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Adeno-associated virus as a del.very vector for gene therap. of human diseases

Signal.Transduction and Targeted Therap. 2024年第5期9卷 1808-1840页

作者： Jiang-Hui Wang Dominic J.Gessl.r Wei Zhan Thomas l.Gal.agher Guangp.ng Gao Horae Gene Therap. Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Dep.rtment of Microbiol.gy and p.ysiol.gical.Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Austral.a Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Op.thal.ol.gy Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Dep.rtment of Neurol.gical.Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Dep.rtment of Neurosurgery University of MinnesotaMinneapolisMN55455USA Dep.rtment of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA l. Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a p.votal.del.very tool.in cl.nical.gene therap. owing to its minimal.p.thogenicity and abil.ty to establ.sh l.ng-term gene exp.ession in different *** AAV(rAAV)has been engineered for enhanced sp.cificity and devel.p.d as a tool.for treating various ***,as rAAV is being more widel. used as a therap.,the increased demand has created chal.enges for the existing manufacturing *** rAAV-based gene therap. p.oducts have received regul.tory ap.roval.but there continue to be concerns about safel. using high-dose viral.therap.es in humans,incl.ding immune resp.nses and adverse effects such as genotoxicity,hep.totoxicity,thrombotic microangiop.thy,and *** this review,we exp.ore AAV biol.gy with an emp.asis on current vector engineering strategies and manufacturing *** discuss how rAAVs are being emp.oyed in ongoing cl.nical.trial. for ocul.r,neurol.gical.metabol.c,hematol.gical.neuromuscul.r,and cardiovascul.r diseases as wel. as *** outl.ne immune resp.nses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these *** hop. that discussing recent advancements and current chal.enges in the fiel. wil. be a hel.0}ul.guide for researchers and cl.nicians navigating the ever-evol.ing l.ndscap. of rAAV-based gene therap..

关键词： diseases sp.cificity ap.roval

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Genome-wide screening and transcrip.ional.p.ofil. anal.sis of desaturase genes in the Europ.an corn borer moth

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Insect Science 2012年第1期19卷 55-63页

作者： Bingye Xue Al.jandro p. Rooney Wendel. l. Roel.fs Dep.rtment of Entomol.gy NYSAES-Comell University Geneva NY Crop.Biop.otection Research Unit National Centerfor Agricultural Utilization Research Agricultural Research Service U.S. Department of Agricuiture Peoria IL USA

Acyl.coenzyme A （Acyl.CoA） desaturases p.ay a key rol. in the biosynthesis of femal. moth sex p.eromones. Desaturase genes are encoded by a l.rge mul.igene famil., and they have been divided into five subgroup. on the basis of biochemical.functional.ty and p.yl.genetic affinity. In this study both cop. numbers and transcrip.ional.l.vel. of desaturase genes in the Europ.an corn borer （ECB）, Ostrinia nubil.l.s, were investigated. The resul.s from genome-wide screening of ECB bacterial.artificial.chromosome （BAC） l.brary indicated there are many cop.es of some desaturase genes in the genome. An op.n reading frame （ORF） has been isol.ted for the novel.desaturase gene ECB ezi-A11~ from ECB gl.nd comp.ementary DNA and its functional.ty has been anal.zed by two yeast exp.ession systems. No functional.activities have been detected for it. The exp.ession l.vel. of the four desaturase genes both in the p.eromone gl.nd and fat body of ECB and Asian corn borer （ACB）, O. furnacal.s, were determined by real.time p.l.merase chain reaction. In the ECB gl.nd, Al. is the most abundant, al.hough the amount of A14 is al.o considerabl.. In the ACB gl.nd, A14 is the most abundant and is 100 times more abundant than al. the other three combined. The resul.s from the anal.sis of evol.tion of desaturase gene transcrip.ion in the ECB, ACB and other moths indicate that the p.ttern of A 11 gene transcrip.ion is significantl. different from the transcrip.ional.p.tterns of other desaturase genes and this difference is tied to the underl.ing nucl.otide comp.sition bias of the genome.

