Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.

BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection

Effects of mold parameters on microscopic properties of cross wedge rolling (CWR) GH4169 alloy shaft parts

Shaft grain size and uniformity play an important role in improving its mechanical properties. Using DEFORM-3D finite element software, the effects of broadening angle and forming angle on the micro performance of the GH4169 alloy shaft parts were studied systematically. The results show that grain refinement is mainly completed in the stretching section. As the broadening angle increases, the grain size expands constantly, and the fluctuation value decreases and then increases, while as the forming angle increases, the grain size and the fluctuation value decrease and then increase. The accuracy of the finite element model was verified through cross wedge rolling experiments

Influence of pass spacing on the spinning process of nickel-based alloy conical casing

High temperature nickel-based alloys are prone to forming defects due to serious work hardening, and the pass spacing is an important parameter in multi-pass drawing and spinning. Using GH4169 superalloy as the material, a Finite Element Model (FEM) was established based on the Simufact platform, and the influence of the pass spacing on the spinning process was explored by using the concave curve and circular arc trajectory. The results show that the stress-strain increases with the increase of the pass spacing. Obtain the optimal pass spacing under specific conditions: blank wall thickness t = 2,5 mm, blank diameter d = 250 mm, feed ratio f = 1,2 mm/rad, mandrel speed n = 300 r/min, pass spacing p = 14 mm

Influence of pass spacing on the spinning process of nickel-based alloy conical casing

High temperature nickel-based alloys are prone to forming defects due to serious work hardening, and the pass spacing is an important parameter in multi-pass drawing and spinning. Using GH4169 superalloy as the material, a Finite Element Model (FEM) was established based on the Simufact platform, and the influence of the pass spacing on the spinning process was explored by using the concave curve and circular arc trajectory. The results show that the stress-strain increases with the increase of the pass spacing. Obtain the optimal pass spacing under specific conditions: blank wall thickness t = 2,5 mm, blank diameter d = 250 mm, feed ratio f = 1,2 mm/rad, mandrel speed n = 300 r/min, pass spacing p = 14 mm

Effect of process parameters on microstructure of 42CrMo steel ball hot skew rolling

Microstructure grain refinement is an effective way to improve the quality of 42CrMo steel ball. A three-dimensional thermal-mechanical-microstructure coupled Finite element model (FEM) of steel ball skew rolling is established in the finite element simulation software. Simufact software was used to simulate the effects of process parameters on the microstructure of steel balls, and the effects of roll Angle, roll temperature and roll speed on the average grain size of rolled pieces were analyzed by single factor variable method. The research results provide some reference for the improvement of 42CrMo steel ball quality

Determination and optimization of mode matching into optical cavities by heterodyne detection

We report on a novel high-sensitivity method to characterize and improve mode matching into optical cavities. This method is based on heterodyne detection of cylindrical transverse cavity modes. A specially designed annular-segmented photodiode is used to measure the amplitude of nonresonant modes reflected by the cavity. Our measurements allow us to optimize cavity mode matching to nearly 99.98% and will play an important diagnostic role in gravitational-wave detectors

Effect of cluster thinning on catechins in berries of Vitis vinifera cv. Cabernet Sauvignon

Research Note

Numerical simulation and optimization of die casting for automotive shift tower cover

The structural characteristics of the car shift tower cover were analyzed, and the pouring system and overflow system were designed according to the empirical formula.The numerical simulation based on Anycasting software shows that the metal liquid flow and solidification rate of the initial process are not smooth.According to the simulation results, the shape of the runner and the number of the gate were modified, and the point cold water pipe was set at the position where the defects might occur to optimize the process.The numerical simulation of the optimized process scheme shows that the filling process is stable and there is no liquid spatter, and good quality die casting is obtained through actual production

Numerical simulation and optimization of die casting for automotive shift tower cover

The structural characteristics of the car shift tower cover were analyzed, and the pouring system and overflow system were designed according to the empirical formula.The numerical simulation based on Anycasting software shows that the metal liquid flow and solidification rate of the initial process are not smooth.According to the simulation results, the shape of the runner and the number of the gate were modified, and the point cold water pipe was set at the position where the defects might occur to optimize the process.The numerical simulation of the optimized process scheme shows that the filling process is stable and there is no liquid spatter, and good quality die casting is obtained through actual production