Identification of Sequence Variants in Genetic Disease-Causing Genes Using Targeted Next-Generation Sequencing

Identification of gene variants plays an important role in research on and diagnosis of genetic diseases. A combination of enrichment of targeted genes and next-generation sequencing (targeted DNA-HiSeq) results in both high efficiency and low cost for targeted sequencing of genes of interest.To identify mutations associated with genetic diseases, we designed an array-based gene chip to capture all of the exons of 193 genes involved in 103 genetic diseases. To evaluate this technology, we selected 7 samples from seven patients with six different genetic diseases resulting from six disease-causing genes and 100 samples from normal human adults as controls. The data obtained showed that on average, 99.14% of 3,382 exons with more than 30-fold coverage were successfully detected using Targeted DNA-HiSeq technology, and we found six known variants in four disease-causing genes and two novel mutations in two other disease-causing genes (the STS gene for XLI and the FBN1 gene for MFS) as well as one exon deletion mutation in the DMD gene. These results were confirmed in their entirety using either the Sanger sequencing method or real-time PCR.Targeted DNA-HiSeq combines next-generation sequencing with the capture of sequences from a relevant subset of high-interest genes. This method was tested by capturing sequences from a DNA library through hybridization to oligonucleotide probes specific for genetic disorder-related genes and was found to show high selectivity, improve the detection of mutations, enabling the discovery of novel variants, and provide additional indel data. Thus, targeted DNA-HiSeq can be used to analyze the gene variant profiles of monogenic diseases with high sensitivity, fidelity, throughput and speed

Structural behavior of concrete-filled steel tubular (CFST) with spherical cap gap subjected to corrosion and long-term tensile loading

Concrete-filled steel tubes (CFSTs) are commonly used as structural specimens in construction. Gaps between the steel tube and enclosed concrete core can form during manufacture or repair procedures. This study developed a computational model to investigate the structural implications of spherical cap gaps in CFSTs subjected to sustained axial tension and chloride-induced corrosion. Finite element analysis (FEA) incorporated appropriate material constitutive laws and elements. Model predictions closely matched experiments for load-displacement response and ultimate capacity. Parametric comparisons between gap and no-gap geometries quantified performance impacts, including reduced stiffness, deteriorated load transfer, internal force redistribution, and diminished flexibility stemming from localized steel tube buckling adjacent to the unrestrained gap. Outcomes highlight the importance of quality control during CFST production and repair to minimize defects like uncoupled zones between the concrete infill and hollow tube. The validated simulation approach provides an efficient tool for exploring gap influences and informing structural design provisions

Manual classification strategies in the ECOD database

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Carbon-Coated Li3V2(Po4)3 Derived From Metal-Organic Framework As Cathode For Lithium-Ion Batteries With High Stability

Recently, Metal-Organic Frameworks (MOFs) derived carbon-based materials have attract wide interest in electrochemical devices due to their large surface area and favorable conductivity. In this work, instead of using MOFs for direct carbon sources, we employed vanadium metal-organic framework (MIL-101(V)) precursor as both carbon sources and vanadium sources for synthesizing carbon-coated Li3V2(PO4)3 nanocomposites (LVP@M-101). The electrochemical property of LVP@M-101 has been investigated as cathode electrode at a voltage of 3.0–4.8 vs Li+/Li, to compare with Li3V2(PO4)3 prepared using V2O5. It is shown that the composite material displays a remarkably improved electrochemical stability with a high reversible capacity of 113.1 and 105.8 mA h g−1 at the rate of 0.5C and 1C after 1000 cycles, together with a superior rate performance at various current densities from 0.1C to 10C. Moreover, we have applied ex-situ PXRD and EPR spectroscopy to investigate the lithiation/delithiation process of LVP@M-101 electrode. Through detailed characterizations and electrochemical tests, we believe that the novel nanocomposites LVP@M-101 retain the two-phase transition nature of Li3V2(PO4)3 and the enhanced cathodic performance in lithium-ion battery is largely due to its unique structural stability

