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The unloading effect by excavation may cause irreversible and severe damage to the surrounding rock masses in underground engineering. In this paper, both conventional triaxial compression (CTC) tests and triaxial unloading confining pressure (TUCP) tests were conducted on fine-grained granite to study its triaxial compression failure processes due to unloading. Based on the crack volumetric strain (CVS) method, the crack axial strain (CAS) method and crack radial area strain (CRAS) method were proposed to identify the failure precursor information (including stress thresholds and axial strain at the initiation point of crack connectivity stage) during the rock failure processes. The results of the CTC tests show that the stable crack development stress σsd, unstable crack development stress σusd, and crack connectivity stress σct identified by the CAS method are 6%, 74%–84%, and 86%–97% of the peak stress, respectively. For the TUCP cases, as the confining pressure increases, the stress thresholds, axial pressure at failure and axial strain at the start of the crack connectivity stage increase, while the time ratio of the crack connectivity stage to the entire unloading stage decreases. This indicates that fine-grained granite is prone to generate more cracks and leads to fail suddenly under high confining pressure. Furthermore, this new method demonstrates that the point at which the derivative of the radial crack area strain transitions from stable to a sudden increase or decrease is defined as the precursor point of rock failure. The results of axial strain at the starting point of the crack connectivity stage are very close to those predicted by the AE method, with β1 no more than 11%.

An ongoing multi-country outbreak of monkeypox was reported in May 2022 with several deaths, affecting 107 countries of all six World Health Organization (WHO) regions. The WHO has declared the current monkeypox outbreak to be a Public Health Emergency of International Concern. It is, thus, necessary to rapidly and accurately detect and distinguish different monkeypox virus (MPXV) clades. We designed primers and probes based on the alignment of 138 complete genomes of poxviruses. In Panel 1, we mixed one pair of primers and three probes to detect and differentiate the MPXV Western Africa (IIa, IIb clade) and Congo Basin (I clade) and other orthopoxviruses. In Panel 2, we mixed one pair of primers and two probes to detect the 2022 MPXV (B.1 lineage and its descendant lineages). In addition, we tested the specificity and sensitivity of the assay using real-time PCR. In Panel 1, the assay reproducibly identified various concentrations of two plasmids of the monkeypox virus, whereas other orthopoxviruses did not cross-react. In Panel 2, the probe annealed well to MPXV B.1 and showed the expected linearity. These two multiple real-time assays are inclusive and highly specific for identifying different clades of MPXV.

Incorporation of noncanonical amino acids into proteins holds great promise for altering structure and function of these proteins. Here the authors generate metabolically modified prokaryotic and eukaryotic cells that can biosynthesize sTyr and incorporate it into proteins in a site-specific manner.

Diffraction gratings play an increasingly important role in various planar optical systems, such as near-eye display systems for virtual reality (VR) and augmented reality (AR). The slanted gratings have more advantages than other elements. A 1 × 2 transmission two-dimensional (2D) slanted grating based on a double-layer cylindrical structure was proposed in this paper. In the initial phase of this study, this kind of grating was proposed and designed. We used rigorous coupled-wave analysis (RCWA) and simulated annealing algorithm (SA) to optimize the grating parameters. The effects of the grating geometric parameters on the diffraction efficiency were investigated using rigorous coupled-wave analysis (RCWA). The simulated annealing algorithm (SA) optimization results show that the diffraction efficiency of the (0, −1) and (−1, 0) order exceed 35% under normal incidence in the range of 429–468 nm wavelength for TE and TM polarization. Meanwhile, the total diffraction efficiency can reach up to 78%. In the last section, we discuss the tolerances for the grating parameters to ensure high quality manufacturing processes. The total effective efficiency is greater than 75% when the MgF2 thickness is from 300 nm to 350 nm and the SiO2 thickness is from 525 nm to 550 nm. Moreover, the grating period has a 53 nm fabrication tolerance, and the slanted angle has a 8.8-degree fabrication tolerance. The relatively large tolerances ensure that it is easy to fabricate the two-dimensional slanted grating and to achieve the targeted objectives. The proposed 2D slanted grating can be applied to 2D exit pupil expansion, which is of great importance in AR/VR applications.

Chongqing is a mountain city in western China with a complex geological environment, which brings many difficulties to the construction of large sections of underground projects. In order to avoid serious problems in the construction of Guobo Station with large sections, intensive coring and laboratory tests were carried out to obtain the rock mass properties in detail. The boreholes reveal that the lithology of the rock mass in the project area consists mainly of mudstone and a small area of sandstone. The uniaxial compressive strength (UCS) and the Brazilian tensile strength (BTS) of mudstone are highly scattered, which are 4.43~42.43 MPa and 0.66~4.30 Mpa, respectively, but they all show a lognormal distribution. The average UCS of sandstone is 65.31 MPa, and the BTS is 3.06 MPa. Meanwhile, the softening coefficients of mudstone and sandstone are 0.33 and 0.73, which indicate that the water content has a great influence on the mechanical properties of the rock. For the in situ stress field, the relationship between the three principal stresses is as follows: the maximum horizontal principal stress > minimum horizontal principal stress > vertical principal stress, and the lateral pressure coefficient is 2.11~5.71. Based on the present experimental results, it is proposed that the potential risks of excavation include: (1) bias pressure (2) high in situ stress; (3) surrounding rock deterioration.

