Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation.

Exposure to high levels of ionizing radiation (IR) leads to debilitating and dose-limiting gastrointestinal (GI) toxicity. Using three-dimensional mouse crypt culture, we demonstrated that p53 target PUMA mediates radiation-induced apoptosis via a cell-intrinsic mechanism, and identified the GSK-3 inhibitor CHIR99021 as a potent radioprotector. CHIR99021 treatment improved Lgr5+ cell survival and crypt regeneration after radiation in culture and mice. CHIR99021 treatment specifically blocked apoptosis and PUMA induction and K120 acetylation of p53 mediated by acetyl-transferase Tip60, while it had no effect on p53 stabilization, phosphorylation or p21 induction. CHIR99021 also protected human intestinal cultures from radiation by PUMA but not p21 suppression. These results demonstrate that p53 posttranslational modifications play a key role in the pathological and apoptotic response of the intestinal stem cells to radiation and can be targeted pharmacologically

Stability and Environmental Analysis of Mixed Traffic Flow – Using the Markov Probabilistic Theory

The rapid growth of CAV (Connected and Automated Vehicle) market penetration highlights the need to gain insight into the overall stability of mixed traffic flows in order to better deploy CAVs. Several studies have examined the modelling process and stability analysis of traffic flow in a mixed traffic environment without considering its inner spatial distribution. In this paper, an innovative Markov chain-based model is established for integrating the spatial distribution of mixed traffic flow in the model process of car-following behaviour. Then the linear stability analysis of the mixed traffic flow is conducted for different CAV market penetration rates, different CAV platoon strength and different cooperation efficiency between two continuous vehicles. Moreover, several simulations under open boundary conditions in multiple scenarios are performed to explicate how CAV market penetration rate, platoon strength and cooperation efficiency jointly influence the stability performance of the mixed traffic flow. The results reveal that the performance of this mixed traffic flow stability could be strengthened in these three factors. In addition to stability, an investigation of the fuel consumption and emission reduction under different market penetration rates and the platoon strength of CAVs are explored, suggesting that substantial potential fuel consumption and emission could be reduced under certain scenarios

A Driving Risk Surrogate and Its Application in Car-Following Scenario at Expressway

Traffic safety is important in reducing death and building a harmonious society. In addition to studies of accident incidences, the perception of driving risk is significant in guiding the implementation of appropriate driving countermeasures. Risk assessment can be conducted in real-time for traffic safety due to the rapid development of communication technology and computing capabilities. This paper aims at the problems of difficult calibration and inconsistent thresholds in the existing risk assessment methods. It proposes a risk assessment model based on the potential field to quantify the driving risk of vehicles. Firstly, virtual energy is proposed as an attribute considering vehicle sizes and velocity. Secondly, the driving risk surrogate(DRS) is proposed based on potential field theory to describe the risk degree of vehicles. Risk factors are quantified by establishing submodels, including an interactive vehicle risk surrogate, a restrictions risk surrogate, and a speed risk surrogate. To unify the risk threshold, acceleration for implementation guidance is derived from the risk field strength. Finally, a naturalistic driving dataset in Nanjing, China, is selected, and 3063 pairs of following naturalistic trajectories are screened out. Based on that, the proposed model and other models use for comparisons are calibrated through the improved particle optimization algorithm. Simulations prove that the proposed model performs better than other algorithms in risk perception and response, car-following trajectory, and velocity estimation. In addition, the proposed model exhibits better car-following ability than existing car-following models

CD133, Stem Cells, and Cancer Stem Cells: Myth or Reality?

CD133, a member of the prominin family, is found in a variety of tissues with at least three variants. The function of CD133 is not well understood, but its expression is subject to changes in the microenvironment cues including bioenergetic stress. Knockout of CD133 does not affect renewal, but mammary gland branching. A point mutation of CD133 (R733C) leads to retinal disorder. CD133 is found in embryonic stem cells, normal tissue stem cells, stem cell niches, and circulating endothelial progenitors as well as cancer stem cells. Maintenance of stemness in cancer may be attributable to asymmetric cell division in association with a set of embryonic expression signatures in CD133+ tumor cells. CD133 could enrich cancer stem cells, which are associated with chemo- and radiation resistance phenotype. High CD133 is associated with poor survival in a variety of solid tumors, including lung, colon, prostate, etc. Monitoring CD133+ cells in peripheral blood, and targeting CD133 in cancer, may further predict and improve the clinical outcomes