Comprehensive DNA methylation profiling in a human cancer genome identifies novel epigenetic targets

Using a unique microarray platform for cytosine methylation profiling, the DNA methylation landscape of the human genome was monitored at more than 21,000 sites, including 79% of the annotated transcriptional start sites (TSS). Analysis of an oligodendroglioma derived cell line LN-18 revealed more than 4000 methylated TSS. The gene-centric analysis indicated a complex pattern of DNA methylation exists along each autosome, with a trend of increasing density approaching the telomeres. Remarkably, 2% of CpG islands (CGI) were densely methylated, and 17% had significant levels of 5 mC, whether or not they corresponded to a TSS. Substantial independent verification, obtained from 95 loci, suggested that this approach is capable of large scale detection of cytosine methylation with an accuracy approaching 90%. In addition, we detected large genomic domains that are also susceptible to DNA methylation reinforced inactivation, such as the HOX cluster on chromosome 7 (CH7). Extrapolation from the data suggests that more than 2000 genomic loci may be susceptible to methylation and associated inactivation, and most have yet to be identified. Finally, we report six new targets of epigenetic inactivation (IRX3, WNT10A, WNT6, RARalpha, BMP7 and ZGPAT). These targets displayed cell line and tumor specific differential methylation when compared with normal brain samples, suggesting they may have utility as biomarkers. Uniquely, hypermethylation of the CGI within an IRX3 exon was correlated with over-expression of IRX3 in tumor tissues and cell lines relative to normal brain samples

The effects of perceived and received support on objective performance outcome.

This is a postprint of an article published in European Journal of Sport Science, 2008, Vol. 8, Issue 6, pp. 359 – 368 © 2008 copyright Taylor & Francis. European Journal of Sport Science is available online at: http://www.tandfonline.com/loi/tejs20In this study, we examined the main and stress-buffering effects of perceived and received support upon objective performance outcome. The sample consisted of 123 male British high performance golfers, mean age 25.3 years (SD = 5.4). Participants completed measures of perceived support, stressors, stress, and received support before competitions. After the competitions, performance outcome (number of shots) was recorded. When both types of support were considered separately, there were significant main effects for perceived (ΔR2 = .08, b = -.81, p < .01) and received support (ΔR2 = .05, b = -.68, p < .01) on performance. There were also significant stress-buffering effects for perceived (ΔR2 = .03, b = -.48, p = .02) and received support (ΔR2 = .06, b = -.61, p < .01). When both types of support were considered simultaneously, the significant main effect (DR2 = .09, p < .01) was primarily attributable to perceived support (b = -.63, p = .02). The significant stress-buffering effect (DR2 = .06, p = .01) was primarily attributable to received support (b = -.56, p = .04). These results demonstrate the beneficial influence of social support on performance. The findings highlight the need to recognise the distinction between perceived and received support, both in terms of theory and the design of social support interventions with athletes

Comparison of selected foreign plans and practices for spent fuel and high-level waste management

This report describes the major parameters for management of spent nuclear fuel and high-level radioactive wastes in selected foreign countries as of December 1989 and compares them with those in the United States. The foreign countries included in this study are Belgium, Canada, France, the Federal Republic of Germany, Japan, Sweden, Switzerland, and the United Kingdom. All the countries are planning for disposal of spent fuel and/or high-level wastes in deep geologic repositories. Most countries (except Canada and Sweden) plan to reprocess their spent fuel and vitrify the resultant high-level liquid wastes; in comparison, the US plans direct disposal of spent fuel. The US is planning to use a container for spent fuel as the primary engineered barrier. The US has the most developed repository concept and has one of the earliest scheduled repository startup dates. The repository environment presently being considered in the US is unique, being located in tuff above the water table. The US also has the most prescriptive regulations and performance requirements for the repository system and its components. 135 refs., 8 tabs

Toll-like receptor 2-modulating pectin-polymers in alginate-based microcapsules attenuate immune responses and support islet-xenograft survival

Encapsulation of pancreatic islets in alginate-microcapsules is used to reduce or avoid the application of life-long immunosuppression in preventing rejection. Long-term graft function, however, is limited due to varying degrees of host tissue responses against the capsules. Major graft-longevity limiting responses include inflammatory responses provoked by biomaterials and islet-derived danger-associated molecular patterns (DAMPs). This paper reports on a novel strategy for engineering alginate microcapsules presenting immunomodulatory polymer pectin with varying degrees of methyl-esterification (DM) to reduce these host tissue responses. DM18-pectin/alginate microcapsules show a significant decrease of DAMP-induced Toll-Like Receptor-2 mediated immune activation in vitro, and reduce peri-capsular fibrosis in vivo in mice compared to higher DM-pectin/alginate microcapsules and conventional alginate microcapsules. By testing efficacy of DM18-pectin/alginate microcapsules in vivo, we demonstrate that low-DM pectin support long-term survival of xenotransplanted rat islets in diabetic mice. This study provides a novel strategy to attenuate host responses by creating immunomodulatory capsule surfaces that attenuate activation of specific pro-inflammatory immune receptors locally at the transplantation site

