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Abstract Background DNA capture technologies combined with high-throughput sequencing now enable cost-effective, deep-coverage, targeted sequencing of complete exomes. This is well suited for SNP discovery and genotyping. However there has been little attention devoted to Copy Number Variation (CNV) detection from exome capture datasets despite the potentially high impact of CNVs in exonic regions on protein function. Results As members of the 1000 Genomes Project analysis effort, we investigated 697 samples in which 931 genes were targeted and sampled with 454 or Illumina paired-end sequencing. We developed a rigorous Bayesian method to detect CNVs in the genes, based on read depth within target regions. Despite substantial variability in read coverage across samples and targeted exons, we were able to identify 107 heterozygous deletions in the dataset. The experimentally determined false discovery rate (FDR) of the cleanest dataset from the Wellcome Trust Sanger Institute is 12.5%. We were able to substantially improve the FDR in a subset of gene deletion candidates that were adjacent to another gene deletion call (17 calls). The estimated sensitivity of our call-set was 45%. Conclusions This study demonstrates that exonic sequencing datasets, collected both in population based and medical sequencing projects, will be a useful substrate for detecting genic CNV events, particularly deletions. Based on the number of events we found and the sensitivity of the methods in the present dataset, we estimate on average 16 genic heterozygous deletions per individual genome. Our power analysis informs ongoing and future projects about sequencing depth and uniformity of read coverage required for efficient detection.

Abstract Background Mucin alterations are a common feature of esophageal neoplasia, and alterations in MUC2 mucin have been associated with tumor progression in the esophagus. Bile acids have been linked to esophageal adenocarcinoma and mucin secretion, but their effects on mucin gene expression in human esophageal adenocarcinoma cells is unknown. Methods Human esophageal adenocarcinoma cells were treated 18 hours with 50–300 μM deoxycholic acid, chenodeoxycholic acid, or taurocholic acid. MUC2 transcription was assayed using a MUC2 promoter reporter luciferase construct and MUC2 protein was assayed by Western blot analysis. Transcription Nuclear factor-κB activity was measured using a Nuclear factor-κB reporter construct and confirmed by Western blot analysis for Nuclear factor-κB p65. Results MUC2 transcription and MUC2 protein expression were increased four to five fold by bile acids in a time and dose-dependent manner with no effect on cell viability. Nuclear factor-κB activity was also increased. Treatment with the putative chemopreventive agent aspirin, which decreased Nuclear factor-κB activity, also decreased MUC2 transcription. Nuclear factor-κB p65 siRNA decreased MUC2 transcription, confirming the significance of Nuclear factor-κB in MUC2 induction by deoxycholic acid. Calphostin C, a specific inhibitor of protein kinase C (PKC), greatly decreased bile acid induced MUC2 transcription and Nuclear factor-κB activity, whereas inhibitors of MAP kinase had no effect. Conclusion Deoxycholic acid induced MUC2 overexpression in human esophageal adenocarcinoma cells by activation of Nuclear factor-κB transcription through a process involving PKC-dependent but not PKA, independent of activation of MAP kinase.

