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Neural Regeneration Research 2024年第9期19卷 1861-1862页

作者： Robert Galinsky Laura Bennet alis.air j.gunn The Ritchie Centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Obstetrics and Gynaecology Monash UniversityMelbourneVICAustralia Department of Physiology The University of AucklandAucklandNew Zealand

Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal *** encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a *** cost of disability associated with preterm brain injury continues to *** of this injury,and disability,would significantly reduce this socioeconomic burden.

关键词： encephalopathy mortality hypoxic

Challenges in developing therapeutic strategies for mild neonatal encephalopathy

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Neural Regeneration Research 2022年第2期17卷 277-282页

作者： Alice McDouall Guido Wassink Laura Bennet alis.air j.gunn joanne O.Davidson Department of Physiology The University of AucklandAucklandNew Zealand

There is increasing evidence that infants with mild neonatal encephalopathy(NE) have significant risks of mortality, brain injury and adverse neurodevelopmental outcomes. In the era of therapeutic hypothermia, infants need to be diagnosed within 6 hours of birth, corresponding with the window of opportunity for treatment of moderate to severe NE, compared to the retrospective grading over 2 to 3 days, typically with imaging and formal electroencephalographic assessment in the pre-hypothermia era. This shift in diagnosis may have increased the apparent prevalence of brain damage and poor neurological outcomes seen in infants with mild NE in the era of hypothermia. Abnormal short term outcomes observed in infants with mild NE include seizures, abnormal neurologic examination at discharge, abnormal brain magnetic resonance imaging and difficulty feeding. At 2 to 3 years of age, mild NE has been associated with an increased risk of autism, language and cognitive deficits. There are no approved treatment strategies for these infants as they were not included in the initial randomized controlled trials for therapeutic hypothermia. However, there is already therapeutic creep, with many centers treating infants with mild NE despite the limited evidence for its safety and efficacy. The optimal duration of treatment and therapeutic window of opportunity for effective treatment need to be specifically established for mild NE as the evolution of injury is likely to be slower, based on preclinical data. Randomized controlled trials of therapeutic hypothermia for infants with mild NE are urgently required to establish the safety and efficacy of treatment. This review will examine the evidence for adverse outcomes after mild NE and dissect some of the challenges in developing therapeutic strategies for mild NE, before analyzing the evidence for therapeutic hypothermia and other strategies for treatment of these infants.

关键词： asphyxia electroencephalogram erythropoietin mild hypoxic ischemic encephalopathy neonatal encephalopathy neurological examination neuroprotection Sarnat score therapeutic hypothermia

Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy?

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Neural Regeneration Research 2019年第10期14卷 1678-1683页

作者： Anthony Davies Guido Wassink Laura Bennet alis.air j.gunn joanne O.Davidson Department of Physiology The University of Auckland

Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and *** hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and *** guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic *** clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong *** are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic *** studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of *** this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.

关键词： hypoxia-ischemia hypoxic-ischemic encephalopathy therapeutic hypothermia neuroprotection therapeutic strategies randomized controlled trials animal models fetal sheep piglets

Glia and hemichannels: key mediators of perinatal encephalopathy

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Neural Regeneration Research 2018年第2期13卷 181-189页

作者： Robert Galinsky joanne O.Davidson justin M.Dean Colin R.Green Laura Bennet alis.air j.gunn Department of Physiology University of Auckland The Ritchie Centre Hudson Institute of Medical Research Department of Ophthalmology University of Auckland

Perinatal encephalopathy remains a major cause of disability, such as cerebral palsy. Therapeutic hypo- thermia is now well established to partially reduce risk of disability in late preterm/term infants. However, new and complementary therapeutic targets are needed to further improve outcomes. There is increasing evidence that glia play a key role in neural damage after hypoxia-ischemia and infection/inflammation. In this review, we discuss the role of astrocytic gap junction （connexin） hemichannels in the spread of neural injury after hypoxia-ischemia and/or infection/inflammation. Potential mechanisms of hemichannel medi- ated injury likely involve impaired intraceUular calcium handling, loss of blood-brain barrier integrity and release of adenosine triphosphate （ATP） resulting in over-activation of purinergic receptors. We propose the hypothesis that inflammation-induced opening of connexin hemichannels is a key regulating event that initiates a vicious cycle of excessive ATP release, which in turn propagates activation of purinergic receptors on microglia and astrocytes. This suggests that developing new neuroprotective strategies for preterm infants will benefit from a detailed understanding of glial and connexin hemichannel responses.

