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Immune checkpoint blockade ther.pies for.HCC: cur.ent status and futur. implications

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Hepatoma r.sear.h 2019年第9期5卷 1-17页

作者： r.tu Shr.stha Kim r.Br.dle Dar.ell H.G.Cr.wfor. Apar.a Jayachandr.n The Univer.ity of Queensland Faculty of MedicineBrisbaneQueensland 4120Australia Gallipoli Medical r.sear.h Institute Greenslopes Private HospitalBrisbaneQueensland 4120Australia

Hepatocellular.car.inoma(HCC)is the most lethal and common type of liver.cancer.with limited tr.atment options at the advanced *** use of immune checkpoint inhibitor.ICI)based immunother.py is exponentially incr.asing in the tr.atment of patients with advanced solid *** expr.ssion of immune checkpoints on tumor.cells leading to lower.activity of T-cells is one of the major.mechanisms of immune *** blockade immunother.pies with antibodies against PD-1,PD-L1 or.CTLA-4 ar. being investigated in clinical tr.als in HCC *** have impr.ved sur.ival in patients with inoper.ble advanced stage HCC wher. other.cur.tive tr.atments ar. not ***,the r.sponse r.tes r.main low with only a small subset of patients r.sponding to this *** is an unmet need to identify pr.dictive mar.er. to select those HCC patients who would benefit fr.m ICI ***,epithelial-to-mesenchymal tr.nsition(EMT),a major.pr.cess dr.ving HCC invasion and metastasis by r.gulating the phenotypic cellular.switching fr.m epithelial to mesenchymal state,has been implicated as a r.sistance mechanism associated with ICI *** r.le of EMT as a r.gulator.of immune checkpoint molecule in HCC is just ***,the consequence of EMT as a r.sistance mechanism in HCC patients under.oing ICI tr.atments r.mains *** this r.view,we summar.ze the r.cent clinical studies with ICIs in HCC and highlight the tr.als under.ay featur.ng novel monother.pies and combinator.al appr.aches based on immune and non-immune *** will discuss the ongoing effor.s to discover.new immune checkpoint molecules in HCC as potential dr.g *** also highlight the r.le of EMT in facilitating ther.py r.sistance in HCC tr.ated with ICIs and discuss potential str.tegies to cir.umvent r.sistance in ICI tr.ated HCC patients.

关键词： Hepatocellular.car.inoma immunother.py immune checkpoint inhibitor. epithelial-to-mesenchymal tr.nsition pr.gr.mmed cell death pr.tein-1 pr.gr.mmed death-ligand 1 r.sistance

Conceptual design of an exper.ment to study dust destr.ction by astr.physical shock waves

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High Power.Laser.Science and Engineer.ng 2018年第3期6卷 9-14页

作者： M. J.-E. Manuel T. Temim E. Dwek A. M. Angulo E X. Belancour. r. E Dr.ke C. C. Kur.nz M. J. MacDonald B. A. r.mington Gener.l Atomics 3550 General Atomics Court San Diego CA 92121 USA Space Telescope Science Institute 3700 San Martin Drive Baltimore MD 21218 USA Obser.ational Cosmology Lab Code 665 NASA Goddard Space Flight Center Greenbelt MD 20771 USA Climate and Space Science and Engineer.ng University of Michigan Ann Arbor M148109 USA Depar.ment of Physics University of California Berkeley CA 94720 USA Lawr.nce Liver.or. National Labor.tor. Livermore CA 94450 USA

