Hyperforin promotes mitochondrial function and development of oligodendrocytes

Major depressive disorder is a common severe psychiatric disorder with unknown etiology. Recent studies show that the loss and malfunction of oligodendrocytes are closely related to the neuropathological changes in depression, which can be reversed by antidepressant treatment. St. John’s wort is an effective and safe herbal treatment for depression in several clinical trials. However, the underlying mechanism of its therapeutic effects is unclear. In this study, we evaluated the effects of hyperforin, a major active component of this herb, on the proliferation, mitochondrial function and development of oligodendrocytes. We have demonstrated that hyperforin increases mitochondrial function and prevents mitochondrial toxin-induced cytotoxicity in oligodendrocyte lineage cells. Hyperforin promotes the maturation of oligodendrocytes but does not increase the proliferation of oligodendrocyte progenitor cell line and neural stem/progenitor cells. Our findings suggest that chronic hyperforin treatment may stimulate the development and function of oligodendrocytes. These results suggest a new mechanism of hyperforin in depression treatment. Future in vitro and in vivo studies are required to further characterize the mechanisms of hyperforin

Code Completion by Modeling Flattened Abstract Syntax Trees as Graphs

Code completion has become an essential component of integrated development environments. Contemporary code completion methods rely on the abstract syntax tree (AST) to generate syntactically correct code. However, they cannot fully capture the sequential and repetitive patterns of writing code and the structural information of the AST. To alleviate these problems, we propose a new code completion approach named CCAG, which models the flattened sequence of a partial AST as an AST graph. CCAG uses our proposed AST Graph Attention Block to capture different dependencies in the AST graph for representation learning in code completion. The sub-tasks of code completion are optimized via multi-task learning in CCAG, and the task balance is automatically achieved using uncertainty without the need to tune task weights. The experimental results show that CCAG has superior performance than state-of-the-art approaches and it is able to provide intelligent code completion.Comment: Accepted in AAAI 2021. This version contains the appendix for the derivation of Eq. 1

Probabilistic Harmonic Calculation in Distribution Networks with Electric Vehicle Charging Stations

Integrating EV charging station into power grid will bring impacts on power system, among which the most significant one is the harmonic pollution on distribution networks. Due to the uncertainty of the EV charging process, the harmonic currents brought by EV charging stations have a random nature. This paper proposed a mathematical simulation method for studying the working status of charging stations, which considers influencing factors including random leaving factor, electricity price, and waiting time. Based on the proposed simulation method, the probability distribution of the harmonic currents of EV charging stations is obtained and used in the calculation of the probability harmonic power flow. Then the impacts of EVs and EV charging stations on distribution networks can be analyzed. In the case study, the proposed simulation and analysis method is implemented on the IEEE-34 distribution network. The influences of EV arrival rates, the penetration rate, and the accessing location of EV charging station are also investigated. Results show that this research has good potential in guiding the planning and construction of charging station

Sumoylation regulates nuclear localization and function of zinc finger transcription factor ZIC3

AbstractZIC3, an X-linked zinc finger transcription factor, was the first identified gene involved in establishing normal left–right patterning in humans. Mutations in the Zic3 gene in patients cause heterotaxy, which includes congenital heart defects. However, very little is known about how the function of the ZIC3 protein is regulated. Sumoylation is a posttranslational modification process in which a group of small ubiquitin-like modifier (SUMO) proteins is covalently attached to targets via a series of enzymatic reactions. Here, we report for the first time that sumoylation targets human ZIC3 primarily on the consensus lysine residue K248, which is critical for the nuclear retention of ZIC3. Consequently, SUMO modification potentiates the repressive activity of ZIC3 on the promoter of its target gene cardiac α-actin, and the mutation of lysine 248 to arginine (K248R) abolishes its repressive function. We further revealed that ZIC3 variants with mutations found in human patients with congenital anomalies exhibit aberrant sumoylation activity, which at least partially accounts for their cytoplasmic diffusion. Improved sumoylation of human disease-associated ZIC3 variants reestablishes their nuclear occupancy in the presence of SUMO E3 ligase and SUMO-1. Thus, the altered sumoylation status of ZIC3 underpins the developmental abnormalities associated with these ZIC3 mutants. The SUMO targeting consensus sequence in ZIC3 is highly conserved in its paralogs and orthologs, pointing to sumoylation as a general mechanism underlying the functional control of ZIC proteins. This study provides a potential therapeutic strategy to regain the normal subcellular distribution and function of ZIC3 mutants by restoring SUMO conjugation

Accurate and efficient hydrodynamic analysis of structures with sharp edges by the Extended Finite Element Method (XFEM): 2D studies

Achieving accurate numerical results of hydrodynamic loads based on the potential-flow theory is very challenging for structures with sharp edges, due to the singular behavior of the local-flow velocities. In this paper, we introduce the Extended Finite Element Method (XFEM) to solve fluid-structure interaction problems involving sharp edges on structures. Four different FEM solvers, including conventional linear and quadratic FEMs as well as their corresponding XFEM versions with local enrichment by singular basis functions at sharp edges, are implemented and compared. To demonstrate the accuracy and efficiency of the XFEMs, a thin flat plate in an infinite fluid domain and a forced heaving rectangle at the free surface, both in two dimensions, will be studied. For the flat plate, the mesh convergence studies are carried out for both the velocity potential in the fluid domain and the added mass, and the XFEMs show apparent advantages thanks to their local enhancement at the sharp edges. Three different enrichment strategies are also compared, and suggestions will be made for the practical implementation of the XFEM. For the forced heaving rectangle, the linear and 2nd order mean wave loads are studied. Our results confirm the previous conclusion in the literature that it is not difficult for a conventional numerical model to obtain convergent results for added mass and damping coefficients. However, when the 2nd order mean wave loads requiring the computation of velocity components are calculated via direct pressure integration, it takes a tremendously large number of elements for the conventional FEMs to get convergent results. On the contrary, the numerical results of XFEMs converge rapidly even with very coarse meshes, especially for the quadratic XFEM

Increasing prevalence of HIV and syphilis but decreasing rate of self-reported unprotected anal intercourse among men who had sex with men in Harbin, China: results of five consecutive surveys from 2006 to 2010

Background To monitor the prevalence of HIV and syphilis as well as behaviours, a sentinel site for men who have sex with men was established in Harbin in 2002. With additional funding, the sentinel surveillance evolved into annual cross-sectional surveys since 2006. Methods Behavioural and serological data collected in five consecutive cross-sectional surveys were analysed. SPSS 13.0 was applied to compare prevalence of HIV and syphilis as well as behavioural variables over time by demographic variables, bivariate and multivariate analysis. Results The prevalence of HIV and syphilis increased from 1.0% in 2006 to 7.5% in 2010 and from 9.2% in 2006 to 22.4% in 2009, respectively, whereas the rate of unprotected anal intercourse decreased from 61.3% in 2006 to 47.1% in 2010. Syphilis positivity and HIV infection are independently associated with each other across years. The rate of unprotected anal sex remains high although it has decreased over the years. Conclusion Findings support an increasing prevalence of HIV and syphilis among men who have sex with men in Harbin. Targeted behavioural intervention and syphilis treatment are urgently needed to prevent the epidemic from growin