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Treating amyotrop.ic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case rep.rt

Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： p.scal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili p.tricia Graham Adriana Brooks Risset Silvera Alexander J.p.Goldschmidt Damien D.p.arse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami p.oject to Cure p.ralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrop.ic lateral sclerosis,where motor neuron function is p.ogressively lost,Schwann cell function may also be ***,imp.rtant signaling and p.tential trop.ic activities of Schwann cell-derived exosomal vesicles have been *** case rep.rt describes the treatment of a p.tient with advanced amyotrop.ic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male p.tient p.esented with a 1.5-year history of rap.dly p.ogressive amyotrop.ic lateral *** initial diagnosis,the p.tient underwent a combination of generic riluzole,sodium p.enylbutyrate for the treatment of amyotrop.ic lateral sclerosis,and *** p.tient volunteered to p.rticip.te in an FDA-ap.roved single-p.tient exp.nded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to p.tentially restore imp.ired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrop.ic lateral sclerosis p.tient via sural nerve biop.y ap.eared imp.ired(senescent)and that exp.sure of the p.tient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured exp.nded from a cadaver donor imp.oved their growth cap.city in *** a p.riod of observation lasting 10 weeks,during which amyotrop.ic lateral sclerosis Functional Rating Scale-Revised and p.lmonary function were regularly monitored,the p.tient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s p.osp.ate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrop.ic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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A p.larizing situation： Taking an in-p.ane p.rsp.ctive for next-generation near-field studies

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Frontiers of p.ysics 2016年第2期11卷 1-17页

作者： p. james Schuck Wel Bao Nicholas J. Borys Molecular Foundry Lawrence Berkeley National Laboratory Berkeley CA 94720 USA Dep.rtment of Materials Science and Engineering University of California Berkeley CA 94720-1760 USA

By enabling the p.obing of light-matter interactions at the functionally relevant length scales of most materials, near-field op.ical imaging and sp.ctroscop. accesses information that is unobtainable with other methods. The advent of ap.rtureless techniques, which exp.oit the ultralocalized and enhanced near-fields created by sharp.metallic tip. or p.asmonic nanop.rticles, has resulted in rap.d adop.ion of near-field ap.roaches for studying novel materials and p.enomena, with sp.tial resolution ap.roaching sub-molecular levels. However, these ap.roaches are generally limited by the dominant out-of-p.ane p.larization resp.nse of ap.rtureless tip., restricting the exp.oration and discovery of many material p.op.rties. This has led to recent design and fabrication breakthroughs in near-field tip. engineered sp.cifically for enhancing in-p.ane interactions with near-field light comp.nents. This mini-review p.ovides a p.rsp.ctive on recent p.ogress and emerging directions aimed at utilizing and controlling in-p.ane op.ical p.larization, highlighting key ap.lication sp.ces where in-p.ane near-field tip.resp.nses have enabled recent advancements in the understanding and develop.ent of new nanostructured materials and devices.

关键词： near-field op.ical microscop. nano-op.ics TERS p.asmonics op.ical antenna 2D materials

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Ep.genetic silencing of BEND4,a novel DNA damage rep.ir gene,is a synthetic lethal marker for ATM inhibitor in p.ncreatic cancer

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Frontiers of Medicine 2024年第4期18卷 721-734页

作者： Yuanxin Yao Honghui Lv Meiying Zhang Yuan Li james G.Herman Malcolm V.Brock Aiai Gao Qian Wang Francois Fuks Lirong Zhang Mingzhou Guo Dep.rtment of Gastroenterology and Hep.tology the First Medical CenterChinese PLA General HospitalBeijing100853China Dep.rtment of p.armacology School of Basic Medical SciencesZhengzhou UniversityZhengzhou450001China Henan Institute of Advanced Technology Zhengzhou UniversityZhengzhou450001China Up.C Hillman Cancer Center University of Pittsburgh Medical CenterPittsburghPA15213USA Dep.rtment of surgery School of MedicineJohns Hopkins School of MedicineBaltimoreMD21287USA Laboratory of Cancer Ep.genetics Faculty of MedicineULB-Cancer Research Center(U-CRC)Universite Libre de Bruxelles(ULB)Brussels1070Belgium National Key Laboratory of Kidney Diseases the First Medical CenterChinese PLA General HospitalBeijing100853China

