Investigation of the functions of 53BP1 in DNA demethylation

DNA damage can be caused by various forms of genotoxic stress, including endogenous (reactive oxygen species, abnormal replication intermediates) and exogenous (UV, IR, and reactive chemicals) sources. DNA double-strand break (DSB) is believed to be one of the most serious lesions to cells because it can result in loss or rearrangement of genetic information, leading to cell death or carcinogenesis. The DNA damage response (DDR) involves multiple signal transduction pathways in that several different components act in concert to activate the cellular checkpoint. These components consist of sensors that sense DNA damage, signal transducers that generate and amplify the DNA damage signal, and effectors that induce cell cycle delay, programmed cell death, and DNA repair. Even though several candidate proteins have been implicated in DNA damage response, an official checkpoint-specific damage sensor is still unknown. 53BP1 seems to be one of the key-sensors of DNA DSBs, upstream of ATM. The function of 53BP1 is important for coupling ATM to its downstream targets, including p53 and Gadd45a. The activation of Gadd45a as a stress protein promotes epigenetic gene activation by repair-mediated DNA demethylation, thus linking both processes. DNA methylation is mediated by MBD2 as well as a class of DNMTs, which encompassing DNMT1, DNMT3a and DNMT3b. Recent studies have demonstrated that the DNA methylation mediated by DNMTs is associated with p53 signalling in maintaining genome stability. Since p53 is one of the downstream targets of 53BP1, it will be of interest to investigate the functions of 53BP1 in DNA demethylation and determine the possible link between 53BP1 and these related genes. The data presented here indicate that 53BP1 can induce DNA demethylation of single copy gene as well as repetitive elements in A549 cells. Meanwhile, the transient expression of 53BP1 can enhance DNA demethylation in combination with IR. Furthermore, the tumor suppressor gene RASSF1A was re-expressed following predominantly demethylation of CpG islands in the promoter analyzed by MSP and RT-PCR. Moreover, overexpression of 53BP1 caused a marked decrease in DNMT1 and DNMT3a mRNA expression as well as a significant increase in Gadd45a and MBD2 mRNA expression. To our best knowledge, the present study shows for the first time the involvement of 53BP1 in DNA demethylation process. Understanding the 53BP1-mediated network will certainly have an impact on numerous fields of medicine. However, how 53BP1 regulates different member of DNMTs need to be characterized. Further experiments of the precise mechanisms of 53BP1 in DNA demethylation may clarify this association and develop therapeutic alternatives designed to promote hypomethylation and re-activation of tumor suppressor genes

Naval battle simulation system optimization

This dissertation is a Computer Science Master degree major report by student Linfang Wang. The main objective of this project is to utilize the object oriented methodologies to design and implement a simple Naval Battle Simulation System. The project is based on a Software Engineering course project taught by Dr. Joey Paquet at Concordia University. The project consists in respecification of the system requirements, optimization of the system design, UML notation improvement, reorganization of the structure of documents and rewriting of the SRS, SDD and STD documents. This document can be taken as an integrated standard for requirement, design, and testing documents for Naval Battle Simulation System, or any other similar Software Engineering project. This will enable Dr. Paquet to re-use this document as a valuable information source for other Software Engineering projects in the future. The project applies the object-oriented design and implementation for all the susbsystems. The developing tool is MFC and OpenGL. For the requirements specification, a requirements identifier scheme is applied to improve the traceability for the whole system. For system implementation, function overloading, virtual function and pure virtual function, multithreading, inheritance and polymorphism are used to improve the system generality, reuseability and flexibility as well

Structure Analysis for Tunnel Longitudinal Deformation Based on Segment Dislocation Mode

AbstractAccording to tunnel structure around joints, tunnel longitudinal deformation is analyzed and a three-dimensional finite element model is built based on segment dislocation mode. Tunnel structure stress analysis is conducted from two aspects of segment in the shear and bolt in the tension. The analysis results show: (1) Segment shear model. When segment dislocation reaches 0.03mm, the principal stressσ1 exceeds 3.0Mpa which is over concrete's tensile strength. Therefore, when convex tenon and concave tenon generate shear, there must be horizontal slipping and bolt is tensioned. (2) Bolt tension model. When joint opening value reaches 2mm, bolt stress exceeds 640Mpa, which is bolt's yield strength. When joint opening value reaches 6mm, which is the waterproof control standard for tunnel, bolt stress reaches 688.7Mpa, which is less than bolt's failure strength. The subway tunnel's structure safety should be controlled from the perspective of waterproof

Probabilistic Shaping for Asymmetric Channels and Low-Density Parity-Check Codes

An algorithm is proposed to encode low-density parity-check (LDPC) codes into codewords with a non-uniform distribution. This enables power-efficient signalling for asymmetric channels. We show gains of 0.9 dB for additive white Gaussian noise (AWGN) channels with on-off keying modulation using 5G LDPC codes.Comment: submitted to ISTC 202

Analysis of the Correlation between Commodity Grade and Quality of Angelica sinensis

The contents of ferulic acid, senkyunolide A, butylidenephthalide, ligustilide, and n-butylphthalide were determined by UPLC analytical method; the correlation among the grade, average weight, and content was explored by correlation analysis and analysis of variance (ANOVA); the different commercial grades with average weight and content were revealed by principal component analysis (PCA) and then rationality analysis grade classification of A. sinensis. The results showed that various commercial grades can be distinguished by PCA analysis. And there was significant negative correlation between the commodity grades and average weight, commodity, and the content of bioactive compounds, while the content of senkyunolide A had significant negative correlation with commodity grades (P<0.01). Average weight had no correlation with chemicals compounds. Additionally, there was significant positive correlation among the bioactive compounds (content of ferulic acid and phthalides) of different grades of A. sinensis. The content of senkyunolide A, butylidenephthalide, and ligustilide had significant positive correlation with the content of ferulic acid. The content of ligustilide and butylidenephthalide had significant positive correlation with the content of senkyunolide A. The content of ligustilide had significant positive correlation with the content of butylidenephthalide. The basis of grades classification is related with the difference levels of the bioactive compounds