关键词： hypoxia-ischemia connexin hemichannels spreading injury connexin 43 astrocytes hypoxicischemic encephalopathy

Hepatocellular Carcinoma:Diagnosis, Treatment Algorithms, and Imaging Appearance after Transarterial Chemoembolization

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journal of Clinical and Translational Hepatology 2018年第2期6卷 175-188页

作者： Patrick Vande Lune Ahmed K.Abdel Aal Sergio Klimkowski jessica G.Zarzour Andrew j.gunn University of Alabama at Birmingham School of Medicine BirminghamALUSA Division of Vascular and Interventional Radiology Department of RadiologyUniversity of Alabama at BirminghamBirminghamALUSA Department of Radiology University of Alabama at BirminghamBirminghamALUSA Division of Abdominal Imaging Department of RadiologyUniversity of Alabama at BirminghamBirminghamALUSA

Hepatocellular carcinoma(HCC)is a common cause of cancer-related death,with incidence increasing ***,the overall prognosis for patients with HCC is poor and many patients present with advanced stages of disease that preclude curative *** and interventional radiologists play a key role in the management of patients with *** radiologists can use contrast-enhanced computed tomography(CT),magnetic resonance imaging,and ultrasound to diagnose and stage HCC,without the need for pathologic confirmation,by following established *** staged,the interventional radiologist can treat the appropriate patients with percutaneous ablation,transarterial chemoem-bolization,or ***-up imaging after these liver-directed therapies for HCC can be characterized according to various radiologic response criteria;although,enhancement-based criteria,such as European Association for the Study of the Liver and modified Response Evaluation Criter in Solid Tumors,are more reflective of treatment effect in *** imaging technologies like volumetric analysis,dual-energy CT,cone beam CT and perfusion CT may provide additional benefits for patients with HCC.

关键词： Interventional radiology Interventional oncology Hepatocellular carcinoma Response criteria Transarterial chemoembolization Diagnostic radiology

Interleukin-1:an important target for perinatal 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： Sharmony B.Kelly Elys Green Rod W.Hunt Claudia A.Nold-Petry alis.air j.gunn Marcel F.Nold Robert Galinsky The Ritchie Centre Hudson Institute of Medical ResearchMelbourneVictoriaAustralia Department of Obstetrics and Gynaecology Monash UniversityVictoriaAustralia Department of Pediatrics Monash UniversityVictoriaAustralia Monash Newborn Monash Children’s HospitalMelbourneAustralia Department of Physiology The University of AucklandAucklandNew Zealand

Perinatal inflammation is a significant risk factor for lifelong neurodevelopmental impairments such as cerebral *** clinical and preclinical evidence links the severity and pattern of perinatal inflammation to impaired maturation of white and grey matters and reduced brain *** pathways are involved in the pathogenesis of perinatal ***,studies of human and experimental perinatal encephalopathy have demonstrated a strong causative link between perinatal encephalopathy and excessive production of the pro-inflammatory effector cytokine *** this review,we summarize clinical and preclinical evidence that underpins interleukin-1 as a critical factor in initiating and perpatuating systemic and central nervous system inflammation and subsequent perinatal brain *** also highlight the important role of endogenous interleukin-1 receptor antagonist in mitigating interleukin-1-driven neuroinflammation and tissue damage,and summarize outcomes from clinical and mechanistic animal studies that establish the commercially available interleukin-1 receptor antagonist,anakinra,as a safe and effective therapeutic *** reflect on the evidence supporting clinical translation of interleukin-1 receptor antagonist for infants at the greatest risk of perinatal inflammation and impaired neurodevelopment,and suggest a path to advance interleukin-1 receptor antagonist along the translational path for perinatal neuroprotection.