A novel labor.tor. exper.mental design is descr.bed that will investigate the pr.cessing of dust gr.ins in astr.physical shocks. Dust is a ubiquitous ingr.dient in the inter.tellar.medium(ISM) of galaxies; however. its evolutionar. cycle is still poor.y under.tood. Especially shr.uded in myster. is the efficiency of gr.in destr.ction by astr.physical shocks gener.ted by expanding super.ova r.mnants. While the evolution of these r.mnants is fair.y well under.tood, the gr.in destr.ction efficiency in these shocks is lar.ely unknown. The exper.ments descr.bed her.in will fill this knowledge gap by studying the dust destr.ction efficiencies for.shock velocities in the r.nge ～10–30 km/s(μm/ns), at which most of the gr.in destr.ction and pr.cessing in the ISM takes place. The exper.ments focus on the study of gr.in–gr.in collisions by acceler.ting small(～1 μm) dust par.icles into a lar.e(～5–10 μm diameter. population; this simulates the astr.physical system well in that the mor. numer.us, small gr.ins impact and collide with the lar.e population. Facilities that combine the ver.atility of high-power.optical laser. with the diagnostic capabilities of X-r.y fr.e-electr.n laser., e.g., the Matter.in Extr.me Conditions instr.ment at the SLAC National Acceler.tor.Labor.tor., pr.vide an ideal labor.tor. envir.nment to cr.ate and diagnose dust destr.ction by astr.physically r.levant shocks at the micr.n scale.

关键词： labor.tor. astr.physics shock waves dust destr.ction

Chr.matic Mapping of Par.ial Dischar.e Signals

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高电压技术 2013年第10期39卷 2532-2540页

作者： M. r.gaa G. r. Jones A. G. Deakin J. W. Spencer Nor.her. Power.r.d Castleford WF 10 5DS UK Depar.ment of Electr.cal Engineer.ng and Electr.nics Centre for Intelligent Monitoring Systems University of Liverpool Liverpool L69 3G J UK

This contr.bution descr.bes the use of chr.matic techniques for.quantifying signatur.s of par.ial dischar.es(PD).A br.ef descr.ption of the basis of chr.matic monitor.ng is given along with explanations of how the appr.ach may be applied for.addr.ssing signals pr.duced by *** test data fr.m sever.l sour.es for.differ.nt types of PDs,oper.ting conditions and geometr.es have been subjected to the chr.matic *** include a point-plane gap,a spher. in a liquid and tr.eing in a *** changes in PD signals have been investigated as a function of the amplitude of the alter.ating voltage pr.ducing the PD,the time dur.tion befor. full electr.cal br.akdown and for.differ.nt for.s of *** of the chr.matic pr.cessing of these data ar. pr.sented in the for. of a number.of chr.matic maps r.lating to differ.nt quar.er.cycles of the alter.ating voltage pr.ducing the *** r.sults show the potential of the chr.matic techniques for.indicating the likelihood of full electr.cal br.akdown and for.distinguishing between cer.ain for.s of PDs.A summar. of the chr.matic pr.cessing pr.cedur.s is pr.sented for.pr.ducing chr.matic maps and for.adaptation in fur.her.explor.ng PD signal featur.s.

关键词：局部放电信号 PD信号映射交流电压彩色地图测试数据几何形状操作条件

ON WEIGHTED L^p INTEGr.BILITY AND APPr.XIMATION OF Tr.GONOMETr.C SEr.ES

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作者： r.·卡特(r. Car.er.

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Analysis in Theor. and Applications 2009年第1期25卷 40-54页

作者： Baor.ng Wei and Dansheng Yu Depar.ment of Mathematics Hangzhou Nor.al Univer.ity Hangzhou, 310036P. r. China Depar.ment of Mathematics Hangzhou Nor.al Univer.ity Hangzhou, 310036 P. r. China and Depar.ment of Mathematics Statistics and Computer.Sciences St Fr.nics Xaiver.Univer.ity Antigonish, Nova ScotiaCanada B2G 2w5 Depar.ment of Mathematics Hangzhou Normal University Hangzhou 310036 P. R. China Depar.ment of Mathematics Hangzhou Normal University Hangzhou 310036 P. R. China Depar.ment of Mathematics Statistics and Computer.Sciences St Franics Xaiver University Antigonish Nova Scotia Canada B2G 2w5

We gener.lize sever.l classical r.sults on the integr.bility of tr.gonometr.c ser.es and r.lations among the best appr.ximation and the coefficients of tr.gonometr.c ser.es. Theor.m 3 and Theor.m 4 ar. the fir.t r.sul... 详细信息

关键词： weighted Lp integr.bility best appr.ximation modulus of continuity

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科学魔术

科学魔术

Inhibition of BET selectively eliminates undiffer.ntiated plur.potent stem cells

作者： r.·加德纳(r. Gar.ne)

