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The human calcium-sensing receptor (CaSR) detects fluctuations in the extracellular Ca2+ concentration and maintains Ca2+ homeostasis1,2. It also mediates diverse cellular processes not associated with Ca2+ balance3–5. The functional pleiotropy of CaSR arises in part from its ability to signal through several G-protein subtypes6. We determined structures of CaSR in complex with G proteins from three different subfamilies: Gq, Gi and Gs. We found that the homodimeric CaSR of each complex couples to a single G protein through a common mode. This involves the C-terminal helix of each Gα subunit binding to a shallow pocket that is formed in one CaSR subunit by all three intracellular loops (ICL1–ICL3), an extended transmembrane helix 3 and an ordered C-terminal region. G-protein binding expands the transmembrane dimer interface, which is further stabilized by phospholipid. The restraint imposed by the receptor dimer, in combination with ICL2, enables G-protein activation by facilitating conformational transition of Gα. We identified a single Gα residue that determines Gq and Gs versus Gi selectivity. The length and flexibility of ICL2 allows CaSR to bind all three Gα subtypes, thereby conferring capacity for promiscuous G-protein coupling.Structures of the human calcium-sensing receptor can be bound into complex with G proteins from three different Gα subtypes while maintaining G-protein-binding specificity. [ABSTRACT FROM AUTHOR]

The advent of single-particle cryo-electron microscopy (cryo-EM) has brought forth a new era of structural biology, enabling the routine determination of large biological molecules and their complexes at atomic resolution. The high-resolution structures of biological macromolecules and their complexes significantly expedite biomedical research and drug discovery. However, automatically and accurately building atomic models from high-resolution cryo-EM density maps is still time-consuming and challenging when template-based models are unavailable. Artificial intelligence (AI) methods such as deep learning trained on limited amount of labeled cryo-EM density maps generate inaccurate atomic models. To address this issue, we created a dataset called Cryo2StructData consisting of 7,600 preprocessed cryo-EM density maps whose voxels are labelled according to their corresponding known atomic structures for training and testing AI methods to build atomic models from cryo-EM density maps. Cryo2StructData is larger than existing, publicly available datasets for training AI methods to build atomic protein structures from cryo-EM density maps. We trained and tested deep learning models on Cryo2StructData to validate its quality showing that it is ready for being used to train and test AI methods for building atomic models. [ABSTRACT FROM AUTHOR]

The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic. [ABSTRACT FROM AUTHOR]

Whether TMPRSS2-ERG fusion and TP53 gene alteration coordinately promote prostate cancer (PCa) remains unclear. Here we demonstrate that TMPRSS2-ERG fusion and TP53 mutation / deletion co-occur in PCa patient specimens and this co-occurrence accelerates prostatic oncogenesis. p53 gain-of-function (GOF) mutants are now shown to bind to a unique DNA sequence in the CTNNB1 gene promoter and transactivate its expression. ERG and β-Catenin co-occupy sites at pyrimidine synthesis gene (PSG) loci and promote PSG expression, pyrimidine synthesis and PCa growth. β-Catenin inhibition by small molecule inhibitors or oligonucleotide-based PROTAC suppresses TMPRSS2-ERG- and p53 mutant-positive PCa cell growth in vitro and in mice. Our study identifies a gene transactivation function of GOF mutant p53 and reveals β-Catenin as a transcriptional target gene of p53 GOF mutants and a driver and therapeutic target of TMPRSS2-ERG- and p53 GOF mutant-positive PCa. TP53 alteration and TMPRSS2-ERG fusion are often found together in prostate cancer. Here, the authors show that gain-of-function mutant p53 collaborates with ERG proto-oncogene to drive prostate cancer tumourigenesis by activating beta-catenin expression and afterwards pyrimidine synthesis. [ABSTRACT FROM AUTHOR]

Ultra-high-performance concrete (UHPC) has attracted wide interests in civil engineering but it has large deadweight, which limits its application in lightweight structures and rehabilitation. Compromising the merits of UHPC and lightweight concrete, ultra-high-performance lightweight concrete (UHPLC) is a potential solution to solve the drawback of high self-weight. Based on particle densely packing theory, this study proposed a UHPLC manufacturing approach using shale ceramic sand and air-entraining agent (AEA). An experimental study was conducted to systematically examine the effects of the types and contents of AEA on various performances of UHPLC, including its workability, mechanical properties, durability and microstructure. The results show the following: (1) The addition of AEA resulted in the decrease of UHPLC in elastic modulus, compressive strength and flexural strength but bring UHPLC higher specific strength; (2) A void system that is featured with homogeneous distribution of pores and an appropriate size and could be formed by adding a suitable amount of AEA; (3) The optimum proportion of AEA in UHPLC was 0.01% in consideration of its influence on UHPLC from the perspectives of microstructure, durability and mechanical properties. [ABSTRACT FROM AUTHOR]