Comparison of Selected Foreign Plans and Practices for Spent Fuel and High-Level Waste Management

This report describes the major parameters for management of spent nuclear fuel and high-level radioactive wastes in selected foreign countries as of December 1989 and compares them with those in the United States. The foreign countries included in this study are Belgium, Canada, France, the Federal Republic of Germany, Japan, Sweden, Switzerland, and the United Kingdom. All the countries are planning for disposal of spent fuel and/or high-level wastes in deep geologic repositories. Most countries (except Canada and Sweden) plan to reprocess their spent fuel and vitrify the resultant high-level liquid wastes; in comparison, the US plans direct disposal of spent fuel. The US is planning to use a container for spent fuel as the primary engineered barrier. The US has the most developed repository concept and has one of the earliest scheduled repository startup dates. The repository environment presently being considered in the US is unique, being located in tuff above the water table. The US also has the most prescriptive regulations and performance requirements for the repository system and its components. 135 refs., 8 tabs

An accurate in vitro model of the E. coli envelope

Gram-negative bacteria are an increasingly serious source of antibiotic-resistant infections, partly owing to their characteristic protective envelope. This complex, 20 nm thick barrier includes a highly impermeable, asymmetric bilayer outer membrane (OM), which plays a pivotal role in resisting antibacterial chemotherapy. Nevertheless, the OM molecular structure and its dynamics are poorly understood because the structure is difficult to recreate or study in vitro. The successful formation and characterization of a fully asymmetric model envelope using Langmuir-Blodgett and Langmuir-Schaefer methods is now reported. Neutron reflectivity and isotopic labeling confirmed the expected structure and asymmetry and showed that experiments with antibacterial proteins reproduced published in vivo behavior. By closely recreating natural OM behavior, this model provides a much needed robust system for antibiotic development

How Does Perceived Support Lead to Better Performance? An Examination of Potential Mechanisms

This is a postprint of an article published in Journal of Applied Sport Psychology, 2009, Vol. 21, pp. 421 – 429 © 2009 copyright Taylor & Francis. Journal of Applied Sport Psychology is available online at: http://www.tandfonline.com/toc/uasp20/currentUsing a high-performance sample of 118 golfers, we examined the relationship between perceived support and performance. Observed variable path analysis revealed that the beneficial effects of perceived support were primarily attributable to esteem support. High levels of esteem support were associated with appraising a competition as less of a threat. Esteem support was also positively associated with situational control, which was positively associated with challenge appraisals and negatively associated with threat appraisals. Challenge appraisals were associated with better performance and threat appraisals with poorer performance. These results highlight possible mechanisms underlying the relationship between esteem support and performance

Calculus Volume 2

Calculus is designed for the typical two- or three-semester general calculus course, incorporating innovative features to enhance student learning. The book guides students through the core concepts of calculus and helps them understand how those concepts apply to their lives and the world around them. Due to the comprehensive nature of the material, we are offering the book in three volumes for flexibility and efficiency. Volume 2 covers integration, differential equations, sequences and series, and parametric equations and polar coordinates.https://commons.erau.edu/oer-textbook/1001/thumbnail.jp

Measuring the quality and quantity of professional intrapartum support: Testing a computerised systematic observation tool in the clinical setting

Background: Continuous support in labour has a significant impact on a range of clinical outcomes, though whether the quality and quantity of support behaviours affects the strength of this impact has not yet been established. To identify the quality and quantity of support, a reliable means of measurement is needed. To this end, a new computerised systematic observation tool, the &lsquo;SMILI' (Supportive Midwifery in Labour Instrument) was developed. The aim of the study was to test the validity and usability of the &lsquo;Supportive Midwifery in Labour Instrument' (SMILI) and to test the feasibility and acceptability of the systematic observation approach in the clinical intrapartum setting. Methods: Systematic observation was combined with a postnatal questionnaire and the collection of data about clinical processes and outcomes for each observed labour. The setting for the study was four National Health Service maternity units in Scotland, UK. Participants in this study were forty five midwives and forty four women. The SMILI was used by trained midwife observers to record labour care provided by midwives. Observations were undertaken for an average of two hours and seventeen minutes during the active first stage of labour and, in 18 cases, the observation included the second stage of labour. Content validity of the instrument was tested by the observers, noting the extent to which the SMILI facilitated the recording of all key aspects of labour care and interactions. Construct validity was tested through exploration of correlations between the data recorded and women's feelings about the support they received. Feasibility and usability data were recorded following each observation by the observer. Internal reliability and construct validity were tested through statistical analysis of the data. Results: One hundred and four hours of labour care were observed and recorded using the SMILI during forty nine labour episodes. Conclusion: The SMILI was found to be a valid and reliable instrument in the intrapartum setting in which it was tested. The study identified that the SMILI could be used to test correlations between the quantity and quality of support and outcomes. The systematic observational approach was found to be an acceptable and feasible method of enquiry