Structural insights into the Cdt1-mediated MCM2–7 chromatin loading

Initiation of DNA replication in eukaryotes is exquisitely regulated to ensure that DNA replication occurs exactly once in each cell division. A conserved and essential step for the initiation of eukaryotic DNA replication is the loading of the mini-chromosome maintenance 2–7 (MCM2–7) helicase onto chromatin at replication origins by Cdt1. To elucidate the molecular mechanism of this event, we determined the structure of the human Cdt1-Mcm6 binding domains, the Cdt1(410–440)/MCM6(708–821) complex by NMR. Our structural and site-directed mutagenesis studies showed that charge complementarity is a key determinant for the specific interaction between Cdt1 and Mcm2–7. When this interaction was interrupted by alanine substitutions of the conserved interacting residues, the corresponding yeast Cdt1 and Mcm6 mutants were defective in DNA replication and the chromatin loading of Mcm2, resulting in cell death. Having shown that Cdt1 and Mcm6 interact through their C-termini, and knowing that Cdt1 is tethered to Orc6 during the loading of MCM2–7, our results suggest that the MCM2–7 hexamer is loaded with its C terminal end facing the ORC complex. These results provide a structural basis for the Cdt1-mediated MCM2–7 chromatin loading

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region

The Kamenev type interval oscillation criteria of mixed nonlinear impulsive differential equations under variable delay effects

Abstract In this paper, a class of mixed nonlinear impulsive differential equations is studied. When the delay σ(t) $\sigma(t)$ is variable, each given interval is divided into two parts on which the quotients of x(t−σ(t)) $x(t-\sigma(t))$ and x(t) $x(t)$ are estimated. Then, by introducing binary auxiliary functions and using the Riccati transformation, several Kamenev type interval oscillation criteria are established. The well-known results obtained by Liu and Xu (Appl. Math. Comput. 215:283–291, 2009) for σ(t)=0 $\sigma(t)=0$ and by Guo et al. (Abstr. Appl. Anal. 2012:351709, 2012) for σ(t)=σ0 $\sigma(t)=\sigma_{0}$ ( σ0≥0 $\sigma_{0}\geq0$) are developed. Moreover, an example illustrating the effectiveness and non-emptiness of our results is also given

A First-Principles Study of F and Cl Doping in LiNi_0.8₃Co_0.₀₈Mn_0.₀₈O₂ Cathode Materials

Ion doping can modify the cell structure, which is one of the effective methods to improve electrochemical performance. However, there is a lack of research on F- and Cl-doped LiNi0.8Co0.1Mn0.1O2. In this paper, the effects of F and Cl doping on the electrochemical properties and cell structure of LiNi0.83Co0.08Mn0.08O2 during the process of lithium removal were studied by a first-principles calculation based on density functional theory. The results show that F doping reduces the change in cell parameters and improves the stability of cell structure. On the contrary, Cl doping reduces the stability of the cell structure. F doping increased the delithiation potential from 3.64 V to 3.76 V, and the delithiation potential was relatively stable in the process of delithiation. Cl doping decreased the delithiation potential from 3.64 V to 3.26 V, and the voltage stability became worse. F doping can effectively reduce the occurrence of Li–Ni mixed arrangement phenomena. Meanwhile, Cl doping can inhibit the formation of oxygen vacancies, and the further degradation of the materials. F doping broadens the Li+ diffusion channel away from the doping site and improves the diffusion rate of Li+ in this layer. In the vicinity of F-doped sites, the electrostatic field in the process of Li+ diffusion is enhanced and the diffusion of Li+ is reduced. Cl doping increases the diffusion barrier of Li+ and slows down the diffusion rate of Li+

Prediction of Thermal Barrier Coatings Microstructural Features Based on Support Vector Machine Optimized by Cuckoo Search Algorithm

