Robust optimization in HTS cable based on design for six sigma

The nonuniform ac current distribution among the multilayer conductors in a high-temperature superconducting (HTS) cable reduces the current capacity and increases the ac loss. Various numerical simulation techniques and optimization methods have been applied in structural optimization of HTS cables. While the existence of fluctuation in design variables or operation conditions has a great influence on the cable quality, in order to eliminate the effects of parameter perturbations in design and to improve the design efficiency, a robust optimization method based on design for six sigma (DFSS) is presented in this paper. The optimization results show that the proposed optimization procedure can not only achieve a uniform current distribution, but also improve significantly the reliability and robustness of the HTS cable quality, comparing with those by using the particle swarm optimization. © 2008 IEEE

Robust optimization of multilayer conductors of HTS AC cable using PSO and perturbation analysis

For a High Temperature Superconducting (HTS) cable, a non-uniform AC current distribution among the multilayer conductors gives rise to increased AC losses. To get a uniform current distribution among the multilayer conductors, a constrained optimization model is constructed with continuous and discrete variables, such as the winding angle, radius and the winding direction of each layer. Under the constraints of the mechanical properties and critical current of the tape, the Particle Swarm Optimization (PSO) algorithm is employed for structural parameter optimization in both warm and cold dielectric type HTS cables. A uniform current distribution among layers is realized by optimizing the structural parameters. The perturbation analysis is employed to evaluate the parameters after optimization. It is found that the robust stabilizations are different among the various optimal results. The PSO is proved to be a more powerful tool than the Genetic Algorithm (GA) for structural parameter optimization. © 2006 IEEE

Current distribution analysis for high temperature superconducting cable considering hysteresis characteristics

This paper presents a hysteresis model for Type-II high temperature superconductor (HTS) by using simplified Preisach Model, in which the Preisach distribution function μ-kα, β) is determined only based on the B-H limiting loop. The nonlinear dynamic circuit model of the superconductor is established. In the circuit model, the hysteresis inductance and hysteresis loss described by using simplified Preisach Model are deduced. Applying the hysteresis circuit model, the currents flowing in different superconductor layers of high temperature superconducting cable are simulated, as well as the hysteresis loss of the superconducting cable. The simulation results are verified by comparison with the data recorded in literatures. Finally, the influences of hysteresis on superconducting cable are analyzed and discussed. © 2010 - IOS Press and the authors. All rights reserved

Alisertib, an Aurora kinase A inhibitor, induces apoptosis and autophagy but inhibits epithelial to mesenchymal transition in human epithelial ovarian cancer cells.

Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects, and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear. This study investigated the effects of ALS on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT), and the underlying mechanisms in human epithelial ovarian cancer SKOV3 and OVCAR4 cells. Our docking study showed that ALS, MLN8054, and VX-680 preferentially bound to AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking. ALS had potent growth-inhibitory, proapoptotic, proautophagic, and EMT-inhibitory effects on SKOV3 and OVCAR4 cells. ALS arrested SKOV3 and OVCAR4 cells in G2/M phase and induced mitochondria-mediated apoptosis and autophagy in both SKOV3 and OVCAR4 cell lines in a concentration-dependent manner. ALS suppressed phosphatidylinositol 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways but activated 5\u27-AMP-dependent kinase, as indicated by their altered phosphorylation, contributing to the proautophagic activity of ALS. Modulation of autophagy altered basal and ALS-induced apoptosis in SKOV3 and OVCAR4 cells. Further, ALS suppressed the EMT-like phenotype in both cell lines by restoring the balance between E-cadherin and N-cadherin. ALS downregulated sirtuin 1 and pre-B cell colony enhancing factor (PBEF/visfatin) expression levels and inhibited phosphorylation of AURKA in both cell lines. These findings indicate that ALS blocks the cell cycle by G2/M phase arrest and promotes cellular apoptosis and autophagy, but inhibits EMT via phosphatidylinositol 3-kinase/Akt/mTOR-mediated and sirtuin 1-mediated pathways in human epithelial ovarian cancer cells. Further studies are warranted to validate the efficacy and safety of ALS in the treatment of ovarian cancer

Long-term in vivo imaging and measurement of dendritic shrinkage of retinal ganglion cells

