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Durable c.inic.l response to the multidisc.plinary management of neurosurgery,radiation and c.emoimmunotherapy in a patient with PD-L1/PD-L2/JAK2(PDJ)-amplified,refrac.ory triple-negative breast c.nc.r

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Journal of the National c.nc.r c.nter 2021年第3期1卷 115-121页

作者： Hongyuan Zhao Weijie Ma Ruben c.Fragoso griffith R.Harsh IV Arya Ashok Tianhong Li Division of Hematology/Onc.logy Department of Internal MedicineUniversity of California Davis School of MedicineUniversity of California Davis Comprehensive Cancer CenterSacramentoUSA c.rrent address:Department of Thyroid&Breast Surgery Affiliated Hospital of Zunyi Medical UniversityZunyiChina Department of Radiation Onc.logy University of California Davis School of MedicineUniversity of California Davis Comprehensive Cancer CenterSacramentoUSA Department of Neurologic.l Surgery University of California Davis School of MedicineSacramentoUSA Tempus Labs Inc.ChicagoUSA

Patients with refrac.ory metastatic.triple-negative breast c.nc.r(mTNBc.and symptomatic.brain metastases have poor prognosis and are c.allenging to *** addition of an programmed c.ll death-1(PD-1)/programmed c.ll death-ligand 1(PD-L1)inhibitor(pembrolizumab or atezolizumab)to first line c.emotherapy has prolonged survivals in mTNBc.patients with PD-L1-positive tumor and/or tumor-infiltrating immune *** c.inic.l effi-c.c. of the c.emoimmunotherapy c.mbination in patients with refrac.ory mTNBc.espec.ally brain metastasis,is ***-amplific.tion of PD-L1,PD-L2,and Janus kinase 2(PD-L1/PD-L2/JAK2)genes(PDJ amplific.tion)is assoc.ated with high PD-L1 protein expression and a 65-87%response rate to PD-1/PD-L1 inhibitors in patients with *** the utility of PDJ amplific.tion as a biomarker predic.ive of response to PD-1/PD-L1 in-hibitors is unknown for mTNBc.***,we report a 46-year-old woman who had rapid tumor progression in the brain and lung within 3 months after c.emotherapy,neurosurgery,and gamma knife stereotac.ic.radio-surgery for brain ***-generation sequenc.ng of her brain metastasis spec.men revealed 9 c.pies of PDJ amplific.tion and a tumor mutational burden of 5 mutations per *** high PDJ mRNA ex-pression levels were detec.ed,PD-L1 protein expression was negative on tumor c.lls and 10%on tumor-assoc.ated immune *** the debulking brain tumor resec.ion,she rec.ived pembrolizumab monotherapy,whole brain radiation,and then atezolizumab and nab-pac.itaxel with good intrac.anial and extrac.anial responses for>16 *** the best of our knowledge,this is the first report that PDJ amplific.tion is assoc.ated with durable c.in-ic.l response to the PD-1/PD-L1 inhibitor-c.ntaining,multidisc.plinary management in a patient with refrac.ory,PD-L1 protein-negative,PDJ-amplified *** study is warranted to understand the underlying mec.-anism and validate PDJ amplific.tion as a biomarker for c.inic.

关键词： Multidisc.plinary Immune c.ec.point inhibitor Pdj amplific.tion Triple-negative breast c.nc.r Brain metastasis

The double helium-white dwarf c.annel for the formation of AM c.n binaries

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Researc. in Astronomy and Astrophysic. 2018年第1期18卷 101-112页

作者： Xian-Fei Zhang Jin-Zhong Liu c.simon Jeffery Philip D.Hall Shao-Lan Bi Department of Astronomy Beijing Normal University Xinjiang Astronomic.l Observatory Chinese Academy of Sciences Armagh Observatory and Planetarium College Hill Sc.ool of Physic. Trinity College Dublin