The monkeypox virus (MPXV) has triggered a current outbreak globally. Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control. It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads, as it is one of the DNA viruses with the largest genome and the most AT-biased, and has a significant number of tandem repeats. Here we evaluated the performance of metagenomic and amplicon sequencing techniques, and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland. We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens. Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes. Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences. Besides, several intra-host single nucleotide variations were identified in the first imported mpox case. This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens. The findings of this study will significantly enhance the surveillance of MPXV. [ABSTRACT FROM AUTHOR]

Immunotherapy is a promising approach for treating metastatic breast cancer (MBC), offering new possibilities for therapy. While checkpoint inhibitors have shown great progress in the treatment of metastatic breast cancer, their effectiveness in patients with bone metastases has been disappointing. This lack of efficacy seems to be specific to the bone environment, which exhibits immunosuppressive features. In this study, we elucidate the multiple roles of the sialic acid-binding Ig-like lectin (Siglec)-15/sialic acid glyco-immune checkpoint axis in the bone metastatic niche and explore potential therapeutic strategies targeting this glyco-immune checkpoint. Our research reveals that elevated levels of Siglec-15 in the bone metastatic niche can promote tumor-induced osteoclastogenesis as well as suppress antigen-specific T cell responses. Next, we demonstrate that antibody blockade of the Siglec-15/sialic acid glyco-immune checkpoint axis can act as a potential treatment for breast cancer bone metastasis. By targeting this pathway, we not only aim to treat bone metastasis but also inhibit the spread of metastatic cancer cells from bone lesions to other organs. [ABSTRACT FROM AUTHOR]

Image segmentation is a significant step in image analysis and computer vision. Many entropy-based approaches have been presented on this topic. Among them, Tsallis entropy isone of the best-performing methods. In this paper, the surface defect images of galvanised steel sheets were studied. Atwo-dimensional asymmetric Tsallis cross-entropy image segmentation algorithm based on chaotic bee colony algorithm optimisation was used to investigate the segmentation of surface defects under complex texture backgrounds. On the basis of Tsallis entropy threshold segmentation, a more concise expression form was used to define the asymmetric Tsallis cross-entropy in order to reduce the calculation complexity of the algorithm. The chaotic algorithm was combined with the artificial bee colony (ABC) algorithm to construct the chaotic bee colony algorithm, so that the optimal threshold of Tsallis entropy could be quickly identified. The experimental results showed that compared with the maximum Shannon entropy algorithm, the calculation time of this algorithm decreased by about 58% and the threshold value increased by about (26%, 54%). Compared with the two-dimensional Tsallis cross-entropy algorithm, the calculation time of this algorithm decreased by about 35% and about 20% was improved in the g-axis direction only. Compared with the two-dimensional asymmetric Tsallis cross-entropy algorithm, the calculation time of this algorithm decreased by about 30% and the threshold values of the two algorithms were almost the same. The algorithm proposed in this paper can rapidly and effectively segment defect targets, making it a more suitable method for detecting surface defects in factories with a rapid production pace. [ABSTRACT FROM AUTHOR]

As a key effector of the Hippo pathway, yes‐associated protein (YAP) is a major regulator of cell proliferation and apoptosis. In this study, 23 hYAP isoforms were identified in HEK293 cells, with 14 isoforms being reported for the first time. These isoforms were classified into hYAP‐a and hYAP‐b isoforms based on the variation in exon 1. The two groups of isoforms showed distinctly different subcellular localizations. hYAP‐a isoforms could activate TEAD‐ or P73‐mediated transcription, affect the proliferation rate, and enhance the cellular chemosensitivity of HEK293 cells. Moreover, different activation abilities and pro‐cytotoxic effects were observed among hYAP‐a isoforms. However, hYAP‐b isoforms were not found to exert any significant biological effects. Our findings add to the knowledge of YAP gene structure and protein‐coding capacity and will help in the elucidation of the function and related molecular mechanisms of the Hippo‐YAP signaling pathway.

Abstract A comprehensive and precise definition of the pluripotency gene regulatory network (PGRN) is crucial for clarifying the regulatory mechanisms in embryonic stem cells (ESCs). Here, after a CRISPR/Cas9-based functional genomics screen and integrative analysis with other functional genomes, transcriptomes, proteomes and epigenome data, an expanded pluripotency-associated gene set is obtained, and a new PGRN with nine sub-classes is constructed. By integrating the DNA binding, epigenetic modification, chromatin conformation, and RNA expression profiles, the PGRN is resolved to six functionally independent transcriptional modules (CORE, MYC, PAF, PRC, PCGF and TBX). Spatiotemporal transcriptomics reveal activated CORE/MYC/PAF module activity and repressed PRC/PCGF/TBX module activity in both mouse ESCs (mESCs) and pluripotent cells of early embryos. Moreover, this module activity pattern is found to be shared by human ESCs (hESCs) and cancers. Thus, our results provide novel insights into elucidating the molecular basis of ESC pluripotency.