关键词： brain inflammation interleukin-1 receptor antagonist interleukin-1 interleukin-1β neonatal encephalopathy neuroprotection preterm brain injury

Chromodynamic Lattice Boltzmann Method for the Simulation of Drops,Erythrocytes,and other Vesicles

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Communications in Computational Physics 2023年第1期33卷 283-309页

作者： j.Spendlove X.Xu T.Schenkel j.P.gunn I.Halliday Department of Engineering and Mathematics Sheffield Hallam UniversityHoward StreetS11WBUK Materials&Engineering Research Institute Sheffield Hallam UniversityHoward StreetS11WBUK Department of Infection Immunity and Cardiovascular DiseaseThe Medical SchoolBeech Hill RoadSheffieldS102RXUK

Recently,we have validated a three-dimensional,single framework multicomponent lattice Boltzmann method,modified to generate vesicles(rather than drops)[“Three-dimensional single framework multicomponent lattice Boltzmann equation method for vesicle hydrodynamics,”*** 33,077110(2021)].This approach implements an immersed boundary force distribution,characterised by bending rigidity,surface tension,preferred curvature and conserved membrane area,in which work we successfully validated isolated vesicle flows against other methodologies and *** most immersed boundary algorithms,our method relies on numerical computation of high-order spatial derivatives and an intricate body force *** next step is to verify that it has sufficient numerical stability to address the anticipated application of high volume fraction flows of highly deformable objects in intimate *** is this in silico verification-of both the class of fluid object attainable and the stability of the later in strong,straining and shearing flows which is at issue,*** extend our method to simulate multiple variously deflated vesicles and multiple liquid droplets still within a single framework,from which our fluid objects emerge as particular *** present data from simulations containing up to four vesicles(five immiscible fluid species),which threshold verifies that simulations containing unlimited fluid objects are possible[“Modeling the flow of dense suspensions of deformable particles in three dimensions,”***.E 75,066707(2007)].These data also assure the ability of our immersed boundary forcing to preserve the character and integrity of fluid objects in interactions characterised by large local velocity gradients(intimate squeezing,shearing and elongational straining).Throughout,we take interfacial or membrane area,A,as a proxy for stability and physical veracity.

关键词： Lattice Boltzmann membranes vesicles

A NOTE ON THE STOCHASTIC ROOTS OF STOCHASTIC MATRICES

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Systems Science and Systems Engineering 2003年第2期12卷 210-223页

作者： Eldon gunn Department of Industrial Engineering Dalhousie University HalifaxCanada B3J 2X4

In this paper, we study the stochastic root matrices of stochastic matrices. All stochastic roots of2×2 stochastic matrices are found explicitly.A method based on characteristic polynomial of matrix isdeveloped to find all real root matrices that are functions of the original 3×3 matrix, including allpossible(function)stochastic root matrices. In addition, we comment on some numerical methods forcomputing stochastic root matrices of stochastic matrices.

关键词： Markov chain stochastic matrix matrix root linear algebra

Observation of a single protein by ultrafast X-ray diffraction

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Light(Science & Applications) 2024年第1期13卷 80-90页