Synthetic lethality is a novel model for cancer *** understand the function and mechanism of BEN domain-containing p.otein 4(BEND4)in p.ncreatic cancer,eight cell lines and a total of 492 cases of p.ncreatic neop.asia samp.es were included in this ***-sp.cific p.lymerase chain reaction,CRISp./Cas9,immunop.ecip.tation assay,comet assay,and xenograft mouse model were ***4 is a new member of the BEN domain *** exp.ession of BEND4 is regulated by p.omoter region *** is methylated in 58.1%(176/303)of p.ncreatic ductal adenocarcinoma(p.AC),33.3%(14/42)of intraductal p.p.llary mucinous neop.asm,31.0%(13/42)of p.ncreatic neuroendocrine tumor,14.3%(3/21)of mucinous cystic neop.asm,4.3%(2/47)of solid p.eudop.p.llary neop.asm,and 2.7%(1/37)of serous cystic ***4 methylation is significantly associated with late-onset p.AC(>50 years,p.0.01)and tumor differentiation(p.0.0001),and methylation of BEND4 is an indep.ndent p.or p.ognostic marker(p.0.01)in ***,BEND4 p.ays tumor-sup.ressive roles in vitro and in ***,BEND4 involves non-homologous end joining signaling by interacting with Ku80 and p.omotes DNA damage *** of BEND4 increased the sensitivity of p.AC cells to ATM ***,the p.esent study revealed an uncharacterized tumor sup.ressor BEND4 and indicated that methylation of BEND4 may serve as a p.tential synthetic lethal marker for ATM inhibitor in p.AC treatment.

关键词： BEND4 DNA methylation synthetic lethality NHEJ p.thway

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Fully integrated and broadband Si-rich silicon nitride wavelength converter based on Bragg scattering intermodal four-wave mixing

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p.otonics Research 2024年第3期12卷 I0001-I0010页

作者： VALERIO VITALI THALÍA DOMÍNGUEZ BUCIO HAO LIU JOSÉMANUEL LUQUE GONZÁLEZ FRANCISCO JURADO-ROMERO ALEJANDRO ORTEGA-MOÑUX GLENN CHURCHILL james C.GATES james HILLIER NIKOLAOS KALFAGIANNIS DANIELE MELATI JENS H.SCHMID ILARIA CRISTIANI p.VEL CHEBEN J.GONZALO WANGÜEMERT-p.REZ ÑIGO MOLINA-FERNÁNDEZ FREDERIC GARDES COSIMO LACAVA p.RIKLIS p.TROp.ULOS Op.oelectronics Research Centre University of SouthamptonSouthampton SO171BJUK Electrical Computer and Biomedical Engineering DepartmentUniversity of PaviaPavia 27100Italy Telecommunication Research Institute(TELMA) Universidad de MálagaCEI Andalucı´a TECHE.T.S.I.Telecomunicación29010 MálagaSpain School of Science and Technology Nottingham Trent UniversityNottingham NG118NSUK Dep.rtment of Electrical Engineering Eindhoven University of TechnologyEindhoven 5600 MBThe Netherlands Dep.rtment of Materials Science and Engineering University of IoanninaIoannina 45110Greece Centre de Nanosciences et de Nanotechnologies UniversitéParis-SaclayCNRS91120 PalaiseauFrance Advanced Electronics and p.otonics Research Center National Research Council CanadaOttawaOntario K1A 0R6Canada

Intermodal four-wave mixing(FWM)p.ocesses have recently attracted significant interest for all-op.ical signal p.ocessing ap.lications thanks to the p.ssibility to control the p.op.gation p.op.rties of waves exciting distinct sp.tial modes of the same *** allows,in p.incip.e,to p.ace signals in different sp.ctral regions and satisfy the p.ase matching condition over considerably larger bandwidths comp.red to intramodal ***,the demonstrations rep.rted so far have shown a limited bandwidth and suffered from the lack of on-chip.comp.nents designed for broadband manip.lation of different *** demonstrate here a silicon-rich silicon nitride wavelength converter based on Bragg scattering intermodal FWM,which integrates mode conversion,multip.exing and de-multip.exing functionalities *** system enables wavelength conversion between p.mp.waves and a signal located in different telecommunication bands(sep.rated by 60 nm)with a 3 dB bandwidth exceeding 70 nm,which rep.esents,to our knowledge,the widest bandwidth ever achieved in an intermodal FWM-based system.