PURPOSE. To monitor and measure dendritic shrinkage of retinal ganglion cells (RGCs) in a strain of transgenic mice (Thy-1 YFP) that expresses yellow fluorescent proteins in neurons under the control of a Thy-1 promoter. METHODS. A total of 125 RGCs from 16 eyes of Thy-1 YFP transgenic mice were serially imaged with a confocal scanning laser ophthalmoscope for 6 months after optic nerve crush. Quantitative analysis of cell body area, axon diameter, dendritic field, number of terminal branches, total dendritic branch length, branching complexity, symmetry, and distance from the optic disc was used to characterize the morphology of RGCs, describe the patterns of axonal and dendritic degeneration, identify the morphologic predictors for cell survival, and estimate the rate of dendritic shrinkage. RESULTS. RGC damage was observed prospectively to begin with progressive dendritic shrinkage, followed by loss of the axon and the cell body. In a small proportion of RGCs, progressive axonal changes including fragmentation, beading, retraction, and bulb formation were also observed. RGCs with a larger dendritic field and a longer total dendritic branch length in general have a better survival probability. The rate of dendritic shrinkage was variable with a slower rate observed in cells having a larger dendritic field, a longer total dendritic branch length, and a greater distance from the optic disc. CONCLUSIONS. Estimating the probability of RGC survival and measuring the rate of dendritic shrinkage could become a new paradigm for investigating neuronal degeneration and evaluating the response of neuroprotective treatment. © 2011 The Association for Research in Vision and Ophthalmology, Inc.postprin

Clonal Immune Responses of Mycobacterium-Specific γδ T Cells in Tuberculous and Non-Tuberculous Tissues during M. tuberculosis Infection

BACKGROUND: We previously demonstrated that unvaccinated macaques infected with large-dose M.tuberculosis(Mtb) exhibited delays for pulmonary trafficking of Ag-specific αβ and γδ T effector cells, and developed severe lung tuberculosis(TB) and "secondary" Mtb infection in remote organs such as liver and kidney. Despite delays in lungs, local immunity in remote organs may accumulate since progressive immune activation after pulmonary Mtb infection may allow IFNγ-producing γδ T cells to adequately develop and traffic to lately-infected remote organs. As initial efforts to test this hypothesis, we comparatively examined TCR repertoire/clonality, tissue trafficking and effector function of Vγ2Vδ2 T cells in lung with severe TB and in liver/kidney without apparent TB. METHODOLOGY/PRINCIPAL FINDINGS: We utilized conventional infection-immunity approaches in macaque TB model, and employed our decades-long expertise for TCR repertoire analyses. TCR repertoires in Vγ2Vδ2 T-cell subpopulation were broad during primary Mtb infection as most TCR clones found in lymphoid system, lung, kidney and liver were distinct. Polyclonally-expanded Vγ2Vδ2 T-cell clones from lymphoid tissues appeared to distribute and localize in lung TB granuloms at the endpoint after Mtb infection by aerosol. Interestingly, some TCR clones appeared to be more predominant than others in lymphocytes from liver or kidney without apparent TB lesions. TCR CDR3 spetratyping revealed such clonal dominance, and the clonal dominance of expanded Vγ2Vδ2 T cells in kidney/liver tissues was associated with undetectable or low-level TB burdens. Furthermore, Vγ2Vδ2 T cells from tissue compartments could mount effector function for producing anti-mycobacterium cytokine. CONCLUSION: We were the first to demonstrate clonal immune responses of mycobacterium-specific Vγ2Vδ2 T cells in the lymphoid system, heavily-infected lungs and lately subtly-infected kidneys or livers during primary Mtb infection. While clonally-expanded Vγ2Vδ2 T cells accumulated in lately-infected kidneys/livers without apparent TB lesions, TB burdens or lesions appeared to impact TCR repertoires and tissue trafficking patterns of activated Vγ2Vδ2 T cells

DSIF and RNA Polymerase II CTD Phosphorylation Coordinate the Recruitment of Rpd3S to Actively Transcribed Genes

Histone deacetylase Rpd3 is part of two distinct complexes: the large (Rpd3L) and small (Rpd3S) complexes. While Rpd3L targets specific promoters for gene repression, Rpd3S is recruited to ORFs to deacetylate histones in the wake of RNA polymerase II, to prevent cryptic initiation within genes. Methylation of histone H3 at lysine 36 by the Set2 methyltransferase is thought to mediate the recruitment of Rpd3S. Here, we confirm by ChIP–Chip that Rpd3S binds active ORFs. Surprisingly, however, Rpd3S is not recruited to all active genes, and its recruitment is Set2-independent. However, Rpd3S complexes recruited in the absence of H3K36 methylation appear to be inactive. Finally, we present evidence implicating the yeast DSIF complex (Spt4/5) and RNA polymerase II phosphorylation by Kin28 and Ctk1 in the recruitment of Rpd3S to active genes. Taken together, our data support a model where Set2-dependent histone H3 methylation is required for the activation of Rpd3S following its recruitment to the RNA polymerase II C-terminal domain