USP7: Novel Drug Target in Cancer Therapy

Ubiquitin specific protease 7 (USP7) is one of the deubiquitinating enzymes (DUB) that erases ubiquitin and protects substrate protein from degradation. Full activity of USP7 requires the C-terminal Ub-like domains fold back onto the catalytic domain, allowing the remodeling of the active site to a catalytically competent state by the C-terminal peptide. Until now, numerous proteins have been identified as substrates of USP7, which play a key role in cell cycle, DNA repair, chromatin remodeling, and epigenetic regulation. Aberrant activation or overexpression of USP7 may promote oncogenesis and viral disease, making it a target for therapeutic intervention. Currently, several synthetic small molecules have been identified as inhibitors of USP7, and applied in the treatment of diverse diseases. Hence, USP7 may be a promising therapeutic target for the treatment of cancer

第828回千葉医学会例会・第6回磯野外科例会 88-3.

Western blotting was performed to examine the protein levels of Twist in the indicated cells; β-actin was used as control. (JPG 151 kb

Performance evaluation of warm mix asphalt containing reclaimed asphalt mixtures

© 2016 Informa UK Limited, trading as Taylor & Francis Group. The objective of this study is to expose the effect of a variety of variables including three reclaimed asphalt pavement (RAP) contents, two warm mix asphalt (WMA) additives and a rejuvenating agent (or lack of) on the performance of WMA containing (WMA–RAP) materials. A laboratory study was conducted to evaluate the performance of WMA–RAP mixtures through rutting, bending and freeze-thaw splitting tests. Analysis of variance (ANOVA) was performed to analyse the significant effect of the variables on the performance. The tests results showed that the increased RAP content led to an increased rutting resistance and the decreased resistance to low-temperature cracking and moisture damage. The addition of the rejuvenating agent into the WMA–RAP mixtures can significantly improve the low-temperature cracking and moisture resistance. The ANOVA results showed that the RAP content had a significant effect on the rutting and low-temperature cracking resistance, and moreover, the rejuvenating agent (or lack of) had a large effect on the low-temperature cracking and moisture resistance

Performance of warm mix asphalt with recycled asphalt mixtures considering the effect of rejuvenating agent

©, 2015, Tongji University. All right reserved. To expose the effect of rejuvenating agent on performance of warm mix asphalt with recycled asphalt mixtures(WRAM), a laboratory study was conducted to evaluate the performance of WRAM containing three reclaimed asphalt pavement(RAP) (mass fraction are 20%, 30%, and 40%, respectively) and three warm mix asphalt (WMA) additives(S-I, DAT, and ET) consisting of surfactant with similar technical properties. Comparative investigation was performed to analyze the performance of WRAM and hot recycled asphalt mixtures (HRAM). The results show that dynamic stability (DS) of WRAM meets the specification requirement no matter whether the rejuvenating agent is used or not. The tensile strength ratio (TSR) and maximum bending tensile strain (ε \u3c inf\u3e m ) of WRAM, except that produced using ET and 30%, 40% RAP, meet the specification requirements when rejuvenating agent is used. However, TSR of WRAM without rejuvenating agent fails to pass the specification requirements. DS of WRAM with rejuvenating agent exhibits a slight decrease, and it has higher TSR and ε \u3c inf\u3e m values in comparison with that of WRAM without rejuvenating agent when the same WMA additive is used. Among the investigated performance indices of WRAM with the same RAP content, DS, TSR, and ε \u3c inf\u3e m of DAT/WRAM perform best, whereas that of ET/WRAM performs minimum no matter whether rejuvenating agent is used or not. DAT/WRAM exhibits a slight increase, and ET/WRAM displays a distinct decrease as compared to HRAM in terms of the performance indices when rejuvenating agent is used. Moreover, high temperature stability of S-I/WRAM performs slightly lower than that of HRAM, and S-I/WRAM shows similar low temperature cracking resistance and moisture susceptibility to those of HRAM. It has also been shown that rejuvenating agent performs a significant influence on low temperature cracking resistance and moisture susceptibility of WRAM, and there is a considerable difference in performance of WRAM with similar technical properties of WMA additive