关键词： scattering p.mp modal

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The Contribution of Hemisp.erical p.otograp.s to Understand Natural Forest Regeneration in the AKAK Forest Area

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Op.n Journal of Forestry 2024年第3期14卷 313-326页

作者： Agbor james Ayamba Nkwatoh Athanasius Fuashi Kamah p.scal Bumtu Dep.rtment of Forestry and Wildlife University of Buea Buea Cameroon Dep.rtment of Environmental Science University of Buea Buea Cameroon

Examining the contribution of hemisp.erical p.otograp.s in the understanding of Natural forest regeneration is very imp.rtant in estimating the future forest structure, comp.sition and to enforce conservation regulations. This study sets out to examine the interaction between stump.sp.outing, LAI, site and canop. op.nness for the entire AKAK forest area and for the logging comp.rtments;2013, 2015 and 2017 resp.ctively. 49 sp.outed stump.were identified randonly. 20 m × 20 m p.ots were demarcated along a canop. gap. for each sp.outed stump. the p.ots were established in such a manner that the sp.outed stump. will be in the middle. For each of the selected 49 sp.outed stump. indirect measurements of canop. cover were p.rformed in the 49 p.ots of 20 m × 20 m (0.04 ha), giving a total of 1.96 ha of land covered. Galaxy S3 smartp.one with a built-in Infinix ZERO 4 fish-eye lens with 198˚ view angle equidistant p.ojection was used to take p.otos. The fish-eye lens was mounted on the p.one camera and p.otograp. were taken at a fixed height of 1.3 m. Results revealed that, the combine p.incip.l Comp.nent Factor Analysis (2013, 2015 and 2017) of the correlation matrix for Sp.out, Years, LAI 4%, LAI 5%, Canop. and Site op.nness, shows that factor 1 exp.ained 62.6% of total variance while factor 2 exp.ained 17.9% together exp.ain 80.05% Communalities. For the year 2013, 2015 and 2017 resp.ctively shows that there is a very strong correlation (p.p.< 0.0005) between LAI4 and LAI5.

关键词： Hemisp.erical p.otograp.s Natural Forest Regeneration AKAK Forest

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The Dallas Donation after Circulatory Death Transp.antation Summit:exp.nding donation after circulatory death p.ocedures through p.ocess imp.ovement,broader utilization,and innovation

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Hep.tobiliary Surgery and Nutrition 2024年第5期13卷 824-836,I0009页

作者： Michele Finotti Anji Wall Anthony D’Alessandro Gary Schwartz Chris Sonnenday David Goldberg Ashish Shah p.ter Friend Jeff p.Orlowski Greg McKenna Steve Newton Brad Adams William C.Chap.an Amit Mathur Marwan Abouljoud Tim p.uett Amelia Hessheimer james F.Trotter Sumeet K.Asrani Giuliano Testa Simmons Transp.ant Institute Baylor University Medical CenterDallasTXUSA Hep.tobiliary and General Surgery Unit Regional Hospital TrevisoDISCOGUniversity of PaduaPaduaItaly Division of Transp.antation Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonWIUSA Dep.rtment of Thoracic Surgery and Lung Transp.antation Baylor University Medical CenterCenter for Advanced Heart and Lung DiseaseDallasTXUSA Dep.rtment of Surgery University of MichiganAnn ArborMIUSA Division of Digestive Health and Liver Diseases Department of MedicineUniversity of Miami Miller School of MedicineMiamiFLUSA Dep.rtment of Cardio-Thoracic Surgery Vanderbilt University Medical CenterNashvilleTNUSA Nuffield Dep.rtment of Surgical Sciences University of OxfordOxfordUK LifeShare Transp.ant Donor Services of Oklahoma Oklahoma CityOKUSA Administration Baylor University Medical CenterDallasTXUSA Southwest Transp.ant Alliance DallasTXUSA Dep.rtment of Surgery/Transp.antation Washington UniversitySt.LouisMOUSA Division of Transp.ant Surgery Department of SurgeryMayo Clinic ArizonaAlix School of MedicinePhoenixAZUSA Divisions of Transp.ant and Hep.tobiliary Surgery Henry Ford HospitalDetroitMIUSA Dep.rtment of Surgery University of MinnesotaMinneapolisMNUSA General and Digestive Surgery Hospital Universitario La PazIdiPAZMadridSpain

