AIM: Disabled-2 (DAB2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observ...AIM: Disabled-2 (DAB2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observed down-regulation of DAB2 transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to determine the clinical significance of loss of DAB2 protein in esophageal tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene silencing may account for loss of the protein. METHODS: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues. To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specifi c PCR. RESULTS: Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%) dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer (Ptrend < 0.001). Promoter hypermethylation of DAB2 was observed in 2 of 10 (20%) DAB2 immuno-negative ESCCs. CONCLUSION: Loss of DAB2 protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in ESCCs suggests that epigenetic genesilencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs.展开更多
The surface texture of the pavement plays a very important role in driving the frictional properties at the tire rubber-pavement interface. Particularly, the hysteretic friction due to viscoelastic deformations of rub...The surface texture of the pavement plays a very important role in driving the frictional properties at the tire rubber-pavement interface. Particularly, the hysteretic friction due to viscoelastic deformations of rubber depends mainly on the pavement surface texture. In the present paper, the effect of micromechanical pavement surface morphology on rubber block friction was brought in by comparing the friction results for three different asphalt mix morphological surfaces, named stone mastic asphalt （SMA）, ultra-thin surfacing （UTS） and porous asphalt （PA）. The asphalt surface morphologies of these mixes were captured by using an X-ray tornographer, from which the resulting images micromechanical finite element （FE） meshes for SMA, UTS and PA pavements were developed by means of the SimpleWare software. In the FE model, the rubber and asphalt binder were modeled as viscoelastic （V-E） materials and the formulation was given in the large deformation frame- work. FE simulations were then carried out by using contact algorithm between rubber and the road surface. It was observed that the rubber friction inversely varies with the sliding speed and positively varies with the pressure for all the pavement morphological and stiffness conditions. Furthermore, it was observed that the highly porous pavement surface results in large dissipation of energy, hence, large rubber friction which shows that the mix characteristics of pavements have a simaificant effect on rubber friction.展开更多
文摘AIM: Disabled-2 (DAB2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observed down-regulation of DAB2 transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to determine the clinical significance of loss of DAB2 protein in esophageal tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene silencing may account for loss of the protein. METHODS: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues. To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specifi c PCR. RESULTS: Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%) dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer (Ptrend < 0.001). Promoter hypermethylation of DAB2 was observed in 2 of 10 (20%) DAB2 immuno-negative ESCCs. CONCLUSION: Loss of DAB2 protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in ESCCs suggests that epigenetic genesilencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs.
基金by the National Priorities Research Program (NPRP) award (NPRP No. 7-482-2-184: Thermo-mechanical Tire-Pavement Interaction: Computational Modeling and Field Measurements) from the Qatar National Research Fund (a member of the Qatar Foundation)
文摘The surface texture of the pavement plays a very important role in driving the frictional properties at the tire rubber-pavement interface. Particularly, the hysteretic friction due to viscoelastic deformations of rubber depends mainly on the pavement surface texture. In the present paper, the effect of micromechanical pavement surface morphology on rubber block friction was brought in by comparing the friction results for three different asphalt mix morphological surfaces, named stone mastic asphalt （SMA）, ultra-thin surfacing （UTS） and porous asphalt （PA）. The asphalt surface morphologies of these mixes were captured by using an X-ray tornographer, from which the resulting images micromechanical finite element （FE） meshes for SMA, UTS and PA pavements were developed by means of the SimpleWare software. In the FE model, the rubber and asphalt binder were modeled as viscoelastic （V-E） materials and the formulation was given in the large deformation frame- work. FE simulations were then carried out by using contact algorithm between rubber and the road surface. It was observed that the rubber friction inversely varies with the sliding speed and positively varies with the pressure for all the pavement morphological and stiffness conditions. Furthermore, it was observed that the highly porous pavement surface results in large dissipation of energy, hence, large rubber friction which shows that the mix characteristics of pavements have a simaificant effect on rubber friction.