Compressive and flexural behavior of prefabricated concrete-filled steel tubular columns with bolted splices

Concrete-filled steel tubular (CFST) structures are technically advantageous for prefabrication because of the easy connection between steel tubes and other prefabricated components. For prefabricated CFST columns, reliable column-column connections are the key to structural integrity and a safe load transfer. Current engineering practice has limited examples regarding the design and detailing of prefabricated CFST column-column connections, and very few tests have been conducted on such connections in previous studies. This study attempts to propose three types of bolted prefabricated column-column connections (splices). A total of 19 specimens with the proposed splices were tested under either axial compression or flexural bending. Strength capacity, stiffness, strain distribution and ductility of these spliced members are investigated, and effects of different tube end conditions and loading scenarios on the member behavior are also discussed. Furthermore, the applicability of various design provisions in predicting the axial and flexural capacities of these spliced members is investigated. At last, suggestions on the selection and detailing of the proposed column splices are provided

Improved ENSO and PDO Prediction Skill Resulting from Finer Parameterization Schemes in a CGCM

Coupled general circulation models (CGCMs), as tools of predicting climate variability, are constantly being improved due to their immense value in a host of theoretical and practical, real-world problems. Consequently, four new parameterization schemes are introduced in the First Institute of Oceanography Earth System Model (FIO-ESM), and a new climate prediction System (CPS) is built up based on modified and original FIO-ESM. Here, turbulence from the sea surface to deep ocean were fully described, and seasonal forecasts of El Niño-Southern Oscillation (ENSO) and year-to-year prediction of Pacific Decadal Oscillation (PDO) were made with both the modified and original FIO-ESM-CPS. The results illustrate that the anomaly correlation coefficient (ACC) of the Niño 3.4 index significantly increased, and the root mean square error (RMSE) significantly decreased, respectively, in the modified FIO-ESM-CPS as compared to the original. The RMSE is improved by over 20% at 4- and 5-month lead times. Over longer leads, and in the modified FIO-ESM-CPS, forecast ENSO amplitudes are far closer to observations than the original CGCM, which significantly overestimates amplitudes. PDO prediction skill is also improved in the modified FIO-ESM-CPS with ACC improving by 36% at the 4-year lead time and RMSE decreasing by 21% at the 3-year lead time

Enzyme-Assisted Amplification and Copper Nanocluster Fluorescence Signal-Based Method for miRNA-122 Detection

At present, a large number of studies have demonstrated that miRNAs can be used as biological indicators for the diagnosis and treatment of diseases such as tumours and cancer, so it is important to develop a new miRNA detection platform. In this work, miRNA-122 is used as the basis for targeting detection agents. We have designed an unlabelled DNA1 that undergoes partial hybridisation and has a 20 T base long strand. The fluorescent signal in this experiment is derived from copper nanoclusters (CuNCs) generated on the circular T-long strand of DNA1. At the same time, DNA1 is able to react with miRNA-122 and achieve hydrolysis of the part bound to miRNA-122 via the action of nucleic acid exonuclease III (Exo III), leaving a part of the DNA, called DNA3, while releasing miRNA-122 to participate in the next reaction, thus achieving circular amplification. DNA3 is able to react with DNA2, which is bound to streptavidin magnetic beads (SIBs) and separated from the reaction solution via the application of a magnetic field. Overall, this is a fluorescence signal reduction experiment, and the strength of the fluorescence signal from the copper nanoclusters can determine whether the target miRNA-122 is present or not. The degree of fluorescence reduction indicates how much DNA1, and thus the amount of target miRNA-122, has been hydrolysed. By evaluating the variations in the fluorescence signal under optimised conditions, we discovered that this method has good sensitivity, with a detection limit as low as 0.46 nM, better than many other previous works on fluorescence signal-based biosensors for miRNA detection. This technique offers high discrimination and selectivity and can serve as a persuasive reference for early diagnosis