Abstract: Highly active TiO2/V–TiO2 composite photocatalysts with an n–n heterojunction semiconductor structure have been prepared by mixing TiO2 sol with sol–gel derived V–TiO2 powders that have adsorbed ammonium oleate in advance, followed by drying and calcination. These composite photocatalysts were characterized by XRD, TEM, BET, XPS, UV–vis and PL spectroscopy. The photodegradation of methyl orange in aqueous solution under UV–vis light irradiation has been investigated over TiO2-based photocatalysts consisting of different TiO2/V–TiO2 ratios and different vanadium contents. TiO2/V–TiO2 composite photocatalysts were generally shown to have a much higher photocatalytic destruction rate than that of undoped TiO2, which is ascribed mainly to the electrostatic-field-driven electron–hole separation in TiO2/V–TiO2 composite photocatalysts. The best TiO2/V–TiO2 composite with the mass ratio of TiO2:0.5at.%V–TiO2 equal to 12:1 demonstrates 5.9 times the photocatalytic activity of that of undoped TiO2 with comparable crystallite size and specific surface area. The effect of photocatalysts composition on the photoactivity was discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Micro- and Meso-scale homogeneity of asphalt mixtures with RAP were experimentally investigated. • Thermal-non-equilibrium condition was considered. • The most unfavourable mixing condition was concluded. Reclaimed asphalt pavement (RAP) is a promising material that can be partially substituted into the newly constructed pavement. An appropriate production procedure is of great significance to produce high-quality recycled asphalt mixtures. This study performed an investigation on the micro and mesoscale homogeneity of asphalt mixtures produced by different mixing conditions. To this end, 36 mixing combinations, including three preheated RAP temperatures, three mixing times, and two aggregate types, were considered in this study. The diffusion sample composed of new and aged bitumen was obtained non-destructively using the aggregate tracking method (ATM). In what follows, the Fourier Transform Infrared Spectroscopy (FTIR) and Dynamic Shear Rheometer (DSR) tests were conducted to quantify the diffusion sample from the mechanical and chemical aspects, respectively. Accordingly, the homogeneity of asphalt mixtures containing RAP was analysed at the micro and mesoscales. The results indicated that mixing temperature dominantly controlled the migration behavior of binders, further determining the diffusion behavior between new bitumen and aged bitumen. Notably, the estimation of homogeneity of asphalt mixtures was found to be indicator-dependent. Using different indicators could induce distinct evaluation results or even opposite results. In general, the increase of mixing time would improve the complex modulus of the diffusion sample. The worst homogeneity was observed when the mixing temperature was around 110℃. Due to the variation in adhering to the bitumen binder, the aggregate type also influenced the micro and mesoscale homogeneity of asphalt mixtures. [ABSTRACT FROM AUTHOR]

• An averaging strategy was introduced to eliminate function noise. • The impact of branch chain on the relaxation time was discussed. • The impact of sampling time and interval on the relaxation time was discussed. From a molecular perspective, the viscosity of bitumen is determined by the motions of its molecules. Therefore, it is crucial to establish a relationship between different fractions of bitumen and their corresponding viscosities. In order to achieve this objective, the utilization of molecular dynamics simulation methodology proves to be promising. However, current practices indicate that there is no consensus on a specific simulation framework that can accurately simulate bitumen with predetermined fractions. Hence, this study proposes an improved averaging strategy as a modification to the existing simulation method. Specifically, the analysis focused on examining the rigidity and flexibility of pyrrole in bitumen to establish a foundation for vector selection. Furthermore, the influence of sampling time and interval was thoroughly discussed. To predict bitumen viscosity using the Debye-Stokes-Einstein (DSE) method, the modified Kohlrausch-Williams-Watts (mKWW) function was employed to fit self-autocorrelation functions. The findings revealed that neglecting the relative flexibility of branch chains would be inadequate when describing self-autocorrelation functions. Additionally, it is crucial to consider both sampling time and interval in order to obtain a more realistic representation of self-autocorrelation functions. This study demonstrates the feasibility of an improved averaging strategy for enhancing viscosity calculation accuracy. [ABSTRACT FROM AUTHOR]

The inclusion of clusters in recycled asphalt pavement (RAP) materials has a substantial negative impact on the mechanical properties, particularly affecting the homogeneity formation in recycled asphalt mixtures. Hence, it is imperative to gain insight into the agglomeration and dispersion of RAP materials during the mixing stage. Due to experimental limitations, this study opted for the discrete element method (DEM) as an alternative approach to simulate the mixing process of hot recycled asphalt mixtures containing RAP clusters. The impact of RAP cluster sizes and aging degree was examined. Parameters for the parallel bond model were determined through static loading and stacking angle tests, while contact bond number and dispersion coefficients were calculated to assess the agglomeration and dispersion behaviors of hot recycled asphalt mixtures. The results indicated that an increase in total bond number and a decrease in RAP-RAP bonds demonstrated the formation of new clusters during the mixing process. A critical cluster size (7.1 mm in this study) was identified, requiring more mixing effort for dispersion. Although following the same principle, the influence of aging degree on RAP materials was found to be significant. [Display omitted] • New clusters are formed in the mixing process. • The decreasing rate of cluster bonds varied with the cluster sizes. • 7.1 mm was the most unfavorable size concerning the dispersion of clusters in this study. [ABSTRACT FROM AUTHOR]