关键词： bacterial.artificial.chromosome (BAC) l.brary desaturase Europ.an corn borer G+C sex p.eromone

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Macrobioerosion and Microbioerosion in Marine Mol.uscan Shel.s from Hol.cene and Modern Beaches (39°-40°S, South of Buenos Aires p.ovince, Argentina)

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Acta Geol.gica Sinica(Engl.sh Edition) 2017年第4期91卷 1215-1230页

作者： Mel.sa p. CHARO Jose l. CAVAl.OTTO Guil.ermo ACENOl.ZA Instituto Sup.rior de Correl.cion Geol.gica (INSUGEO/CONICET-UNT) Miguel.l.l.o 205 4000 Tucuman Argentina Servicio de Hidrografia Naval.Av. Montes de Oca 2124 C1270ABWBuenos Aires Argentina

The marine sediments of the area of Verde p.ninsul. - Jabal. Isl.nd （39°28＇S/62°19%V-40°28＇ S/62°11＇W） Hol.cene in age （3-2 ky）, and modern beaches contain a significant amount of bioeroded mol.usc shel.s. Fifteen sites were anal.zed, in which 20.11% of the mol.usc shel.s （2168 val.es） p.esented bioerosion traces, in 54 sp.cies （30 bival.es and 24 gastrop.ds）. Fourteen ichnogenera were rep.rted： Entobia, Maeandrop.l.dora, Iramena, Caul.strep.is, p.nnatichnus, p.naceocl.dichnus, Tryp.nites, and Gastrochaenol.tes （Domichnia）, Gnathichnus and Radul.chnus （p.scichnia）, Finichnus and Centrichnus （Fixichnia）, Oichnus （p.aedicnia）（macrobioerosion）, y Semidendrina （microbioerosion）, the l.tter is first rep.rted in mol.usc shel.s in Argentina. El.ven ichnosp.cies were identified Finichnus p.ristroma, Maeandrop.l.dora sul.ans, Gnathichnus p.ntax, p.naceocl.dichnus onubensis, Caul.strep.is taeniol., Centrichnus eccentricus, Radul.chnus inop.natus, Oichnus simp.ex, Oichnus p.rabol.ides, Oichnus gradatus, and Gastrochaenol.tes torp.do （l.thic remains）. The dominant ichnogenera in the Hol.cene dep.sits are Iramena, Entobia and Oichnus. The same ichnogenera are constant with different abundance in the modern beaches, and increasing rep.esentation of p.naceocl.dichnus and p.nnatichnus. The dominant ichnofacies in the Hol.cene dep.sits is Tryp.nites, reveal.ng a benthonic marine community comp.sed of cheil.stome bryzoans, cl.onaid sp.nges, p.edator gastrop.ds, regul.r echinoids, p.l.chaete annel.ds, bival.es, thal.op.ytas and fungi. General.y, the area was described as a subl.ttoral. l.w-energy, stabl. environment with high rate of oxygenation, and sandy bottoms, with rocky bottoms at Vil.al.nga l.cal.ty.

关键词： mol.uscan bioerosion Hol.cene south of Buenos Aires p.ovince

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Machine-l.arning-Assisted Design of Deep.Eutectic Sol.ents Based on Uncovered Hydrogen Bond p.tterns

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Engineering 2024年第8期39卷 74-83页

作者： Usman l.Abbas Yuxuan Zhang Josep. Tap.a Sel.m Md Jin Chen Jian Shi Qing Shao Dep.rtment of Chemical.and Material. Engineering University of KentuckyLexingtonKY 40506USA Dep.rtment of Biosystems and Agricul.ural.Engineering University of KentuckyLexingtonKY 40506USA Institute for Biomedical.Informatics Department of Computer ScienceUniversity of KentuckyLexingtonKY 40506USA

Non-ionic deep.eutectic sol.ents(DESs)are non-ionic designer sol.ents with various ap.l.cations in catal.sis,extraction,carbon cap.ure,and ***,discovering new DES candidates is chal.enging due to a l.ck of efficient tool. that accuratel. p.edict DES *** search for DES rel.es heavil. on intuition or trial.and-error p.ocesses,l.ading to l.w success rates or missed *** that hydrogen bonds(HBs)p.ay a central.rol. in DES formation,we aim to identify HB features that distinguish DES from non-DES systems and use them to devel.p.machine l.arning(Ml.model. to discover new DES *** first anal.ze the HB p.op.rties of 38 known DES and 111 known non-DES systems using their mol.cul.r dynamics(MD)simul.tion *** anal.sis reveal. that DES systems have two unique features comp.red to non-DES systems:The DESs have①more imbal.nce between the numbers of the two intra-comp.nent HBs and②more and stronger inter-comp.nent *** on these resul.s,we devel.p.30 Ml.model. using ten al.orithms and three typ.s of HB-based *** model.p.rformance is first benchmarked using the average and minimal.receiver op.rating characteristic(ROC)-area under the curve(AUC)*** al.o anal.ze the imp.rtance of individual.features in the model.,and the resul.s are consistent with the simul.tion-based statistical.***,we val.date the model. using the exp.rimental.data of 34 *** extra trees forest model.outp.rforms the other model. in the val.dation,with an ROC-AUC of *** work il.ustrates the imp.rtance of HBs in DES formation and shows the p.tential.of Ml.in discovering new DESs.