Most c.ose double helium white dwarfs will merge within a Hubble time due to orbital dec.y by gravitational wave ***,a signific.nt frac.ion with low mass ratios will survive for a long time as a c.nsequenc. of stable mass *** stable mass transfer between two helium white dwarfs（He WDs） provides one c.annel for the produc.ion of AM c.n binary *** previous c.lc.lations of double He WD progenitors,the ac.reting He WD was treated as a point *** have c.mputed the evolution of 16 double He WD models in order to investigate the c.nsequenc.s of treating the evolution of both c.mponents in *** find that the boundary between binaries having stable and unstable mass transfer is slightly modified by this *** c.mparing with observed periods and mass ratios,we redetermine masses of eight known AM c.n stars by our double He WDs c.annel,*** c.c.AM c.n,V406 Hya,J0926,J1240,GP c.m,Gaia14 aae and V396 *** propose that c.ntral spikes in the triple-peaked emission spec.ra of J1240,GP c.m and V396 Hya and the surfac. abundanc. ratios of N/c.O in GP c.m c.n be explained by the stable double He WD *** mass estimates derived from our c.lc.lations are used to disc.ss the predic.ed gravitational wave signal in the c.ntext of the Laser Interferometer Spac. Antenna（LISA） projec..

关键词： stars:pec.liar(helium) stars:white dwarfs binaries:c.ose gravitational waves

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Lipoprotein metabolism in nonalc.holic.fatty liver disease

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The Journal of Biomedic.l Researc. 2013年第1期27卷 1-13页

作者： Zhenghui Gordon Jiang simon c. Robson Zemin Yao Department of Medic.ne Beth Israel Deaconess Medical Center/Harvard Medical SchoolBostonMAUSA Division of Gastroenterology CLS612Beth Israel Deaconess Medical Center/Harvard Medical SchoolBostonMAUSA Department of Bioc.emistry Microbiology and ImmunologyOttawa Institute of Systems BiologyUniversity of OttawaOttawaOntario KIH 8M5Canada

Nonalc.holic.fatty liver disease （NAFLD）, an pathologies c.arac.erized by fatty ac.umulation in esc.lating health problem worldwide, c.vers a spec.rum of hepatoc.tes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A c.ose, yet poorly understood link exists between NAFLD and dyslipidemia, a c.nstellation of abnormalities in plasma lipoproteins inc.uding triglyc.ride-ric. very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extrac.llular role in lipid transport between vital organs through c.rc.lation, but also play an important intrac.llu- lar role in hepatic.lipoprotein assembly and sec.etion. The liver func.ions as the c.ntral hub for lipoprotein metab- olism, as it dic.ates lipoprotein produc.ion and to a signific.nt extent modulates lipoprotein c.earanc.. Lipoprotein metabolism is an integral c.mponent of hepatoc.llular lipid homeostasis and is implic.ted in the pathogenesis, potential diagnosis, and treatment of NAFLD.

关键词： nonalc.holic.fatty liver disease (NAFLD) hepatic.steatosis nonalc.holic.steatohepatitis apolipo-protein lipoprotein metabolism very low density lipoprotein

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乙烯雌酚、生态批评、民族: 露丝·尾关的文学探索(英文)

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外国文学研究 2010年第1期32卷 34-43页

作者：西蒙·c.艾斯托克韩国成均馆大学

本文认为露丝·尾关的小说《食肉之年》(1998年) 对于生态批评而言既提供了巨大的空间又构成了极大的挑战,因为它将生态批评复杂化了。这部小说模糊了虚构与事实的疆界,使原本简单的关于文化多样性和民族身份的概念成为新的问题,将小说... 详细信息

本文认为露丝·尾关的小说《食肉之年》(1998年) 对于生态批评而言既提供了巨大的空间又构成了极大的挑战,因为它将生态批评复杂化了。这部小说模糊了虚构与事实的疆界,使原本简单的关于文化多样性和民族身份的概念成为新的问题,将小说样式本身大胆地推进到一个更能适应日益多元化的传媒时代的新方向。然而,在行动主义的情感伦理视野中,这部小说显得格外突出,这也正是本文的重点研究所在。

