The production of municipal solid waste incineration bottom ash (MSWIBA) is substantial and has the potential to replace cement, despite challenges such as complex composition, uneven particle size ...distribution, and low reactivity. This paper employs sodium silicate activation of MSWIBA composite Ground-granulated Blast Furnace slag (GGBS) to improve the reactivity in preparing composite cementitious materials. It explores the hydration performance of the composite cementitious materials using isothermal calorimetric analysis, Fourier-transform infrared (FTIR) spectroscopy, XRD physical diffraction analysis, and SEM tests. SEM tests were used to explore the hydration properties of the composite gelling. The results show that with an increase in MSWIBA doping, the porosity between the materials increased, the degree of hydration decreased, and the compressive strength decreased. When the sodium silicate concentration increased from 25% to 35%, excessive alkaline material occurred, impacting the alkaline effect. This inhibited particle hydration, leading to a decrease in the degree of hydration and, consequently, the compressive strength. The exothermic process of hydration can be divided into five main stages; quartz and calcite did not fully participate in the hydration reaction, while aluminum did. The vibrational peaks of Si-O-Ti (T = Si and Al) were present in the material. The vibrational peaks of XRD, FTIR, and SEM all indicate the presence of alumosilicate network structures in the hydration products, mainly N-A-S-H and C-A-S-H gels.
Whole-genome sequencing data allow detection of copy number variation (CNV) at high resolution. However, estimation based on read coverage along the genome suffers from bias due to GC content and ...other factors. Here, we develop an algorithm called BIC-seq2 that combines normalization of the data at the nucleotide level and Bayesian information criterion-based segmentation to detect both somatic and germline CNVs accurately. Analysis of simulation data showed that this method outperforms existing methods. We apply this algorithm to low coverage whole-genome sequencing data from peripheral blood of nearly a thousand patients across eleven cancer types in The Cancer Genome Atlas (TCGA) to identify cancer-predisposing CNV regions. We confirm known regions and discover new ones including those covering KMT2C, GOLPH3, ERBB2 and PLAG1 Analysis of colorectal cancer genomes in particular reveals novel recurrent CNVs including deletions at two chromatin-remodeling genes RERE and NPM2 This method will be useful to many researchers interested in profiling CNVs from whole-genome sequencing data.
Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals ...with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.
Since tumor often has a high level of intra-tumor heterogeneity, multiple tumor samples from the same patient at different locations or different time points are often sequenced to study tumor ...intra-heterogeneity or tumor evolution. In virus-related tumors such as human papillomavirus- and Hepatitis B Virus-related tumors, virus genome integrations can be critical driving events. It is thus important to investigate the integration sites of the virus genomes. Currently, a few algorithms for detecting virus integration sites based on high-throughput sequencing have been developed, but their insufficient performance in their sensitivity, specificity and computational complexity hinders their applications in multiple related tumor sequencing.
We develop VirTect for detecting virus integration sites simultaneously from multiple related-sample data. This algorithm is mainly based on the joint analysis of short reads spanning breakpoints of integration sites from multiple samples. To achieve high specificity and breakpoint accuracy, a local precise sandwich alignment algorithm is used. Simulation and real data analyses show that, compared with other algorithms, VirTect is significantly more sensitive and has a similar or lower false discovery rate.
VirTect can provide more accurate breakpoint position and is computationally much more efficient in terms both memory requirement and computational time.
Abstract
Single-molecule Real-time Isoform Sequencing (Iso-seq) of transcriptomes by PacBio can generate very long and accurate reads, thus providing an ideal platform for full-length transcriptome ...analysis. We present an integrated computational toolkit named TAGET for Iso-seq full-length transcript data analyses, including transcript alignment, annotation, gene fusion detection, and quantification analyses such as differential expression gene analysis and differential isoform usage analysis. We evaluate the performance of TAGET using a public Iso-seq dataset and newly sequenced Iso-seq datasets from tumor patients. TAGET gives significantly more precise novel splice site prediction and enables more accurate novel isoform and gene fusion discoveries, as validated by experimental validations and comparisons with RNA-seq data. We identify and experimentally validate a differential isoform usage gene
ECM1
, and further show that its isoform ECM1b may be a tumor-suppressor in laryngocarcinoma. Our results demonstrate that TAGET provides a valuable computational toolkit and can be applied to many full-length transcriptome studies.
While the somatic mutation profiles of renal cell carcinoma (RCC) have been revealed by several studies worldwide, the overwhelming majority of those were not derived from Chinese patients. The ...landscape of somatic alterations in RCC from Chinese patients still needs to be elucidated to determine whether discrepancies exist between Chinese patients and sufferers from other countries and regions.
