197 research outputs found

    Predicting Peptide Binding Sites on Protein Surfaces by Clustering Chemical Interactions

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    Context-sensitive graph representation learning

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    Graph Convolutional Network (GCN) is a powerful emerging deep learning technique for learning graph data. However, there are still some challenges for GCN. For example, the model is shallow; the performance is poor when labelled nodes are severely scarce. In this paper, we propose a Multi-Semantic Aligned Graph Convolutional Network (MSAGCN), which contains two fundamental operations: multi-angle aggregation and semantic alignment, to resolve two challenges simultaneously. The core of MSAGCN is the aggregation of nodes that belong to the same class from three perspectives: nodes, features, and graph structure, and expects the obtained node features to be mapped nearby. Specifically, multi-angle aggregation is applied to extract features from three angles of the labelled nodes, and semantic alignment is utilised to align the semantics in the extracted features to enhance the similar content from different angles. In this way, the problem of over-smoothing and over-fitting for GCN can be alleviated. We perform the node clustering task on three citation datasets, and the experimental results demonstrate that our method outperforms the state-of-the-art (SOTA) baselines

    Nanostructured Fe 2

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    In the present work, a method combining arc plasma evaporation of a metal followed by oxidation in air was developed to produce nanosized metal oxide based composites in large scale. As an example, Fe2O3 based nanocomposites were prepared through such a method. With increasing the oxidation temperature, Ī±-Fe2O3 content in the composites increases, while Ī³-Fe2O3 and residual Ī±-Fe contents decrease. As anode materials for lithium batteries, the electrochemical properties of nanosized Fe2O3 composites were tested. It was found that the anode materials changed to tiny crystallites and then followed by grain growth during the galvanostatic charge/discharge cycles. A capacity rising was observed for the composites obtained at 400Ā°C and 450Ā°C, which was more prominent with increasing the oxidation temperature. Among these composites, the one obtained at 450Ā°C showed the best performance: a specific capacity of 507.6ā€‰mAh/g remained after 150 cycles at a current density of 200ā€‰mA/g, much higher than that of the commercial nano-Fe2O3 powder (~180ā€‰mAh/g after 30 cycles)

    Feature recommendation strategy for graph convolutional network

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    Graph Convolutional Network (GCN) is a new method for extracting, learning, and inferencing graph data that builds an embedded representation of the target node by aggregating information from neighbouring nodes. GCN is decisive for node classification and link prediction tasks in recent research. Although the existing GCN performs well, we argue that the current design ignores the potential features of the node. In addition, the presence of features with low correlation to nodes can likewise limit the learning ability of the model. Due to the above two problems, we propose Feature Recommendation Strategy (FRS) for Graph Convolutional Network in this paper. The core of FRS is to employ a principled approach to capture both node-to-node and node-to-feature relationships for encoding, then recommending the maximum possible features of nodes and replacing low-correlation features, and finally using GCN for learning of features. We perform a node clustering task on three citation network datasets and experimentally demonstrate that FRS can improve learning on challenging tasks relative to state-of-the-art (SOTA) baselines

    CFTR Gating II: Effects of Nucleotide Binding on the Stability of Open States

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    Previously, we demonstrated that ADP inhibits cystic fibrosis transmembrane conductance regulator (CFTR) opening by competing with ATP for a binding site presumably in the COOH-terminal nucleotide binding domain (NBD2). We also found that the open time of the channel is shortened in the presence of ADP. To further study this effect of ADP on the open state, we have used two CFTR mutants (D1370N and E1371S); both have longer open times because of impaired ATP hydrolysis at NBD2. Single-channel kinetic analysis of Ī”R/D1370N-CFTR shows unequivocally that the open time of this mutant channel is decreased by ADP. Ī”R/E1371S-CFTR channels can be locked open by millimolar ATP with a time constant of āˆ¼100 s, estimated from current relaxation upon nucleotide removal. ADP induces a shorter locked-open state, suggesting that binding of ADP at a second site decreases the locked-open time. To test the functional consequence of the occupancy of this second nucleotide binding site, we changed the [ATP] and performed similar relaxation analysis for E1371S-CFTR channels. Two locked-open time constants can be discerned and the relative distribution of each component is altered by changing [ATP] so that increasing [ATP] shifts the relative distribution to the longer locked-open state. Single-channel kinetic analysis for Ī”R/E1371S-CFTR confirms an [ATP]-dependent shift of the distribution of two locked-open time constants. These results support the idea that occupancy of a second ATP binding site stabilizes the locked-open state. This binding site likely resides in the NH(2)-terminal nucleotide binding domain (NBD1) because introducing the K464A mutation, which decreases ATP binding affinity at NBD1, into E1371S-CFTR shortens the relaxation time constant. These results suggest that the binding energy of nucleotide at NBD1 contributes to the overall energetics of the open channel conformation