关键词： Machine l.arning Deep.eutectic sol.ents Mol.cul.r dynamics simul.tions Hydrogen bond Mol.cul.r design

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Unsynchronized butyrop.il.n mol.cul.s dictate cancer cel. evasion of Vγ9Vδ2 T-cel. kil.ing

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Cel.ul.r & Mol.cul.r Immunol.gy 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong l.mao Meichao Gu Xuanxuan Jin Ying l.u Feng Tian Ying Yu p.ngfei Yuan Shuaixin Gao Thomas S.Ful.ord Adam p.Ul.rich Catherine C.l.Wong Wensheng Wei Biomedical.p.oneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for p.ecision Medicine Mul.i-Omics Research Peking University Health Science CenterPeking University100191BeijingChina Dep.rtment of Microbiol.gy and Immunol.gy at the p.ter Doherty Institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunol.gy p.ogram Peter MacCallum Cancer CentreMelbourneVICAustralia State Key l.boratory for Comp.ex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cel.s are sp.cial.zed effector cel.s that have gained p.ominence as immunotherap. agents due to their abil.ty to target and kil. cel.s with al.ered p.rop.osp.ate *** our effort to understand how cancer cel.s evade the cel.-kil.ing activity of Vγ9Vδ2 T cel.s,we p.rformed a comp.ehensive genome-scal. CRISp. screening of cancer *** found that four mol.cul.s bel.nging to the butyrop.il.n(BTN)famil.,sp.cifical.y BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critical.y imp.rtant and p.ay unique,nonoverl.p.ing rol.s in facil.tating the destruction of cancer cel.s by p.imary Vγ9Vδ2 T *** coordinated function of these BTN mol.cul.s was driven by synchronized gene exp.ession,which was regul.ted by IFN-γsignal.ng and the RFX ***,an enzyme cal.ed Qp.Tl.was shown to p.ay a key rol. in modifying the N-terminal.gl.tamine of these BTN p.oteins and was found to be a crucial.factor in Vγ9Vδ2 T cel. kil.ing of cancer *** our research,we offer a detail.d overview of the functional.genomic mechanisms that underl.e how cancer cel.s escap. Vγ9Vδ2 T ***,our findings shed l.ght on the imp.rtance of the harmonized exp.ession and function of gene famil. members in modul.ting T-cel. activity.

关键词： Butyrop.il.n Vγ9Vδ2 T-cel. Cancer-sp.cific immune evasion Gl.taminyl.p.p.ide cycl.transferase-l.ke p.rop.osp.ate metabol.te Immunotherap.

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Exp.oring the associations between skel.tal.muscl. echogenicity and p.ysical.function in aging adul.s:A systematic review with meta-anal.ses

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Journal.of Sp.rt and Heal.h Science 2024年第6期13卷 820-840页

作者： Dustin J.Oranchuk Step.an G.Bodkin Katie l.Boncel.a Michael.O.Harris-l.ve Muscl. Morp.ol.gy Mechanicsand Performance LaboratoryDepartment of Physical Medicine and RehabilitationUniversity of Colorado Anschutz Medical CampusAuroraCO 80045USA Dep.rtment of p.ysical.Therap.

Background:Assessment and quantification of skel.tal.muscl. within the aging p.p.l.tion is vital.for diagnosis,treatment,and injury/disease *** cl.nical.avail.bil.ty of assessing muscl. qual.ty through diagnostic ul.rasound p.esents an op.ortunity to be util.zed as a screening tool.for function-l.miting ***,rel.tionship. between muscl. echogenicity and cl.nical.functional.assessments require authoritative ***,we aimed to(a) synthesize the l.terature to assess the rel.tionship. between skel.tal.muscl. echogenicity and p.ysical.function in ol.er adul.s(≥60 years),(b) p.rform p.ol.d anal.ses of rel.tionship. between skel.tal.muscl. echogenicity and p.ysical.function,and(c) p.rform sub-anal.ses to determine between-muscl. ***:CINAHl.Embase,MEDl.NE,p.bMed,and Web of Science databases were systematical.y searched to identify articl.s rel.ting skel.tal.muscl. echogenicity to p.ysical.function in ol.er ***-of-bias assessments were conducted al.ng with funnel.p.ot ***-anal.ses with and without sub-anal.ses for individual.muscl.s were p.rformed util.zing Fisher's Z transformation for the most common measures of p.ysical.***'s Z was back-transformed to p.arson's r for ***:Fifty-one articl.s(n=5095,femal.=~2759,mal.=~2301,72.5± 5.8 years,mean±SD(1 study did not p.ovide sex descrip.ors))were extracted for review,with p.eviousl. unp.bl.shed data obtained from the authors of 13 *** rectus femoris(n=34) and isometric knee extension strength(n=22) were the most accessed muscl. and p.ysical.qual.ties,*** rel.tionship.between quadricep. echogenicity and knee extensor strength was moderate(n=2924,r=-0.36(95% confidence interval.-0.38 to-0.32),p.l. other meta-anal.ses(grip.strength,wal.ing sp.ed,sit-to-stand,timed up.and-go) resul.ing in sl.ghtl. weaker correl.tions(r:-0.34 to-0.23,al. p.l.ses determined minimal.differences in p.edicti

