Lipoarabinomannan (LAM) is one of the major constituents of the Mycobacterium tuberculosis cell wall and an attractive molecular scaffold for antituberculosis drug and vaccine development. In this paper, a convergent strategy was developed for the synthesis of LAM oligosaccharides with an α-1,2-linked dimannopyranose cap at the nonreducing end. The strategy was highlighted by efficient coupling of separately prepared nonreducing end and reducing end oligosaccharides. Glycosylations were mainly achieved with thioglycoside donors, which gave excellent yields and stereoselectivity even for reactions between complex oligosaccharides. The strategy was utilized to successfully synthesize tetra-, hepta-, and undecasaccharides of LAM from d-arabinose in 10, 15, and 14 longest linear steps and 7.84, 7.50, and 2.59% overall yields, respectively. The resultant oligosaccharides with a free amino group at their reducing end were effectively conjugated with carrier proteins, including bovine serum albumin and keyhole limpet hemocyanin (KLH), via a bifunctional linker. Preliminary immunological studies on the KLH conjugates revealed that they could elicit robust antibody responses in mice and that the antigen structure had some influence on their immunological property, thus verifying the potential of the oligosaccharides for vaccine development and other immunological studies.

The aim of this study is to investigate the dynamic response of a multi-segment model of the thoracolumbar spine and determine how the sitting posture affects the response under the impact of ejection. A nonlinear finite element model of the thoracolumbar-pelvis complex (T9-S1) was developed and validated. A multi-body dynamic model of a pilot was also constructed so an ejection seat restraint system could be incorporated into the finite element model. The distribution of trunk mass on each vertebra was also considered in the model. Dynamics analysis showed that ejection impact induced obvious axial compression and anterior flexion of the spine, which may contribute to spinal injuries. Compared with a normal posture, the relaxed posture led to an increase in stress on the cortical wall, endplate, and intradiscal pressure of 43%, 10%, 13%, respectively, and accordingly increased the risk of inducing spinal injuries.

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In this paper, we investigate the vanishing viscosity limit for solutions to the Navier-Stokes equations with a Navier slip boundary condition on general compact and smooth domains in R 3 . We first obtain the higher order regularity estimates for the solutions to Prandtl's equation boundary layers. Furthermore, we prove that the strong solution to Navier-Stokes equations converges to the Eulerian one in C([0, T ]; H 1 (Ω)) and L ∞ ((0, T ) × Ω), where T is independent of the viscosity, provided that initial velocity is regular enough. Furthermore, rates of convergence are obtained also.

A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. The same tetrasaccharide was also coupled with MPLA at the 1-O-position. Immunological activities of the two synthetic conjugates were evaluated in mice and compared. Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection. It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. Moreover, the 6'-N-conjugate afforded antibody titers much higher than those of the 1-O-conjugate. These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines.