A Combination Method of SVD And Neuro－Controller for Identifying Uncertain Systems

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Structural basis for site-specific ribose methylation by box C/D RNA protein complexes

Box C/D RNA protein complexes (RNPs) direct site-specific 2'-O-methylation of RNA and ribosome assembly. The guide RNA in C/D RNP forms base pairs with complementary substrates and selects the modification site using a molecular ruler. Despite many studies of C/D RNP structure, the fundamental questions of how C/D RNAs assemble into RNPs and how they guide modification remain unresolved. Here we report the crystal structure of an entire catalytically active archaeal C/D RNP consisting of a bipartite C/D RNA associated with two substrates and two copies each of Nop5, L7Ae and fibrillarin at 3.15-? resolution. The substrate pairs with the second through the eleventh nucleotide of the 12-nucleotide guide, and the resultant duplex is bracketed in a channel with flexible ends. The methyltransferase fibrillarin binds to an undistorted A-form structure of the guide-substrate duplex and specifically loads the target ribose into the active site. Because interaction with the RNA duplex alone does not determine the site specificity, fibrillarin is further positioned by non-specific and specific protein interactions. Compared with the structure of the inactive C/D RNP, extensive domain movements are induced by substrate loading. Our results reveal the organization of a monomeric C/D RNP and the mechanism underlying its site-specific methylation activity.     

Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity

The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response. Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity. However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER stress in obesity. We found suppression of protein but stimulation of lipid synthesis in the obese ER without significant alterations in chaperone content. Alterations in ER fatty acid and lipid composition result in the inhibition of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and ER stress. Correcting the obesity-induced alteration of ER phospholipid composition or hepatic Serca overexpression in vivo both reduced chronic ER stress and improved glucose homeostasis. Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity.     

Mapping copy number variation by population-scale genome sequencing

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.     

In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche

Stem cells reside in a specialized regulatory microenvironment or niche, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity. The niche may also protect stem cells from environmental insults including cytotoxic chemotherapy and perhaps pathogenic immunity. The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression. We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche in the bone marrow, a site where immune reactivity exists. We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30?days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (T(reg)) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with T(reg) cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. T(reg) cells seem to participate in creating a localized zone where HSPCs reside and where T(reg) cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.     

SrF2颗粒涂覆增强Si/C负极电化学性能

The silicon-based material exhibits a high theoretical specific capacity and is one of the best anode for the next generation of advanced lithium-ion batteries (LIBs). However, it is difficult for the silicon-based anode to form a stable solid-state interphase (SEI) during Li alloy/de-alloy process due to the large volume change (up to 300%) between silicon and Li_4.4Si, which seriously limits the cycle life of the LIBs. Herein, we use strontium fluoride (SrF₂) particle to coat the silicon?carbon (Si/C) electrode (SrF₂@Si/C) to help forming a stable and high mechanical strength SEI by spontaneously embedding the SrF₂ particle into SEI. Meanwhile the formed SEI can inhibit the volume expansion of the silicon?carbon anode during the cycle. The electrochemical test results show that the cycle performance and the ionic conductivity of the SrF₂@Si/C anode has been significantly improved. The X-ray photoelectron spectroscopy (XPS) analysis reveals that there are fewer electrolyte decomposition products formed on the surface of the SrF₂@Si/C anode. This study provides a facile approach to overcome the problems of Si/C electrode during the electrochemical cycling, which will be beneficial to the industrial application of silicon-based anode materials.     

关于钢水质量窄窗口稳定控制的思考

In order to promote the intelligent transformation and upgrading of the steel industry, intelligent technology features based on the current situation and challenges of the steel industry are discussed in this paper. Based on both domestic and global research, functional analysis, reasonable positioning, and process optimization of each aspect of steel making are expounded. The current state of molten steel quality and implementation under narrow window control is analyzed. A method for maintaining stability in the narrow window control technology of steel quality is proposed, controlled by factors including composition, temperature, time, cleanliness, and consumption (raw material). Important guidance is provided for the future development of a green and intelligent steel manufacturing process.     

钠离子电池苯醌电极材料放电平台改性研究

p-Benzoquinone (BQ) is a promising candidate for next-generation sodium-ion batteries (SIBs) because of its high theoretical specific capacity, good reaction reversibility, and high resource availability. However, practical application of BQ faces many challenges, such as a low discharge plateau (~2.7 V) as cathode material or a high discharge plateau as anode material compared with inorganic materials for SIBs and high solubility in organic electrolytes, resulting in low power and energy densities. Here, tetrahydroxybenzoquinone tetrasodium salt (Na₄C₆O₆) is synthesized through a simple neutralization reaction at low temperatures. The four –ONa electron-donating groups introduced on the structure of BQ greatly lower the discharge plateau by over 1.4 V from ~2.70 V to ~1.26 V, which can change BQ from cathode to anode material for SIBs. At the same time, the addition of four –ONa hydrophilic groups inhibits the dissolution of BQ in the organic electrolyte to a certain extent. As a result, Na₄C₆O₆ as the anode displays a moderate discharge capacity and cycling performance at an average work voltage of ~1.26 V versus Na/Na+. When evaluated as a Na-ion full cell (NIFC), a Na₃V₂(PO₄)₃ || Na₄C₆O₆ NIFC reveals a moderate discharge capacity and an average discharge plateau of ~1.4 V. This research offers a new molecular structure design strategy for reducing the discharge plateau and simultaneously restraining the dissolution of organic electrode materials.