Toll-like Receptor-8 Agonistic Activities in C2, C4, and C8 Modified Thiazolo[4,5-c]quinolines

Toll-like receptor (TLR)-8 agonists typified by the 2-alkylthiazolo[4,5-c]quinolin-4-amine (CL075) chemotype are uniquely potent in activating adaptive immune responses by inducing robust production of T helper 1-polarizing cytokines, suggesting that TLR8-active compounds could be promising candidate vaccine adjuvants, especially for neonatal vaccines. Alkylthiazoloquinolines with methyl, ethyl, propyl and butyl groups at C2 displayed comparable TLR8-agonistic potencies; activity diminished precipitously in the C2-pentyl compound, and higher homologues were inactive. The C2-butyl compound was unique in possessing substantial TLR7-agonistic activity. Analogues with branched alkyl groups at C2 displayed poor tolerance of terminal steric bulk. Virtually all modifications at C8 led to abrogation of agonistic activity. Alkylation on the C4-amine was not tolerated, whereas N-acyl analogues with short acyl groups (other than acetyl) retained TLR8 agonistic activity, but were substantially less water-soluble. Immunization in rabbits with a model subunit antigen adjuvanted with the lead C2-butyl thiazoloquinoline showed enhancements of antigen-specific antibody titers

Combined effects of grain size and strain rate on the dislocation substructure and mechanical properties in aluminum

Abstract not availabl

On the inter-layer magneto-electric coupling in BiFeO3/SrRuO3 heterostructure

Interlayer magneto-electric coupling in BiFeO3/SrRuO3 heterostructures was investigated by impedance spectroscopy over a temperature range of 80 K-260 K. In-plane impedance measurements were performed using interdigitated gold electrodes fabricated on the BiFeO3 layer. The Nyquist plots at different temperatures were fitted with an equivalent circuit model of the hetero-structure. A pronounced dip in the temperature coefficient of equivalent-capacitance and a distinct increase in the temperature coefficient of equivalent-resistance of the BiFeO3 layer were observed on cooling across ferromagnetic TC of the bottom SrRuO3 layer. Temperature dependent capacitance (at 0 T magnetic fields) and magneto-capacitance (at 5 T magnetic fields) plots showed anomalies near 160 K. A shift of the hysteresis loop along the magnetization axis in field cooled M-H measurements was also found, which indicates the presence of pinned SrRuO3 moments due to the magnetic interaction at the interface. These observations suggest a strong magneto-electric coupling between the BiFeO3 and SrRuO3 layers of this heterostructure. Published by AIP Publishing

Metagenomic sequencing generates the whole genomes of porcine rotavirus A, C, and H from the United States.

The genus Rotavirus comprises eight species, designated A to H, and two recently identified tentative species I in dogs and J in bats. Species Rotavirus A, B, C and H (RVA, RVB, RVC and RVH) have been detected in humans and animals. While human and animal RVA are well characterized and defined, complete porcine genome sequences in the GenBank are limited compared to human strains. Here, we used a metagenomic approach to sequence the 11 segments of RVA, RVC and RVH strains from piglets in the United States (US) and explore the evolutionary relations of these RV species. Metagenomics identified Astroviridae, Picornaviridae, Caliciviridae, Coronoviridae in samples MN9.65 and OK5.68 while Picobirnaviridae and Arteriviridae were only identified in sample OK5.68. Whole genome sequencing and phylogenetic analyses identified multiple genotypes with the RVA of strain MN9.65 and OK5.68, with the genome constellation of G5/G9-P[7]/P[13]-I5/I5- R1/R1-C1-M1-A8-N1-T7-E1/E1-H1 and G5/G9-P[6]/P[7]-I5-R1/R1-C1-M1-A8-N1-T1/T7-E1/E1-H1, respectively. The RVA strains had a complex evolutionary relationship with other mammalian strains. The RVC strain OK5.68 had a genome constellation of G9-P[6]-I1-R1-C5-M6-A5-N1-T1-E1-H1, and shared an evolutionary relationship with porcine strains from the US. The RVH strains MN9.65 and OK5.68 had the genome constellation of G5-P1-I1-R1-C1-M1-A5-N1-T1-E4-H1 and G5-P1-I1-R1-C1-M1-A5-N1-T1-E1-H1, indicating multiple RVH genome constellations are circulating in the US. These findings allow us to understand the complexity of the enteric virome, develop improved screening methods for RVC and RVH strains, facilitate expanded rotavirus surveillance in pigs, and increase our understanding of the origin and evolution of rotavirus species