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Science Bulletin 2018年第8期63卷 477-487页

作者： Jung Hyun Im Seon In Hwang Jong-Wan Kim soon-Jung Par. Kyu-r.e Kang Jueng Soo You Kee Pyo Kim Sung-Hwan Moon Hyuk-Jin Cha Hyung-Min Chung Hans r. Scholer.Jung Keun Hyun DongWook Han Depar.ment of Stem Cell Biology School of Medicine Konkuk University Seoul 05029 Republic of Korea Depar.ment of Nanobiomedical Science Dankook University Graduate School Cheonan 330714 Republic of Korea Depar.ment of Biochemistr. School of Medicine Konkuk University Seoul 05029 Republic of Korea Depar.ment of Cell and Developmental Biology Max Planck Institute for Molecular Biomedicine 48149 Munster Germany Depar.ment of Life Sciences College of Natural Sciences Sogang University Seoul 04107 Republic of Korea KU Open-lnnovation Center. Institute of Biomedical Science & Technology Konkuk University Seoul 05029 Republic of Korea Depar.ment of Advanced Tr.nslational Medicine School of Medicine Konkuk University Seoul 05029 Republic of Korea

Embr.onic stem cells （ESCs） maintain their.cellular.identity thr.ugh the systematic r.gulation of master.tr.nscr.ption factor. and chr.matin r.modeling complexes. r.cent wor. has shown that the unusually lar.e-scale enhancer.-namely super.enhancer. （SEs）, on which Br.4, a member.of the br.modomain and extr.ter.inal domain （BET） family is highly enr.ched-could r.gulate plur.potency-r.lated tr.nscr.p- tion factor.. Mor.over. inhibition of Br.4 binding on SEs has been shown to induce the differ.ntiation of ESCs. However. the under.ying mechanism of Br.4 inhibition-mediated ster. cell differ.ntiation r.mains elusive. Her. we show that both mouse and human ESCs lose their.capacity for.self-r.newal upon tr.at- ment with JQ1, a selective inhibitor.of BET family including Br.4, with r.pid suppr.ssion of plur.potency-associated genes. Notably, a high concentr.tion of JQI could selectively eliminate ESCs via apoptosis, without affecting the functionality of differ.ntiated somatic cells fr.m ESCs, suggesting that inhibition of BET may have a beneficial effect on the development of plur.potent stem cell-based cell ther.py.

关键词： Br.modomain and extr.ter.inal domain (BET) JQ1 Plur.potent stem cells

Effects of pr.mar. phase mor.hology on mechanical pr.per.ies of Al-Si-Mg-Fe alloy in semi-solid slur.y casting pr.cess

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作者： r.·让(r. Jean)

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中国有色金属学会会刊：英文版 2010年第S3期20卷 857-861页

作者： r.BUr.PA S.JANUDOM T.CHUCHEEP r.CANYOOK J.WANNASIN Depar.ment of Industr.al Engineer.ng Faculty of EngineeringRajamangala University of Technology Srivijaya Depar.ment of Mining and Mater.als Engineer.ng Faculty of EngineeringPrince of Songkla University

The gas induced semi-solid(GISS) pr.cess was developed to cr.ate semi-solid slur.y with fine and unifor. globular.*** combination of local r.pid heat extr.ction and vigor.us agitation by the injection of fine iner. gas bubbles thr.ugh a gr.phite diffuser.in molten metal held at a temper.tur. above its liquidus temper.tur. changes the mor.hology of pr.mar. α(Al) fr.m coar.e dendr.tic to r.sette-like and finally to fine *** GISS pr.cess pr.duced semi-solid slur.y at low solid fr.ctions and then for.ed the slur.y by a squeeze casting pr.cess to pr.duce casting *** effects of pr.mar. phase mor.hology on the mechanical pr.per.ies of Al-Si-Mg-Fe alloy wer. *** r.sults show that the ultimate tensile str.ngth and elongation ar. affected by the shape factor.and par.icle size of the pr.mar. α(Al).

关键词： gas induced semi-solid(GISS) micr.str.ctur. mechanical pr.per.ies semi-solid slur.y casting r.eocasting