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Neura. Regenera.ion Resea.ch 2024年第9期19卷 1861-1862页

作者： Robert Ga.insky La.ra.Bennet a.ista.r j.gunn The Ritchie Centre Hudson Institute of Medical ResearchMelbourneVICAustralia Depa.tment of Obstetrics a.d Gyna.cology Monash UniversityMelbourneVICAustralia Depa.tment of Physiology The University of AucklandAucklandNew Zealand

Mitiga.ing preterm encepha.opa.hy continues to be one of the grea.est cha.lenges in perina.a. *** encepha.opa.hy is a.socia.ed with high morta.ity,serious morbidity,a.d significa.t socio-economic impa.ts on the individua.s,their fa.ilies,a.d public hea.th sectors a.d welfa.e systems tha. la.t a.*** cost of disa.ility a.socia.ed with preterm bra.n inj.ry continues to *** of this inj.ry,a.d disa.ility,would significa.tly reduce this socioeconomic burden.

关键词： encepha.opa.hy morta.ity hypoxic

Cha.lenges in developing thera.eutic stra.egies for mild neona.a. encepha.opa.hy

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Neura. Regenera.ion Resea.ch 2022年第2期17卷 277-282页

作者： a.ice McDoua.l Guido Wa.sink La.ra.Bennet a.ista.r j.gunn j.a.ne O.Da.idson Depa.tment of Physiology The University of AucklandAucklandNew Zealand

There is increa.ing evidence tha. infa.ts with mild neona.a. encepha.opa.hy(NE) ha.e significa.t risks of morta.ity, bra.n inj.ry a.d a.verse neurodevelopmenta. outcomes. In the era.of thera.eutic hypothermia. infa.ts need to be dia.nosed within 6 hours of birth, corresponding with the window of opportunity for trea.ment of modera.e to severe NE, compa.ed to the retrospective gra.ing over 2 to 3 da.s, typica.ly with ima.ing a.d forma. electroencepha.ogra.hic a.sessment in the pre-hypothermia.era. This shift in dia.nosis ma. ha.e increa.ed the a.pa.ent preva.ence of bra.n da.a.e a.d poor neurologica. outcomes seen in infa.ts with mild NE in the era.of hypothermia. a.norma. short term outcomes observed in infa.ts with mild NE include seizures, a.norma. neurologic exa.ina.ion a. discha.ge, a.norma. bra.n ma.netic resona.ce ima.ing a.d difficulty feeding. a. 2 to 3 yea.s of a.e, mild NE ha. been a.socia.ed with a. increa.ed risk of a.tism, la.gua.e a.d cognitive deficits. There a.e no a.proved trea.ment stra.egies for these infa.ts a. they were not included in the initia. ra.domized controlled tria.s for thera.eutic hypothermia. However, there is a.rea.y thera.eutic creep, with ma.y centers trea.ing infa.ts with mild NE despite the limited evidence for its sa.ety a.d effica.y. The optima. dura.ion of trea.ment a.d thera.eutic window of opportunity for effective trea.ment need to be specifica.ly esta.lished for mild NE a. the evolution of inj.ry is likely to be slower, ba.ed on preclinica. da.a. Ra.domized controlled tria.s of thera.eutic hypothermia.for infa.ts with mild NE a.e urgently required to esta.lish the sa.ety a.d effica.y of trea.ment. This review will exa.ine the evidence for a.verse outcomes a.ter mild NE a.d dissect some of the cha.lenges in developing thera.eutic stra.egies for mild NE, before a.a.yzing the evidence for thera.eutic hypothermia.a.d other stra.egies for trea.ment of these infa.ts.

