1,131 publications from this institution
Many bacteria modulate and evade the immune defenses of their hosts through peptidoglycan (PG) deacetylation. The PG deacetylases from Streptococcus pneumonia, Listeria monocytogenes and Lactococcus lactis have been characterized. However, thus far, the PG deacetylase of Mycobacterium tuberculosis has not been identified. In this study, we cloned the Rv1096 gene from the M. tuberculosis H37Rv strain and expressed Rv1096 protein in both Escherichia coli and M. smegmatis. The results showed that the purified Rv1096 protein possessed metallo-dependent PG deacetylase activity, which increased in the presence of Co2+. The kinetic parameters of the PG deacetylase towards M. smegmatis PG as a substrate were as follows: Km, 0.910 ± 0.007 mM; Vmax, 0.514 ± 0.038 μMmin-1; and Kcat = 0.099 ± 0.007 (S-1). Additionally, the viability of M. smegmatis in the presence of over-expressed Rv1096 protein was 109-fold higher than that of wild-type M. smegmatis after lysozyme treatment. Additionally, light microscopy and scanning electron microscopy showed that in the presence of over-expressed Rv1096 protein, M. smegmatis kept its regular shape, with an undamaged cell wall and smooth surface. These results indicate that Rv1096 caused deacetylation of cell wall PG, leading to lysozyme resistance in M. smegmatis. We have determined that M. tuberculosis Rv1096 is a PG deacetylase. The PG deacetylase activity of Rv1096 contributed to lysozyme resistance in M. smegmatis. Our findings suggest that deacetylation of cell wall PG may be involved in evasion of host immune defenses by M. tuberculosis.
A refined higher-order shear deformation theory for bending, vibration and buckling analysis of functionally graded sandwich plates is presented in this paper. It contains only four unknowns, accounts for a hyperbolic distribution of transverse shear stress and satisfies the traction free boundary conditions. Equations of motion are derived from Hamilton\'s principle. The Navier-type and finite element solutions are derived for plate with simply-supported and various boundary conditions, respectively. Numerical examples are presented for functionally graded sandwich plates with homogeneous hardcore and softcore to verify the validity of the developed theory. It is observed that the present theory with four unknowns predicts the response accurately and efficiently.
Despite significant advances in therapeutic developments for prostate cancer over the last 2 decades, metastatic prostate cancer remains a lethal disease. Prostate-specific membrane antigen (PSMA), which is markedly overexpressed in prostate cancer cells and metastatic sites but has low normal-tissue expression, has emerged as an important theranostic target for this disease. Both β-emitting and α-emitting PSMA-targeted radionuclide therapy (RNT) are in clinical development. Several of these agents have already shown promising activity; however, a subset of patients have primary resistant disease, and secondary resistance invariably occurs. Further, the effect of these therapies on healthy organs limits their therapeutic window. Elucidating the biology of PSMA and characterizing the pharmacokinetic and pharmacodynamic properties of PSMA-targeted RNT and mechanisms of resistance will facilitate therapeutic approaches aimed at improving efficacy and safety. In this review, we provide an overview of existing PSMA-targeting RNT and novel RNT combinatorial approaches, such as those with novel hormonal agents, poly-[adenosine diphosphate-ribose]-polymerase inhibitors and immunotherapy, currently under investigation.
电气自动化在电气工程中的应用,是电气工程现代化建设的重要手段,在推动电气工程数字化、自动化、智能化发展上发挥着至关重要的作用.随着科技驱动创新发展战略的提出,电气自动化技术应用重要性愈发明显.基于此,本文从电气自动化概述出发,就其在电气工程中的应用进行了简要分析,以期加深对电气自动化的认识与了解,为其实践应用与推广提供可借鉴性理论指导.
Abstract Purpose: IL6 is important for the growth and survival of myeloma cells. This study evaluated blocking IL6 with siltuximab to delay the transition from high-risk smoldering multiple myeloma (SMM) to multiple myeloma. Patients and Methods: In a randomized, double-blind, placebo-controlled, multicenter study, 85 patients with high-risk SMM were randomized to 15 mg/kg siltuximab (43 patients) or placebo (42 patients). The primary endpoint was 1-year progression-free survival (PFS) rate, based on IMWG CRAB criteria. Secondary endpoints included progressive disease indicator rate, PFS, and safety. Results: Median age was 62 years (range: 21–84); 57% were male and 87% had a baseline Eastern Cooperative Oncology Group score of 0. The 1-year PFS rate was 84.5% (siltuximab) and 74.4% (placebo). After a median follow-up of 29.2 months, 32.6% of PFS events occurred with siltuximab and 42.9% with placebo. Median PFS was not reached with siltuximab but was 23.5 months with placebo [HR 0.50 (95% confidence interval, 0.24–1.04); P = 0.0597]. The safety profile of siltuximab was comparable with placebo. Most adverse events in the siltuximab group were grade 2/3; the most common serious adverse events were infections/infestations, and renal/urinary disorders. Mortality was low in both groups (3 deaths in the siltuximab group and 4 in the placebo group). Conclusions: Although this study did not meet the prespecified protocol hypothesis criteria, data suggest that siltuximab may delay the progression of high-risk SMM.
