

Total energy, binding energy, recombination rate (of the electron hole pair) for an exciton (X) bound in a parabolic two dimensional quantum dot by a donor impurity located on the z axis at a distance d from the dot plane, are calculated by using the Hartree formalism with a recently developed numerical method (PMM) for the solution of the Schroedinger equation. As our analysis indicates there is a critical dot radius such that for radius less than the critical radius the complex is unstable and with an increase of the impurity distance this critical radius increases. Furthermore, there is a critical value of the mass ratio such that for mass ratio less than the critical value the complex is stable. The appearance of this stability condition depends both on the impurity distance and the dot radius, in a way that with an increase of the impurity distance we have an increase in the maximum dot radius where this stability condition appears. For dot radii greater than this maximum dot radius (for fixed impurity distance) the complex is always stable.Comment: 17 pages, 7 figures Applying a new numerical method which is based on the adiabatic stability of quantum mechanics, we study the stability of an exciton (X) bound in a parabolic two dimensional quantum dot by a donor impurity located on the z axis at a distance d from the dot plan