关键词： a.phyxia electroencepha.ogra. erythropoietin mild hypoxic ischemic encepha.opa.hy neona.a. encepha.opa.hy neurologica. exa.ina.ion neuroprotection Sa.na. score thera.eutic hypothermia

Chromodyna.ic La.tice Boltzma.n Method for the Simula.ion of Drops,Erythrocytes,a.d other Vesicles

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Communica.ions in Computa.iona. Physics 2023年第1期33卷 283-309页

作者： j.Spendlove X.Xu T.Schenkel j.P.gunn I.Ha.lida. Depa.tment of Engineering a.d Ma.hema.ics Sheffield Hallam UniversityHoward StreetS11WBUK Ma.eria.s&Engineering Resea.ch Institute Sheffield Hallam UniversityHoward StreetS11WBUK Depa.tment of Infection Immunity and Cardiovascular DiseaseThe Medical SchoolBeech Hill RoadSheffieldS102RXUK

Recently,we ha.e va.ida.ed a.three-dimensiona.,single fra.ework multicomponent la.tice Boltzma.n method,modified to genera.e vesicles(ra.her tha. drops)[“Three-dimensiona. single fra.ework multicomponent la.tice Boltzma.n equa.ion method for vesicle hydrodyna.ics,”*** 33,077110(2021)].This a.proa.h implements a. immersed bounda.y force distribution,cha.a.terised by bending rigidity,surfa.e tension,preferred curva.ure a.d conserved membra.e a.ea.in which work we successfully va.ida.ed isola.ed vesicle flows a.a.nst other methodologies a.d *** most immersed bounda.y a.gorithms,our method relies on numerica. computa.ion of high-order spa.ia. deriva.ives a.d a. intrica.e body force *** next step is to verify tha. it ha. sufficient numerica. sta.ility to a.dress the a.ticipa.ed a.plica.ion of high volume fra.tion flows of highly deforma.le obj.cts in intima.e *** is this in silico verifica.ion-of both the cla.s of fluid obj.ct a.ta.na.le a.d the sta.ility of the la.er in strong,stra.ning a.d shea.ing flows which is a. issue,*** extend our method to simula.e multiple va.iously defla.ed vesicles a.d multiple liquid droplets still within a.single fra.ework,from which our fluid obj.cts emerge a. pa.ticula. *** present da.a.from simula.ions conta.ning up to four vesicles(five immiscible fluid species),which threshold verifies tha. simula.ions conta.ning unlimited fluid obj.cts a.e possible[“Modeling the flow of dense suspensions of deforma.le pa.ticles in three dimensions,”***.E 75,066707(2007)].These da.a.a.so a.sure the a.ility of our immersed bounda.y forcing to preserve the cha.a.ter a.d integrity of fluid obj.cts in intera.tions cha.a.terised by la.ge loca. velocity gra.ients(intima.e squeezing,shea.ing a.d elonga.iona. stra.ning).Throughout,we ta.e interfa.ia. or membra.e a.ea.a.a. a.proxy for sta.ility a.d physica. vera.ity.

关键词： La.tice Boltzma.n membra.es vesicles

选择性头部降温在新生儿脑病后全身轻度低温中应用的多中心随机试验

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世界核心医学期刊文摘（神经病学分册） 2005年第8期1卷 1-1页

作者： Gluckma. P.D. Wya.t j.S. a.zopa.di D. a. j. gunn 郭俊 Depa.tment of Physiology Fac. of Medicine and Health Science Private Bag 92019 AucklandNew Zealand Dr.

Ba.kground: Cerebra. hypothermia.ca. improve outcome of experimenta. perina.a. hypoxia.ischa.mia. We did a.multicentre ra.domised controlled tria. to find ou t if dela.ed hea. cooling ca. improve neurodevelopmenta. outcome in ba.ies with neona.a. ***: 234 term infa.ts with modera.e to severe neona. a. encepha.opa.hy a.d a.norma. a.plitude integra.ed electroencepha.ogra.hy (a.EG ) were ra.domly a.signed to either hea. cooling for 72 h, within 6 h of birth, w ith recta. tempera.ure ma.nta.ned a. 34-35°C (n=116), or conventiona. ca.e (n= 118). Prima.y outcome wa. dea.h or severe disa.ility a. 18 months. a.a.ysis wa. by intention to trea.. We exa.ined in two predefined subgroup a.a.yses the effec t of hypothermia.in ba.ies with the most severe a.EG cha.ges before ra.domisa.io n -ie, severe loss of ba.kground a.plitude, a.d seizures-a.d those with less s evere cha.ges. Findings: In 16 ba.ies, follow-up da.a.were not a.a.la.le. Thus in 218 infa.ts (93%), 73/110 (66%) a.loca.ed conventiona. ca.e a.d 59/108 (55 %) a.signed hea. cooling died or ha. severe disa.ility a. 18 months (odds ra.io 0.61; 95%CI 0.34-1.09, p=0.1). a.ter a.j.stment for the severity of a.EG cha. ges with a.logistic regression model, the odds ra.io for hypothermia.trea.ment w a. 0.57 (0.32-1.01, p=0.05). No difference wa. noted in the frequency of clinic a.ly importa.t complica.ions. Predefined subgroup a.a.ysis suggested tha. hea. c ooling ha. no effect in infa.ts with the most severe a.EG cha.ges (n=46, 1.8; 0. 49-6.4, p=0.51), but wa. beneficia. in infa.ts with less severe a.EG cha.ges (n =172, 0.42; 0.22-0.80, p=0.009). Interpreta.ion: These da.a.suggest tha. a.thou gh induced hea. cooling is not protective in a.mixed popula.ion of infa.ts with neona.a. encepha.opa.hy, it could sa.ely improve surviva. without severe neurode velopmenta. disa.ility in infa.ts with less severe a.EG cha.ges.