    Contraceptive practices and induced abortions status among internal migrant women in Guangzhou, China: a cross-sectional study

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    Background: China is facing the unprecedented challenges of internal migration. Migrants tend to have poorer utilization of health and family planning services as compared to the local residents. Migrant women are at greater risk of induced abortions due to their poor contraceptive knowledge and attitude. This study aims to understand the contraceptive practices and history of induced abortions, explore the potential factors influencing induced abortions, and evaluate the utilization of family planning services among migrant women in Guangzhou, China. Methods: An anonymous, self-administered questionnaire survey was conducted with 1003 migrant women aged 18-49 in Guangzhou, China in 2013. A multi-stage sampling method was employed. Binary logistic regression model was used for analyzing risk factors of induced abortions. Results: Among the 1003 participants, 810 (80.8 %) reported having sex in the past 6 months, including 715 (88.3 %) married and 95 (11.7 %) unmarried. The most reported contraceptive method was male condom (44.9 %), while 8.1 % never used any contraceptive methods. Only 10.4 % reported having attained free condoms from family planning service stations (FPSSs) and 39.3 % reported having acquired contraceptive knowledge from family planning workers. Of all the participants, 417 (41.6 %) had a history of induced abortion. Of married and unmarried women, 389 (49.1 %) and 28 (14.0 %) had induced abortion respectively. Of these, 152 (36.5 %) had repeated abortions. The most reported reason for having induced abortion was failure of contraception (31.9 %), followed by nonuse of any contraceptives (21.1 %). Migrants who had induced abortion tended to be older, have household registration outside Guangdong province, receive no annual health checkup, have lower education, have urban household registration, have lived longer in Guangzhou and have children (P < 0.05). Conclusions: The prevalence rate of induced abortion, especially repeated abortions among migrant women was high in Guangzhou, China. There is an urgent need to improve the awareness of regular and appropriate use of contraceptives. The utilization of FPSSs among migrant women was reportedly low. Family planning system should be improved to provide better access for migrants and better integrated with the general health services. 2015 Zeng et al.This paper outlines some of the findings from a QAA (Scotland) funded project exploring first year curriculum design (Bovill et al. 2008). Whilst many examples exist of curricula being designed in ways to engage first year students, there are fewer published examples of active student participation in curriculum design processes. In the current higher education context where student engagement in learning is emphasised (Carini et al,2006), this paper asks more generally whether students should be actively participating in curriculum design.In order to answer this question, several elements of the project findings are explored: student views gathered in focus groups; staff views collected in workshops; and the case studies where students were actively involved in curriculum design. The data are examined for lessons that inform the debate about whether students should be participating in curriculum design, in first year and at other levels. Alongside these findings, relevant literature is critiqued in order to ascertain the desirability and feasibility of adopting curriculum design approaches that offer opportunities for active student participation.sch_iih15pub3989pub55

    The Two ATP Binding Sites of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Play Distinct Roles in Gating Kinetics and Energetics

