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The protein factor Glomulin (Glmn) is a regulator of the SCF (Skp1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. Mutations of Glmn lead to glomuvenous malformations. Glmn has been reported to be associated with FK506-binding proteins (FKBP). Here we present in vitro binding analyses of the FKBP-Glmn interaction. Interestingly, the previously described interaction of Glmn and FKBP12 was found to be comparatively weak. Instead, the closely related FKBP12.6 and FKBP51 emerged as novel binding partners. We show different binding affinities of full length and truncated FKBP51 and FKBP52 mutants. Using FKBP51 as a model system, we show that two amino acids lining the FK506-binding site are essential for binding Glmn and that the FKBP51-Glmn interaction is blocked by FKBP ligands. This data suggest FKBP inhibition as a pharmacological approach to regulate Glmn and Glmn-controlled processes.

The primary objective of this study is to compare pedestrian evacuation strategies in the large-scale public space (LPS) using microscopic model. Data were collected by video recording from Tian-yi square for 36 hours in city of Ningbo, China. A pedestrian evacuation simulation model was developed based on the social force model (SFM). The simulation model parameters, such as reaction time, elasticity coefficient, sliding coefficient, et al, were calibrated using the real data extracted from the video. Five evacuation strategies, strategy 1 (S1) to strategy 5 (S5) involving distance, density and capacity factors were simulated and compared by indicators of evacuation time and channel utilization rate, as well as the evacuation efficiency. The simulation model parameters calibration results showed that a) the pedestrians walking speed is 1.0 ~ 1.5m/s; b) the pedestrians walking diameter is 0.3 ~ 0.4m; c) the frequency of pedestrian arrival and departure followed multi-normal distribution. The simulation results showed that, (a) in terms of total evacuation time, the performance of S4 and S5 which considering the capacity and density factors were best in all evacuation scenarios, the performance of S3 which only considering the density factor was the worst, relatively, and S1 and S2 which considering the distance factor were in the middle. (b) the utilization rate of channels under S5 strategy was better than other strategies, which performs best in the balance of evacuation. S3 strategy was the worst, and S1, S2 and S4 were in the middle. (c) in terms of the evacuation efficiency, when the number of evacuees is within 2, 500 peds, the S1 and S2 strategy which considering the distance factor have best evacuation efficiency than other strategies. And when the number of evacuees is above 2, 500 peds, the S4 and S5 strategy which considering the capacity factor are better than others.