Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer

Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2’–deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.

Facial emotion modulates the neural mechanisms responsible for short interval time perception

Emotionally arousing events can distort our sense of time. We used mixed block/event-related fMRI design to establish the neural basis for this effect. Nineteen participants were asked to judge whether angry, happy and neutral facial expressions that varied in duration (from 400 to 1,600 ms) were closer in duration to either a short or long duration they learnt previously. Time was overestimated for both angry and happy expressions compared to neutral expressions. For faces presented for 700 ms, facial emotion modulated activity in regions of the timing network Wiener et al. (NeuroImage 49(2):1728–1740, 2010) namely the right supplementary motor area (SMA) and the junction of the right inferior frontal gyrus and anterior insula (IFG/AI). Reaction times were slowest when faces were displayed for 700 ms indicating increased decision making difficulty. Taken together with existing electrophysiological evidence Ng et al. (Neuroscience, doi: 10.3389/fnint.2011.00077, 2011), the effects are consistent with the idea that facial emotion moderates temporal decision making and that the right SMA and right IFG/AI are key neural structures responsible for this effect.

Fine-mapping the HOXB region detects common variants tagging a rare coding allele : evidence for synthetic association in prostate cancer

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

Factors influencing bike share membership : an analysis of Melbourne and Brisbane

The number of bike share programs has increased rapidly in recent years and there are currently over 700 programs in operation globally. Australia’s two bike share programs have been in operation since 2010 and have significantly lower usage rates compared to Europe, North America and China. This study sets out to understand and quantify the factors influencing bike share membership in Australia’s two bike share programs located in Melbourne and Brisbane. An online survey was administered to members of both programs as well as a group with no known association with bike share. A logistic regression model revealed several significant predictors of membership including reactions to mandatory helmet legislation, riding activity over the previous month, and the degree to which convenience motivated private bike riding. In addition, respondents aged 18 - 34 and having docking station within 250m of their workplace were found to be statistically significant predictors of bike share membership. Finally, those with relatively high incomes increased the odds of membership. These results provide insight as to the relative influence of various factors impacting on bike share membership in Australia. The findings may assist bike share operators to maximize membership potential and help achieve the primary goal of bike share – to increase the sustainability of the transport system.

The burden of cancer in member countries of the association of southeast asian nations (ASEAN)

This paper presents the most recent data on cancer rates and the burden of cancer in the ASEAN region. Epidemiological data were sourced from GLOBOCAN 2008 and disability adjusted life years (DALYs) lost were estimated using the standard methodology developed within the World Health Organization's Global Burden of Disease study. Overall, it was estimated there were over 700,000 new cases of cancer and 500,000 cancer deaths in ASEAN in the year 2008, leading to approximately 7.5 million DALYs lost in one year. The most commonly diagnosed cancers were lung (98,143), breast (86,842) and liver cancers (74,777). The most common causes of cancer death were lung cancer (85,772), liver cancer (69,115) and colorectal cancer (44,280). The burden of cancer in terms of DALYs lost was highest in Laos, Viet Nam and Myanmar and lowest in Brunei, Singapore and the Philippines. Significant differences in the patterns of cancer from country to country were observed. Another key finding was the major impact played by population age distribution on cancer incidence and mortality. Cancer rates in ASEAN are expected to increase with ageing of populations and changes in lifestyles associated with economic development. Therefore, ASEAN member countries are strongly encouraged to put in place cancer-control health carepolicies, focussed on strengthening the health systems to cope with projected increases in cancer prevention, treatment and management needs.

Transmittance properties of contact lens multipurpose solutions and their effects on a hydrogel lens