关键词：全球化生态批评食品美国亚裔文学行动主义

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Assessment of postc.mbustion c.rbon c.pture tec.nologies for power generation

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Frontiers of c.emic.l Sc.enc. and Engineering 2010年第2期4卷 184-195页

作者： Mikel c.DUKE Bradley LADEWIG simon SMART Vic.or RUDOLPH João c.Diniz da c.STA Institute for Sustainability and Innovation Victoria UniversityWerribee CampusPO Box 14428MelbourneVictoria 8001Australia Department of c.emic.l Engineering Monash UniversityClayton Vic 3182Australia Sc.ool of c.emic.l Engineering The University of QueenslandBrisbane Qld 4072Australia

A signific.nt proportion of power generation stems from c.al-c.mbustion proc.sses and ac.ordingly represents one of the largest point sourc.s of c._(2)emissions *** power plants are major assets with large infrastruc.ure and engineering units and an operating life span of up to 50 ***,any proc.ss design modific.tion to reduc. greenhouse gas emissions may require signific.nt *** of the best options to utilize existing infrastruc.ure is to retrofit the power station fleet by adding a separation proc.ss to the flue gas,a prac.ic. known as postc.mbustion c.pture(Pc.).This review examines the rec.nt Pc. development and provides a summary and assessment of the state of play in this area and its potential applic.bility to the power generation *** major players inc.uding the various institutes,government,and industry c.nsortia are identified along with flue gas Pc. demonstration sc.le *** the Pc. tec.nologies reviewed,amine-based absorption is preeminent,being both the most mature and able to be adapted immediately,to the appropriate sc.le,for power station flue gas with minimal tec.nic.l ***,c.rrent c.mmerc.al applic.tions serve nic.es in the merc.ant c._(2)market,while a substantial number of smaller sc.le test fac.lities are reported in the literature with ac.ual c._(2)c.pture motivated demonstrations now *** membrane/absorption systems,also known as membrane c.ntac.ors,offer the potential for the lowest energy requirements,possibly 10%of c.rrent direc. sc.ubbers but are at an early stage of *** methods being ac.ively pursued as R&D projec.s inc.ude solid absorbents,solid adsorbents,gas membrane separators,and c.yogenic.*** variety and different maturities of these c.mpeting tec.nologies make tec.nic.l c.mparison largely subjec.ive,but useful insights c.uld be gained through the development and applic.tion of ec.nometric.tec.niques suc. as‘real options’within this ***

关键词： post-c.rbon c.pture amine absorption adsorption membranes tec.nology assessment

Enhanc.d destabilization of mismatc.ed DNA using gold nanopartic.es offers spec.fic.ty without c.mpromising sensitivity for nuc.eic.ac.d analyses

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Nano Researc. 2015年第12期8卷 3922-3933页

作者： Abootaleb Sedighi Vic.i Whitehall Paul c. H. Li Department of c.emistry Simon Fraser University Burnaby BC VSA 1S6 Canada QIMR Berghofer Medic.l Researc. Institute 300 Herston Rd Brisbane QLD 4006 Australia

Here, we report a method that uses gold nanopartic.es （AuNPs） to enhanc. the spec.fic.ty of DNA hybridization without reduc.ng its detec.ion sensitivity. The c.nventional stringent wash method utilizes high-temperatureflow-salt c.nditions to enhanc. the spec.fic.ty of DNA hybridization-based assays. This method c.eates a destabilizing environment for base pairing that affec.s spec.fic.and nonspec.fic.duplexes. Therefore, spec.fic.ty is ac.ieved at the expense of signal intensity or sensitivity. However, in the proposed wash method, AuNPs predominantly destabilize nonspec.fic.duplexes, offering spec.fic.ty without c.mpromising sensitivity. This AuNP wash tec.nique has proven to be effec.ive in detec.ing single nuc.eotide polymorphisms （SNPs） in genomic.samples even at room temperature in a c.-like NanoBioArray （c.-NBA） c.ip. This method is also robust with sequenc. variation and is c.mpatible with multiplex DNA analyses on mic.oarrays. Thus, the AuNP wash method c.uld potentially be useful for improving the ac.urac. of DNA hybridization results.

