Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

Identification of type 2 diabetes loci in 433,540 East Asian individuals

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes—NKX6-3 and ANK1—in different tissues4–6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways

Cognitive apprenticeship and its application to the teaching of Smalltalk in a multimedia interactive learning environment

10.1007/BF00890449Instructional Science231-3133-16

Applying Gentner's theory of analogy to the teaching of computer programming

10.1006/imms.1993.1016International Journal of Man-Machine Studies383347-368IJMM

Intelligent pedagogical agents with multiparty interaction support

Proceedings - IEEE/WIC/ACM International Conference on Intelligent Agent Technology. IAT 2004134-14

Automatic diagnosis of student programs in programming learning environments

IJCAI International Joint Conference on Artificial Intelligence21102-110

Grounding concept in percept: Learning physics experientially in multi-user virtual worlds

Proceedings - IEEE International Conference on Advanced Learning Technologies, ICALT 2004340-34

Designing and implementing virtual enactive role-play and structured argumentation: Promises and pitfalls

This paper focuses on the design and implementation of an innovative technologically mediated intervention for argumentation pedagogy in two classes comprising 17- to 18-year-old students in Singapore. The design research involves integrating the Second Life immersive virtual environment and web-based scaffolding through a customized structured argumentation board into a language-based curriculum at the pre-university level (Grade 12), the General Paper, which emphasizes argumentation and critical thinking. Of specific interest in this paper are the processes and factors that impact both the technical aspects of implementation and pedagogical findings. It discusses the benefits and drawbacks arising from the design, planning and implementation of both platforms of technology into the curriculum. Recommendations to overcome problems identified and suggestions for future research in the field are proposed

Designing multiparty interaction support in Elva, an embodied tour guide

Proceedings of the International Conference on Autonomous Agents1061-106