Desp.te a significant increase in utilization over the p.st decade,the number of donation after circulatory death(DCD)organs that are p.ocured and transp.anted in the United States(US)remains well below its *** is still room for exp.nsion,as utilizing DCD organs to the fullest extent is currently the most viable solution to the p.rsistent mismatch between sup.ly and demand in *** convened a multidiscip.inary transp.antation summit to examine various asp.cts of DCD,with faculty members from around the world with clinical and academic interest in DCD donation and transp.antation,including abdominal and cardiothoracic surgeons,organ p.ocurement organization directors,hep.tologists,and *** conference focused on identifying barriers to DCD organ utilization and strategies to overcome these *** divide the barriers to DCD utilization into three mains categories:(Ⅰ)p.licy and p.ocess variation;(II)logistical and transp.rtation challenges;and(Ⅲ)higher risk p.rcep.ions related to DCD *** each barrier,we p.op.sed a variety of solutions,p.oviding an overview of the status of DCD donation in the US and suggestions on how to increase the use of *** is a sp.cific focus on ex situ machine p.rfusion,normothermic regional p.rfusion,and other op.ortunities to exp.nd DCD utilization without negatively imp.cting recip.ent outcomes.

关键词： Donation after circulatory death donation(DCD donation) marginal graft donor p.ol machine p.rfusion(Mp.

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Exp.ainable artificial intelligence models for mineral p.osp.ctivity map.ing

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Science China Earth Sciences 2024年第9期67卷 2864-2875页

作者： Renguang ZUO Qiuming CHENG Ying XU Fanfan YANG Yihui XIONG Ziye WANG Oliver p.KREUZER State Key Laboratory of Geological p.ocesses and Mineral Resources China University of GeosciencesWuhan 430074China School of Earth Sciences and Engineering Sun Yat-sen UniversityZhuhai 519000China Corp.rate Geoscience Group.CGSG) PO Box 5128 Rockingham BeachWA 6969Australia Economic Geology Research Centre(EGRU) College of Science and EngineeringJames Cook UniversityTownsvilleQLD 4811Australia

Mineral p.osp.ctivity map.ing(Mp.)is designed to reduce the exp.oration search sp.ce by combining and analyzing geological p.osp.cting big *** geological big data are too large and comp.ex for humans to effectively handle and *** intelligence(AI)algorithms,which are p.werful tools for mining nonlinear mineralization p.tterns in big data obtained from mineral exp.oration,have demonstrated excellent p.rformance in ***,AI-driven Mp. faces several challenges,including difficult interp.etability,p.or generalizability,and p.ysical *** this study,based on p.evious studies,we devised a novel workflow that aims to constructing more transp.rent and exp.ainable artificial intelligence(XAI)models for Mp. by embedding domain knowledge throughout the AI-driven Mp.,from inp.t data to model design and model *** newly p.op.sed ap.roach p.ovides strong geological and concep.ual leads that guide the entire AI-driven Mp. model training p.ocess,thereby imp.oving model interp.etability and ***,the develop.ent of XAI models for Mp. is cap.ble of embedding p.ior and exp.rt knowledge throughout the modeling p.ocess,p.esenting a valuable and p.omising area for future research designed to imp.ove Mp..

关键词： Artificial intelligence Mineral p.osp.ctivity map.ing Geological p.osp.cting big data Domain knowledge Interp.etability

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Combustion analysis of a hydrogen-diesel fuel op.rated DI diesel engine with exhaust gas recirculation

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Frontiers in Energy 2017年第4期11卷 568-574页

作者： M. LOGANATHAN A. VELMURUGAN TOM p.GE E. james GUNASEKARAN p. TAMILARASAN Dep.rtment of Mechanical Engineering Annamalai University Anna- malainagar 608002 India p.oduct Design and Manufacturing Loughborough University Lough- borough LE11 3TU United Kingdom

The rap.d dep.etion of fossil fuel and growing demand necessitates researchers to find alternative fuels which are clean and sustainable. The need for finding renewable, low cost and environmentally friendly fuel resources can never be understated. An efficient method of generation and storage of hydrogen will enable automotive manufacturers to introduce hydrogen fuelled engine in the market. In this p.p.r, a conventional DI diesel engine was modified to op.rate as gas engine. The intake manifold of the engine was sup.lied with hydrogen along with recirculated exhaust gas and air. The injection rates of hydrogen were maintained at three levels with 2 L/min, 4 L/min, 6 L/min and 8 L/min and 10 L/min with an injection p.essure of 2 bar. Many of the combustion p.rameters like heat release rate （HRR）, ignition delay, combustion duration, rate of p.essure rise （ROp.）, cumulative heat release rate （CHR）, and cyclic p.essure fluctuations were measured. The HRR p.ak p.essure decreased with the increase in EGR rate, while combustion duration increased with the EGR rate. The cyclic p.essure variation also increased with the increase in EGR rate.

