Transcription and splicing regulation in human umbilical vein endothelial cells under hypoxic stress conditions by exon array

<p>Abstract</p> <p>Background</p> <p>The balance between endothelial cell survival and apoptosis during stress is an important cellular process for vessel integrity and vascular homeostasis, and it is also pivotal in angiogenesis during the development of many vascular diseases. However, the underlying molecular mechanisms remain largely unknown. Although both transcription and alternative splicing are important in regulating gene expression in endothelial cells under stress, the regulatory mechanisms underlying this state and their interactions have not yet been studied on a genome-wide basis.</p> <p>Results</p> <p>Human umbilical vein endothelial cells (HUVECs) were treated with cobalt chloride (CoCl₂) both to mimic hypoxia and to induce cell apoptosis and alternative splicing responses. Cell apoptosis rate analysis indicated that HUVECs exposed to 300 μM CoCl₂for 24 hrs were initially counterbalancing apoptosis with cell survival. We therefore used the Affymetrix exon array system to determine genome-wide transcript- and exon-level differential expression. Other than 1583 differentially expressed transcripts, 342 alternatively spliced exons were detected and classified by different splicing types. Sixteen alternatively spliced exons were validated by RT-PCR. Furthermore, direct evidence for the ongoing balance between HUVEC survival and apoptosis was provided by Gene Ontology (GO) and protein function, as well as protein domain and pathway enrichment analyses of the differentially expressed transcripts. Importantly, a novel molecular module, in which the heat shock protein (HSP) families play a significant role, was found to be activated under mimicked hypoxia conditions. In addition, 46% of the transcripts containing stress-modulated exons were differentially expressed, indicating the possibility of combinatorial regulation of transcription and splicing.</p> <p>Conclusion</p> <p>The exon array system effectively profiles gene expression and splicing on the genome-wide scale. Based on this approach, our data suggest that transcription and splicing not only regulate gene expression, but also carry out combinational regulation of the balance between survival and apoptosis of HUVECs under mimicked hypoxia conditions. Since cell survival following the apoptotic challenge is pivotal in angiogenesis during the development of many vascular diseases, our results may advance the knowledge of multilevel gene regulation in endothelial cells under physiological and pathological conditions.</p

Research on aerodynamic drag of a solid attitude control thruster based on PWM principle

Solid attitude control thrusters based on PWM principle are widely used in kinetic kill vehicle to control its attitude. In this paper, a kind of solid attitude control thruster is proposed and its piston’s motion model is established. One of the most important variables which has significant effect on the validity of the model is aerodynamic drag of rocker arm. We did research on the aerodynamic drag by throttle theory, numerical simulation and experiment. The results were consistent and proved to be valid by testing the pressure in the two control chambers. The result is expected to provide reference for the calculation and test of the aerodynamic drag and design of the solid attitude control

Numerical Investigation into the Critical Speed and Frequency of the Hunting Motion in Railway Vehicle System

The critical speed and hunting frequency are two basic research objects of vehicle system dynamics and have a significant influence on the dynamic performance. A lateral dynamic model with 17 degrees of freedom was established in this study to investigate the critical speed and hunting frequency of a high-speed railway vehicle. The nonlinearities of wheel/rail contact geometry, creep forces, and yaw damper were all considered. A heuristic nonlinear creep model was employed to estimate the contact force between the wheel and the rail. The Maxwell model, which covers the influence of the stiffness characteristic, is used to simulate the yaw damper. To reflect the blow-off of the yaw damper, the damping coefficient is described by stages. Based on the mathematical model, the combined effects of vehicle parameters on the critical speed in the straight line and hunting frequency of the wheelset were investigated innovatively. The novel phenomenon that the hunting frequency exhibits a sudden increase from a smaller value to a larger value when the blow-off of the yaw damper occurs was discovered during the calculations. The extents to which various parameters affect the critical speed and hunting frequency are clear on the basis of the numerical results. Moreover, all of the parameter values were divided into three sections to determine the sensitive range for the critical speed and hunting frequency. The results show that the first section of values plays the decisive role on both the critical speed and the hunting frequency for all parameters analyzed. The investigation in this paper enriches the study of hunting stability and gives some ideas to probably solve the abnormal vibrations during the actual operation

Research on aerodynamic drag of a solid attitude control thruster based on PWM principle

Solid attitude control thrusters based on PWM principle are widely used in kinetic kill vehicle to control its attitude. In this paper, a kind of solid attitude control thruster is proposed and its piston’s motion model is established. One of the most important variables which has significant effect on the validity of the model is aerodynamic drag of rocker arm. We did research on the aerodynamic drag by throttle theory, numerical simulation and experiment. The results were consistent and proved to be valid by testing the pressure in the two control chambers. The result is expected to provide reference for the calculation and test of the aerodynamic drag and design of the solid attitude control

Suspension Force-Coupling Analysis of Flux-Reversal Bearingless Slice Motor Based on Advanced Magnetic Field Model

Flux-reversal bearingless slice motor with direct suspension current (DC-FRBLM) is a novel slice bearingless motor. The robust rotor structure of the DC-FRBLM brings benefits including high compactness and ease of manufacturing. However, the disparate frequencies of torque current and suspension currents cause undesirable suspension force-coupling in different radial directions. This feature leads to rotor vibrations and poses challenges for suspension control. To addresses these issues, an advanced magnetic field model and a suspension decoupling control strategy based on this model are proposed in this paper. The proposed model incorporates a precise double-salient permeance model, accounting for variations in rotor magnetic potential and leakage flux. The accurate calculation of the active radial force is achieved using the Maxwell stress tensor method, which agrees well with the finite element analysis (FEA) results. Then an analysis is conducted to identify the magnetic field components responsible for suspension force-coupling. Furthermore, the decoupling strategy based on the proposed analytical model effectively reduces force fluctuation and mitigates rotor vibrations. Experimental results on a prototype of DC-FRBLM validate the improved levitation performance achieved by the proposed decoupling strategy