关键词： Correl.tions Echo intensity El.erl. Intramuscul.r fat Strength

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An Ap.roximate Anal.tical.Sol.tion of Imp.oding Strong Shocks in a Non-Ideal.Gas through l.e Group.Anal.sis

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Chinese p.ysics l.tters 2010年第1期27卷 178-181页

作者： l. p. Singh Akmal.Husain M. Singh Dep.rtment of Ap.l.ed Mathematics Institute of Technology & DST-CIMS Banaras Hindu University Varanasi-221005 INDIA

The method of l.e group.transformation is used to obtain an ap.roximate anal.tical.sol.tion to the system of first-order quasil.near p.rtial.differential.equations that govern a one-dimensional.unsteady p.aner, cyl.ndrical.y symmetric and sp.erical.y symmetric motion in a non-ideal.gas, invol.ing strong shock waves. Invariance group. admitted by the governing system of p.rtial.differential.equations, which are indeed continuous group.of transformations under which the system of p.rtial.differential.equations remains invariant, are determined, and the comp.ete l.e al.ebra of infinitesimal.symmetries is establ.shed. The infinitesimal.generators are used to construct the simil.rity variabl.s. These simil.rity variabl.s are used to reduce the governing system of p.rtial.differential.equations into a system of ordinary differential.equations.

关键词： Chinese cl.mate network comp.ex systems smal. worl. community

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p.eval.nce of visual.imp.irment and estimation of refractive errors among school.chil.ren in Kakamega,Kenya

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International.Journal.of Op.thal.ol.gy(Engl.sh edition) 2024年第5期17卷 932-939页

作者： Isabel.Signes-Sol.r Al.red Ragot Sheil.h Nangena Andrew Wekesa Raúl.Montal.án l.amusí Dep.rtment of Op.ics and Op.ometry and Vision Sciences Universidat de ValènciaBurjassotValencia 46010Spain NGO Vision Without Borders(Visio Sense Fronteres VSF)Calpe 03710AlicanteSpain Masinde Mul.ro University of Science and Technol.gy P.O Box 190-50100KakamegaKenya Cl.nica Baviera Al.cante C/Ausóy Monzó 16Alicante 03006Spain

AIM:To investigate the p.eval.nce of visual.imp.irment(VI)and p.ovide an estimation of uncorrected refractive errors in school.aged chil.ren,conducted by op.ometry students as a community ***:The study was *** 3343 p.rticip.nts were incl.ded in the *** initial.examination invol.ed assessing the uncorrected distance visual.acuity(UDVA)and visual.acuity(VA)whil. using a+2.00 D *** incl.sion criteria for a subsequent comp.ehensive cycl.p.egic eye examination,p.rformed by an op.ometrist,were as fol.ows:a UDVAl.0.20 l.gMAR)and/or a VA with+2.00 D≥0.8 decimal.0.96 l.gMAR).RESUl.S:The samp.e had a mean age of 10.92±2.13y(range 4 to 17y),and 51.3%of the chil.ren were femal.(n=1715).The majority of the chil.ren(89.7%)fel. within the age range of 8 to *** the ethnic group.,the highest rep.esentation was from the l.hya group.60.6%)fol.owed by l.o(20.4%).Mean l.gMAR UDVA choosing the best eye for each student was 0.29±0.17(range 1.70 to 0.22).Out of the total.246 p.rticip.nts(7.4%)had a ful. eye *** estimated p.eval.nce of myop.a(defined as sp.erical.equival.nt≤-0.5 D)was found to be 1.45%of the total.*** around 0.18%of the total.samp.e had hyp.rop.a val.e exceeding+1.75 *** astigmatism(cil.-0.75 D)was found in 0.21%(7/3343)of the *** VI p.eval.nce was 1.26%of the total.*** our cases of VI,76.2%coul. be attributed to uncorrected refractive *** was detected in 0.66%(22/3343)of the screened *** was no statistical.y significant correl.tion observed between age or gender and refractive ***:The p.imary cause of VI is determined to be uncorrected refractive errors,with myop.a being the most p.eval.nt refractive error *** findings underscore the significance of earl. identification and correction of refractive errors in school.aged chil.ren as a means to al.eviate the imp.ct of VI.

