Deubiquitination and Stabilization of PD-L1 by CSN5

Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6

<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Radiation induced grain boundary segregation in ferritic/martensitic steels

Xia, L.D.,Ji, Y.Z.,Liu, W.B.,Chen, H.,Yang, Z.G.,Zhang, C.,Chen, L.Q. Korean Nuclear Society 2020 Nuclear Engineering and Technology Vol.52 No.1

The radiation induced segregation of Cr at grain boundaries (GBs) in Ferritic/Martensitic steels was modeled assuming vacancy and interstitialcy diffusion mechanisms. In particular, the dependence of segregation on temperature and grain boundary misorientation angle was analyzed. It is found that Cr enriches at grain boundaries at low temperatures primarily through the interstitialcy mechanism while depletes at high temperatures predominantly through the vacancy mechanism. There is a crossover from Cr enrichment to depletion at an intermediate temperature where the Cr:Fe vacancy and interstitialcy diffusion coefficient ratios intersect. The bell-shape Cr enrichment response is attributed to the decreasing void sinks inside the grains as temperature rises. It is also shown that low angle grain boundaries (LAGBs) and special Σ coincidence-site lattice (CSL) grain boundaries exhibit suppressed radiation induced segregation (RIS) response while high angle grain boundaries (HAGBs) have high RIS segregation. This different behavior is attributed to the variations in dislocation density at different grain boundaries.

Radiation damage in helium ion – irradiated reduced activation ferritic/martensitic steel

L.D. Xia,W.B. Liu,H.P. Liu,J.H. Zhang,H. Chen,Z.G. Yang,C. Zhang 한국원자력학회 2018 Nuclear Engineering and Technology Vol.50 No.1

Nanocrystalline reduced activation ferritic/martensitic (RAFM) steel samples were prepared using surfacemechanical attrition treatment (SMAT). Un-SMATed and SMATed reduced activation ferritic/martensitic samples were irradiated by helium ions at 200 C and 350 C with 2 dpa and 8 dpa, respectively,to investigate the effects of grain boundaries (GBs) and temperature on the formation of Hebubbles during irradiation. Experimental results show that He bubbles are preferentially trapped at GBsin all the irradiated samples. Bubble denuded zones are clearly observed near the GBs at 350 C, whereasthe bubble denuded zones are not obvious in the samples irradiated at 200 C. The average bubble sizeincreases and the bubble density decreases with an increasing irradiation temperature from 200 C to350 C. Both the average size and density of the bubbles increase with an increasing irradiation dose from2 dpa to 8 dpa. Bubbles with smaller size and lower density were observed in the SMATed samples butnot in the un-SMATed samples irradiated in the same conditions, which indicate t

CHARACTERISTICS OF CONCENTRATION FIELD IN THE INITIAL REGION OF A JET IN COFLOW

XIA L. P.,LAM K. M. 한국수자원학회 2005 한국수자원학회 학술대회 Vol.2005 No.1

Synthesis and biological evaluation of diverse tetrahydrobenzofuran-4-ones as potent antibacterial agents

Xia, L.,Idhayadhulla, A.,Lee, Y.R.,Kim, S.H.,Wee, Y.J. Korean Society of Industrial and Engineering Chemi 2015 Journal of industrial and engineering chemistry Vol.22 No.-

Diverse 3,5,6,7-tetrahydrobenzofuran-4-one derivatives (3a-3n) were synthesized in high yields by ruthenium complex or rhodium complex catalyzed [3+2] cycloaddition. The antibacterial activities of these 3,5,6,7-tetrahydrobenzofuran-4-ones were evaluated against Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Enterobacter aerogenes) and Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus). In particular, compound 3b showed the highest antibacterial activity against P. aeruginosa and S. aureus (both MICs: 2μg/mL). Compound 3l, which has the 2H-pyrano[2,3-b]benzofuran skeleton, exhibited excellent inhibitory activity against B. cereus (MIC: 0.5μg/mL) as compared with ciprofloxacin (MIC: 2μg/mL) and ampicillin (MIC: 1μg/mL).

Childcare policies and services in Hong Kong after the handover: Beyond a feminist critique

Lily L. L. Xia,Joyce L. C. Ma 한국사회복지학회 2019 Asian Social Work and Policy Review Vol.13 No.3

This article reviews the development of childcare policies and services in Hong Kong after the handover, gauging it with two standards: promoting the equal development of children and gender equality in our society. Statistics derived from data taken from multiple sources show that the government has been sticking to a “positive non-in-tervention approach” to welfare development and that the male breadwinner/female carer model prevalent in this region was shaped and strengthened by current child-care policies and services. The current provision of childcare services is insufficient to guarantee the equal use of childcare among children of different socioeconomic backgrounds, or to ease the tension between the needs of childcare and job require-ments in a family, or to emancipate married women from the domestic sphere. A “generative welfare approach” that collects fiscal resources and redistributes them strategically with a systemic mind-set has been suggested for social policy and ser-vice planning, including spending the money in the right place, launching smart and practical policies that can achieve both pragmatic effects and ideological improve-ment in the area of gender equality, providing financial support or subsidies to a company for the provision of parental leave, and increasing the provision of quality childcare services.