Purpose The aim was to assess the compatibility of different multipurpose solutions (MPSs) with one type of silicone hydrogel (SiH) contact lens by, assessing the changes in both ultraviolet (UV) and visible light transmissibility of the hydrogel lens caused by the MPSs. Methods The light transmittance from 200-700 nm were measured for the lotrafilcon B blister pack solution (BPS), six MPSs namely, ReNuMultiPlus Multi-Purpose Solution (Bausch and Lomb Inc., Rochester NY, USA.); Complete RevitaLens Multi-Purpose (Abbott Medical Optics Inc., Quarryvale Co. Dublin, Ireland); All In One Light (Sauflon Pharmaceuticals Ltd., Twickenham, England); SOLO-care AQUA™ (Ciba Vision Corporation Duluth, Georgia, USA.); Biomedics All-in-one solution (CooperVision, Hamble, UK); and HippiaMultiPlus All-in-one solution (Interojo Inc., Kyeonggi-do, Korea), and a lotrafilcon B SiH lens (before and after storage), using a spectrophotometer. Results The UV transmitted through the BPS and the MPS were similar (p >.05, for all), except for the HippiaMultiPlus which was lower (p < 0.001) by 19.8%. Mean transparency values were statistically (p<.001) significantly different between the BPS and the MPSs. All MP solution/SiH lens combinations resulted in relatively high UV transmittance values especially in the UVC spectrum, and significantly increased (p <.001) the visible light transmittance values of the SiH lens. Greater changes in transparency were observed in the ReNu/SiH lens (28.5%) and the Complete RevitaLens/SiH lens (24.9%) combinations. Conclusion The six MPSs showed significant variations in the transmitted UV and visible light. Similar to the BPS, all MPSs were equally transparent, but showed very poor UVA & UVB attenuation, except for the Hippia MultiPlus. The MPS/SiH lens combinations did not significantly affect the lens transparency but it significant increased the lens transmittance of UV radiation, after storage. Further in-vivo studies are needed to validate if this effect is constant.

Experimental studies of cold-formed steel hollow section columns at elevated temperatures

This paper reports the details of an experimental study of cold-formed steel hollow section columns at ambient and elevated temperatures. In this study the global buckling behaviour of cold-formed Square Hollow Section (SHS) slender columns under axial compression was investigated at various uniform elevated temperatures up to 700℃. The results of these column tests are reported in this paper, which include the buckling/failure modes at elevated temperatures, and ultimate load versus temperature curves. Finite element models of tested columns were also developed and their behaviour and ultimate capacities at ambient and elevated temperatures were studied. Fire design rules given in European and American standards including the Direct Strength Method (DSM) based design rules were used to predict the ultimate capacities of tested columns at elevated temperatures. Elevated temperature mechanical properties and stress-strain models given in European steel design standards and past researches were used with design rules and finite element models to investigate their effects on SHS column capacities. Comparisons of column capacities from tests and finite element analyses with those predicted by current design rules were used to determine the accuracy of currently available column design rules in predicting the capacities of SHS columns at elevated temperatures and the need to use appropriate elevated temperature material stress-strain models. This paper presents the important findings derived from the comparisons of these column capacities.

Analytical study of implementation issues of NTRU

Nth-Dimensional Truncated Polynomial Ring (NTRU) is a lattice-based public-key cryptosystem that offers encryption and digital signature solutions. It was designed by Silverman, Hoffstein and Pipher. The NTRU cryptosystem was patented by NTRU Cryptosystems Inc. (which was later acquired by Security Innovations) and available as IEEE 1363.1 and X9.98 standards. NTRU is resistant to attacks based on Quantum computing, to which the standard RSA and ECC public-key cryptosystems are vulnerable to. In addition, NTRU has higher performance advantages over these cryptosystems. Considering this importance of NTRU, it is highly recommended to adopt NTRU as part of a cipher suite along with widely used cryptosystems for internet security protocols and applications. In this paper, we present our analytical study on the implementation of NTRU encryption scheme which serves as a guideline for security practitioners who are novice to lattice-based cryptography or even cryptography. In particular, we show some non-trivial issues that should be considered towards a secure and efficient NTRU implementation.

Thermogravimetric analysis of tetradecyltrimethylammonium bromide-modified beidellites

The surfaces of natural beidellite clay were modified with cationic surfactant, tetradecyltrimethylammonium bromide, at different concentrations. The organo-beidellites were analysed using thermogravimetric analysis which shows four thermal oxidation/decomposition steps. The first step of mass loss is observed from room temperature to 130 °C due to the dehydration of adsorbed water. The second step of mass loss between 130 and 400 °C is attributed to the oxidation step of the intercalated organic surfactant with the formation of charcoal. The third mass loss happens between 400 and 500 °C which is assigned to the loss of hydroxyl groups on the edge of clays and the further oxidation step of charcoal. The fourth step is ascribed to the loss of structural OH units as well as the final oxidation/decomposition step of charcoal which takes place between 500 and 700 °C. Thermogravimetric analysis has proven to be a useful tool for estimating loaded surfactant amount.