Generally, the corrosion of magnesium (Mg) and its alloys is accompanied by hydrogen production, which can cause gas pockets and severe biological problems when they are used as implants. Germanium (Ge) as an alloy additive can moderate the cathodic reaction of Mg alloys and significantly delay the corrosion of Mg alloys via the cathode "poisoning" effect. In this study, the influence of Ge (0–0.75 wt.%) on the mechanical properties and corrosion resistance of Mg-0.7Zn were evaluated using electrochemical tests, weight loss experiments, and compression tests to optimize the composition of the Mg-Zn-Ge alloy having a low corrosion rate and high mechanical properties. The results show that the eutectic mixture (α-Mg + Mg2Ge) is formed in the Mg matrix after adding Ge to the Mg alloys. Small amounts of Ge addition can effectively reduce the cathodic reaction rate and improve the corrosion resistance via the cathode poisoning effect, and strengthen the mechanical properties of the alloy due to the formation of Mg2Ge. However, a relatively high content of Ge results in the formation of mesh-like precipitates, causing strong galvanic corrosion between the α-Mg matrix and secondary phases compared with the cathode poisoning effect of Ge, thereby deteriorating the mechanical properties of the alloy. [ABSTRACT FROM AUTHOR]

Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structures of biological macromolecular complexes. Picking single-protein particles from cryo-EM micrographs is a crucial step in reconstructing protein structures. However, the widely used template-based particle picking process is labor-intensive and time-consuming. Though machine learning and artificial intelligence (AI) based particle picking can potentially automate the process, its development is hindered by lack of large, high-quality labelled training data. To address this bottleneck, we present CryoPPP, a large, diverse, expert-curated cryo-EM image dataset for protein particle picking and analysis. It consists of labelled cryo-EM micrographs (images) of 34 representative protein datasets selected from the Electron Microscopy Public Image Archive (EMPIAR). The dataset is 2.6 terabytes and includes 9,893 high-resolution micrographs with labelled protein particle coordinates. The labelling process was rigorously validated through 2D particle class validation and 3D density map validation with the gold standard. The dataset is expected to greatly facilitate the development of both AI and classical methods for automated cryo-EM protein particle picking. [ABSTRACT FROM AUTHOR]

To monitor, diagnose, and suppress the inter-turn short-circuit faults (ITSCFs) of a submersible motor, an approach for the on-line identification of its winding faults has been proposed based on monitoring the stator current. First, an ITSCF model with the global leakage referred to the stator is given. With this model, the detection parameter, which is equal to the ratio of the turns of the fault windings to the total turns of the windings in the healthy phase, can be derived. Second, a faulty model described by the fourth order state-space equation of the motor with a winding fault has been given. Based on sampled stator voltage and stator current, the detection parameter has been solved and used to estimate the location and the turns of inter-turn short-circuit windings of the motor in real time. The accuracy and the robustness of the proposed approach has been illustrated with a 1.5 kW motor that is fed by a 10 kW inverter. Experiment shows that the identification accuracy in terms of the number of the ITSCF windings of the motor stator is less than 3. It can give a reference for the on-line diagnose the ITSCFs of the stator windings of a submersible motor that works in 2 km deep well. [ABSTRACT FROM AUTHOR]

The problem of boreholes deflection in coal mines is common, especially in soft and hard composite coal seams. As a result, the distribution of boreholes is uneven and forms a blank zone in the drainage area, which fails to achieve the regional pre-draining, causing gas explosion or coal and gas outburst accidents. Aiming at the above problems, this paper developed the technology of anti-inclination for drilling based on the causes of borehole deflection in detail. The anti-inclination advice integrates straight keeping, slag removal and smooth back drilling with reasonable technical parameters. Full hole drilling was adopted to realize straight drilling. Three spiral grooving, vertical grooving and three-edge short-circuit were adopted for collaborative slag removal. Three alloy pieces were welded at the rear end of anti-inclination device to act as reverse drill bit, realizing smooth drilling withdrawal. For sticking problems, we improved the anti-inclination device. Three 20 mm millimeters wide vertical grooves were milled in each 120° direction around the device. After using the improved anti-inclination device, the average deviation of dip and azimuth was only 4.8 and 4.5 degrees, respectively, which were reduced by 51 and 44%. The borehole offset was reduced from 9.9 m to 2.9 m, a decrease of 71%, which improved the gas drainage effect and ensured the safe production of the mine. [ABSTRACT FROM AUTHOR]

Bromodomain and extraterminal (BET) proteins including BRD4 play important roles in oncogenesis and immune inflammation. Here we demonstrate that cancer cells with loss of the retinoblastoma (RB) tumor suppressor became resistant to small molecule bromodomain inhibitors of BET proteins. We find that RB binds to bromodomain-1 (BD1) of BRD4, but binding is impeded by CDK4/6-mediated RB phosphorylation at serine-249/threonine-252 (S249/T252). ChIP-seq analysis shows RB knockdown increases BRD4 occupancy at genomic loci of genes enriched in cancer-related pathways including the GPCR-GNBIL-CREB axis. S249/T252-phosphorylated RB positively correlates with GNBIL protein level in prostate cancer patient samples. BET inhibitor resistance in RB-deficient cells is abolished by co-administration of CREB inhibitor. Our study identifies RB protein as a bona fide intrinsic inhibitor of BRD4 and demonstrates that RB inactivation confers resistance to small molecule BET inhibitors, thereby revealing a regulatory hub that converges RB upstream signaling onto BRD4 functions in diseases such as cancer. Here the authors identify retinoblastoma (RB) protein as an intrinsic inhibitor of BRD4 and demonstrate that loss of RB induces BRD4 cistrome changes in the genome and enrichment of GPCR-cAMP signaling pathway, conferring resistance to small molecule BET inhibitor. [ABSTRACT FROM AUTHOR]