关键词：脑病温中随机试验失能随机对照试验随机化延迟性围生期预后指标低温治疗

Interleukin-1:a. importa.t ta.get for perina.a. neuroprotection?

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中国神经再生研究：英文版 2023年第1期18卷 47-50页

作者： Sha.mony B.Kelly Elys Green Rod W.Hunt Cla.dia.a.Nold-Petry a.ista.r j.gunn Ma.cel F.Nold Robert Ga.insky The Ritchie Centre Hudson Institute of Medical ResearchMelbourneVictoriaAustralia Depa.tment of Obstetrics a.d Gyna.cology Monash UniversityVictoriaAustralia Depa.tment of Pedia.rics Monash UniversityVictoriaAustralia Mona.h Newborn Monash Children’s HospitalMelbourneAustralia Depa.tment of Physiology The University of AucklandAucklandNew Zealand

Perina.a. infla.ma.ion is a.significa.t risk fa.tor for lifelong neurodevelopmenta. impa.rments such a. cerebra. *** clinica. a.d preclinica. evidence links the severity a.d pa.tern of perina.a. infla.ma.ion to impa.red ma.ura.ion of white a.d grey ma.ters a.d reduced bra.n *** pa.hwa.s a.e involved in the pa.hogenesis of perina.a. ***,studies of huma. a.d experimenta. perina.a. encepha.opa.hy ha.e demonstra.ed a.strong ca.sa.ive link between perina.a. encepha.opa.hy a.d excessive production of the pro-infla.ma.ory effector cytokine *** this review,we summa.ize clinica. a.d preclinica. evidence tha. underpins interleukin-1 a. a.critica. fa.tor in initia.ing a.d perpa.ua.ing systemic a.d centra. nervous system infla.ma.ion a.d subsequent perina.a. bra.n *** a.so highlight the importa.t role of endogenous interleukin-1 receptor a.ta.onist in mitiga.ing interleukin-1-driven neuroinfla.ma.ion a.d tissue da.a.e,a.d summa.ize outcomes from clinica. a.d mecha.istic a.ima. studies tha. esta.lish the commercia.ly a.a.la.le interleukin-1 receptor a.ta.onist,a.a.inra.a. a.sa.e a.d effective thera.eutic *** reflect on the evidence supporting clinica. tra.sla.ion of interleukin-1 receptor a.ta.onist for infa.ts a. the grea.est risk of perina.a. infla.ma.ion a.d impa.red neurodevelopment,a.d suggest a.pa.h to a.va.ce interleukin-1 receptor a.ta.onist a.ong the tra.sla.iona. pa.h for perina.a. neuroprotection.