Estimating the burden of disease attributable to diabetes in South Africa in 2000

OBJECTIVES To estimate the burden of disease attributable to diabetes by sex and age group in South Africa in 2000. DESIGN The framework adopted for the most recent World Health Organization comparative risk assessment (CRA) methodology was followed. Small community studies used to derive the prevalence of diabetes by population group were weighted proportionately for a national estimate. Population-attributable fractions were calculated and applied to revised burden of disease estimates. Monte Carlo simulation-modelling techniques were used for uncertainty analysis. SETTING South Africa. SUBJECTS Adults 30 years and older. OUTCOME MEASURES Mortality and disability-adjusted life years (DALYs) for ischaemic heart disease (IHD), stroke, hypertensive disease and renal failure. RESULTS Of South Africans aged >or= 30 years, 5.5% had diabetes which increased with age. Overall, about 14% of IHD, 10% of stroke, 12% of hypertensive disease and 12% of renal disease burden in adult males and females (30+ years) were attributable to diabetes. Diabetes was estimated to have caused 22,412 (95% uncertainty interval 20,755 - 24,872) or 4.3% (95% uncertainty interval 4.0 - 4.8%) of all deaths in South Africa in 2000. Since most of these occurred in middle or old age, the loss of healthy life years comprises a smaller proportion of the total 258,028 DALYs (95% uncertainty interval 236,856 - 290,849) in South Africa in 2000, accounting for 1.6% (95% uncertainty interval 1.5 - 1.8%) of the total burden. CONCLUSIONS Diabetes is an important direct and indirect cause of burden in South Africa. Primary prevention of the disease through multi-level interventions and improved management at primary health care level are needed.

The effect of BCMO1 gene variants on macular pigment optical density in young healthy Caucasians

Background Serum lutein (L) and zeaxanthin (Z) positively correlate with macular pigment optical density (MPOD), hence the latter is a valuable indirect tool for measuring L and Z content in the macula. L and Z have been attributed antioxidant capacity and protection from certain retinal diseases but their uptake within the eye is thought to depend on genetic, age and environmental factors. In particular gene variants within beta-carotene monooxygenase (BCMO1) are thought to modulate MPOD in the macula. Objectives: To determine the effect of BCMO1 single nucleotide polymorphisms (SNPs) rs11645428, rs6420424 and rs6464851 on macular pigment optical density (MPOD) in a cohort of young healthy participants of Caucasian origin with normal ocular health. Design In this cohort study, MPOD was assessed in 46 healthy participants (22 male and 24 female) with a mean age of 24 ± 4.0 years (range 19-33). The three SNPs, rs11645428, rs6420424, rs6564851 that have established associations with MPOD were determined using MassEXTEND (hME) Sequenom assay. One-way analysis of variance (ANOVA) was performed on groups segregated into homozygous and heterozygous BCMO1 genotypes. Correlations between body mass index (BMI), iris colour, gender, central retinal thickness (CRT), diet and MPOD were investigated. Results MPOD did not significantly vary with BCMO1 rs11645428 (F2,41 = 0.700, p = 0.503), rs6420424 (F2,41 = 0.210, p = 0.801) nor rs6464851 homozygous or heterozygous genotypes (F2,41 = 0,13, p = 0.88), in this young healthy cohort. The combination of these three SNPs into triple genotypes based on plasma conversion efficiency did not affect MPOD (F2,41 = 0.07, p = 0.9). There was a significant negative correlation with MPOD and central retinal thickness (r = - 0.39, p = 0.01) but no significant correlation between BMI, iris colour, gender and MPOD. Conclusion Our results indicate that macular pigment deposition within the central retina is not dependent on BCMO1 gene variants in young healthy people. We propose that MPOD is saturated in younger persons and/or other gene variant combinations determine its deposition.

