KPN. The oral agents, cefuroxime, amoxicillin-clavulanate, TMP-SMX, and levofloxacin showed susceptibility rates ranging from 63.1% to 87.1% against ENT, EC, and KPN. TBP (MIC 50/90 , 0.12/0.12 mg/L) inhibited all PM at £0.25 mg/L. PM isolates were susceptible to ERT (100.0%), CAZ (98.7%), cefuroxime (94.4%), and amoxicillin/ clavulanate (96.6%), whereas susceptibility rates of 71.8-76.8% were noted for TMP-SMX and levofloxacin.CONCLUSIONS: TBP displayed potent activity against ENT UTI pathogens recovered from patients in the US. TBP demonstrated in vitro activity against these UTI pathogens similar to that of ERT. In addition, these data showed compromised activity of intravenous and oral agents used for treating UTI. This data supports the development of tebipenem as an oral option for management of UTI in the US.
Many mammalian genes, including a number involved in immune development and function, use multiple promoters encoding expression of the same protein product. To understand the function of alternative promotors during T cell development, we carried out genome-wide RNA-Seq analysis of DN, DP, CD4 and CD8 thymocytes. 26% (2469/9595) of genes expressed by thymocytes used two or more alternative promotors at some point in T cell development. However, only 3.2% (80/2469) of the genes which utilized two or more promoters showed the difference of promotor activity among different T cell developmental stages which were validated by selected representative genes with qPCR assay. To analyze mechanisms of alternative promoter regulation, DNase hypersensitivity sites were mapped, and ChIP-Seq with anti-H3K4me3 antibodies was performed in the same thymic subpopulations. To determine the in vivo functional role of alternative promotors for T cell development, several genes were selected for study by deletion of individual promoters by CRISPR technology. We have initially generated mice with deletion of distal or proximal promotor of the lck gene and demonstrated distinct functional roles of the two promoters: the proximal lck promoter is critical for early stages of thymic T cell development while the distal promoter was necessary for normal T cell activation. Ongoing studies will characterize more broadly the functional role of alternative promoter expression in thymocyte development, and the mechanisms mediating selective promoter activity.
Shear reinforcement is one of the common measures used to strengthen slab–column connections. It can make the joint’s load capacity increase. However, when the connection is subjected to an unbalanced bending moment, the reduction effect of the shear reinforcement on the bending moment is worth investigating. Nonlinear finite element analysis was performed on reinforced concrete slabs with shear reinforcement for various moment-to-shear (M/V) ratios. The effects of the number and diameter of shear reinforcement and different loading methods on the slab were investigated, as along with a correction to the ACI-318 and China Concrete Structure Design code GB50010 formula for the moment transfer coefficient. The 3D finite element modeling was performed using appropriate element types and a constitutive model for concrete. The concrete damage plasticity model parameters were calibrated using the experimental results of a specimen. The amount of shear reinforcement had a certain contribution to the strength of the slab, but the diameter of the shear reinforcement had little effect. The plate’s bearing capacity decreased as the M/V increased. The corrected moment transfer coefficient formula demonstrates that M/V is positively correlated with the coefficient and that the calculated values specified in ACI-318 and GB50010 are overly conservative.
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