Quantum Hydrodynamic Model by Moment Closure of Wigner Equation

In this paper, we derive the quantum hydrodynamics models based on the moment closure of the Wigner equation. The moment expansion adopted is of the Grad type firstly proposed in \cite{Grad}. The Grad's moment method was originally developed for the Boltzmann equation. In \cite{Fan_new}, a regularization method for the Grad's moment system of the Boltzmann equation was proposed to achieve the globally hyperbolicity so that the local well-posedness of the moment system is attained. With the moment expansion of the Wigner function, the drift term in the Wigner equation has exactly the same moment representation as in the Boltzmann equation, thus the regularization in \cite{Fan_new} applies. The moment expansion of the nonlocal Wigner potential term in the Wigner equation is turned to be a linear source term, which can only induce very mild growth of the solution. As the result, the local well-posedness of the regularized moment system for the Wigner equation remains as for the Boltzmann equation

Effect of Litter Addition on Amino Acid Content and Composition in Alpine Meadow Soil

Litter plays an important role in plant-soil nutrient cycling. However, the response of soil amino acid pools to litter input is unclear. Therefore, the aim of this study was to explore the effects of litter addition on the content and composition of soil amino acids in an alpine meadow soil. Soil was amended with litter of its dominant species, Kobresia graminifolia, and incubated for four weeks. Our results show that litter addition significantly increased the exchangeable amino acid content and protease activity in the soil. These results are crucial for understanding the amino acid cycling in soil

Anomalous in-plane magnetoresistance of electron-doped cuprate La2−xCexCuO4±δ

We report systematic in-plane magnetoresistance measurements on the electron-doped cuprate La2−xCexCuO4±δ thin films as a function of Ce doping and oxygen content in the magnetic field up to 14T. A crossover from negative to positive magnetoresistance occurs between the doping level x = 0.07 and 0.08. Above x = 0.08, the positive magnetoresistance effect appears, and is almost indiscernible at x = 0.15. By tuning the oxygen content, the as-grown samples show negative magnetoresistance effect, whereas the optimally annealed ones display positive magnetoresistance effect at the doping level x = 0.15. Intriguingly, a linear-field dependence of in-plane magnetoresistance is observed at the underdoping level x = 0.06, the optimal doping level x = 0.1 and slightly overdoping level x = 0.11. These anomalies of in-plane magnetoresistance may be related to the intrinsic inhomogeneity in the cuprates, which is discussed in the framework of network model

Life Beyond Kinases: Structure-Based Discovery of Sorafenib as Nanomolar Antagonist of 5-HT Receptors

Of great interest in recent years has been computationally predicting the novel polypharmacology of drug molecules. Here, we applied an “induced-fit” protocol to improve the homology models of 5-HT2A receptor, and we assessed the quality of these models in retrospective virtual screening. Subsequently, we computationally screened the FDA approved drug molecules against the best induced-fit 5-HT2A models, and chose six top scoring hits for experimental assays. Surprisingly, one well-known kinase inhibitor, sorafenib has shown unexpected promiscuous 5-HTRs binding affinities, Ki = 1959, 56 and 417 nM against 5-HT2A, 5-HT2B and 5-HT2C, respectively. Our preliminary SAR exploration supports the predicted binding mode, and further suggests sorafenib to be a novel lead compound for 5HTR ligand discovery. Although it has been well known that sorafenib produces anticancer effects through targeting multiple kinases, carefully designed experimental studies are desirable to fully understand whether its “off-target” 5-HTR binding activities contribute to its therapeutic efficacy or otherwise undesirable side effects

Tanshinones Inhibit the Growth of Breast Cancer Cells through Epigenetic Modification of Aurora A Expression and Function