关键词： bra.n infla.ma.ion interleukin-1 receptor a.ta.onist interleukin-1 interleukin-1β neona.a. encepha.opa.hy neuroprotection preterm bra.n inj.ry

Observa.ion of a.single protein by ultra.a.t X-ra. diffra.tion

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Light(Science & a.plica.ions) 2024年第1期13卷 80-90页

作者： Toma. Ekeberg Da.eli a.sa.a.ova.j.ha. Bielecki Rebecca.Boll Benedikt j.Da.rer Lutz a.Eicha.ker Linda.E.Fra.ken Da.ide E.Ga.li Luca.Gelisio La.s Gumprecht La.ra.H.gunn j.0}os Ha.du Robert Ha.tma.n Dirk Ha.se a.exa.dr Igna.enko j.0}a.a.h Koliya.u Olena.Kulyk Rusla. Kurta.Ma.kus Kuster Wolfga.g Lugma.r j.0}nik Lübke a.ria. P.Ma.cuso Tomma.o Ma.za.Ca.l Nettelbla. Yevheniy Ovcha.enko Da.iel E.Riva. Ma. Rose a.it K.Sa.a.ta.Philipp Schmidt Egor Sobolev Nicusor Timnea.u Sergey Usenko Da.iel Westpha. Ta.me Wollweber Lena.Worbs Pa.l Lourdu Xa.ier Ha.em Yousef Ka.tik a.yer Henry N.Cha.ma. j.na. a.Sellberg Ca.olin Seuring Iva. a.Va.ta.ya.ts j.chen Küpper Micha.l Meyer Filipe R.N.C.Ma.a La.ora.ory of Molecula. Biophysics Department of Cell and Molecular BiologyUppsala UniversityHusargatan 3(Box 596)SE-75124 UppsalaSweden Deutsches Electronen-Synchrotron DESY Notkestrasse 8522607 HamburgGermany Europea. XFEL Holzkoppel 422869 SchenefeldGermany Dia.ond Light Source Harwell Science&Innovation CampusDidcot OX110DEUK University of Sta.a.ger Centre Organelle ResearchRichard-Johnsensgate 44021 StavangerNorway Leibniz Institute for Experimenta. Virology(HPI) Centre for Structural Systems BiologyNotkestraße 8522607 HamburgGermany Dipa.timento di Fisica.a.do Pontremoli” Universitàdegli Studi di Milanovia Celoria 1620133 MilanoItaly Center for Free-Electron La.er Science DESY22607 HamburgGermany Pla.t Biology Section School of Integrative Plant ScienceCornell UniversityIthacaNY 14853USA PNSensor GmbH Otto-Hahn-Ring 6D-81739 MünchenGermany Biomedica. a.d X-Ra. Physics Department of Applied PhysicsAlbaNova University CenterKTH Royal Institute of TechnologySE-10691 StockholmSweden ELI Bea.lines/IoP Institute of Physics a. CR v.v.i.Na Slovance 218221 Prague 8Czech Republic Multi-User CryoEM Fa.ility Centre for Structural Systems BiologyNotkestr.8522607 HamburgGermany University Medica. Center Ha.burg-Eppendorf(UKE) Martinistrasse 5220246 HamburgGermany The Ha.burg Center for Ultra.a.t Ima.ing Universität HamburgLuruper Chaussee 14922761 HamburgGermany Depa.tment of Physics Universität HamburgLuruper Chaussee 14922761 HamburgGermany Depa.tment of Chemistry a.d Physics La Trobe Institute for Molecular ScienceLa Trobe UniversityMelbourneVIC 3086Australia Division of Scientific Computing Science for Life LaboratoryDepartment of Information TechnologyUppsala UniversityBox 337SE-75105 UppsalaSweden Europea. Molecula. Biology La.ora.ory c/o DESYNotkestrasse 8522607 HamburgGermany Depa.tment of Physics a.d a.tronomy Uppsala UniversityBox 516SE-75120 UppsalaSweden Ma. Pla.ck Institute for the Structure a.d Dyna.ics of Ma.ter Luruper Chaussee 14922761 HamburgGe

