Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background DNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for enrichment of methylated genomic fragments using the methyl-binding domain of the human MBD2 protein (MBD2-MBD) followed by analysis with high-density tiling microarrays. This MBD-chip approach was used to characterize DNA methylation patterns across all non-repetitive sequences of human chromosomes 21 and 22 at high-resolution in normal and malignant prostate cells. Results Examining this data using computational methods that were designed specifically for DNA methylation tiling array data revealed widespread methylation of both gene promoter and non-promoter regions in cancer and normal cells. In addition to identifying several novel cancer hypermethylated 5' gene upstream regions that mediated epigenetic gene silencing, we also found several hypermethylated 3' gene downstream, intragenic and intergenic regions. The hypermethylated intragenic regions were highly enriched for overlap with intron-exon boundaries, suggesting a possible role in regulation of alternative transcriptional start sites, exon usage and/or splicing. The hypermethylated intergenic regions showed significant enrichment for conservation across vertebrate species. A sampling of these newly identified promoter (ADAMTS1 and SCARF2 genes) and non-promoter (downstream or within DSCR9, C21orf57 and HLCS genes) hypermethylated regions were effective in distinguishing malignant from normal prostate tissues and/or cell lines. Conclusions Comparison of chromosome-wide DNA methylation patterns in normal and malignant prostate cells revealed significant methylation of gene-proximal and conserved intergenic sequences. Such analyses can be easily extended for genome-wide methylation analysis in health and disease.Published versio

Genetic programming based structure optimisation

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Anisotropic Elastoplastic Damage Mechanics Method to Predict Fatigue Life of the Structure

New damage mechanics method is proposed to predict the low-cycle fatigue life of metallic structures under multiaxial loading. The microstructure mechanical model is proposed to simulate anisotropic elastoplastic damage evolution. As the micromodel depends on few material parameters, the present method is very concise and suitable for engineering application. The material parameters in damage evolution equation are determined by fatigue experimental data of standard specimens. By employing further development on the ANSYS platform, the anisotropic elastoplastic damage mechanics-finite element method is developed. The fatigue crack propagation life of satellite structure is predicted using the present method and the computational results comply with the experimental data very well

Analysis of influencing factors for conversion of laparoscopic cholecystectomy to open surgery

ObjectiveTo analyze the influencing factors for conversion of laparoscopic cholecystectomy to open surgery, and to provide a clinical reference for developing surgical procedures. MethodsA total of 278 patients receiving laparoscopic cholecystectomy in our hospital from January 2009 to December 2013 were analyzed. Among them, 31 patients were converted to open surgery during laparoscopic cholecystectomy, while the remaining 274 patients were not. The influencing factors for conversion to open surgery were investigated. The t test was applied in the comparison of continuous data, whereas the χ2 test was used for categorical data. The univariate logistic regression analysis was performed to investigate significant influencing factors, and the independent influencing factors were determined by multivariate logistic regression analysis. ResultsThe univariate analysis showed that sex (P=0.022), arteriosclerosis (P＜0.001), diabetes (P＜0.001), heart failure (P=0.002), previous upper abdominal surgery (P＜0.001), age (P＜0.001), body mass index (BMI) (P=0.003), gallbladder wall thickness (P＜0.001), the count of white blood cells (P＜0.001), and serum total bilirubin level (P=0.046) were significantly different between groups. The multivariate logistic regression analysis further showed that previous upper abdominal surgery (P＜0.001), sex (P=0.001), BMI (P=0.002), and the count of white blood cells (P=0.019) were independent influencing factors, among which previous upper abdominal surgery was the most significant one (OR=4.646， 95%CI: 2.012-10.729). ConclusionPrevious upper abdominal surgery, sex, BMI, and the count of white blood cells were independent influencing factors for conversion of laparoscopic cholecystectomy to open surgery. Careful evaluation of these factors before surgery would help to increase the operation efficacy, possessing an important clinical value

Autonomous cruise method of unmanned surface vessles cluster based on bacterial obstacle avoidance strategy