Parallel streaming signature EM-tree: A clustering algorithm for web scale applications

The proliferation of the web presents an unsolved problem of automatically analyzing billions of pages of natural language. We introduce a scalable algorithm that clusters hundreds of millions of web pages into hundreds of thousands of clusters. It does this on a single mid-range machine using efficient algorithms and compressed document representations. It is applied to two web-scale crawls covering tens of terabytes. ClueWeb09 and ClueWeb12 contain 500 and 733 million web pages and were clustered into 500,000 to 700,000 clusters. To the best of our knowledge, such fine grained clustering has not been previously demonstrated. Previous approaches clustered a sample that limits the maximum number of discoverable clusters. The proposed EM-tree algorithm uses the entire collection in clustering and produces several orders of magnitude more clusters than the existing algorithms. Fine grained clustering is necessary for meaningful clustering in massive collections where the number of distinct topics grows linearly with collection size. These fine-grained clusters show an improved cluster quality when assessed with two novel evaluations using ad hoc search relevance judgments and spam classifications for external validation. These evaluations solve the problem of assessing the quality of clusters where categorical labeling is unavailable and unfeasible.

Size-resolved particle distribution and gaseous concentrations by real-world road tunnel measurement

Measurements of aerosol particle number size distributions (15-700 nm), CO and NOx were performed in a bus tunnel, Australia. Daily mean particle size distributions of mixed diesel/CNG (Compressed Natural Gas) buses traffic flow were determined in 4 consecutive measurement days. EFs (Emission Factors) of Particle size distribution of diesel buses and CNG buses were obtained by MLR (Multiple Linear Regression) methods, particle distributions of diesel buses and CNG buses were observed as single accumulation mode and nuclei-mode separately. Particle size distributions of mixed traffic flow were decomposed by two log-normal fitting curves for each 30 minutes interval mean scans, all the mix fleet PSD emission can be well fitted by the summation of two log-normal distribution curves, and these were composed of nuclei mode curve and accumulation curve, which were affirmed as the CNG buses and diesel buses PN emission curves respectively. Finally, particle size distributions of diesel buses and CNG buses were quantified by statistical whisker-box charts. For log-normal particle size distribution of diesel buses, accumulation mode diameters were 74.5～87.5nm, geometric standard deviations were 1.89～1.98. As to log-normal particle size distribution of CNG buses, nuclei-mode diameters were 21～24 nm, geometric standard deviations were 1.27～1.31.

Field performance of in-service cast iron water reticulation pipe buried in reactive clay

Field monitoring is an important means for understanding soil behaviour and its interaction with buried structures such as pipeline. This paper details the successful instrumentation of a section of an in-service cast iron water main buried in an area of reactive clay where frequent water pipe breakage has been observed. The instrumentation included measurement of pipe strain; pipe water pressure and temperature; soil pressure, temperature, moisture content and matric suction, as well as the meteorological conditions on site. The data generally indicated that changes in soil temperature, suction and moisture content were directly related to the local climatic variations. The suction and moisture content data indicated that the soil profile at the site down to around 700 mm, and probably down to 1000 mm, is affected by changes in surface weather, while soil conditions below this depth appear to be more stable. Analysis of pipe strain indicated that the pipe behaves like a cantilever beam, with the top experiencing predominantly tensile strains during summer. Subsequently, these trends reduce to compressive strains as soil swelling occurs due to increase of moisture content with the onset of winter.

Pentacene on Ni(111): room-temperature molecular packing and temperature-activated conversion to graphene

We investigate, using scanning tunnelling microscopy, the adsorption of pentacene on Ni(111) at room temperature and the behaviour of these monolayer films with annealing up to 700 °C. We observe the conversion of pentacene into graphene, which begins from as low as 220 °C with the coalescence of pentacene molecules into large planar aggregates. Then, by annealing at 350 °C for 20 minutes, these aggregates expand into irregular domains of graphene tens of nanometers in size. On surfaces where graphene and nickel carbide coexist, pentacene shows preferential adsorption on the nickel carbide phase. The same pentacene to graphene transformation was also achieved on Cu(111), but at a higher activation temperature, producing large graphene domains that exhibit a range of moiré superlattice periodicities.