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    Cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ABC (ATP binding cassette) transporter family, is a chloride channel whose activity is controlled by protein kinaseā€“dependent phosphorylation. Opening and closing (gating) of the phosphorylated CFTR is coupled to ATP binding and hydrolysis at CFTR's two nucleotide binding domains (NBD1 and NBD2). Recent studies present evidence that the open channel conformation reflects a head-to-tail dimerization of CFTR's two NBDs as seen in the NBDs of other ABC transporters (Vergani et al., 2005). Whether these two ATP binding sites play an equivalent role in the dynamics of NBD dimerization, and thus in gating CFTR channels, remains unsettled. Based on the crystal structures of NBDs, sequence alignment, and homology modeling, we have identified two critical aromatic amino acids (W401 in NBD1 and Y1219 in NBD2) that coordinate the adenine ring of the bound ATP. Conversion of the W401 residue to glycine (W401G) has little effect on the sensitivity of the opening rate to [ATP], but the same mutation at the Y1219 residue dramatically lowers the apparent affinity for ATP by >50-fold, suggesting distinct roles of these two ATP binding sites in channel opening. The W401G mutation, however, shortens the open time constant. Energetic analysis of our data suggests that the free energy of ATP binding at NBD1, but not at NBD2, contributes significantly to the energetics of the open state. This kinetic and energetic asymmetry of CFTR's two NBDs suggests an asymmetric motion of the NBDs during channel gating. Opening of the channel is initiated by ATP binding at the NBD2 site, whereas separation of the NBD dimer at the NBD1 site constitutes the rate-limiting step in channel closing

    Comprehensive Numerical Investigations of Unsteady Internal Flows and Cavitation Characteristics in Double-Suction Centrifugal Pump

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    The RNG k-Īµ turbulence model combined with cavitation model was used to simulate unsteady cavitating flows inside a double-suction centrifugal pump under different flow rate conditions based on hexahedral structured grid. The numerical external characteristic performances agree well with the experimental performances. The predicted results show that the turbulence kinetic energy and the turbulence dissipation rate inside the impeller at design flow rate are lower than those at other off-design flow rates, which are caused by various vortexes. Based on frequency-domain analyses in the volute casing, the blade passing frequency is the dominant one of the pressure fluctuations except the vicinity of volute tongue for all operating cases, and the dominant frequency near the volute tongue ranges from 0 to 0.5 times the blade passing frequency for other off-design points, while the blade passing one near the volute tongue is the dominant one of the pressure fluctuations at design point. The increase of flow rate reduces the pressure fluctuations amplitude. For cavitation cases, the blade loading of the middle streamline increases a bit during the initial stage, but, for serious cavitation, the blade loading near the blade inlet reduces to 0 and even negative values, and the serious cavitation bubbles block the blade channels, which results in a sharp drop in pump head. Under noncavitation condition, the predicted power related to the pressure in the impeller channels increases from the inlet to the exit, while, under different cavitation conditions at the design flow rate, these power-transformation distributions in the impeller channels show that these power conversions are affected by the available NPSHa and the corresponding work in leading regions of the blades increases increases gradually a bit, and then it increases sharply in the middle regions, but it decreases in the blade trailing regions and is greatly influenced by secondary flows

    The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-Ī² Production by Targeting TNF Receptor-Associated Factor 3

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    Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-Ī² transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-Ī² pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3). This results in an attenuation of the type I IFN signaling pathway. We found that the NS1 C-terminal ED (named NS1/126-225) inhibits the active caspase activation and recruitment domain-containing form of RIG-I [RIG-I(N)]-induced IFN-Ī² reporter activity, the phosphorylation of IRF3, and the induction of IFN-Ī². Further analysis showed that NS1/126-225 binds to TRAF3 through the TRAF domain, subsequently decreasing TRAF3 K63-linked ubiquitination. NS1/126-225 binding also disrupted the formation of the mitochondrial antiviral signaling (MAVS)ā€“TRAF3 complex, increasing the recruitment of IKKĪµ to MAVS; ultimately shutting down the RIG-I(N)-mediated signal transduction and cellular antiviral responses. This attenuation of cellular antiviral responses leads to evasion of the innate immune response. Taken together, our findings offer an important insight into the interplay between the influenza virus and host innate immunity
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