A boundary preserving numerical algorithm for the Wright-Fisher model with mutation

The Wright-Fisher model is an Itô stochastic differential equation that was originally introduced to model genetic drift within finite populations and has recently been used as an approximation to ion channel dynamics within cardiac and neuronal cells. While analytic solutions to this equation remain within the interval [0,1], current numerical methods are unable to preserve such boundaries in the approximation. We present a new numerical method that guarantees approximations to a form of Wright-Fisher model, which includes mutation, remain within [0,1] for all time with probability one. Strong convergence of the method is proved and numerical experiments suggest that this new scheme converges with strong order 1/2. Extending this method to a multidimensional case, numerical tests suggest that the algorithm still converges strongly with order 1/2. Finally, numerical solutions obtained using this new method are compared to those obtained using the Euler-Maruyama method where the Wiener increment is resampled to ensure solutions remain within [0,1].

Reply to William B. Grant

THE UVI working group acknowledges the contribution of Vitamin D to bone health as stated in our paper. However, we concluded that an optimal level of Vitamin D for humans has not yet been established with any certainty...

Teaching digital media to digital natives

The majority of today's undergraduate students are 'digital natives'; a generation born into a world shaped by digital technologies. It is important to understand the significance of this when considering how to teach Digital Media to digital natives. This paper examines the analogies to literacy that recur in digital native debates. It argues that if the concept of digital literacy is to be useful, educators must attend to the multiple layers and proficiencies that comprise literacy. Rather than completely dispose of old teaching methods, updated pedagogical practices should integrate analysis and critique with exploratory and creative modes of learning.

Targeting amino acid transport in metastatic castration-resistant prostate cancer : effects on cell cycle, cell growth, and tumor development

Background L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. Methods We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. Results LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4–7 months of neoadjuvant hormone therapy (4–7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4–mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Conclusion Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

Cungellela by William ‘Dura Danje’ Leisha and Shem ‘Curan Danje’ Leisha

Research background: Cungelela is an intercultural music project undertaken in collaboration with William ‘Dura Danje’ Leisha and Shem ‘Curan Danje’ Leisha. The project contributes to cultural maintenance for Australian First Nations peoples, and is informed by prior work in this area by scholars including Peter Dunbar-Hall, Chris Gibson and Karl Neuenfeldt. These existing studies have discussed the complexities of intercultural collaboration, and the types of cultural politics that are involved when Indigenous and non-Indigenous musicians and scholars work together on projects of cultural significance. Critical race theory has also informed the creative work, as a means of interpreting the implicit and explicit discourses of race that arise through intercultural creative practice. The project asked the research question, in what ways can collaborative music making contribute to intercultural understanding and support cultural maintenance for Australian First Nations people affected by the Stolen Generations? Research contribution: This project has identified that collaborative production of recorded popular music can produce shared affective, embodied and transformative forms of knowledge about the impact of the Stolen Generations on Australian First Nations peoples. Research significance: The compact disc was presented by Aunty Anne Leisha as part of an invited presentation at the World Indigenous Nations Higher Education Consortium in New Mexico, 2013. The work also formed part of a refereed conference presentation at the 2013 conference of the International Association for the Study of Popular Music held at the University of Oviedo, Gijon, Spain.

Tumor-suppressor gene promoter hypermethylation in saliva of head and neck cancer patients

Head and neck squamous cell carcinoma (HNSCC) accounts for a bulk of the oral and laryngeal cancers, the majority (70%) of which are associated with smoking and excessive drinking, major known risk factors for the development of HNSCC. In contrast to reports that suggest an inverse relationship between smoking and global DNA CpG methylation, hypermethylation of promoters of a number of genes was detected in saliva collected from patients with HNSCC. Using a sensitive methylation-specific polymerase chain reaction (MSP) assay to determine specific methylation events in the promoters of RASSF1A, DAPK1, and p16 genes, we demonstrate that we can detect tumor presence with an overall accuracy of 81% in the DNA isolated from saliva of patients with HNSCC (n = 143) when compared with the DNA isolated from the saliva of healthy nonsmoker controls (n = 31). The specificity for this MSP panel was 87% and the sensitivity was 80%(with a Fisher exact test P < .0001). In addition, the test panel performed extremely well in the detection of the early stages of HNSCCs, with a sensitivity of 94% and a specificity of 87%, and a high. concordance value of 0.8, indicating an excellent overall agreement between the presence of HNSCC and a positive MSP panel result. In conclusion, we demonstrate that the promoter methylation of RASSF1A, DAPK1, and p16 MSP panel is useful in detecting hypermethylation events in a noninvasive manner in patients with HNSCC.

Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

William James, Sciences of Mind, and Anti-imperial Discourse

In the past few decades, the humanities and social sciences have developed new methods of reorienting their conceptual frameworks in a “world without frontiers.” In this book, Bernadette M. Baker offers an innovative approach to rethinking sciences of mind as they formed at the turn of the twentieth century, via the concerns that have emerged at the turn of the twenty-first. The less-visited texts of Harvard philosopher and psychologist William James provide a window into contemporary debates over principles of toleration, anti-imperial discourse, and the nature of ethics. Baker revisits Jamesian approaches to the formation of scientific objects including the child mind, exceptional mental states, and the ghost to explore the possibilities and limits of social scientific thought dedicated to mind development and discipline formation around the construct of the West.