Micro-encapsulated phase change materials (micro-PCMs) were utilized to equip fiber-reinforced concrete (FRC) with stronger ductility and better energy storage capacity. Experimental results indicated that 6.0 wt% addition of micro-PCMs not only improved the tensile strain capacity of FRC by 2.8 times, but also prolonged the time to reach the phase change temperature and inner surface peak temperature by 12.8 min and 2.0 min, respectively, which were attributed to the reduced interfacial strength of fiber/cement matrix and enhanced energy storage properties from micro-PCMs. The research outcomes promoted the development of sustainable concrete with the integration of ductility and energy conservation. [ABSTRACT FROM AUTHOR]

A proper understanding of large-diameter mechanical caving drilling technology is essential, because this technology can effectively improve the efficiency of gas extraction. Therefore, this paper firstly introduces a novelty equipment of large-diameter mechanical caving drilling and then analyzes the permeability improvement mechanism through theoretical and numerical simulation. Finally, the field test on large-diameter mechanical caving drilling technology was conducted in Xinjing Coal Mine of Yangquan Mining Area, Shanxi Province, China. The results show that the evolution of stress, damage, and permeability around the caving borehole has obvious zoning characteristics. The increase of caving intensity increases the permeability improvement range and reduces the impact of stress concentration on permeability and then reduces the barrier effect of the permeability reduction area. Besides, the coal mass between caving boreholes has larger range and higher amplitude of unloading and damage compared to normal boreholes, changing the permeability distribution significantly. And under the condition of multi-stage caving drilling, the existence of high permeability area around the caving drilling section can promote gas drainage of the adjacent section as well. The radial influence range of the caving section to the normal section is about 2 m. The underground test showed that the drainage concentration of mechanical caving boreholes increased by 2 times and the methane drainage rate increased by 57% compared with normal boreholes, and the construction period of pre-drainage boreholes was reduced from 15 to 5 days. Therefore, the results of this study could provide theoretical basis for the field application of large-diameter mechanical caving drilling technology. [ABSTRACT FROM AUTHOR]

The generalized regression neural network (GRNN) is one of the most effective neural models in the field of information prediction. In this paper, we take advantage of the hesitant fuzzy set (HFS) and develop the GRNN under the hesitant fuzzy environment. However, the performance of the GRNN only depends on the smooth factor after determining the input and output variables. To determine the most appropriate smooth factor of network, we propose an improved fruit fly optimization algorithm with fast decreasing step (FDS-FOA) based on a dynamic step size function. A specific implementation process of the optimized GRNN based on FDS-FOA is also presented. Moreover, we apply the proposed model to the prediction of air quality index (AQI) in Beijing. Comparative analysis and sensitivity analysis are further conducted to illustrate the advantages of the optimized GRNN based on FDS-FOA. [ABSTRACT FROM AUTHOR]

As shallow coal resources deplete in industrialized nations, mining operations expand to the deeper resources to meet the requirements of the society. Deep coal seams in China have the characteristics of high gas pressure and high gas content. There is a persistent track record of gas-related accidents in Chinese coal mines. In an effort to eliminate gas explosions and gas outbursts, a new permeability improvement technology of "hydraulic punching plus air blasting" is developed for soft and low-permeability coal seams. To intensively enhance the permeability and achieve efficient extraction of gas from low-permeability coal seams, hydraulic punching is performed first, followed by air blasting. The LS-DYNA software was used to simulate the blasting process by the air cannons. Results were obtained from the Guhanshan mine. Comparisons were done for the stress field, deformation field of the coal body using the law of coal body deformation. Deformation at different blasting times was compared in combination with the field air blasting tests. With 40 times air blasting, the gas drainage increased by about two times compared to drainage without air blasting. The pure gas extraction volume was also observed to be about 2.2 times higher than that without air blasting. The results proved improvement of the coal permeability and gas drainage by this new technology. [ABSTRACT FROM AUTHOR]

Geminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. SPOP is frequently mutated in certain human cancer types and implicated in tumorigenesis. We show that cancer-associated SPOP mutations impair Geminin K27-linked poly-ubiquitination and induce replication origin over-firing and re-replication. The replication stress caused by SPOP mutations triggers replication catastrophe and cell death upon ATR inhibition. Our results reveal a tumor suppressor role of SPOP in preventing DNA replication over-firing and genome instability and suggest that SPOP-mutated tumors may be susceptible to ATR inhibitor therapy. Geminin-Cdt1 plays essential roles in the regulation of DNA replication. Here the authors reveal that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP prevents DNA replication over-firing and genome instability by affecting Geminin ubiquitination. [ABSTRACT FROM AUTHOR]

