Current cancer vaccines induce tumor-specific T cell responses without sustained tumor regression because immunosuppressive elements within the tumor induce exhaustion of effector T cells and infiltration of immune-suppressive regulatory T cells (Tregs). Therefore, much effort has been made to generate agonistic Abs targeting members of the TNFR superfamily, such as OX40, 4- 1BB, and GITR, expressed on effector T cells and Tregs, to reinvigorate T cell effector function and block Treg-suppressive function. In this article, we describe the development of a panel of anti-human OX40 agonistic mouse mAbs that could promote effector CD4+ and CD8+ T cell proliferation, inhibit the induction of CD4+ IL-10 -producing type 1 regulatory T cells, inhibit the expansion of ICOS+IL-10+ Tregs, inhibit TGF-b–induced FOXP3 expression on naive CD4+ T cells, and block natural Treg–suppressive function. We humanized two anti–human OX40 mAb clones, and they retained the potency of their parental clones. These Abs should provide broad opportunities for potential combination therapy to treat a wide realm of cancers and preventative vaccines against infectious diseases.

A feeding experiment was conducted in floating cages (1.5 ± 1.0 ± 2.0 m) to determine the requirement of dietary phosphorus by juvenile orange‐spotted grouper Epinephelus coicodes. Five isonitrogenous (approximately 54% CP) fishmeal‐casein‐based diets that contained 0.68, 0.77, 0.86, 1.02 and 1.21% total phosphorus from ingredients and supplemental monocalcium phosphate (MCP: 0, 0.75,1.51,2.26,3.02%) were fed to the fish previously fed a basal diet (0.68% total phosphorus) for 2 wk. Fish were fed in triplicate cages with one of the diets twice daily to satiation. After 8 wk of feeding, survival ranged from 70.0% to 81.7% with no significant difference among dietary treatments. The relative weight gain, specific growth rate, muscle lipid, ash, calcium, iron, zinc and phosphorus, bone ash, phosphorus, iron, and zinc were significantly affected by dietary phosphorus level. There were no significant effects of increasing total dietary phosphorus on hepatosomatic index, viscerasomatic index, condition factor, muscle moisture and protein, muscle magnesium, and manganese; and bone calcium, magnesium and manganese. Based on relative weight gain, specific growth rate and bone phosphorus, a dietary level of 0.86% total phosphorus is recommended for juvenile grouper growing in floating cages.

Water–sand inrush is one of the most serious disasters for mining in China. The evaluation of the occurrence and development of a high-concentration water and sand mixed fluid is an important issue for mining in China. In this study, contraposing to the 3 phases of water–sand inrush, three kinds of experiments are designed for the investigation of initiation, development, and occurrence of the disaster. A new sand–water transport testing system is setup to perform the tests. The results show that there are two key points in the disaster: (1) sand particle incipient motion and (2) porous skeleton structural instability. The incipient motion of sand grains is accompanied with the phenomena of volumetric dilatation and granular fluidization. The critical velocity of the incipient motion of the water–sand mixed fluid is significantly affected by the particle size and external stress. The interaction between water and sand grains is the key factor affecting the motion characteristics of water–sand mixture. When the hydraulic conditions exceed the threshold, the water and sand grains are mutually promoted, and the aquifer skeleton becomes unstable. Furthermore, during the water–sand inrush, the curves of volumetric flow rates of sand and water, respectively, for different samples manifest as two distinct waveforms.