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56. T-cell death following immune activation is mediated by mitochondria-localized SARM

Author

Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Chen, Jianzhu, Panneerselvam, P., Singh, L. P., Selvarajan, V., Chng, W. J., Ng, S. B., Tan, N. S., Ho, B., Ding, Jeak Ling, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Chen, Jianzhu, Panneerselvam, P., Singh, L. P., Selvarajan, V., Chng, W. J., Ng, S. B., Tan, N. S., Ho, B., and Ding, Jeak Ling

Abstract

Singapore-MIT Alliance Computational and Systems Biology Flagship Project

Published
2014

79. Experimental design and performance analysis of alumina coatings deposited by a detonation spray process

Author

Saravanan, P., Selvarajan, V., Joshi, S. V., Sundararajan, G., Saravanan, P., Selvarajan, V., Joshi, S. V., and Sundararajan, G.

Abstract

The increasing demands for high-quality coatings has made it inevitable that the surface coating industry would put more effort into precisely controlling the coating process. Statistical design of experiments is an effective method for finding the optimum spray parameters to enhance thermal spray coating properties. In the present investigation, an attempt is made to produce high-quality alumina (Al2O3) coatings by optimizing the detonation spray process parameters following a (L16-24) factorial design approach. The process parameters that were varied include the fuel ratio, carrier gas flow rate, frequency of detonations and spray distance. The coating characteristics were quantified with respect to roughness, hardness and porosity. The performance of the coatings was quantitively evaluated using erosion, abrasion and sliding wear testing. Through statistical analysis of the experimental results, performed by the ANOVA method, the significance of each process parameter together with an optimal variable combination was obtained for the desired coating attributes. Confirmation experiments were conducted to verify the optimal spray parameter combination, which clearly showed the possibility of producing high-quality Al2O3 coatings.

Published
2001

80. Application of Taguchi method to the optimization of detonation spraying process

Author

Saravanan, P., Selvarajan, V., Srinivasa Rao, D., Joshi, S. V., Sundararajan, G., Saravanan, P., Selvarajan, V., Srinivasa Rao, D., Joshi, S. V., and Sundararajan, G.

Abstract

The present study deals with an application of the Taguchi method to the optimization of a detonation spray process for alumina coatings. Coating experiments were conducted using the Taguchi-fractional factorial (L8) design parametric study to optimize spray process parameters. The Taguchi design evaluated the effects of four detonation spray process parameters: acetylene to oxygen ratio, carrier gas flow rate, frequency of detonations and spray distance. The coating qualities evaluated were surface roughness, porosity, microhardness, and abrasion mass loss. The influence of process parameters on the as-sprayed coating qualities is discussed. The results of the study indicate that the higher fuel ratio and lower spray distance will result in higher hardness, lower porosity and lower abrasion mass loss. The Taguchi analysis employed in the present investigation led to optimized process parameters for the most abrasive wear resistant alumina coatings.

Published
2000

81. Influence of spraying variables on structure and properties of plasma sprayed alumina coatings

Author

Saravanan, P., Selvarajan, V., Srivastava, M. P., Joshi, S. V., Sundararajan, G., Saravanan, P., Selvarajan, V., Srivastava, M. P., Joshi, S. V., and Sundararajan, G.

Abstract

An experimental statistical design study on the plasma spraying of alumina powder has been carried out.Coating experiments were conducted, using a Taguchi full factorial L16 design parametric approach, to study the effect of four key plasma processing variables on the coating quality, namely, primary gas flow rate, arc current, powder feed rate, and spray distance. Optical microscopy, scanning electron microscopy, XRD, image analysis, and hardness testing were used for characterization. The resulting as sprayed coating characteristics were quantified with respect to roughness, microhardness, porosity, and microstructure. Through statistical calculation (analysis of variance), the parameters that have significant influence on the structure and properties of the coatings were identified and their relative importance and contribution ratios to overall variance were studied. The Taguchi evaluation employed in the present investigation showed that an improvement in the coating properties could be achieved using an optimum combination of variables.

Published
2000

97. T-cell death following immune activation is mediated by mitochondria-localized SARM.

Author

Panneerselvam, P, Singh, L P, Selvarajan, V, Chng, W J, Ng, S B, Tan, N S, Ho, B, Chen, J, and Ding, J L

Subjects
CELL death, T cells, MITOCHONDRIA, AUTOIMMUNE diseases, CELL proliferation, APOPTOSIS
Abstract

Following acute-phase infection, activated T cells are terminated to achieve immune homeostasis, failure of which results in lymphoproliferative and autoimmune diseases. We report that sterile α- and heat armadillo-motif-containing protein (SARM), the most conserved Toll-like receptors adaptor, is proapoptotic during T-cell immune response. SARM expression is significantly reduced in natural killer (NK)/T lymphoma patients compared with healthy individuals, suggesting that decreased SARM supports NK/T-cell proliferation. T cells knocked down of SARM survived and proliferated more significantly compared with wild-type T cells following influenza infection in vivo. During activation of cytotoxic T cells, the SARM level fell before rising, correlating inversely with cell proliferation and subsequent T-cell clearance. SARM knockdown rescued T cells from both activation- and neglect-induced cell deaths. The mitochondria-localized SARM triggers intrinsic apoptosis by generating reactive oxygen species and depolarizing the mitochondrial potential. The proapoptotic function is attributable to the C-terminal sterile alpha motif and Toll/interleukin-1 receptor domains. Mechanistically, SARM mediates intrinsic apoptosis via B cell lymphoma-2 (Bcl-2) family members. SARM suppresses B cell lymphoma-extra large (Bcl-xL) and downregulates extracellular signal-regulated kinase phosphorylation, which are cell survival effectors. Overexpression of Bcl-xL and double knockout of Bcl-2 associated X protein and Bcl-2 homologous antagonist killer substantially reduced SARM-induced apoptosis. Collectively, we have shown how T-cell death following infection is mediated by SARM-induced intrinsic apoptosis, which is crucial for T-cell homeostasis. [ABSTRACT FROM AUTHOR]

Published
2013
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