The serotonin receptor 1A (encoded by the HTR1A gene) plays a critical role in serotonergic transmission and was linked with many human diseases. A 33-year-old woman with rare menstrual cycle-dependent fever showed abnormal estrogen profile and responded well to the HTR1A agonist buspirone, suggesting that her fevers were allied to estrogen-related HTR1A deficiency. We identified an adenine deletion 480-bases upstream of the translation start site (i.e., -480delA) of HTR1A in this patient. To determine the underlying mechanism of -480delA-mediated HTR1A deficiency, we first showed that HTR1A -480 region can be bound by multiple nuclear protein(s). We then identified poly(ADP-ribose) polymerase (PARP1) as one of the proteins that binds to HTR1A -480 region. Using PARP1 overexpression and knockdown, our data demonstrated that PARP1 represses HTR1A transcription. Furthermore, HTR1A -480delA promoter possesses increased interaction with PARP1 and caused an additional reduction in transcription. Finally, 17β-estradiol administration further reduced transcription associated with the mutant promoter. Altogether, these data suggest that estrogen-induced hyperactivity of HTR1A mutant promoter causes the reduction of HTR1A mRNA and leads to the disruption of HTR1A-mediate hypothermic regulation. This is the first report of HTR1A mutation underlying menstrual cycle-dependent febrile episodes, and implies that similar "febrile episode" cases may also result from the dysfunction of serotonin transmission.
The failure cause of the worm drive in the NMRV reducer of the grounding knife-switch mechanism of State Grid was analyzed in this paper. The macroscopic analysis, chemical composition inspection, microscopic metallographic observation, hardness test, SEM analysis were carried out to evaluate the worm gear failure mechanism. The stress distributions of the tooth flank using dynamic contact finite element simulation were obtained based on ANSYS Workbench software. The results showed that an initial crack at the root position of softer worm gear was caused by excessively high impact at the initial stage of meshing in the worm drive, whose value was 308MPa higher than the allowable contact stress of 220MPa. The main reason for the hardness of the worm gear decreasing was that the amount of (α+δ) eutectoids fell and distributed unevenly.
High speed cutting technology has become one of the most important technology in manufacturing of automobile panel dies. The range of each motion axis of numerical control equipment is large and the entire process system exist certain differences of the dynamic characteristic cause of the large type surface size of automobile panel dies. And affect the stability of the processing conditions directly. In this paper, different locations dynamics of large CNC machining equipment was analysed, then getting the influence of processing on the dynamics of the processing position. Simulation results show the machine dynamic characteristic mainly affected by the working position of the spindle box, and the location of the workbench has smaller impact. In the low speed mode, the stiffness characteristics of the spindle box in the operating position on both sides is better and in the high-speed mode the stiffness characteristics is better in the right side of the spindle box. When the table near the right end position in X, Y have weak stiffness near 90Hz.It has weak stiffness in the left side of table near 80Hz and in middle position it has weak stiffness near 80Hz or 140Hz . In the cutting process to provide guidance for the selection of appropriate processing location and process parameters.
Plate-cone reticulated shell is a new type of space steel structures with good mechanical behavior and technical economy. In this paper, shell analogy method is put forward. Based on mechanical characteristics of plate-cone spherical reticulated shell, it is equated to a special type of three-layer thin shell working interactively, the governing differential equations are derived on the basis of the theory of thin shells, these differential equations being from the mixed method of derivation. The solution of this system of differential equations gives the displacements and internal forces of plate-cone spherical reticulated shell. 1
In this paper, the mechanical behavior of steel-concrete composite slim beams was investigated by experiments, and the influence of sectional dimension of steel beams on the bending stiffness and flexural capacity of composite slim beams was evaluated. Test results show that good cooperative performance can be achieved in steel-concrete composite slim beams and the relative slip between steel and concrete is very small. The steel-concrete slim beam presents considerable deformation ability beyond the service stage, which indicates that the composite slim beam has good ductility. In addition, sectional dimension of steel beams is proved to have significant influence on both the bending stiffness and flexural capacity of composite slim beams.
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