Research on the numerical simulation of aerodynamic noises of shear flow based on linearized Euler equations

This paper numerically simulated the propagation of different sound sources in inhomogeneous media through solving linearized Euler equations (LEE). In space, dispersion-relation-preserving (DRP) scheme and compact difference scheme of high-order accuracy were used for dispersion. In time, Runge-Kutta (Low Dispersion and Dissipation Runge-Kutta) method with low-dispersion and low-dissipation was applied to push ahead. Nonreflecting boundary condition was adopted at the far-field boundary. In the meanwhile, numerical filtering was conducted for numerically computational results. The scattering of Gaussian pulse source around a cylinder was taken as a verification example. Numerical simulation results were compared with theoretical solutions to verify the correctness of numerical simulation method of aerodynamic noises in this paper. Numerical simulation was conducted for the sound propagation of monopole sound source in the shear layer and the sound propagation of different modes of sound sources in and out the tailpipe nozzle of engines. Numerical simulation results showed: The treatment for dispersion schemes and boundary conditions in this paper could well simulate the propagation process of aerodynamic noises in the shear layer; the shear flow would have an impact on the amplitude and propagation direction of aerodynamic noises in the flow field; for different modes of pipe sound sources, the shear layer would cause different refraction effects; the direction of sound radiation was rather centralized for the single pipe mode and dispersive for the multi-pipe mode. In addition, the dispersive-ness of sound radiation became stronger and stronger with the increased pipe modes. Namely, the directivity of sound presented to be a petal. The shear layer would reduce the dispersion effect of multi-pipe modes in the direction of sound radiation

Unraveling Epigenetic Regulation in Embryonic Stem Cells

Embryonic stem (ES) cells can replicate indefinitely while retaining the capacity to differentiate into functionally distinct cell types. ES cells proliferate and differentiate without detectable genetic changes, indicating that these processes are controlled by epigenetic factors. Here we describe what is known about the epigenetics of ES cells and speculate that a dynamic balance among at least three epigenetic elements (chromatin structure, DNA methylation, and microRNAs), in conjunction with transcription factors, contributes to the maintenance of pluripotence. Understanding the interactions among these factors will be critical to the development of improved strategies to reprogram differentiated cells or direct differentiation of pluripotent cells

Artemisinin Directly Targets Malarial Mitochondria through Its Specific Mitochondrial Activation

The biological mode of action of artemisinin, a potent antimalarial, has long been controversial. Previously we established a yeast model addressing its mechanism of action and found mitochondria the key in executing artemisinin's action. Here we present data showing that artemisinin directly acts on mitochondria and it inhibits malaria in a similar way as yeast. Specifically, artemisinin and its homologues exhibit correlated activities against malaria and yeast, with the peroxide bridge playing a key role for their inhibitory action in both organisms. In addition, we showed that artemisinins are distributed to malarial mitochondria and directly impair their functions when isolated mitochondria were tested. In efforts to explore how the action specificity of artemisinin is achieved, we found strikingly rapid and dramatic reactive oxygen species (ROS) production is induced with artemisinin in isolated yeast and malarial but not mammalian mitochondria, and ROS scavengers can ameliorate the effects of artemisinin. Deoxyartemisinin, which lacks an endoperoxide bridge, has no effect on membrane potential or ROS production in malarial mitochondria. OZ209, a distantly related antimalarial endoperoxide, also causes ROS production and depolarization in isolated malarial mitochondria. Finally, interference of mitochondrial electron transport chain (ETC) can alter the sensitivity of the parasite towards artemisinin. Addition of iron chelator desferrioxamine drastically reduces ETC activity as well as mitigates artemisinin-induced ROS production. Taken together, our results indicate that mitochondrion is an important direct target, if not the sole one, in the antimalarial action of artemisinins. We suggest that fundamental differences among mitochondria from different species delineate the action specificity of this class of drugs, and differing from many other drugs, the action specificity of artemisinins originates from their activation mechanism

Profiling alternatively spliced mRNA isoforms for prostate cancer classification

BACKGROUND: Prostate cancer is one of the leading causes of cancer illness and death among men in the United States and world wide. There is an urgent need to discover good biomarkers for early clinical diagnosis and treatment. Previously, we developed an exon-junction microarray-based assay and profiled 1532 mRNA splice isoforms from 364 potential prostate cancer related genes in 38 prostate tissues. Here, we investigate the advantage of using splice isoforms, which couple transcriptional and splicing regulation, for cancer classification. RESULTS: As many as 464 splice isoforms from more than 200 genes are differentially regulated in tumors at a false discovery rate (FDR) of 0.05. Remarkably, about 30% of genes have isoforms that are called significant but do not exhibit differential expression at the overall mRNA level. A support vector machine (SVM) classifier trained on 128 signature isoforms can correctly predict 92% of the cases, which outperforms the classifier using overall mRNA abundance by about 5%. It is also observed that the classification performance can be improved using multivariate variable selection methods, which take correlation among variables into account. CONCLUSION: These results demonstrate that profiling of splice isoforms is able to provide unique and important information which cannot be detected by conventional microarrays