Microstructural features have a vital effect on the comprehensive performance of thermal barrier coatings (TBCs) and highly depend on the thermal spray processing parameters. Herein, a novel hybrid machine-learning method was proposed to predict the microstructural features of TBCs using thermal spray processing parameters based on a support vector machine method optimized by the cuckoo search algorithm (CS-SVM). In this work, atmospheric-plasma-sprayed (APS) TBCs samples with multifarious microstructural features were acquired by modifying the spray powder size, spray distance, and spray power during thermal spray processing. The processing parameters were used as the inputs for the CS-SVM model. Then, the porosity, the pore-to-crack ratio, the maximum Feret’s diameter, the aspect ratio, and the circularity were counted and treated as the targets for the CS-SVM model. After optimization and training procedure of the CS-SVM model, the predicted results were compared to the results of experimental data, as a result, the squared correlation coefficient (R2) of CS-SVM model showed that the prediction accuracy reached by over 95%, and the root mean square error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE) were less than 0.1, which also verified the reliability of the CS-SVM model. Finally, this study proposed a novel and efficient microstructural feature prediction that could be potentially employed to improve the performance of TBCs in service

Fabrication of Superhydrophobic Porous Brass by Chemical Dealloying for Efficient Emulsion Separation

By taking advantage of typical dealloying and subsequent aging methods, a novel homogeneous porous brass with a micro/nano hierarchical structure was prepared without any chemical modification. The treatment of commercial brass with hot concentrated HCl solution caused preferential etching of Zn from Cu62Zn38 alloy foil, leaving a microporous skeleton with an average tortuous channel size of 1.6 μm for liquid transfer. After storage in the atmosphere for 7 days, the wettability of the dealloyed brass changed from superhydrophilic to superhydrophobic with a contact angle > 156° and sliding angle 2O on the surface. By virtue of the opposite wettability to water and oil, the aged brass separated surfactant-stabilized water-in-oil emulsions with separation efficiency of over 99.4% and permeate flux of about 851 L·m−2·h−1 even after recycling for 60 times. After 10 times of tape peeling or sandpaper abrasion, the aged brass maintained its superhydrophobicity, indicating its excellent mechanical stability. Moreover, the aged brass still retained its superhydrophobicity after exposure to high temperatures or corrosive solutions, displaying high resistance to extreme environments. The reason may be that the bicontinuous porous structure throughout the whole foil endows stable mechanical properties to tolerate extreme environments. This method should have a promising future in expanding the applications of alloys

Preliminary study on the initiation mechanism of hydrodynamic-driven bedding rock landslides based on physical model tests

Hydrodynamic-driven bedding rock landslides are the focus of research in the field of landslide geological hazards due to their large number, frequent disasters, and excessive harm. However, the understanding of the initiation mechanism of landslides is still insufficient, and the accurate prediction of landslides still faces great challenges. Because of this, this paper takes moderate-dip angle bedding rock landslides with weak interlayers as the research object and conducts a series of landslide model tests under the action of hydrodynamics by constructing an ideal single-layer landslide physical model. On this basis, the macroscopic deformation evolution process of the landslide and the erosion degradation characteristics of the slide zone soil is analyzed in depth. The results show that the failure of bedding rock landslides is associated with the slip surface roughness and dip angle and can go through four stages: the initial deformation stage, uniform deformation stage, accelerated deformation stage, and failure stage.The seepage erosion in the sliding zone causes the loss of aggregates, which reduces the shear strength and causes the slope to slide. Simultaneously, the compression-shear action and the deformation of the overlying slope also adversely affect erosion strength.Based on the variation law of soil cohesion in the sliding zone with hydraulic gradient and erosion time, a seepage-driven evolution model of soil cohesion in the sliding zone is proposed, which can describe the degradation process of soil cohesion in the sliding zone well. The existence of sliding surface roughness not only significantly affects the deterioration law of the sliding zone, but also changes the failure modes of different regions of the sliding zone. By considering the influence of the roughness on the failure modes of different areas of the sliding zone, the multi-effect correlation analysis of dynamic water is carried out, and the mechanical model of the landslide is established, which realizes the effective evaluation of the dynamic stability of the landslide. The research achievements in this study can provide a theoretical reference for predicting and preventing actual hydrodynamic-driven bedding rock landslides