Mutations in SPOP E3 ligase gene are reportedly associated with genome-wide DNA hypermethylation in prostate cancer (PCa) although the underlying mechanisms remain elusive. Here, we demonstrate that SPOP binds and promotes polyubiquitination and degradation of histone methyltransferase and DNMT interactor GLP. SPOP mutation induces stabilization of GLP and its partner protein G9a and aberrant upregulation of global DNA hypermethylation in cultured PCa cells and primary PCa specimens. Genome-wide DNA methylome analysis shows that a subset of tumor suppressor genes (TSGs) including FOXO3, GATA5, and NDRG1, are hypermethylated and downregulated in SPOP-mutated PCa cells. DNA methylation inhibitor 5-azacytidine effectively reverses expression of the TSGs examined, inhibits SPOP-mutated PCa cell growth in vitro and in mice, and enhances docetaxel anti-cancer efficacy. Our findings reveal the GLP/G9a-DNMT module as a mediator of DNA hypermethylation in SPOP-mutated PCa. They suggest that SPOP mutation could be a biomarker for effective treatment of PCa with DNA methylation inhibitor alone or in combination with taxane chemotherapeutics. The molecular mechanism underlying the DNA hypermethylation phenotype observed in the SPOP-mutant prostate cancers is unclear. Here, the authors show that mutant SPOP induces global aberrant DNA methylation patterns through GLP/G9a and renders prostate cancer cells susceptible to DNA demethylating agents. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has created global health and economic emergencies. SARS-CoV-2 viruses promote their own spread and virulence by hijacking human proteins, which occurs through viral protein recognition of human targets. To understand the structural basis for SARS-CoV-2 viral-host protein recognition, here we use cryo-electron microscopy (cryo-EM) to determine a complex structure of the human cell junction protein PALS1 and SARS-CoV-2 viral envelope (E) protein. Our reported structure shows that the E protein C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains of PALS1. Our structural analysis provides an explanation for the observation that the viral E protein recruits PALS1 from lung epithelial cell junctions. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1-E interactions to reduce E-mediated virulence. SARS-CoV-2 viruses are known to hijack human proteins in order to facilitate their own virulence and replication. In this study, Liu and colleagues present structural analysis of how this phenomenon occurs between SARS-CoV-2 viral envelope protein and human PALS1. The findings provide insights in to viral-host recognition. [ABSTRACT FROM AUTHOR]

Purpose: Supratentorial extraventricular ependymoma (SEE) is a rare subset of ependymomas located in the supratentorial parenchyma, and little is known regarding its management and prognosis. Our study aimed to reveal the prognostic factors in patients with SEE and the roles of programmed death ligand-1 (PD-L1), programmed cell death protein 1 (PD-1), Ki-67, and neural cell adhesion molecule L1 (L1CAM) in predicting these patients' outcomes. Methods: We retrospectively studied the clinical features and prognostic factors in 48 patients with SEE admitted to our center from April 2008 to October 2018. Tissue slides were constructed from patient samples, and PD-L1, PD-1, Ki-67, and L1CAM expression levels were evaluated by immunohistochemistry. Results: Patients with gross total resection (GTR) had better progression-free survival than patients with subtotal resection (STR). Moreover, the recurrence hazard ratios in patients with STR at 3, 5, and 10 years were 8.746, 6.866 and 3.962 times those of patients with GTR, respectively. PD-L1 positivity predicted worse progression-free survival, while the recurrence hazard ratios for patients with PD-L1 positivity at 3, 5, and 10 years were 10.445, 5.539, and 3.949 times those of patients with PD-L1 negativity, respectively. Multivariate analysis revealed that PD-L1 expression and GTR could independently predict outcomes in patients with SEE. Conclusion: PD-L1 expression was an independent and more readily obtained predictor of outcomes, representing a simple and reliable biological prognostic factor for patients with SEE. Further studies are needed to explore PD-L1 inhibitor treatment for patients with ependymoma. Clinical trial registration: No clinical trials were performed in the study. [ABSTRACT FROM AUTHOR]

Implant therapy after osteosarcoma surgery is a major clinical challenge currently, especially the requirements for mechanical properties, degradability of the implants, and their inhibition of residual tumor cells. Biodegradable magnesium (Mg) alloy as medical bone implant material has full advantages and huge potential development space. Wherein, Mg–lithium (Li) based alloy, as an ultra-light alloy, has good properties for implants under certain conditions, and both Mg and Li have inhibitory effects on tumor cells. Therefore, Mg–Li alloy is expected to be applied in bone implant materials for mechanical supporting and inhibiting tumor cells simultaneously. In this contribution, the Mg–xLi–Zinc (Zn) series alloys (x = 3 wt%, 6 wt%, 9 wt%) were prepared to study the influence of different elements and contents on the structure and properties of the alloy, and the biosafety of the alloy was also evaluated. Our data showed that the yield strength, tensile strength, and elongation of as-cast Mg–xLi–Zn alloy were higher than those of as-cast Mg–Zn alloy; Mg–xLi–Zn alloy can kill osteosarcoma cells (MG-63) in a concentration-dependent manner, wherein Mg–3Li–Zn alloy (x = 3 wt%) and Mg–6Li–Zn alloy (x = 6 wt%) promoted the proliferation of osteoblasts (MC3T3) at a certain concentration of Li. In summary, our study demonstrated that the Mg–6Li–Zn alloy could be potentially applied as a material of orthopedic implant for its excellent multi-functions. [ABSTRACT FROM AUTHOR]

