A Customized Pigmentation SNP Array Identifies a Novel SNP Associated with Melanoma Predisposition in the SLC45A2 Gene

As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date

Effect of fine to coarse aggregate ratio on the rheology and fracture energy of steel fibre reinforced self-compacting concretes

In this study, the influence of aggregate grading and steel fibre properties on the flow properties and fracture energy of steel fibre reinforced self-compacting concrete (SFRSCC) has been investigated. Two types of hooked-end steel fibres at three different dosages (20,40 and 60 kg/m(3)) were incorporated into self-compacting mixtures having similar paste contents but different fine to coarse aggregate (FA/CA) ratios (0.94, 1.72 and 2.50 by weight). Besides the flowability and passing ability of fresh concrete, the mechanical properties of hardened concrete including the fracture energy have also been investigated. The relations between flexural parameters and fibre orientation were established by image analysis technique. Test results showed that hooked-end steel fibre inclusion into the plain self-compacting concrete negatively affects the flowability and passing ability of the mixture. Increasing FA/CA ratio enhances these rheological parameters and provides better fibre orientation. On the other hand, increasing FA/CA ratio decreases the fracture energy of plain SCC mixtures and the fibre incorporated series which were less affected from fibre inclusion follow the same trend with the plain SCC. The proper FA/CA ratio for the best rheological and mechanical performance depends on the fibre content, aspect ratio and their influence on the flowability of the mixture. In order to obtain better fibre orientation and hence higher fracture energy, relatively higher FA/CA ratios should be used when the fibre content and aspect ratio are relatively high