作者： Tomas Ekeberg Dameli Assalauova johan Bielecki Rebecca Boll Benedikt j.Daurer Lutz A.Eichacker Linda E.Franken Davide E.Galli Luca Gelisio Lars Gumprecht Laura H.gunn janos Hajdu Robert Hartmann Dirk Hasse Alexandr Ignatenko jayanath Koliyadu Olena Kulyk Ruslan Kurta Markus Kuster Wolfgang Lugmayr jannik Lübke Adrian P.Mancuso Tommaso Mazza Carl Nettelblad Yevheniy Ovcharenko Daniel E.Rivas Max Rose Amit K.Samanta Philipp Schmidt Egor Sobolev Nicusor Timneanu Sergey Usenko Daniel Westphal Tamme Wollweber Lena Worbs Paul Lourdu Xavier Hazem Yousef Kartik Ayyer Henry N.Chapman jonas A.Sellberg Carolin Seuring Ivan A.Vartanyants jochen Küpper Michael Meyer Filipe R.N.C.Maia Laboratory of Molecular Biophysics Department of Cell and Molecular BiologyUppsala UniversityHusargatan 3(Box 596)SE-75124 UppsalaSweden Deutsches Electronen-Synchrotron DESY Notkestrasse 8522607 HamburgGermany European XFEL Holzkoppel 422869 SchenefeldGermany Diamond Light Source Harwell Science&Innovation CampusDidcot OX110DEUK University of Stavanger Centre Organelle ResearchRichard-Johnsensgate 44021 StavangerNorway Leibniz Institute for Experimental Virology(HPI) Centre for Structural Systems BiologyNotkestraße 8522607 HamburgGermany Dipartimento di Fisica“Aldo Pontremoli” Universitàdegli Studi di Milanovia Celoria 1620133 MilanoItaly Center for Free-Electron Laser Science DESY22607 HamburgGermany Plant Biology Section School of Integrative Plant ScienceCornell UniversityIthacaNY 14853USA PNSensor GmbH Otto-Hahn-Ring 6D-81739 MünchenGermany Biomedical and X-Ray Physics Department of Applied PhysicsAlbaNova University CenterKTH Royal Institute of TechnologySE-10691 StockholmSweden ELI Beamlines/IoP Institute of Physics AS CR v.v.i.Na Slovance 218221 Prague 8Czech Republic Multi-User CryoEM Facility Centre for Structural Systems BiologyNotkestr.8522607 HamburgGermany University Medical Center Hamburg-Eppendorf(UKE) Martinistrasse 5220246 HamburgGermany The Hamburg Center for Ultrafast Imaging Universität HamburgLuruper Chaussee 14922761 HamburgGermany Department of Physics Universität HamburgLuruper Chaussee 14922761 HamburgGermany Department of Chemistry and 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 European Molecular Biology Laboratory c/o DESYNotkestrasse 8522607 HamburgGermany Department of Physics and Astronomy Uppsala UniversityBox 516SE-75120 UppsalaSweden Max Planck Institute for the Structure and Dynamics of Matter Luruper Chaussee 14922761 HamburgGe

The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired *** was one of the arguments for building X-ray free-electron *** to theory,the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier,and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably *** was first demonstrated on biological samples a decade ago on the giant *** then,a large collaboration has been pushing the limit of the smallest sample that can be *** ability to capture snapshots on the timescale of atomic vibrations,while keeping the sample at room temperature,may allow probing the entire conformational phase space of *** we show the first observation of an X-ray diffraction pattern from a single protein,that of Escherichia coli GroEL which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays,and demonstrate that the concept of diffraction before destruction extends to single *** the pattern,it is possible to determine the approximate orientation of the *** experiment demonstrates the feasibility of ultrafast imaging of single proteins,opening the way to single-molecule time-resolved studies on the femtosecond timescale.

关键词： smallest intense ultrafast

选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

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复旦学报（医学版） 2007年第4期34卷 527-531页

作者：骆菲曹云 Guan j.gunn Aj Bennet L George S Gluckman PD 杨毅陈莲复旦大学附属儿科医院新生儿科复旦大学儿科研究所上海200032 新西兰奥克兰大学医学院Liggins研究所

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为：损伤组（n=10）、2h低温组（损伤后2h开始亚低温治... 详细信息

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为：损伤组（n=10）、2h低温组（损伤后2h开始亚低温治疗,n=7）和6h低温组（损伤后6h开始亚低温治疗,n=8）,另设正常对照组（n=5）。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3（半胱天冬氨酸酶-3）,GFAP（胶质纤维酸性蛋白）和PCNA（增殖细胞核抗原）的表达。结果①纹状体神经元凋亡：正常对照组中,caspase-3表达极少（11.00±13.77）,损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加（P=0.000）,损伤后2h治疗组（54.14±39.44,P=0.000）和损伤后6h治疗组（122.43±52.36,P=0.017）均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖：与正常对照组（163.40±21.98）相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多（433.25±66.69,P=0.000）,损伤后2h开始亚低温治疗（219.50±35.31,P=0.000）和损伤后6h开始亚低温治疗（272.50±86.20,P=0.000）均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达：在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多（353.70±45.60,P=0.000）,损伤后2h开始亚低温治疗（187.14±26.26,P=0.000）和损伤后6h开始亚低温治疗（230.25±67.46,P=0.000）均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。

关键词：亚低温缺氧缺血脑损伤纹状体胎羊细胞凋亡星形细胞