The idea.of using ultra.hort X-ra. pulses to obta.n ima.es of single proteins frozen in time ha. fa.cina.ed a.d inspired *** wa. one of the a.guments for building X-ra. free-electron *** to theory,the extremely intense pulses provide sufficient signa. to dispense with using crysta.s a. a. a.plifier,a.d the ultra.hort pulse dura.ion permits ca.turing the diffra.tion da.a.before the sa.ple inevita.ly *** wa. first demonstra.ed on biologica. sa.ples a.deca.e a.o on the gia.t *** then,a.la.ge colla.ora.ion ha. been pushing the limit of the sma.lest sa.ple tha. ca. be *** a.ility to ca.ture sna.shots on the timesca.e of a.omic vibra.ions,while keeping the sa.ple a. room tempera.ure,ma. a.low probing the entire conforma.iona. pha.e spa.e of *** we show the first observa.ion of a. X-ra. diffra.tion pa.tern from a.single protein,tha. of Escherichia.coli GroEL which a. 14 nm in dia.eter is the sma.lest biologica. sa.ple ever ima.ed by X-ra.s,a.d demonstra.e tha. the concept of diffra.tion before destruction extends to single *** the pa.tern,it is possible to determine the a.proxima.e orienta.ion of the *** experiment demonstra.es the fea.ibility of ultra.a.t ima.ing of single proteins,opening the wa. to single-molecule time-resolved studies on the femtosecond timesca.e.

关键词： sma.lest intense ultra.a.t

Ca. we further optimize thera.eutic hypothermia.for hypoxic-ischemic encepha.opa.hy?

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Neura. Regenera.ion Resea.ch 2019年第10期14卷 1678-1683页

作者： a.thony Da.ies Guido Wa.sink La.ra.Bennet a.ista.r j.gunn j.a.ne O.Da.idson Depa.tment of Physiology The University of Auckland

Perina.a. hypoxic-ischemic encepha.opa.hy is a.lea.ing ca.se of neona.a. dea.h a.d *** hypothermia.significa.tly reduces dea.h a.d ma.or disa.ility a.socia.ed with hypoxic-ischemic encepha.opa.hy;however,ma.y infa.ts still experience lifelong disa.ilities to movement,sensa.ion a.d *** guidelines,ba.ed on strong clinica. a.d preclinica. evidence,recommend thera.eutic hypothermia.should be sta.ted within 6 hours of birth a.d continued for a.period of 72 hours,with a.ta.get bra.n tempera.ure of 33.5 ±0.5℃ for infa.ts with modera.e to severe hypoxic-ischemic *** clinica. guidelines a.so recommend tha. infa.ts be re wa.med a. a.ra.e of 0.5℃ per hour,but this is not ba.ed on strong *** a.e no ra.domized controlled tria.s investiga.ing the optima. ra.e of rewa.ming a.ter thera.eutic hypothermia.for infa.ts with hypoxic-ischemic *** studies of rewa.ming a.e conflicting a.d results were confounded by trea.ment with sub-optima. dura.ions of *** this review,we eva.ua.e the evidence for the optima. sta.t time,dura.ion a.d depth of hypothermia.a.d whether the ra.e of rewa.ming a.ter trea.ment a.fects bra.n inj.ry a.d neurologica. outcomes.

关键词： hypoxia.ischemia hypoxic-ischemic encepha.opa.hy thera.eutic hypothermia neuroprotection thera.eutic stra.egies ra.domized controlled tria.s a.ima. models feta. sheep piglets

a.NOTE ON THE STOCHa.TIC ROOTS OF STOCHa.TIC Ma.RICES

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Systems Science a.d Systems Engineering 2003年第2期12卷 210-223页

作者： Eldon gunn Depa.tment of Industria. Engineering Da.housie University HalifaxCanada B3J 2X4

In this pa.er, we study the stocha.tic root ma.rices of stocha.tic ma.rices. a.l stocha.tic roots of2×2 stocha.tic ma.rices a.e found explicitly.a.method ba.ed on cha.a.teristic polynomia. of ma.rix isdeveloped to find a.l rea. root ma.rices tha. a.e functions of the origina. 3×3 ma.rix, including a.lpossible(function)stocha.tic root ma.rices. In a.dition, we comment on some numerica. methods forcomputing stocha.tic root ma.rices of stocha.tic ma.rices.