Resistance to next-generation anti-androgen enzalutamide (ENZ) constitutes a major challenge for the treatment of castration-resistant prostate cancer (CRPC). By performing genome-wide ChIP-seq profiling in ENZ-resistant CRPC cells we identify a set of androgen receptor (AR) binding sites with increased AR binding intensity (ARBS-gained). While ARBS-gained loci lack the canonical androgen response elements (ARE) and pioneer factor FOXA1 binding motifs, they are highly enriched with CpG islands and the binding sites of unmethylated CpG dinucleotide-binding protein CXXC5 and the partner TET2. RNA-seq analysis reveals that both CXXC5 and its regulated genes including ID1 are upregulated in ENZ-resistant cell lines and these results are further confirmed in patient-derived xenografts (PDXs) and patient specimens. Consistent with the finding that ARBS-gained loci are highly enriched with H3K27ac modification, ENZ-resistant PCa cells, organoids, xenografts and PDXs are hyper-sensitive to NEO2734, a dual inhibitor of BET and CBP/p300 proteins. These results not only reveal a noncanonical AR function in acquisition of ENZ resistance, but also posit a treatment strategy to target this vulnerability in ENZ-resistant CRPC. Resistance to second generation anti-androgen therapies such as enzalutamide (ENZ) can emerge in prostate cancer patients. Here, the authors identify an ENZ-resistant mechanism driven by AR-dependent transcription of noncanonical targets that make resistant cells susceptible to dual inhibition of BET and CBP/p300 signaling. [ABSTRACT FROM AUTHOR]

In this study, a micro-patterned hydroxyapatite/silk fibroin (HA-SF) coating was firstly fabricated on the surface of Mg-Zn-Y-Nd-Zr alloy by template-assisted electrospraying technique coupling with spin coating technique. Two types of micro-patterns were achieved with high contour accuracy, namely HA-SF(line-pattern) and HA-SF(dot-pattern). The microstructure, composition, surface wettability and corrosion behaviors of the coatings were investigated by SEM, EDS, FTIR, XRD, water contact angle and potentiodynamic polarization test. The results revealed the hydrophilic nature of coatings and two orders of magnitude reduction of corrosion density (icorr) as compared with that of the substrate. All the micro-patterned surfaces promoted the attachment of MC3T3-E1 cells with visible filopodia after 1 d incubation. In addition, coatings with line pattern exhibited the superior guidance to cell migration as compared to dot pattern, and the preference of cell attachment in the convex zone was observed. In summary, the obtained micro-patterned HA-SF coatings possessed the remarkably improvement of anticorrosion ability and good efficacy in guidance of cell attachment and alignment, which can serve as a promising strategy for cellular response modulation at the interface of magnesium-based implants and bone. [ABSTRACT FROM AUTHOR]

A series of highly active amorphous manganese oxide catalysts for soot combustion were synthesized using colloidal solution combustion synthesis (CSCS) method. The surface morphological and structural properties were systematically tested via various techniques: X-ray diffraction, N2 adsorption-desorption, temperature-programmed reduction, scanning electron microscopy, and X-ray photoelectron spectroscopy. Manganese precursors and calcination temperatures affect the crystal structure, redox properties, and surface properties of MnOx. With the calcination temperature increasing from 550 to 850 °C, the crystalline structure of manganese oxides changed from amorphous phase to crystal phase. In general, the amorphous MnOx with a hierarchical porous structure showed better catalytic activity for soot oxidation than the crystal ones (T10 as indicator), which can be ascribed to the improved low-temperature reducibility, more surface active oxygen species, and abundant surface Mn4+ ions. The presence of NO in O2 also promoted soot oxidation which follows the NO2-assisted mechanism. Our work may provide a rational comparison between high-efficient amorphous and crystal MnOx catalysts for soot oxidation. [ABSTRACT FROM AUTHOR]

The Dengfeng coalfield belongs to the typical "three soft" coal seam and has a high gas content ranging from 10 to 13 m3/t, and the coal seam gas content reaches a maximum 13.69 m3/t. Because of its coal seam occurrence, no protective layer can be mined. The conventional regional pre-pumping measures have several problems. For example, the construction of a pre-pumping borehole is difficult, and it easily causes a coal and gas outburst. The low permeability and rheological characteristics of the coal seam lead to the collapse of the borehole and seriously affects the drainage effect. The influence radius of the drainage borehole is small, which results in a larger quantity of new drilling boreholes and significantly increases the operational cost. Compared to the conventional regional pre-pumping measures, floor roadway hydraulic flushing rapid outburst technology can effectively overcomes these issues. Hydraulic flushing uses water to flush the borehole, and the newly formed fractures and the release of free gas greatly reduce the elastic potential and gas expansion energy of coal and rock, which thus significantly improve the permeability of the coal and improve the coal seam degasification efficiency for outburst risk control. In this paper, a hydraulic punching method is utilized for coal seam stimulation in the Machi mine. Reasonable technical parameters of hydraulic punching were obtained: the water pressure of punching and breaking coal is 8–15 MPa, and the equivalent diameter of the hydraulic punching nozzle should be < 7.47 mm. After the implementation of the hydraulic punching measures, the gas extraction capacity of the coal around the borehole is greatly improved. For 90 days gas extraction after stimulation, the gas content of the 11,061 lane decreased from 8.42–12.12 m3/t to 3.09–5.75 m3/t, relieving pressure and increasing permeability of "three soft" coal and simultaneously eliminating the outburst danger of the coal seam. [ABSTRACT FROM AUTHOR]

