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Purpose::With the increasing level of automation in automobiles, the advent of autonomous vehicles has reduced the tendency of drivers and passengers to focus on the task of driving. The increasing automation in automobiles reduced the drivers' and passengers' focus on driving, which allowed occupants to choose a more relaxed and comfortable sitting position. Meanwhile, the occupant's sitting position went from a frontal, upright position to a more relaxed and reclined one, which resulted in the existing restraint systems cannot to keep occupants safe and secure. This study aimed to determine the effects of different reclining states on occupants' lumbar and neck injuries.Methods::This is an original research on the field of automotive safety engineering. Occupants in different initial sitting positions (25°, 35°, 45°, and 55°) were adapted to changes in seat back angle and restraint systems and placed in the same frontal impact environment. Neck injury indexes, lumbar axial compression force and acceleration, as well as occupant dynamic response during the impact, were compared in different sitting positions. The injury response and kinematic characteristics of occupants in different reclining positions were analyzed by the control variable method.Results::As the sitting angle increased, the occupant's head acceleration decreased, and the forward-lean angle decreased. Occupants in the standard sitting position had the greatest neck injury, with an N ij of 0.95, and were susceptible to abbreviated injury scale 2+ cervical medullary injuries. As the seatback angle increased, the geometric position of the lumbar spine tended to be horizontal, and the impact load transmitted greater forces to the lumbar spine. The occupant's lumbar injury was greatest in the lying position, with a peak axial compression force on the lumbar region of 5.5 KN, which was 2.3 KN greater than in the standard sitting position. Conclusion::The study of occupant lumbar and neck injuries based on different recline states can provide a theoretical basis for optimizing lumbar evaluation indexes, which is conducive to the understanding of the lumbar injury mechanism and the comprehensive consideration of occupant safety protection.

8.Development of a novel screening assay for inhibitors targeting HIF-1alpha and P300 interaction.

Fang-Fang LAI ; Fei NIU ; Han-Ze YANG ; Wan-Qi ZHOU ; Xiao-Guang CHEN

Acta Pharmaceutica Sinica 2014;49(6):849-853

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Cell Hypoxia ; Disulfides ; pharmacology ; Drug Screening Assays, Antitumor ; E1A-Associated p300 Protein ; antagonists & inhibitors ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; Indole Alkaloids ; pharmacology ; Two-Hybrid System Techniques