We collected specimens from 26 Chinese patients with primary RCC, including 15 clear cell renal cell carcinoma (ccRCC) samples, 5 papillary renal cell carcinoma (PRCC) samples and 6 chromophobe renal cell carcinoma (ChRCC) samples. Genomic DNAs were isolated from paired tumor-normal tissues and subjected to whole exome sequencing (WES). Immunohistochemistry analysis was performed to detect the programmed death ligand 1 (PD-L1) expression in tumor tissues.
A total of 1920 nonsynonymous somatic variants in exons and 86 mutations at splice junctions were revealed. The tumor mutation burden of ccRCC was significantly higher than that of ChRCC (P < 0.05). For both ccRCC and PRCC, the most frequent substitution in somatic missense mutations was T:A > A:T, which was different from that recorded in the COSMIC database. Among eight significantly mutated genes in ccRCC in the TCGA database, six genes were verified in our study including
(67%)
(13%)
(13%),
(7%)
(7%) and
(7%). All the mutations detected in those genes had not been reported in ccRCC before, except for alterations in
and
. Regarding the frequently mutated genes in PRCC in our study,
(p.E293A, p.T279A),
(p.N401Y, p.F342L) and
(p.H554Q, p.M1T) were newly detected gene mutations predicted to be deleterious. As the most recurrently mutated gene in ChRCC in the TCGA dataset,
(p.R81Q) was somatically altered only in one ChRCC case in this study. The HIF-1 signaling pathway was the most affected pathway in ccRCC, while the PI3K-Akt signaling pathway was altered in all of the three RCC types. Membranous PD-L1 expression was positive in tumor cells from 6/26 (23%) RCC specimens. The PD-L1-positive rate was higher in RCC samples with the somatically mutated genes
,
,
and
than in specimens without those (P < 0.05).
Using WES, we identified somatic mutations in 26 Chinese patients with RCC, which enriched the racial diversity of the somatic mutation profiles of RCC subjects, and revealed a few discrepancies in molecular characterizations between our study and published datasets. We also identified numerous newly detected somatic mutations, which further supplements the somatic mutation landscape of RCC. Moreover, 4 somatically mutated genes, including
,
,
and
, might be promising predictive factors of PD-L1-positive expression in RCC tumor cells.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has elicited a worldwide pandemic since late 2019. There has been ~675 million confirmed coronavirus disease 2019 (COVID-19) ...cases, leading to more than 6.8 million deaths as of March 1, 2023. Five SARS-CoV-2 variants of concern (VOCs) were tracked as they emerged and were subsequently characterized. However, it is still difficult to predict the next dominant variant due to the rapid evolution of its spike (S) glycoprotein, which affects the binding activity between cellular receptor angiotensin-converting enzyme 2 (ACE2) and blocks the presenting epitope from humoral monoclonal antibody (mAb) recognition. Here, we established a robust mammalian cell-surface-display platform to study the interactions of S-ACE2 and S-mAb on a large scale. A lentivirus library of S variants was generated via in silico chip synthesis followed by site-directed saturation mutagenesis, after which the enriched candidates were acquired through single-cell fluorescence sorting and analyzed by third-generation DNA sequencing technologies. The mutational landscape provides a blueprint for understanding the key residues of the S protein binding affinity to ACE2 and mAb evasion. It was found that S205F, Y453F, Q493A, Q493M, Q498H, Q498Y, N501F, and N501T showed a 3-12-fold increase in infectivity, of which Y453F, Q493A, and Q498Y exhibited at least a 10-fold resistance to mAbs REGN10933, LY-CoV555, and REGN10987, respectively. These methods for mammalian cells may assist in the precise control of SARS-CoV-2 in the future.
Availability of data and materials All the raw data generated and analyzed during this study are available from the corresponding author on reasonable request.
•Failure sequence and load sharing for standing seam metal roofs examined.•Load redistribution occurs at high wind loads with significant deformations.•Significant load is transferred to eaves and ...gable ridge edges under high wind.•Global buckling was observed prior to connection failures of clips.
In this paper, the failure sequence and load sharing for standing seam metal roofs (SSMR), up to the limit state, were investigated using full-scale experiments. The tested SSMR system had full-scale dimensions and boundary conditions, which provided the opportunity to investigate the performance of SSMR systems under realistic conditions. The results show that there is a linear relationship between the wind pressure and clip reaction under low wind pressure (less than 500 Pa). Load redistribution happens along with the deformation of roof panels with greater load transfer to the ridge and eaves of the roof at higher pressure. Near the corner of the roof, between 27 and 46 % of the applied load is transferred to edges of the eaves and gable end. Away from the roof corner, between 17 and 23 % of the applied load is transferred to eave edge. Global buckling of panels occurs before connection failures and the initial location of global buckling is near the seam and in the middle of two adjacent clips. Two failure modes for the connections, clip slippage and fastener failure, were observed during the tests. However, the failure modes vary with the clip arrangement and boundary conditions.
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