Cryo-electron microscopy (cryo-EM) has become a leading technology for determining protein structures. Recent advances in this field have allowed for atomic resolution. However, predicting the backbone trace of a protein has remained a challenge on all but the most pristine density maps (<2.5 Å resolution). Here we introduce a deep learning model that uses a set of cascaded convolutional neural networks (CNNs) to predict Cα atoms along a protein's backbone structure. The cascaded-CNN (C-CNN) is a novel deep learning architecture comprised of multiple CNNs, each predicting a specific aspect of a protein's structure. This model predicts secondary structure elements (SSEs), backbone structure, and Cα atoms, combining the results of each to produce a complete prediction map. The cascaded-CNN is a semantic segmentation image classifier and was trained using thousands of simulated density maps. This method is largely automatic and only requires a recommended threshold value for each protein density map. A specialized tabu-search path walking algorithm was used to produce an initial backbone trace with Cα placements. A helix-refinement algorithm made further improvements to the α-helix SSEs of the backbone trace. Finally, a novel quality assessment-based combinatorial algorithm was used to effectively map protein sequences onto Cα traces to obtain full-atom protein structures. This method was tested on 50 experimental maps between 2.6 Å and 4.4 Å resolution. It outperformed several state-of-the-art prediction methods including Rosetta de-novo, MAINMAST, and a Phenix based method by producing the most complete predicted protein structures, as measured by percentage of found Cα atoms. This method accurately predicted 88.9% (mean) of the Cα atoms within 3 Å of a protein's backbone structure surpassing the 66.8% mark achieved by the leading alternate method (Phenix based fully automatic method) on the same set of density maps. The C-CNN also achieved an average root-mean-square deviation (RMSD) of 1.24 Å on a set of 50 experimental density maps which was tested by the Phenix based fully automatic method. The source code and demo of this research has been published at https://github.com/DrDongSi/Ca-Backbone-Prediction. [ABSTRACT FROM AUTHOR]

The adverse effects of high concentration of phenolic compounds in wastewater on aquatic organisms are a major environmental issue. In recent years, treating organic wastewater by algae has attracted attention because this treatment is economic, efficient and eco-friendly. Here we review the use of algae in removing phenol and phenolic derivatives. We discuss phenolic wastewater treatment, mechanisms of adsorption and degradation, and effects of excessive phenols on algal cells. [ABSTRACT FROM AUTHOR]

A series of promising Ce–Co–Fe catalysts were successfully synthesized using a cetyl-trimethylammonium-bromide-assisted co-precipitation method and investigated for diesel soot combustion. The surface morphological and structural properties were systematically examined using various techniques: X-ray diffraction, scanning electron microscope, N2 adsorption–desorption, Raman spectroscopy, temperature-programmed reduction and in situ diffuse reflection infrared Fourier transform spectroscopy. The catalyst–soot combustion activities were tested in O2 and NO + O2 using a temperature-programmed technique. Nanometer crystalline solid solutions were formed with high surface areas when the Fe and Co cations were co-doped in the ceria lattice. Transition metals doping played a key role in increasing oxygen vacancies and promoting the redox performance of Ce–Co–Fe catalysts. Co–Fe co-doping accelerated the oxidation of soot under both "tight" and "loose" contact conditions. Among all the ceria-based catalysts, Ce80Co15Fe5 showed superior activity with T10 = 256 °C and high selectivity with S CO 2 = 100 % under tight a contact mode. The observed high catalytic activity following co-doping was proved to have occurred because of various reasons such as improved redox properties, increased oxygen vacancies and high surface area. The presence of NO in O2 also promoted soot oxidation, which follows the NO2-assisted mechanism. Moreover, the in situ DRIFTS performed under an isothermal condition in NO + O2 confirmed the strong adsorption capacity for NOx species on the doped ceria catalyst. [ABSTRACT FROM AUTHOR]

Aiming to investigate the mix design of eco-friendly UHPC with supplementary cementitious materials and coarser aggregates, we comprehensively studied the workability, microstructure, porosity, compressive strength, flexural strength, and Young's modulus of UHPC. Relationship between compressive strength and Young's modulus was obtained eventually. It is found that the compressive strength, flexural strength, and Young's modulus of UHPC increase by 19.01%, 10.81%, and 5.99%, respectively, when 40wt% cement is replaced with supplementary cementitious materials. The relationship between compressive strength and Young's modulus of UHPC is an exponential form. [ABSTRACT FROM AUTHOR]