A dynamic obstacle avoidance algorithm is proposed for the obstacle avoidance problem in the cruise task of unmanned boat cluster. Firstly, the square grid trajectory cell (SGTC) situation matrix of the waters around the unmanned surface vessle is obtained. Then, based on the principle of bacterial walking foraging, the optimal obstacle avoidance path is dynamically matched in the SGTC set. Finally, on the basis of dynamic obstacle avoidance, the autonomous cruise process of unmanned surface vessle is divided into stages of moving towards the target, dynamic obstacle avoidance, and return replenishment, so as to realize the normal cruise of unmanned surface vessle to the designated waters. The simulation results show that the proposed method has efficient avoidance ability for static point, surface obstacle and moving obstacle. Based on the algorithm, it can realize the normalized unmanned cruise of unmanned boat cluster. The algorithm is not only suitable for obstacle avoidance of unmanned surface vessle, but also has broad application prospects in other heterogeneous unmanned equipment

Experimental Study on the Mechanical Properties and Seepage Characteristics of Red Sandstone with a Single Persistent Joint under Triaxial Compression

In this research, the conventional triaxial compression experiments for intact red sandstone specimens and the specimens with a single persistent joint at different inclination angles, i.e., 0°, 30°, 45°, and 90°, were conducted at first. Based on the results of the conventional tests, the effects of the confining pressure and the joint inclination angle on the mechanical properties including deformation behavior and strength parameters were summarized and analyzed, respectively. We find that the strength and deformation of jointed red sandstone are enlarged due to the increment of confining pressure, and the mechanical parameters of specimens show a U-shaped development with the rise of the joint angle. Besides, to investigate the effects of the pore pressure on seepage characteristics of rocks with joint angles at 0°, 45°, and 90°, a series of triaxial compression drainage tests on the jointed red sandstone were performed. The results show that the pore pressure has a weakening effect on the strength of jointed specimens, which can reduce the strengthening effect induced by confining pressure. Meanwhile, the tested specimens mostly present shear failure modes. As a result, the mechanical responses, seepage characteristics, and cracking modes in red sandstone containing a single persistent joint under triaxial compression are revealed

A multi-mode real-time terrain parameter estimation method for wheeled motion control of mobile robots

For motion control of wheeled planetary rovers traversing on deformable terrain, real-time terrain parameter estimation is critical in modeling the wheel-terrain interaction and compensating the effect of wheel slipping. A multi-mode real-time estimation method is proposed in this paper to achieve accurate terrain parameter estimation. The proposed method is composed of an inner layer for real-time filtering and an outer layer for online update. In the inner layer, sinkage exponent and internal frictional angle, which have higher sensitivity than that of the other terrain parameters to wheel-terrain interaction forces, are estimated in real time by using an adaptive robust extended Kalman filter (AREKF), whereas the other parameters are fixed with nominal values. The inner layer result can help synthesize the current wheel-terrain contact forces with adequate precision, but has limited prediction capability for time-variable wheel slipping. To improve estimation accuracy of the result from the inner layer, an otter layer based on recursive Gauss-Newton (RGN) algorithm is introduced to refine the result of real-time filtering according to the innovation contained in the history data. With the two-layer structure, the proposed method can work in three fundamental estimation modes: EKF, REKF and RGN, making the method applicable for flat, rough and non-Uniform terrains. Simulations have demonstrated the effectiveness of the proposed method under three terrain types, showing the advantages of introducing the two-layer structure. (C) 2017 Elsevier Ltd. All rights reserved

Evaluating the relationship between Clinical G6PD enzyme activity and gene variants

Glucose-6-phosphate dehydrogenase (G6PD) is a the first and rate-limiting enzyme that plays a critical role in G6PD deficiency, the most common enzyme disorder worldwide, is related to intravascular hemolysis. To determine the clinical enzyme activity level in different G6PD variants, we evaluated 15 variant from 424 clinical blood samples by using multicolor melting curve analysis and DNA sequencing. The results showed that the enzyme activities of the hemizygous deficient were 1.5–2.4 U/gHb, which was significantly lower than those of the heterozygous (P T (Chinese-5) mutation affects the kinetic parameters of G6PD and increase utilization of analogues, its enzyme activity is more than those of other mutations that mutated in the β+α region of G6PD. The heterozygous enzyme levels ranged from 6.5–20.1 U/gHb; and there was no significant difference among different heterozygous variants (P > 0.05). The enzyme activity levels of the compound heterozygous mutation were mainly in the range of 1.7–3.8 U/gHb, which was much lower than that of the heterozygous mutation (P < 0.001). In summary, our findings revealed that the enzyme activity of G6PD in blood have a significant relationship with genotype of G6PD