Synthesis of structure-defined ß-1,4-GlcNAc-modified wall teichoic acids as potential vaccine against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a high priority pathogen due to its life-threating infections to human health. Development of prophylactic or therapeutic anti-MRSA vaccine is a potential approach to treat S. aureus infections and overcome the resistance crisis. ß-1,4-GlcNAc glycosylated wall teichoic acids (WTAs) derived from S. aureus are a new type of antigen that is closely associated with ß-lactam resistance. In this study, structure-defined ß-1,4-GlcNAc-modified WTAs varied in chain length and numbers of GlcNAc modification were synthesized by an ionic liquid-supported oligosaccharide synthesis (ILSOS) strategy in high efficiency and chromatography-free approach. Then the obtained WTAs were conjugated with tetanus toxin (TT) as vaccine candidates and were further evaluated in a mouse model to determine the structure-immunogenicity relationship. In vivo immunological studies revealed that the WTAs-TT conjugates provoked robust T cell-dependent responses and elicited high levels of specific anti-WTAs IgG antibodies production associated with the WTAs structure including chain length as well as the ß-1,4-GlcNAc modification pattern. Heptamer WTAs conjugate T6, carrying three copy of ß-1,4-GlcNAc modified RboP, was identified to elicit the highest titers of specific antibody production. The T6 antisera exhibited the highest recognition and binding affinity and the most potent OP-killing activities to MSSA and MRSA cells. This study demonstrated that ß-1,4-GlcNAc glycosylated WTAs are promising antigens for further development against MRSA.

Study on the Directional Solidification Process of an Aluminum Alloy Bar in Multishell Mold Being Gradually Immersed in Water.

A multishell mold structure and water-immersion cooling method (MSMWI) is proposed for the directional solidification of castings. A four-layer-shell sand mold was designed for a bar with diameter of 40 mm. As the aluminum melt was poured, the multishell mold was gradually immersed in water, and the water level drove the advancement of the solidification front from bottom to top. The multishell mold was helpful for the heat insulation of its upper part, and its bottom was chilled by the water. Therefore, directional solidification of the bar was vertically realized. The water-cooled solidification process of the bar was 5.8 times faster than that by air natural cooling (MSMNC), and the temperature gradient was increased by 78 times. The secondary dendrite arm spacing (SDAS) and eutectic silicon were significantly refined. Its tensile strength, elongation, and hardness were increased by 56%, 185%, and 62.6%, respectively.

Modeling and Simulation of the Casting Process with Skeletal Sand Mold.

The author-proposed skeletal sand mold, which mainly includes a shell, air cavities and a truss support structure, has been experimentally proven to be very useful in controlling the cooling of casting at local areas and at different periods of the casting process. The modeling and simulation of the casting process using a skeletal sand mold were systemically analyzed. Complicated casting/mold and mold/air boundaries, and the thermal and mechanical behavior of the skeletal sand mold during the casting process were highlighted. A numerical simulation of the casting process of a stress frame specimen using a skeletal sand mold was performed. The temperature, stress and displacement fields of the casting and skeletal sand mold were obtained and compared with those using a traditional sand mold. The simulated results were validated with experiments. Using the skeletal sand mold, the cooling rate of the casting can be greatly improved due to the significant heat release from mold surface to environment. The residual stress and deformation of the casting can be reduced because of the decreased stiffness of this kind of mold. Although the skeletal sand mold is susceptible to cracking, it can be avoided by filleting in the conjunctions and increasing the shell thickness.

Effect of Layer-Wise Varying Parameters on the Microstructure and Soundness of Selective Laser Melted INCONEL 718 Alloy.

Selective laser melting (SLM) is a promising powder bed fusion additive manufacturing technique for metal part fabrication. In this paper, varying scanning speed in the range of 500 mm/s to 1900 mm/s, and laser power in the range of 100 W to 200 W, were realized from layer to layer in a cycle of 56 layers in a single cuboid Inconel 718 alloy specimen through SLM. Layer-wise variation of microstructure and porosity were acquired, showing the layer-wise controlling capability of microstructural soundness. The melt pool size and soundness are closely linked with the energy input. High energy density led to sound regions with larger, orderly stacked melt pools and columnar grains, while low energy density resulted in porous regions with smaller, mismatched melt pools, un-melted powder, and equiaxed grains with finer dendrites. With the increase of laser energy density, the specimen shifts from porous region to sound region within several layers.