Numerous land-use policies have been implemented in China in recent decades for ecological restoration and conservation to reduce environmental disasters and promote environmental sustainability. Many of these policies follow a top-down approach to implementation and as such, emphasize the hierarchical control within government structures. An understanding of local perceptions of land-use policies is important if the disconnect between policy makers and the target population is to be reduced and if program support is to improve. This study aimed to help improve local implementation, attitude toward, and engagement by examining the influence of socio-economic characteristics on the target population's (local farmers) perception of the conversion of cropland to forestland program (CFPP) land use policy in Jiangxi, Sichuan, and Shaanxi provinces. It uses logistical regression models, with robust aspects of perception including confidence, support, transparency, prospects, fairness, and willingness to participate. Results indicate that social aspects as well as economic aspects are most important in influencing farmers' perceptions towards the CFPP. The farmers who have received technical support, rural male habitants, educated, and non-middle-aged farmers exhibit more positive perceptions of the program and are much more likely to support it, whereas farmers without any technical support or formal education, and female and middle-aged farmers are less likely to support the program. Importantly, this study also reveals the differences in responses, experiences and perceptions of the farmers living across different provinces. These empirical results provide insight into the influence of socio-economic characteristics on the perception of farmers towards land-use policies, which has important implications for designing targeted policy instruments and increasing farmer support for these policies. This knowledge can be harnessed and further evaluated in future research to improve citizen engagement, support, and understanding in order to help ecological restoration and conservation objectives be more effectively achieved. [ABSTRACT FROM AUTHOR]

The soot combustion on Pd-doped La2Sn2O7 pyrochlore oxides was studied. Palladium promoter was doped into the pyrochlore system via two ways: bulk substitution (La2Sn1.9Pd0.1O7) and surface impregnation (Pd/La2Sn2O7). The catalysts were characterized by XRD, BET, SEM, HRTEM, PL, XPS and H2-TPR measurements. Pd modifications increased the concentration of surface oxygen vacancy, especially Pd/La2Sn2O7. The different morphologies of palladium promoters were revealed in the two palladium-doped catalysts. Palladium was present primarily in the form of a lattice Pd2+ in the bulk-doping sample, with trace of metal palladium deposited on the surface. As for the surface-doping sample, PdO was the predominant form, accompanied with some of highly dispersed metallic palladium. Due to the adhesion of massive surface palladium species on Pd/La2Sn2O7, a strong metal oxide interaction occurred in the interface between Pd species and La2Sn2O7. The activity evaluation results show that Pd/La2Sn2O7 possesses the highest performance, exhibiting the lowest activation energy (98.83 kJ/mol) for soot combustion. Surface Pd/PdO redox couples as well as Pd-O-Sn interface species were identified to be the active phases for the superior catalytic behavior of Pd/La2Sn2O7. A possible oxidation mechanism for the reactions has been speculated. [ABSTRACT FROM AUTHOR]

Apoptosis is one of the main fundamental biological processes required for development of multicellular organisms. Inappropriate regulation of apoptosis can lead to severe developmental abnormalities and diseases. Therefore, the control of apoptosis, not only for its activation but also for its inhibition, is critically important during development. In contrast to the extensive studies of apoptosis induction, its inhibitory mechanisms that are even more vital in certain populations of cells actually are very far from being well understood. Here we report an inhibitory role of protein phosphatase V (PpV), a serine/threonine protein phosphatase, in controlling the apoptosis during Drosophila wing development. We observed that inhibition of ppv by RNAi in wing imaginal discs induced ectopic cell death and caspase activation, thus, resulted in a defective adult wing. Moreover, knocking-down ppv triggered the activation of c-Jun N-terminal kinase (JNK) signal, an evolutionarily conserved intracellular signaling that has been implicated to modulate the apoptotic machinery in many biological and experimental systems. Disrupting the JNK signal transduction was adequate to suppress the ppv effects for wing development. Together, we provided the evidence to demonstrate that ppv is required for normal wing development in maintaining the silence of apoptotic signal possibly through JNK pathway. [ABSTRACT FROM AUTHOR]

In this paper, an improved version of locally linear Embedding is proposed. In the proposed method, spectral correlation angle is invited to describe the distance between data points, which is expected to fit the hyperspectral image (HSI). The neighborhood graph of the data points is constructed based on supervised method. Different from traditional supervised feature extraction methods, the weight factors, which are used to control the transform, are adaptively achieved. In this way, the input arguments of original algorithm are not increased. To justify the effectiveness of the proposed method, experiments are conducted on two HSIs. Results show that the proposed method can improve the separability of HSI especially in low dimensions. [ABSTRACT FROM AUTHOR]

