Construction and application of an intelligent prediction model for the coal pillar width of a fully mechanized caving face based on the fusion of multiple physical parameters

The scientific and reasonable width of coal pillars is of great significance to ensure safe and sustainable mining in the western mining area of China. To achieve a precise analysis of the reasonable width of coal pillars in fully mechanized caving face sections of gently inclined coal seams in western China, this paper analyzes and studies various factors that affect the retention of coal pillars in the section, and calculates the correlation coefficients between these influencing factors. We selected parameters with good universality and established a data set of gently inclined coal seams based on 106 collected engineering cases. We used the LSTM algorithm loaded with a simulated annealing algorithm for training, and constructed a coal pillar width prediction model. Compared with other prediction algorithms such as the original LSTM algorithm, the residual sum of squares and root mean square error were reduced by 27.2% and 24.2%, respectively, and the correlation coefficient was increased by 12.6%. An engineering case analysis was conducted using the W1123 working face of the Kuangou Coal Mine. The engineering verification showed that the SA-CNN-LSTM coal pillar width prediction model established in this paper has good stability and accuracy for multi-parameter nonlinear coupling prediction results. We have established an effective solution for achieving the accurate reservation of coal pillar widths in the fully mechanized caving faces of gently inclined coal seams

High-throughput analysis of the mutagenic and cytotoxic properties of DNA lesions by next-generation sequencing

Human cells are constantly exposed to environmental and endogenous agents which can induce damage to DNA. Understanding the implications of these DNA modifications in the etiology of human diseases requires the examination about how these DNA lesions block DNA replication and induce mutations in cells. All previously reported shuttle vector-based methods for investigating the cytotoxic and mutagenic properties of DNA lesions in cells have low-throughput, where plasmids containing individual lesions are transfected into cells one lesion at a time and the products from the replication of individual lesions are analyzed separately. The advent of next-generation sequencing (NGS) technology has facilitated investigators to design scientific approaches that were previously not technically feasible or affordable. In this study, we developed a new method employing NGS, together with shuttle vector technology, to have a multiplexed and quantitative assessment of how DNA lesions perturb the efficiency and accuracy of DNA replication in cells. By using this method, we examined the replication of four carboxymethylated DNA lesions and two oxidatively induced bulky DNA lesions including (5′S) diastereomers of 8,5′-cyclo-2′-deoxyguanosine (cyclo-dG) and 8,5′-cyclo-2′-deoxyadenosine (cyclo-dA) in five different strains of Escherichia coli cells. We further validated the results obtained from NGS using previously established methods. Taken together, the newly developed method provided a high-throughput and readily affordable method for assessing quantitatively how DNA lesions compromise the efficiency and fidelity of DNA replication in cells

Kinetics of deamination and Cu(II)/H2O2/Ascorbate-induced formation of 5-methylcytosine glycol at CpG sites in duplex DNA

Mutation in p53 tumor suppressor gene is a hallmark of human cancers. Six major mutational hotspots in p53 contain methylated CpG (mCpG) sites, and C →T transition is the most common mutation at these sites. It was hypothesized that the formation of 5-methylcytosine glycol induced by reactive oxygen species, its spontaneous deamination to thymine glycol and the miscoding property of the latter may account, in part, for the ubiquitous C →T mutation at CpG site. Here, we assessed the kinetics of deamination for two diastereomers of 5-methylcytosine glycol in duplex DNA. Our results revealed that the half-lives for the deamination of the (5S,6S) and (5R,6R) diastereomers of 5-methylcytosine glycol in duplex DNA at 37°C were 37.4 ± 1.6 and 27.4 ± 1.0 h, respectively. The deamination rates were only slightly lower than those for the two diastereomers in mononucleosides. Next, we assessed the formation of 5-methyl-2′-deoxycytidine glycol in the form of its deaminated product, namely, thymidine glycol (Tg), in methyl-CpG-bearing duplex DNA treated with Cu(II)/H2O2/ascorbate. LC-MS/MS quantification results showed that the yield of Tg is similar as that of 5-(hydroxymethyl)-2′-deoxycytidine. Together, our data support that the formation and deamination of 5-methylcytosine glycol may contribute significantly to the C →T transition mutation at mCpG dinucleotide site

Formation and genotoxicity of a guanine–cytosine intrastrand cross-link lesion in vivo

Reactive oxygen species (ROS) can be induced by both endogenous and exogenous processes, and they can damage biological molecules including nucleic acids. Exposure of isolated DNA to X/γ-rays and Fenton reagents was shown to lead to the formation of intrastrand cross-link lesions where the neighboring nucleobases in the same DNA strand are covalently bonded. By employing HPLC coupled with tandem mass spectrometry (LC-MS/MS) with the isotope dilution method, we assessed quantitatively the formation of a guanine–cytosine (G[8-5]C) intrastrand cross-link lesion in HeLa-S3 cells upon exposure to γ-rays. The yield of the G[8-5]C cross-link was 0.037 lesions per 109 nucleosides per Gy, which was ∼300 times lower than that of 5-formyl-2′-deoxyuridine (0.011 lesions per 106 nucleosides per Gy) under identical exposure conditions. We further constructed a single-stranded M13 genome harboring a site-specifically incorporated G[8-5]C lesion and developed a novel mass spectrometry-based method for interrogating the products emanating from the replication of the genome in Escherichia coli cells. The results demonstrated that G[8-5]C blocked considerably DNA replication as represented by a 20% bypass efficiency, and the lesion was significantly mutagenic in vivo, which included a 8.7% G→T and a 1.2% G→C transversion mutations. DNA replication in E. coli hosts deficient in SOS-induced polymerases revealed that polymerase V was responsible for the error-prone translesion synthesis in vivo

Dynamic behaviours of geomaterials in underground infrastructures

Geomaterials (e.g. cement, concrete and rock) are easily damaged and collapsed in underground infrastructures and during earth resource extraction where extreme loading conditions (like earthquakes, rockbursts, and explosion) and complicated stress states are frequently encountered. A comprehensive investigation of dynamic behaviours (including mechanical, fracturing and deformation properties) of geomaterials can help understand their failure mechanisms and predict the failure process in such scenarios. The obtained knowledge can be further used for warning and protection in advance during mining and infrastructure constructions

and CpG-methylated DNA induced by Fenton-type reagents

intrastrand cross-link lesions in unmethylate

Gold/Benzenedithiolate/Gold Molecular Junction: A Driven Dynamics Simulation on Structural Evolution and Breaking Force under Pulling

Dynamic evolutions of molecular binding structures and breaking forces of gold/thiolate molecular junctions under pulling are still not well understood. We perform driven dynamics simulations to show that there are essentially two distinct breaking force traces corresponding to the Au–Au and Au–S bond ruptures. The latter is attributed to the formation and breaking of an additional “–Au–SR–Au–” unit in the molecular junction. The force histogram shows two force quanta at 1.5 and 2.0 nN, corresponding to the Au–Au and Au–S bond breaking. Our findings provide new molecular insights into the gold–thiolate interactions. The intermediate metal–molecule–metal binding structures could be used for further molecular transport calculations