A-319

Aminooxypentane (AOP)-RANTES efficiently and specifically blocks entry of non-syncytium-inducing (NSI), CCR5-tropic (R5) human immunodeficiency virus type 1 (HIV-1) into host cells. Inhibition appears to be mediated by increased intracellular retention of the CCR5 coreceptor- AOP-RANTES complex and/or competitive binding of AOP-RANTES with NSI R5 HIV-1 isolates for CCR5. Although AOP-RANTES and other β-chemokine analogs are potent inhibitors, the extreme heterogeneity of the HIV-1 envelope glycoproteins (gp120 and gp41) and variable coreceptor usage may affect the susceptibility of variant HIV-1 strains to these drugs. Using the same peripheral blood mononuclear cells (PBMC) with all isolates, we observed a significant variation in AOP-RANTES inhibition of 13 primary NSI R5 isolates; 50% inhibitory concentrations (IC 50 ) ranged from 0.04 nM with HIV-1 A-92RW009 to 1.3 nM with HIV-1 B-BaL . Experiments performed on the same isolate (HIV-1 B-BaL ) with PBMC from different donors revealed no isolate-specific variation in AOP-RANTES IC 50 values but did show a considerable difference in virus replication efficiency. Exclusive entry via the CCR5 coreceptor by these NSI R5 isolates suggests that variable inhibition by AOP-RANTES is not due to alternative coreceptor usage but rather differential CCR5 binding. Analysis of the envelope V3 loop sequence linked a threonine or arginine at position 319 (numbering based on the HXB2 genome) with AOP-RANTES resistance. With the exception of one isolate, A319 was associated with increased sensitivity to AOP-RANTES inhibition. Distribution of AOP-RANTES IC 50 values with these isolates has promoted ongoing screens for new CCR5 agonists that show broad inhibition of HIV-1 variants.

Advanced metallurgical processing techniques are required to produce aluminum matrix composites due to the tendency of the reinforcement particles to agglomerate. In this study, graphene nano-platelet reinforcement particles were effectively incorporated into an automotive A319 aluminum alloy matrix using a liquid metallurgical route. Due to its low density, it is a highly difficult task to produce an aluminum matrix composite reinforced with graphene. Hence, this study explored a novel approach to prevent particle floating to the melt surface and agglomeration. This was achieved via a hybrid semi-solid stirring of A319, followed by ultrasonic treatment of the liquid melt using a sonication probe. The microstructure and graphene particles were characterized using optical microscopy and scanning electron microscopy. Furthermore, the interfacial products produced with the incorporation of graphene in liquid aluminum were analyzed with X-ray diffraction. The tensile test results exhibited 10, 11 and 32% improvements in ultimate tensile strength, yield strength, and ductility of A319 reinforced with 0.05 wt.% addition of graphene. Analysis of strengthening models demonstrated primary contribution from Hall-Petch followed by CTE mismatch and load bearing mechanism. The results from this research enable the potential for using cost-effective, efficient and simple liquid metallurgy methods to produce aluminum reinforced graphene composites with improved mechanical properties.