Rare Variants in Genes Encoding MuRF1 and MuRF2 Are Modifiers of Hypertrophic Cardiomyopathy

Modifier genes contribute to the diverse clinical manifestations of hypertrophic cardiomyopathy (HCM), but are still largely unknown. Muscle ring finger (MuRF) proteins are a class of muscle-specific ubiquitin E3-ligases that appear to modulate cardiac mass and function by regulating the ubiquitin-proteasome system. In this study we screened all the three members of the MuRF family, MuRF1, MuRF2 and MuRF3, in 594 unrelated HCM patients and 307 healthy controls by targeted resequencing. Identified rare variants were confirmed by capillary Sanger sequencing. The prevalence of rare variants in both MuRF1 and MuRF2 in HCM patients was higher than that in control subjects (MuRF1 13/594 (2.2%) vs. 1/307 (0.3%), p = 0.04; MuRF2 22/594 (3.7%) vs. 2/307 (0.7%); p = 0.007). Patients with rare variants in MuRF1 or MuRF2 were younger (p = 0.04) and had greater maximum left ventricular wall thickness (p = 0.006) than those without such variants. Mutations in genes encoding sarcomere proteins were present in 19 (55.9%) of the 34 HCM patients with rare variants in MuRF1 and MuRF2. These data strongly supported that rare variants in MuRF1 and MuRF2 are associated with higher penetrance and more severe clinical manifestations of HCM. The findings suggest that dysregulation of the ubiquitin-proteasome system contributes to the pathogenesis of HCM.     

An improved evidence fusion algorithm in multi-sensor systems

Multi-sensor information fusion plays an important role in practical application. Although D-S evidence theory can handle this information fusion task regardless of prior knowledge, counter-intuitive conclusions may arise when dealing with highly conflicting evidence. To address this weakness, an improved algorithm of evidence theory is proposed. First, a new distribution distance measurement method is first proposed to measure the conflict between the evidences, and the credibility degree of the evidences can be obtained. Next, a modified information volume calculation method is also introduced to measure the effect of the evidence itself, and the information volume of the evidences can be generated. Afterwards, the credibility degree of each evidence can be modified based on the information volume to obtain the weight of each evidence. Ultimately, the weights of the evidences will be used to adjust the body of evidence before fusion. A numerical example for engine fault diagnosis exhibits the availability and effectiveness of the proposed method, where the BPA of the true fault is 89.680%. Furthermore, an application for target recognition is given to show the validity of the proposed algorithm, where the BPA of the true target is 98.948%. The experimental results show that the proposed algorithm has the best performance than other methods.

     

临海既有混凝土氯离子侵蚀及钢筋初锈时间预测

临海混凝土结构承受着荷载和氯盐侵蚀等多种因素的共同作用,工作环境严酷.根据取得的温州市瓯江口一座既有水闸的闸墩混凝土芯样,推定了混凝土的实际配合比;测定了芯样中不同深度处的自由氯离子浓度,分析了在自然环境下该既有水闸闸墩混凝土的氯离子侵蚀规律;基于Fick第二定律和Monte Carlo法,计算了该闸墩混凝土的氯离子扩散系数及钢筋初始锈蚀时间.结果表明：使用5350d的临海水闸闸墩混凝土中存在明显的氯离子对流区,其厚度超过20mm;在多种因素作用下,临海水闸闸墩混凝土抗氯盐侵蚀的性能严重降低,钢筋初始锈蚀的临界氯离子浓度（质量分数）为012%～018%,其初始锈蚀时间约为3000d;采用Monte Carlo法预测自然氯盐环境下混凝土中钢筋初锈时间是可行的.