Laboratory performance of warm mix asphalt containing recycled asphalt mixtures

This study aims to evaluate the laboratory performance of warm mix asphalt containing reclaimed asphalt pavement (WMA-RAP) materials. The WMA mixtures containing 0% and 40% RAP were produced using Evotherm-DAT and S-I WMA additives. The laboratory performance tests included rutting, bending, freeze-thaw splitting, Marshall immersion, aging, freeze-thaw cycles splitting, and fatigue tests. The moisture and low temperature cracking resistance were evaluated for aged mixtures. The results showed the WMA mixtures without RAP performed better moisture and low temperature cracking resistance, and lower rutting resistance than the WMA-RAP mixtures. The WMA mixtures suffered from the short-term aging exhibited a slight increase as compared to the unaged mixtures, whereas the long-term aging resulted in a distinct reduction in terms of the moisture resistance. After the short- and long-term aging, the WMA mixtures exhibited a greater decrease than the unaged mixtures in terms of the low temperature cracking resistance. The tensile strength ratio (TSR) results of the WMA-RAP mixtures generally decreased with the increase of freeze-thaw cycles, while the TSR results showed an obvious increase after three freeze-thaw cycles. The addition of RAP significantly reduced the fatigue resistance of the WMA-RAP mixtures in comparison with the WMA mixtures without RAP. Based upon the study findings, the moisture resistance under freeze-thaw cycles conditioning remains an issue to be considered in the WMA-RAP mixtures. © 2014 Elsevier Ltd. All rights reserved

Experiment Development of foam Slurry Materials

AbstractBased on the problems of goaf, such as serious air leakage, frequent spontaneous combustion, using foam cement material to reduce or even eliminate the spontaneous combustion of mined-out areas was put forward. Foam cement was made up with cement, blister, flash–setting agent and other materials, which breakthrough the limits of existing fire prevention foam material. Through a series of experiments, characters of foam stabilizing time, mobility density, strength and air leaking stoppage were tested under different proportions of blister and water. According to the experimental results, the fact was obtained that foam cement has minimal air-leakage rate and best effect of air leaking stoppage and the longest foam stabilizing time when the ratio between blister and water is 1:55. Cement samples with different content of flash-setting agent were compounded. By analyzing the cement condensation time under different content of flash-setting agent, it has been found that the content of flash-setting agent were best between 4.6% and 5.0%, which has the shorter condensation time and better condensation effect

Optimum test section on simulation test of asphalt mixtures

To expose the internal mechanics response and the optimum test section of asphalt mixtures specimen under planar simulation test, the asphalt mixtures specimens are fabricated by two laboratory compaction methods (hammer and static compaction) in China, and moreover, heterogeneous numerical models along the height direction of the specimens are established based on X-ray computed technique, digital image processing technique and finite element method, simulation splitting test and simulation creep test are performed to analyze the internal stress behaviors of heterogeneous model and study the location of the optimum test section according to laboratory test. The results show the creep deformation curves of simulation creep test for different sections are almost uniform, the difference of creep deformation is lesser, and that has better consistency than laboratory creep test result. The internal stress distribution trend of different test sections is identical on analysis path, but there are considerable distinctions for the position of peak value and the maximum stress. Therefore, the sections along the height direction of the asphalt mixtures specimens can be chosen arbitrarily to be the optimum test section for simulation creep test, but the optimum section, for simulation splitting test, can\u27t be selected. © 2013 American Society of Civil Engineers

Per-cell histone acetylation is associated with terminal differentiation in human T cells

Abstract Background Epigenetic remodeling at effector gene loci has been reported to be critical in regulating T cell differentiation and function. However, efforts to investigate underlying epigenetic mechanisms that control T cell behaviors have been largely hindered by very limited experimental tools, especially in humans. Results In this study, we employed a flow cytometric assay to analyze histone acetylation at single-cell level in human T cells. The data showed that histone acetylation was increased during T cell activation. Among T cell subsets, terminally differentiated effector memory T (TEMRA) cells robustly producing effector cytokines were hyper-acetylated. Conversely, these TEMRA cells had lower expression levels of TCF-1, a key transcription factor for maintaining stem cell features. Pharmaceutical inhibition of histone acetylation using a small molecule C646 restrained the production of effector molecules, but retained stem cell-like properties in T cells after expansion. Conclusions Per-cell histone acetylation is associated with terminal differentiation and poor stemness in human T cells. These observations suggest a new approach to enhance the stem cell-like properties of T cells and improve the efficacy of immunotherapy