The problem of topic modeling can be seen as a generalization of the clustering problem, in that it posits that observations are generated due to multiple latent factors (e.g., the words in each document are generated as a mixture of several active topics, as opposed to just one). This increased representational power comes at the cost of a more challenging unsupervised learning problem of estimating the topic probability vectors (the distributions over words for each topic), when only the words are observed and the corresponding topics are hidden.We provide a simple and efficient learning procedure that is guaranteed to recover the parameters for a wide class of mixture models, including the popular latent Dirichlet allocation (LDA) model. For LDA, the procedure correctly recovers both the topic probability vectors and the prior over the topics, using only trigram statistics (i.e., third order moments, which may be estimated with documents containing just three words). The method, termed Excess Correlation Analysis (ECA), is based on a spectral decomposition of low order moments (third and fourth order) via two singular value decompositions (SVDs). Moreover, the algorithm is scalable since the SVD operations are carried out on k × k matrices, where k is the number of latent factors (e.g. the number of topics), rather than in the d-dimensional observed space (typically d ≫ k).

Background Apoptosis of chondrocyte is involved in osteoarthritis (OA) pathogenesis, and mechanical stress plays a key role in this process by activation of Piezo1. However, the negative regulation of signal conduction mediated by mechanical stress is still unclear. Here, we elucidate that the critical role of G protein coupled estrogen receptor (GPER) in the regulation of mechanical stress-mediated signal transduction and chondrocyte apoptosis. Methods The gene expression profile was detected by gene chip upon silencing Piezo1. The expression of GPER in cartilage tissue taken from the clinical patients was detected by RT-PCR and Western blot as well as immunohistochemistry, and the correlation between GPER expression and OA was also investigated. The chondrocytes exposed to mechanical stress were treated with estrogen, G-1, G15, GPER-siRNA and YAP (Yes-associated protein)-siRNA. The cell viability of chondrocytes was measured. The expression of polymerized actin and Piezo1 as well as the subcellular localization of YAP was observed under laser confocal microscope. Western blot confirmed the changes of YAP/ Rho GTPase activating protein 29 (ARHGAP29) /RhoA/LIMK /Cofilin pathway. The knee specimens of osteoarthritis model were stained with safranin and green. OARSI score was used to evaluate the joint lesions. The expressions of GPER and YAP were detected by immunochemistry. Results Expression profiles of Piezo1- silenced chondrocytes showed that GPER expression was significantly upregulated. Moreover, GPER was negatively correlated with cartilage degeneration during OA pathogenesis. In addition, we uncovered that GPER directly targeted YAP and broadly restrained mechanical stress-triggered actin polymerization. Mechanism studies revealed that GPER inhibited mechanical stress-mediated RhoA/LIMK/cofilin pathway, as well as the actin polymerization, by promoting expression of YAP and ARHGAP29, and the YAP nuclear localization, eventually causing the inhibition of Piezo1. YAP was obviously decreased in degenerated cartilage. Silencing YAP caused significantly increased actin polymerization and activation of Piezo1, and an increase of chondrocyte apoptosis. In addition, intra-articular injection of G-1 to OA rat effectively attenuated cartilage degeneration. Conclusion We propose a novel regulatory mechanism underlying mechanical stress-mediated apoptosis of chondrocyte and elucidate the potential application value of GPER as therapy targets for OA.

Recycling phosphogypsum (PG) for cemented paste backfill (CPB) has been widely used at phosphate mines in China. However, the impurities in PG prolong the setting time and reduce the uniaxial compressive strength (UCS), limiting the engineering application of PG. This paper aims to investigate the feasibility of treated PG (TPG) washed repeatedly using deionised water (DW) for CPB. A water-washing pre-experiment was first conducted to find the proportion with the least DW demand and the effects of water-washing on ordinary PG (OPG). Then, based on the PG:DW ratio obtained from the pre-experiment, the properties of the OPG-based CPB (OCPB) and TPG-based CPB (TCPB) were tested using slump tests, UCS tests, and microstructural analysis. The results show that (1) after 11 water-washings at the PG:DW ratio of 1:1.75, the pH of the supernatant (pH = 6.328) meets the requirements of Chinese standard GB 8978-1996. (2) Water-washing improves the particle gradation quality of PG and removes the soluble impurities adsorbed at the surface of PG crystals. (3) The initial slump values of TCPB are 0.19–1.15 cm higher than that of OCPB, furthermore, the diffusivity values of TCPB are better than the performance of OCPB, with 0.61–1.68 cm of superiority. (4) The UCS values of TCPB are up to 0.838 MPa, 1.953 MPa, and 2.531 MPa, after curing for 7, 14, and 28 days. These are 0.283 MPa, 0.823 MPa, and 0.881 MPa higher than that of OCPB, respectively. It can be concluded that water-washing pre-treatment greatly improves the workability and mechanical property of PG-based CPB. These results are of great value for creating a reliable and environmentally superior alternative for the recycling of PG and for safer mining production.

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T cell Ig and mucin domain (Tim) protein family members were identified to be important regulators of the immune response. As their name indicates, Tim proteins were originally considered a T cell-specific markers, and they mainly regulate the responses of T helper cells. However, accumulating evidence indicates that Tims are also expressed on antigen-presenting cells (APCs), such as monocytes, macrophages, dendritic cells (DCs) and B cells, and even plays various roles in natural killer cells (NKs) and mast cells. In recent years, the expression and function of Tims on different cells and the identification of new ligands for the Tim family have suggested that the Tim family plays a crucial role in immune regulation. In addition, the relationship between Tim family gene polymorphisms and susceptibility to several autoimmune diseases has expanded our knowledge of the role of Tim proteins in immune regulation. In this review, we discuss how the Tim family affects immunomodulatory function and the potential role of the Tim family in typical autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D). A deeper understanding of the immunoregulatory mechanism of the Tim family might provide new insights into the clinical diagnosis and treatment of autoimmune diseases.