The objectives of this study were to evaluate the effects of tanshinones from a Chinese herb Salvia Miltiorrhiza on the growth of breast cancer cells, and to elucidate cellular and molecular mechanisms of action. Tanshinones showed the dose-dependent effect on the growth inhibition of breast cancer cells in vitro, with tanshinone I (T1) the most potent agent. T1 was also the only tanshinone to have potent activity in inhibiting the growth of the triple-negative breast cancer cell line MDA-MB231. T1 caused cell cycle arrests of both estrogen-dependent and estrogen-independent cell lines associated with alterations of cyclinD, CDK4 and cyclinB, and induced breast cancer cell apoptosis associated with upregulation of c-PARP and downregulation of survivin and Aurora A. Among these associated biomarkers, Aurora A showed the most consistent pattern with the anti-growth activity of tanshinones. Overexpression of Aurora A was also verified in breast tumors. The gene function assay showed that knockdown of Aurora A by siRNA dramatically reduced the growth-inhibition and apoptosis-induction activities of T1, suggesting Aurora A as an important functional target of T1 action. On the other hand, tanshinones had much less adverse effects on normal mammary epithelial cells. Epigenetic mechanism studies showed that overexpression of Aurora A gene in breast cancer cells was not regulated by gene promoter DNA methylation, but by histone acetylation. T1 treatment significantly reduced acetylation levels of histone H3 associated with Aurora A gene. Our results supported the potent activity of T1 in inhibiting the growth of breast cancer cells in vitro in part by downregulation of Aurora A gene function. Our previous studies also demonstrated that T1 had potent anti-angiogenesis activity and minimal side effects in vivo. Altogether, this study warrants further investigation to develop T1 as an effective and safe agent for the therapy and prevention of breast cancer

Identification and Characterization of Paramyosin from Cyst Wall of Metacercariae Implicated Protective Efficacy against Clonorchis sinensis Infection

Human clonorchiasis has been increasingly prevalent in recent years and results in a threat to the public health in epidemic regions, motivating current strategies of vaccines to combat Clonorchis sinensis (C. sinensis). In this study, we identified C. sinensis paramyosin (CsPmy) from the cyst wall proteins of metacercariae by proteomic approaches and characterized the expressed recombinant pET-26b-CsPmy protein (101 kDa). Bioinformatics analysis indicated that full-length sequences of paramyosin are conserved in helminthes and numerous B-cell/T-cell epitopes were predicted in amino acid sequence of CsPmy. Western blot analysis showed that CsPmy was expressed at four life stages of C. sinensis, both cyst wall proteins and soluble tegumental components could be probed by anti-CsPmy serum. Moreover, immunolocalization results revealed that CsPmy was specifically localized at cyst wall and excretory bladder of metacercaria, as well as the tegument, oral sucker and vitellarium of adult worm. Both immunoblot and immunolocalization results demonstrated that CsPmy was highly expressed at the stage of adult worm, metacercariae and cercaria, which could be supported by real-time PCR analysis. Both recombinant protein and nucleic acid of CsPmy showed strong immunogenicity in rats and induced combined Th1/Th2 immune responses, which were reflected by continuous high level of antibody titers and increased level of IgG1/IgG2a subtypes in serum. In vaccine trials, comparing with control groups, both CsPmy protein and DNA vaccine exhibited protective effect with significant worm reduction rate of 54.3% (p<0.05) and 36.1% (p<0.05), respectively. In consistence with immune responses in sera, elevated level of cytokines IFN-γ and IL-4 in splenocytes suggested that CsPmy could induce combined cellular immunity and humoral immunity in host. Taken together, CsPmy could be a promising vaccine candidate in the prevention of C. sinensis regarding its high immunogenicity and surface localization

Identifying Compound-Target Associations by Combining Bioactivity Profile Similarity Search and Public Databases Mining

Molecular target identification is of central importance to drug discovery. Here, we developed a computational approach, named bioactivity profile similarity search (BASS), for associating targets to small molecules by using the known target annotations of related compounds from public databases. To evaluate BASS, a bioactivity profile database was constructed using 4296 compounds that were commonly tested in the US National Cancer Institute 60 human tumor cell line anticancer drug screen (NCI-60). Each compound was used as a query to search against the entire bioactivity profile database, and reference compounds with similar bioactivity profiles above a threshold of 0.75 were considered as neighbor compounds of the query. Potential targets were subsequently linked to the identified neighbor compounds by using the known targets o

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder:The ENIGMA adventure

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