title: DNA methylation-associated colonic mucosal immune and defense responses in treatment-naïve pediatric ulcerative colitis

authors: Harris, R. Alan

subjects: Machine learning

abstract: Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn’s disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P &lt; 0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.

text: DNA methylation-associated colonic mucosal immune and defense responses in treatment-naïve pediatric ulcerative colitis Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn’s disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P &lt; 0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.

year: 2014

title: Anomalous transport of cosmic rays in a nonlinear diffusion model

authors: Litvinenko, Yuri E.

subjects: mathematics

abstract: We investigate analytically and numerically the transport of cosmic rays following their escape from a shock or another localized acceleration site. Observed cosmic-ray distributions in the vicinity of heliospheric and astrophysical shocks imply that anomalous, superdiffusive transport plays a role in the evolution of the energetic particles. Several authors have quantitatively described the anomalous diffusion scalings, implied by the data, by solutions of a formal transport equation with fractional derivatives. Yet the physical basis of the fractional diffusion model remains uncertain. We explore an alternative model of the cosmic-ray transport: a nonlinear diffusion equation that follows from a self-consistent treatment of the resonantly interacting cosmic-ray particles and their self-generated turbulence. The nonlinear model naturally leads to superdiffusive scalings. In the presence of convection, the model yields a power-law dependence of the particle density on the distance upstream of the shock. Although the results do not refute the use of a fractional advection–diffusion equation, they indicate a viable alternative to explain the anomalous diffusion scalings of cosmic-ray particles.

text: Anomalous transport of cosmic rays in a nonlinear diffusion model We investigate analytically and numerically the transport of cosmic rays following their escape from a shock or another localized acceleration site. Observed cosmic-ray distributions in the vicinity of heliospheric and astrophysical shocks imply that anomalous, superdiffusive transport plays a role in the evolution of the energetic particles. Several authors have quantitatively described the anomalous diffusion scalings, implied by the data, by solutions of a formal transport equation with fractional derivatives. Yet the physical basis of the fractional diffusion model remains uncertain. We explore an alternative model of the cosmic-ray transport: a nonlinear diffusion equation that follows from a self-consistent treatment of the resonantly interacting cosmic-ray particles and their self-generated turbulence. The nonlinear model naturally leads to superdiffusive scalings. In the presence of convection, the model yields a power-law dependence of the particle density on the distance upstream of the shock. Although the results do not refute the use of a fractional advection–diffusion equation, they indicate a viable alternative to explain the anomalous diffusion scalings of cosmic-ray particles.

year: 2017

title: Ngā Tuakiri o te Tangata: Being Māori in Early Childhood Education

authors: Rameka, Lesley Kay

abstract: Before the arrival of Europeans in Aotearoa, New Zealand and their subsequent settlement in the 1800s, there was no concept of a Māori identity. Over time, however, as a result of rapid colonisation, Māori became a minority population in New Zealand. Consequently, the term Māori as normal or usual, began to lose its meaning (Webber, 2008), and another meaning began to emerge based on contrasts with the Pākehā settler population. This paper explores the complex and increasingly diverse nature of Māori identities in contemporary Aotearoa/New Zealand, including contemporary early childhood contexts. It discusses the importance of negotiating the terrains of cultural knowledge, values and understandings in order to define what ‘being Māori’ means for teachers and children in an increasingly diverse and complex settings.

text: Ngā Tuakiri o te Tangata: Being Māori in Early Childhood Education Before the arrival of Europeans in Aotearoa, New Zealand and their subsequent settlement in the 1800s, there was no concept of a Māori identity. Over time, however, as a result of rapid colonisation, Māori became a minority population in New Zealand. Consequently, the term Māori as normal or usual, began to lose its meaning (Webber, 2008), and another meaning began to emerge based on contrasts with the Pākehā settler population. This paper explores the complex and increasingly diverse nature of Māori identities in contemporary Aotearoa/New Zealand, including contemporary early childhood contexts. It discusses the importance of negotiating the terrains of cultural knowledge, values and understandings in order to define what ‘being Māori’ means for teachers and children in an increasingly diverse and complex settings.

year: 2016