Mode of action for inorganic arsenic toxicity and carcinogenesis

Inorganic arsenic(iAs) at high doses is a known human carcinogen, inducing tumors of the skin,urinary bladder, and lung. It is also associated with noncancer toxicities. An understanding of the mode of action(MOA) for arsenic-induced effects is needed to develop a scientifically-based risk assessment. To determine an MOA for iAs induced toxicities, it is necessary to understand the metabolism, kinetics, cell transport, and interaction with specific proteins of iAs. Based on in vitro investigations using animal and human cells, studies from animal models,and clinical and epidemiological studies, we have proposed an MOA involving formation of sufficient levels of reactive trivalent metabolites which interact with critical free sulfhydryl groups, leading to cytotoxicity and regenerative cell proliferation. There is a strong correlation between in vitro cytotoxicity([0.1 lmol/L trivalent arsenicals) and the no effect levels in rodents [approximately 1 ppm(1 ppm = 1 mg/L) of water or diet]. In epithelial target tissues, the cytotoxic effects of iAs result in chronic precursor lesions which have the potential for an increased risk of developing cancer. In non-epithelial tissues, noncancer toxicities such as hypertension and atherosclerosis develop. This MOA implies a non-linear, threshold dose–response relationship for both non-cancer and cancer end points of exposure to iAs.     

不连续应力作用的Ⅰ型动态裂纹

针对研究材料特性下的裂纹动态扩展时遇到的不连续应力作用Ⅰ型动态裂纹扩展问题,利用复变函数理论的方法进行了研究.采用自相似函数的途径可以获得应力、位移及动态应力强度因子的解析解的一般表达式.应用该法可以很容易地将所讨论的问题转化为Riemann-Hilbert问题,而后一问题可以用通常的Muskhelishvili方法进行求解,并可以相当简单地得到问题的闭合解.利用这些解并采用叠加原理,可以求得任意复杂问题的解.