Lots of heat generated in the cutting deformation zone can cause the temperature rising of cutting tool and workpiece during the cutting process. Tool temperature is mainly depended on the heat energy entering into tool in the secondary deformation zone. Higher working temperature can weaken the cutting tool strength and then deteriorate the tool wear. Advanced coating layer deposited on the tool substrate can change the tool-chip friction and affect the heat partition in the tool-chip interface. In order to reveal the mechanism of heat conduction in the secondary deformation zone, the model of heat partition into cutting tool was built. With the aid of finite element method (FEM), the relative parameters which were necessary for the solving of heat partition model were quantified. Actual cutting experiments were carried out to the verification of the FEM models by means of the cutting force and temperature measurement. Influences of coatings (i.e., coating materials, coating thickness) and cutting speeds on the heat partition were analyzed. And then, rake face temperatures obtained at four kinds of coated tools were compared. The investigation results showed that TiC coating appears as the maximum value and Al2O3 coating appears as the minimum value of heat partition coefficient into cutting tool among these four kinds of coatings (i.e., TiC, TiN, TiAlN, Al2O3). With the increasing of coating thickness and cutting speeds, heat partition into cutting tool all showed a decrease trend. Al2O3-coated tool had the maximum rake face temperature among these four kinds of coated tools; however, the location of peak temperature on the rake face of Al2O3-coated tool was the shortest distance from the tool tip. [ABSTRACT FROM AUTHOR]

Synthesis of HDC by methoxycarbonylation of HDA with DMC was carried out over the bulk and hybrid heteropoly acid (HPA) catalyst. The catalysts were systematically characterized by XRD, FTIR, SEM and NH-TPD techniques. The by-products produced in the reaction were identified and a possible reaction pathway was proposed based on the by-products analysis. The performances of bulk and hybrid HPA catalysts were evaluated. The H[SiWO] catalyst revealed high performance compared with other catalysts and its high performance was attributed to its acidic properties. Effects of reaction parameters and reusability of the H[SiWO] catalyst were also investigated. Under the optimized reaction conditions, HDA conversion reached 93.2% with 64.8% HDC selectivity and only 3.8% by-product selectivity. Moreover, a possible reaction mechanism was proposed for the synthesis of HDC over H[SiWO] catalyst. [ABSTRACT FROM AUTHOR]

Purpose: We compared the outcomes in patients who were <1 year old and had hydronephrosis with SFU grade 3-4 PUJ obstruction to observe the potential recovery of renal morphology and DRF after successful pyeloplasty. Methods: All children younger than 1 year old with SFU grade 3-4 PUJ obstruction from January 2013 to June 2015 were retrospectively analyzed. A total of 92 children were grouped according to their DRF value at pyeloplasty as follows: DRF from 30 to ≤35% (group I) and DRF from 35 to ≤40% (group II). We evaluated changes in anteroposterior diameter and differential renal function using ultrasound and diuretic renography. Outcomes were compared using Student t test. Results: Group I comprised 45 patients, and group II included 47 patients. No significant difference was observed in the initial APD, final APD and the improvement of APD after pyeloplasty between two groups. Significant differences were observed between the initial and final DRF values in both groups. The difference in DRF improvement after pyeloplasty between groups I and II was significant. The DRF improved to a normal stage significantly more frequently in group II (21/47; 44.7%) than in group I (13/45; 28.9%). Conclusion: The improvement in DRF after pyeloplasty was significant for patients with an initial DRF from 30 to ≤35%. However, patients with an initial DRF from 35 to ≤40% had a greater probability of achieving normal renal function. Patients with severely impaired initial renal function had a marginal probability of achieving a normal value. [ABSTRACT FROM AUTHOR]

Magnesium alloy has great potential for bone implantation. However, its corrosion rate is fast in physiological environment. In this paper, biological Mg–Zn–Ca alloy was processed by high pressure torsion (HPT) and subsequently annealed at 90–270 °C for 30 min. The microstructure and corrosion resistance in simulated body fluid were investigated. The results revealed that with the rise of the annealing temperature, the grain size of the HPT alloy gradually increased and the relative diffraction peak intensity of (0002) grain orientation decreased. The amount of second phases increased first and then decreased, while the surface stress decreased first and then increased. All of these changes affected the corrosion rate simultaneously. The corrosion resistance of the HPT alloy increased first and then decreased with the rise of annealing temperature. After annealing at 210 °C for 30 min, the corrosion resistance was the best. Therefore, it was feasible to control the corrosion rate via annealing treatment. [ABSTRACT FROM PUBLISHER]

The electron and hole transport properties in a high-mobility n-type copolymer poly{[ N, N′-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diy1]-alt-5,5′-(2,2′-dithiophene)}[P(NDI2OD-T2), PolyeraActivInk™ N2200] are investigated. The electron mobility is observed to be more than two orders of magnitude higher than the hole mobility. The thickness-dependent current density versus voltage ( J- V) characteristics of N2200 electron-only and hole-only devices cannot be well described using the conventional mobility model. However, the thickness-dependent and temperature-dependent J- V characteristics of N2200 electron-only and hole-only devices can be accurately described using our recently introduced improved mobility model only with a single set of parameters. Within the improved model, the mobility depends on three important physical quantities: the temperature, carrier density, and electric field. For the semiconducting polymer studied, we find the width of the Gaussian density of states σ = 0.082 eV and the lattice constant a = 0.8 nm for electron transport, while the width of the Gaussian density of states σ = 0.11 eV and the lattice constant a = 0.8 nm for hole transport. It is clear that hole transport exhibits a significantly stronger disorder than electron transport. This is also reflected in the lower hole mobility, as compared to the electron mobility. [ABSTRACT FROM AUTHOR]