Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3

We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.     

A Unified Framework for Multilingual Text-to-Speech Synthesis with SSML Specification as Interface

This paper describes the design of a unified framework for a multilingual text-to-speech (TTS) synthesis engine – Crystal. The unified framework defines the common TTS modules for different languages and/or dialects. The interfaces between consecutive modules conform to the speech synthesis markup language (SSML) specification for standardization, interoperability, multilinguality, and extensibility. Detailed module divisions and implementation technologies for the unified framework are introduced, together with possible extensions for the algorithm research and evaluation of the TTS synthesis. Implementation of a mixed-language TTS system for Chinese Putonghua, Chinese Cantonese, and English demonstrates the feasibility of the proposed unified framework.     

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.     

Towards a Darwinian Approach to Mathematics

In the past decades, recent paradigm shifts in ethology, psychology, and the social sciences have given rise to various new disciplines like cognitive ethology and evolutionary psychology. These disciplines use concepts and theories of evolutionary biology to understand and explain the design, function and origin of the brain. I shall argue that there are several good reasons why this approach could also apply to human mathematical abilities. I will review evidence from various disciplines (cognitive ethology, cognitive psychology, cognitive archaeology and neuropsychology) that suggests that the human capacity for mathematics is a category-specific domain of knowledge, hard-wired in the brain, which can be explained as the result of natural selection.