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Lefrancois, Emmanuel,Brandely, Anais,Mottelet, Stephane Techno-Press 2016 Coupled systems mechanics Vol.5 No.3
A numerical model for fluid-structure interactions (abbr. FSI) is presented in the context of sloshing effects in movable, partially filled tanks to improve understanding of interactions between the fluid and the dynamics of a tank flexibly attached to a vehicle. The purpose of this model is to counteract the penalizing impact of the added mass effect on classical partitioned FSI coupling scheme: the proposed investigation is based on an added mass corrected version of the classical strongly coupled partitioned scheme presented in (Song et al. 2013). Results show that this corrected version systematically allows convergence to the coupled solution. In the rare cases where convergence is already obtained, the corrected version significantly reduces the number of iterations required. Finally, it is shown that the convergence limit imposed by added mass effect for the non-corrected coupling scheme, is directly dependent on the aspect ratio of the fluid domain and highly related to the precision order of the temporal discretization scheme.
Myers, Lara,Lee, Seung Woo,Rossi, Robert J.,Lefrancois, Leo,Kwon, Byoung S.,Mittler, Robert S.,Croft, Michael,Vella, Anthony T. Oxford University Press 2006 International immunology Vol.18 No.2
<P>In practice, vaccines should induce lasting and efficacious T cell immunity without promoting deleterious pathological consequences. To accomplish this goal we immunized mice with ovalbumin peptide, polyinosinic–polycytidylic and anti-CD137. Vaccinated mice retained a massive functional CD8 T cell memory pool in lymphoid and non-lymphoid tissues for >1 year. The memory T cells clonally expanded, produced substantial amounts of IFNγ, and responded vigorously to vesicular stomatitis virus infection. To understand how the vaccine might function, we showed that the antigen-specific T cells must bear CD137 in order for optimal priming to occur. Thus, anti-CD137 agonist mAb directly stimulated peptide-specific CD8 T cells and conditioned them to survive. In contrast, CD137-deficient CD8 T cells did not survive despite CD137 expression by antigen presenting cells. Taken together, the data indicate that CD137 and adjuvant combined therapy is an efficacious vaccine strategy for immunization with non-replicating inert antigen.</P>
Thangada, Shobha,Khanna, Kamal M.,Blaho, Victoria A.,Oo, Myat Lin,Im, Dong-Soon,Guo, Caiying,Lefrancois, Leo,Hla, Timothy The Rockefeller University Press 2010 The Journal of experimental medicine Vol.207 No.7
<P>The sphingosine 1-phosphate receptor 1 (S1P<SUB>1</SUB>) promotes lymphocyte egress from lymphoid organs. Previous work showed that agonist-induced internalization of this G protein–coupled receptor correlates with inhibition of lymphocyte egress and results in lymphopenia. However, it is unclear if S1P<SUB>1</SUB> internalization is necessary for this effect. We characterize a knockin mouse (<I>S1p1r<SUP>S5A/S5A</SUP></I>) in which the C-terminal serine-rich S1P<SUB>1</SUB> motif, which is important for S1P<SUB>1</SUB> internalization but dispensable for S1P<SUB>1</SUB> signaling, is mutated. T cells expressing the mutant S1P<SUB>1</SUB> showed delayed S1P<SUB>1</SUB> internalization and defective desensitization after agonist stimulation. Mutant mice exhibited significantly delayed lymphopenia after S1P<SUB>1</SUB> agonist administration or disruption of the vascular S1P gradient. Adoptive transfer experiments demonstrated that mutant S1P<SUB>1</SUB> expression in lymphocytes, rather than endothelial cells, facilitated this delay in lymphopenia. Thus, cell-surface residency of S1P<SUB>1</SUB> on T cells is a primary determinant of lymphocyte egress kinetics in vivo.</P>