No abstract

In the purely theoretical approach of pavement design, percentage fatigue cracking is related to damage in a probabilistic manner according to the Miner's law. Two methods that are currently widely in use are based on assumptions of damage distribution. One method assumes fatigue damage being normally distributed, while the other one assumes fatigue damage being lognormally distributed. Since mechanistic-empirical pavement design and pavement management require precise forecasting of pavement fatigue cracking, much effort should be taken to characterize and predict fatigue cracking in terms of damage distribution. In this paper, we formulate the probability density distribution of fatigue damage of flexible pavements according to the underlying structure of fatigue cracking equations so that pavement fatigue-cracking damage can be interpreted in a more meaningful way. Numerical computation is conducted for a case study. It is found that damage is neither normally nor lognormally distributed. It is therefore recommended that methodology and damage distribution model established in this paper be used in practice to predict damage distribution and percentage cracking so that a better estimation of fatigue cracking can be made.

Diabetes mellitus (DM) is a group of metabolic diseases caused by absolute or relative deficiency of insulin secretion and characterized by chronic hyperglycemia. Its complications affect almost every tissue of the body, usually leading to blindness, renal failure, amputation, etc. and in the final stage, it mostly develops into cardiac failure, which is the main reason why diabetes mellitus manifests itself as a high clinical lethality. The pathogenesis of diabetes mellitus and its complications involves various pathological processes including excessive production of mitochondrial reactive oxygen species (ROS) and metabolic imbalance. Hypoxia-inducible Factor (HIF) signaling pathway plays an important role in both of the above processes. Roxadustat is an activator of Hypoxia-inducible Factor-1α, which increases the transcriptional activity of Hypoxia-inducible Factor-1α by inhibiting hypoxia-inducible factor prolyl hydroxylase (HIF-PHD). Roxadustat showed regulatory effects on maintaining metabolic stability in the hypoxic state of the body by activating many downstream signaling pathways such as vascular endothelial growth factor (VEGF), glucose transporter protein-1 (GLUT1), lactate dehydrogenase (LDHA), etc. This review summarizes the current research findings of roxadustat on the diseases of cardiomyopathy, nephropathy, retinal damage and impaired wound healing, which also occur at different stages of diabetes and greatly contribute to the damage caused by diabetes to the organism. We attempts to uncover a more comprehensive picture of the therapeutic effects of roxadustat, and inform its expanding research about diabetic complications treatment.