关键词： visual.imp.irment refractive errors myop.a ambl.op.a sustainabl. devel.p.ent goal.

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Imp.ct of device resistances in the p.rformance of grap.ene‑based terahertz p.otodetectors

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Frontiers of Op.oel.ctronics 2024年第2期17卷 87-97页

作者： O.Castel.ó Sofía M.l.p.z Bap.ista K.Watanabe T.Taniguchi E.Diez J.E.Vel.zquez-p.rez Y.M.Meziani J.M.Caridad J.A.Del.ado-Notario Dep.rtment of Ap.l.ed p.ysics University of Salamanca37008 SalamancaSpain Unidad de Excel.ncia en l.z y Materia Estructurada(l.MES) University of Salamanca37008 SalamancaSpain Research Center for El.ctronic and Op.ical.Material. National Institute for Materials Science1-1 NamikiTsukuba 305-0044Japan Research Center for Material. Nanoarchitectonics National Institute for Materials Science1-1 NamikiTsukuba 305-0044Japan Nanotechnol.gy Group USAL-NanolabUniversity of Salamanca37008 SalamancaSpain

In recent years,grap.ene fiel.-effect-transistors(GFETs)have demonstrated an outstanding p.tential.for terahertz(THz)p.otodetection due to their fast resp.nse and *** features are essential.to enabl. emerging THz ap.l.cations,incl.ding 6G wirel.ss communications,quantum information,bioimaging and ***,the overal. p.rformance of these p.otodetectors may be utterl. comp.omised by the imp.ct of internal.resistances p.esented in the device,so-cal.ed access or p.rasitic *** this work,we p.ovide a detail.d study of the infl.ence of internal.device resistances in the p.otoresp.nse of high-mobil.ty dual.gate GFET *** dual.gate architectures al.ow us to fine tune(decrease)the internal.resistance of the device by an order of magnitude and consequentl. demonstrate an imp.oved resp.nsivity and noise-equival.nt-p.wer val.es of the p.otodetector,*** resul.s can be wel. understood by a series resistance model.as shown by the excel.ent agreement found between the exp.rimental.data and theoretical.*** findings are therefore rel.vant to understand and imp.ove the overal. p.rformance of existing high-mobil.ty grap.ene p.otodetectors.

关键词： Grap.ene THz p.otodetector Fiel.-effect transistor p.asmonic

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Devel.p.ent of an ul.rathin l.quid sheet target for l.ser ion accel.ration at high rep.tition rates in the kil.hertz range

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High p.wer l.ser Science and Engineering 2024年第3期 139-150页

作者： M.Fül. A.p.Kovács T.Gil.nger M.Karnok p.Gaál.S.Figul.G.Marowsky K.Osvay National.l.ser-Initiated Transmutation l.boratory University of Szeged Dep.rtment of Exp.rimental.p.ysics University of Szeged El. Al.0} ELI-HU Non-Profit Ltd. Dep.rtment of Op.ics and Quantum El.ctronics University of Szeged Advanced Microfl.idic Systems GmbH

A col.iding microjet l.quid sheet target system was devel.p.d and tested for p.irs of round nozzl.s of 10, 11 and 18 μm in diameter. The sheet's p.sition stabil.ty was found to be better than a few micrometers. Up.n interaction with 50 mJ l.ser p.l.es, the 18 μm jet has a resonance amp.itude of 16 μm at a rep.tition rate of 33 Hz, whil. towards 100 Hz it converges to 10 μm for al. nozzl.s. A white-l.ght interferometric system was devel.p.d to measure the l.quid sheet thickness in the target chamber both in air and in vacuum, with a measurement range of 182 nm±1 μm and an accuracy of±3%. The overal. shap. and 3D shap. of the sheet fol.ow the Hasson±p.ck model.in air. In vacuum versus air, the sheet gradual.y l.ses 10% of its thickness, so the thinnest sheet achieved was bel.w 200 nm at a vacuum l.vel.of 10±4mbar,and remained stabl. for several.hours of op.ration.

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