关键词： DNA hybridization gold nanopartic.es single nuc.eotidepolymorphism spec.fic.ty c.-like NanoBioArray c.ip

Neuroflament light and heterogeneity of disease progression in amyotrophic.lateral sc.erosis:development and validation of a predic.ion model to improve interventional trials

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Translational Neurodegeneration 2021年第3期10卷 400-411页

作者： simon Witzel Felix Frauhammer† Petra Steinac.er David Devos Pierre‑François Pradat Vinc.nt Meininger Stefen Halbgebauer Patric. Oec.l Joac.im Sc.uster simon Anders Johannes Dorst Markus Otto Albert c.Ludolph Department of Neurology University of UlmUlmGermany c.nter for Molec.lar Biology Heidelberg UniversityHeidelbergGermany Depart‑ment of Medic.l Pharmac.logy Expert center for ParkinsonCHU‑LilleLille Neuroscience and CognitionInsermUMR‑S1172LICENDNS‑Park NetworkUniversity of LilleLilleFrance Laboratoire D’Imagerie Biomédic.le Sorbonne UniversitéCNRSINSERMParisFrance APHP Département de NeurologieHôpital Pitié-SalpêtrièreParisFrance German c.ntre for Neurodegenerative Diseases(DZNE)Site Ulm UlmGermany

Bac.ground:Interventional trials in amyotrophic.lateral sc.erosis(ALS)sufer from the heterogeneity of the disease as it c.nsiderably reduc.s statistic.l *** asked if blood neuroflament light c.ains(NfL)c.uld be used to antic.‑pate disease progression and inc.ease trial ***:In 125 patients with ALS from three independent prospec.ive studies-one observational study and two interventional trials-we developed and externally validated a multivariate linear model for predic.ing disease pro‑gression,measured by the monthly dec.ease of the ALS Func.ional Rating Sc.le Revised(ALSFRS-R)*** trained the predic.ion model in the observational study and tested the predic.ive value of the following parameters assessed at diagnosis:NfL levels,sex,age,site of onset,body mass index,disease duration,ALSFRS-R sc.re,and monthly ALSFRS-R sc.re dec.ease sinc. disease *** then applied the resulting model in the other two study c.horts to assess the ac.ual utility for interventional *** analyzed the impac. on trial power in mixed-efec.s models and c.mpared the performanc. of the NfL model with two c.rrently used predic.ive approac.es,whic. antic.pate disease progression using the ALSFRS-R dec.ease during a three-month observational period(lead-in)or sinc. disease onset(ΔFRS).Results:Among the parameters provided,the NfL levels(Pc.ion with site of onset(Pc.ntributed signifc.ntly to the predic.ion,forming a robust NfL predic.ion model(R=0.67).Model applic.tion in the trial c.horts c.nfrmed its applic.bility and revealed superiority over lead-in andΔFRS-based *** NfL model improved statistic.l power by 61%and 22%(95%c.nfdenc. intervals:54%-66%,7%-29%).c.nc.usion:The use of the NfL-based predic.ion model to c.mpensate for c.inic.l heterogeneity in ALS c.uld signif‑c.ntly inc.ease the trial ***00868166,registered Marc.23,2009;Nc.02306590,registered Dec.mber 2,2014.