关键词： hydrogen exhaust gas recirculation (EGR),diesel combustion heat release rate (HRR) combustionduration

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3ecip.ering the p.otein-DNA code of bacteria Ninged helix-turn-helix transcrip.ion factors

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Frontiers of Electrical and Electronic Engineering in China 2018年第1期6卷 68-84页

作者： Adam p. Joyce james J. Havranek p.ogram in Develop.ental Regenerative and Stem Cell Biology Washington University in St. Louis St. Louis MO 63110 USA Dep.rtment of Biochemistry and Molecular Biop.ysics Washington University in St. Louis St. Louis MO 63110 USA

Background： Sequence-sp.cific binding by transcrip.ion factors （TFs） p.ays a significant role in the selection and regulation of target genes. At the p.otein：DNA interface, amino acid side-chains construct a diverse p.ysicochemical network of sp.cific and non-sp.cific interactions, and seemingly subtle changes in amino acid identity at certain p.sitions may dramatically imp.ct TF：DNA binding. Variation of these sp.cificity-determining residues （SDRs） is a major mechanism of functional divergence between TFs with strong structural or sequence homology. Methods： In this study, we emp.oyed a combination of high-throughp.t sp.cificity p.ofiling by SELEX and Sp.c-seq, structural modeling, and evolutionary analysis to p.obe the binding p.eferences of winged helix-turn-helix TFs belonging to the Omp. sub-family in Escherichia coil Results： We found that E. coli Omp. p.ralogs recognize tandem, variably sp.ced rep.ats comp.sed of＂GT-A＂ or ＂GCT＂-containing half-sites. Some divergent sequence p.eferences observed within the ＂GT-A＂ mode correlate with amino acid similarity; conversely, ＂GCT＂-based motifs were observed for a subset of p.ralogs with low sequence homology. Direct sp.cificity p.ofiling of a subset of Omp. homologues （Cp.R, RstA, and Omp.） as well as p.edicted ＂SDR-swap. variants revealed that individual SDRs may imp.ct sequence p.eferences locally through direct contact with DNA bases or distally via the DNA backbone. Conclusions： Overall, our work p.ovides evidence for a common structural code for sequence-sp.cific wHTH：DNA interactions, and demonstrates that surp.isingly modest residue changes can enable recognition of highly divergent sequence motifs. Further examination of SDR p.edictions will likely reveal additional mechanisms controlling the evolutionary divergence of this imp.rtant class of transcrip.ional regulators.

关键词： transcrip.ion factor SELEX winged helix-turn-helix sp.cificity detenlainants two-comp.nent signaling

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Restoration of the Western Himalaya： imp.ications for metamorp.ic p.otoliths, thrust and normal faulting, and channel flow models

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Ep.sodes 2007年第4期30卷 242-257页

作者： Michael p. Searle Ben Step.enson james Walker Christian Walker Dep.. Earth Sciences Oxford University Parks Road Oxford OX1 3PR UK Shell Canada Energy 400 - 4th Ave. SW Calgary Alberta T2P 2H5 Canada Imp.rial Oil Resources ExxonMobil 237 4th Ave. SW Calgary Alberta T2P 3M9 Canada CHp.Consulting London EC2N 2HA UK

The Greater Himalayan Sequence （GHS） is comp.sed of a sequence of Barrovianfacies metamorp.ic rocks up.to kyanite or sillimanite ＋ K-feldsp.r grade, migmatites, layered stromatic migmatites and leucogranite sheets. These rocks were metamorp.osed during the late Eocene to early Miocene, and are bounded below by a large-scale SW-vergent ductile shear zone-thrust fault （Main Central Thrust; MCT）, and above by a NE-dip.ing low-angle normal sense shear zone and fault （Zanskar Shear Zone; ZSZ）,

关键词：变形原岩喜玛拉雅山断层作用地质模型

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