Dynamic interaction analysis of a LIM train and elevated bridge system

H. Xia,W. W. Guo,C. Y. Xia,Y.-L. Pi,M. A. Bradford 대한기계학회 2009 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.23 No.12

A three-dimensional dynamic interaction model is developed for a LIM (linear induction motor) train and elevated bridge system, which is composed of a LIM-driven vehicle submodel and a finite element bridge submodel. Each LIM vehicle is modeled by a 27 degrees-of-freedom dynamic system. The expressions for the electromagnetic force between the linear motor and the reaction plate are derived, and the force model is established. By applying a modal superposition technique to the bridge submodel and using the measured track irregularities as the self-excitations of the train-bridge system, the equations of motion are established for analyzing the dynamic responses of the LIM vehicle and the elevated bridge. The proposed framework is applied to a 3-span elevated bridge with 29.9 m simply-supported girders. The full histories of the LIM train traversing the bridge are simulated, from which the dynamic responses of the LIM vehicle and elevated bridge system are obtained. The proposed method may help to find a way to assess the dynamic properties of elevated bridges and the running safety of a LIM train with reasonable computational effort.

Field Measurements of the New CCTV Tower in Beijing

Xu, Y.L.,Zhan, S.,Xia, H.,Xia, Y.,Zhang, N. Council on Tall Building and Urban Habitat Korea 2013 International journal of high-rise buildings Vol.2 No.3

The emergence of a growing number of tall buildings, often with unusual shapes and innovative structural systems, has led to the realization of the need for and the importance of field measurements. The new China Central Television (CCTV) Tower in Beijing is one of tall buildings with a highly unusual shape and a complex structural system, requiring field measurements to identify its dynamic characteristics for the subsequent dynamic analysis of the tower under wind excitation, seismic-induced ground motion and traffic-induced ground motion. The structural system and the finite element model of the CCTV Tower are first introduced in this paper. The computed natural frequencies and mode shapes are then presented as a reference for the field measurement. After introducing the arrangement of the ambient vibration measurement, the field measured natural frequencies and damping ratios of the CCTV Tower are presented and the measured natural frequencies are finally compared with the computed ones. It was found that the structural damping ratios of the CCTV Tower are small and the computed natural frequencies are smaller than the measured ones by about 12~17%.

R&D Status of High-current Accelerators at IFP

J. J. Deng,J. S. Shi,W. P. Xie,L. W. Zhang,K. Z. Zhang,S. P. Feng,J. Li,M. Wang,Y. He,L. S. Xia,Z. Y. Dai,H. T. Li,L. Wen,S. F. Chen,X. Li,Q. G. Lai,M. H. Xia,Y. C. Guan,S. Y. Song,L. Chen 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.61

High-current accelerators have many important applications in Z-pinches, high-power microwaves, and free electron lasers, imploding liners and radiography and so on. Research activities on Zpinches, imploding liners, radiography at the Institute of Fluid Physics (IFP) are introduced. Several main high-current accelerators developed and being developed at IFP are described, such as the Linear Induction Accelerator X-Ray Facility Upgrade (LIAXFU, 12 MeV, 2.5 kA, 90 ns), the Dragon-I linear induction accelerator (20 MeV, 2.5 kA, 60 ns), and the Primary Test Stand for Z-pinch (PTS, 10 MA, 120 ns). The design of Dragon-II linear induction accelerator (20 MeV, 2.5 kA, 3 × 60 ns) to be built will be presented briefly.

Effects of Copper-bearing Montmorillonite (Cu-MMT) on Escherichia coli and Diarrhea on Weanling Pigs

Xia, M.S.,Hu, C.H.,Xu, Z.R.,Ye, Y.,Zhou, Y.H.,Xiong, L. Asian Australasian Association of Animal Productio 2004 Animal Bioscience Vol.17 No.12

Copper-bearing montmorillonite (Cu-MMT) was produced by $Cu^{2+}$ cation exchange reaction. X-ray diffraction analysis showed that that the (001) basal spacing of the MMT crystal lattice increased from 1.544 to 1.588 nm after $Cu^{2+}$ exchange. This indicated that $Cu^{2+}$ entered into interlayer position of MMT as a hydrated cation or composite cation. In vitro results indicated that Cu-MMT had antibacterial activity on Escherichia coli $K_{88}$. Cu-MMT had unbalanced positive charge after cation exchange. Its antibacterial activity resulted from two aspects, one was electrostatic attraction which made E. coli $K_{88}$ being adhered on the montmorillonite surface, the other was the $Cu^{2+}$ slowly released, which could kill bacteria. In an in vivo study, four replicates of eight weanling pigs were assigned to each of two dietary treatments to study the effects of Cu-MMT on diarrhea, E. coli in the lumen of the jejunum and morphology of jejunal mucosa. As compared to the control, supplementation of the diet with 0.2% Cu-MMT improved average daily gain by 12.50% (p<0.05) and decreased F/G by 9.42% (p<0.05). The mean diarrhrea incidence was decreased by 71.80% (p<0.05). The viable counts of Escherichia coli in jejunal contents were significantly reduced (p<0.05). Villus height and the villus height to crypt depth ratio at the jejunal mucosa were increased by 19.09% (p<0.05) and 37.10% (p<0.05), respectively.