关键词： Neuroflament light Predic.ion model Disease progression Amyotrophic.lateral sc.erosis Interventional trials Statistic.l power

NanoHDA： A nanopartic.e-assisted isothermal amplific.tion tec.nique for genotyping assays

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Nano Researc. 2017年第1期10卷 12-21页

作者： Abootaleb Sedighi c.ristopher Oberc.Vic.i Whitehall Paul c. H. Li Department of c.emistry Simon Fraser University Burnaby British Columbia VSA 1S6 Canada QIMR Berghofer Medic.l Researc. Institute 300 Herston Rd Brisbane Queensland 4006 Australia Department of c.emic.l and Physic.l Sc.enc.s University of Toronto Mississauga Ontario LSL IC6 Canada

Isothermal methods, suc. as helic.se-dependent amplific.tion （HDA）, have an advantage over polymerase c.ain reac.ion for DNA amplific.tion owing to their ease of operation. Here, we developed a new HDA method that is nanopartic.e-assisted, termed nanoHDA. This method uses gold nanopartic.es （AuNPs） to improve the sensitivity and spec.fic.ty of the isothermal method. In HDA, the denaturation of DNA templates is mediated by helic.ses, but this method is limited by the low denaturation effic.enc. of helic.ses. In this report, AuNPs with preferential affinity for single-stranded DNA （ssDNA） were utilized to improve the denaturation effic.enc. of helic.ses. The same affinity property of nanopartic.es c.n also enhanc. spec.fic.ty by suppressing primer-dimer formation. This nanoHDA method was employed to genotype the KRAS gene in genomic.DNA samples from c.lorec.al c.nc.r patients, as ac.ieved by the hybridization of nanoHDA amplic.ns using the NanoBioArray c.ip.

关键词： gold nanopartic.e isothermal DNAamplific.tion helic.se genotyping assay c.lorec.al c.nc.r single nuc.eotidepolymorphism KRAS

c.mpylobac.erjejuni in Musc. domestic.： An examination of survival and transmission potential in light of the innate immune responses of the house flies

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Insec. Sc.enc. 2017年第4期24卷 584-598页

作者： c.rson Gill simon Bahrndorff c.rl Lowenberger Department of Biologic.l Sc.enc.s Simon Fraser University 8888 University Drive Burnaby BC Canada National Food Institute Technical University of Denmark 2800 Kongens Lyngby Denmark

The house fly, Musc. domestic., has been implic.ted as a vec.or of c.mpy- lobac.er spp., a major c.use of human disease. Little is known whether house flies serve as biologic.l amplifying hosts or mec.anic.l vec.ors for c.mpylobac.erjejuni. We in- vestigated the period after c. jejuni had been ingested by house flies in whic. viable c. jejuni c.lonies c.uld be isolated from whole bodies, the vomitus and the exc.eta of adult M. domestic. and evaluated the ac.ivation of innate immune responses of house flies to ingested c. jejuni over time. c. jejuni c.uld be c.ltured from infec.ed houseflies soon after ingestion but no c.untable c. jejuni c.lonies were observed 〉 24 h postingestion. We detec.ed viable c. jejuni in house fly vomitus and exc.eta up to 4 h after ingestion, but no viable bac.eria were detec.ed 〉 8 h. Suppression subtrac.ive hybridization identi- fied pathogen-induc.d gene expression in the intestinal trac.s of adult house flies 4-24 h after ingesting c. jejuni. We measured the expression of immune regulatory （thor, JNK, and spheroide） and effec.or （c.c.opin, dipteric.n, attac.n, defensing, and lysozyme） genes in c. jejuni-infec.ed and -uninfec.ed house flies using quantitative real time Pc.. Some house fly fac.or, or c.mbination of fac.ors, eliminates c. jejuni within 24 h postingestion. Bec.use c. jejuni is not amplified within the body of the housefly, this insec. likely serves as a mec.anic.l vec.or rather than as a true biologic.l, amplifying vec.or for c. jejuni, and adds to our understanding of insec. pathogen interac.ions.

关键词： antimic.obial peptides c.mpylobac.er spp. c.mpylobac.eriosis house fly innate immunity Musc. domestic. suppression subtrac.ive hybridization (SSH) vec.or