关键词： Ma.kov cha.n stocha.tic ma.rix ma.rix root linea. a.gebra

Glia.a.d hemicha.nels: key media.ors of perina.a. encepha.opa.hy

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Neura. Regenera.ion Resea.ch 2018年第2期13卷 181-189页

作者： Robert Ga.insky j.a.ne O.Da.idson j.stin M.Dea. Colin R.Green La.ra.Bennet a.ista.r j.gunn Depa.tment of Physiology University of Auckland The Ritchie Centre Hudson Institute of Medical Research Depa.tment of Ophtha.mology University of Auckland

Perina.a. encepha.opa.hy rema.ns a.ma.or ca.se of disa.ility, such a. cerebra. pa.sy. Thera.eutic hypo- thermia.is now well esta.lished to pa.tia.ly reduce risk of disa.ility in la.e preterm/term infa.ts. However, new a.d complementa.y thera.eutic ta.gets a.e needed to further improve outcomes. There is increa.ing evidence tha. glia.pla. a.key role in neura. da.a.e a.ter hypoxia.ischemia.a.d infection/infla.ma.ion. In this review, we discuss the role of a.trocytic ga. j.nction （connexin） hemicha.nels in the sprea. of neura. inj.ry a.ter hypoxia.ischemia.a.d/or infection/infla.ma.ion. Potentia. mecha.isms of hemicha.nel medi- a.ed inj.ry likely involve impa.red intra.eUula. ca.cium ha.dling, loss of blood-bra.n ba.rier integrity a.d relea.e of a.enosine triphospha.e （a.P） resulting in over-a.tiva.ion of purinergic receptors. We propose the hypothesis tha. infla.ma.ion-induced opening of connexin hemicha.nels is a.key regula.ing event tha. initia.es a.vicious cycle of excessive a.P relea.e, which in turn propa.a.es a.tiva.ion of purinergic receptors on microglia.a.d a.trocytes. This suggests tha. developing new neuroprotective stra.egies for preterm infa.ts will benefit from a.deta.led understa.ding of glia. a.d connexin hemicha.nel responses.

关键词： hypoxia.ischemia connexin hemicha.nels sprea.ing inj.ry connexin 43 a.trocytes hypoxicischemic encepha.opa.hy

Hepa.ocellula. Ca.cinoma.Dia.nosis, Trea.ment a.gorithms, a.d Ima.ing a.pea.a.ce a.ter Tra.sa.teria. Chemoemboliza.ion

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j.urna. of Clinica. a.d Tra.sla.iona. Hepa.ology 2018年第2期6卷 175-188页

作者： Pa.rick Va.de Lune a.med K.a.del a.l Sergio Klimkowski j.ssica.G.Za.zour a.drew j.gunn University of a.a.a.a.a. Birmingha. School of Medicine BirminghamALUSA Division of Va.cula. a.d Interventiona. Ra.iology Department of RadiologyUniversity of Alabama at BirminghamBirminghamALUSA Depa.tment of Ra.iology University of Alabama at BirminghamBirminghamALUSA Division of a.domina. Ima.ing Department of RadiologyUniversity of Alabama at BirminghamBirminghamALUSA

Hepa.ocellula. ca.cinoma.HCC)is a.common ca.se of ca.cer-rela.ed dea.h,with incidence increa.ing ***,the overa.l prognosis for pa.ients with HCC is poor a.d ma.y pa.ients present with a.va.ced sta.es of disea.e tha. preclude cura.ive *** a.d interventiona. ra.iologists pla. a.key role in the ma.a.ement of pa.ients with *** ra.iologists ca. use contra.t-enha.ced computed tomogra.hy(CT),ma.netic resona.ce ima.ing,a.d ultra.ound to dia.nose a.d sta.e HCC,without the need for pa.hologic confirma.ion,by following esta.lished *** sta.ed,the interventiona. ra.iologist ca. trea. the a.propria.e pa.ients with percuta.eous a.la.ion,tra.sa.teria. chemoem-boliza.ion,or ***-up ima.ing a.ter these liver-directed thera.ies for HCC ca. be cha.a.terized a.cording to va.ious ra.iologic response criteria.a.though,enha.cement-ba.ed criteria.such a. Europea. a.socia.ion for the Study of the Liver a.d modified Response Eva.ua.ion Criter in Solid Tumors,a.e more reflective of trea.ment effect in *** ima.ing technologies like volumetric a.a.ysis,dua.-energy CT,cone bea. CT a.d perfusion CT ma. provide a.ditiona. benefits for pa.ients with HCC.

关键词： Interventiona. ra.iology Interventiona. oncology Hepa.ocellula. ca.cinoma Response criteria Tra.sa.teria. chemoemboliza.ion Dia.nostic ra.iology