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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili Patricia graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt Damien D.Pearse 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 Project to Cure Paralysis 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 *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic 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 patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient 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 phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Critics, coteries, and Pre-Raphaelite celebrity

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作者： wendy graham.

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产科并发症能解释30岁以上妇女的高剖宫产率吗?一项回顾性分析

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英国医学杂志中文版 2001年第3期4卷 136-136页

作者： jacqueline S Bell Doris M Campbell wendy j graham Gillian C Penney Mandy Ryan Marion H Hall 翁梨驹 Dugald Baird Centre for Research in Women's Health Department of Obstetrics and Gynaecology Aberdeen Maternity Hospital

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Molecular phylogeny, morphology and life-history comparisons within Circus cyaneus reveal the presence of two distinct evolutionary lineages

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Chinese Birds 2016年第4期7卷 187-198页

作者： graham j.Etherington jason A.Mobley Museum of Vertebrate Zoology 3101 Valley Life Science Building University of California Organisms and Ecosystems The Earlham Institute Norwich Research Park Aquasis Caucaia

Background: Circus cyaneus is a medium-sized bird of prey that is widely distributed across the Northern Hemisphere. There are two currently recognized forms, the Palearctic form C. c. cyaneus(Hen Harrier), and the Nearctic form C. c. hudsonius(Northern Harrier). The forms have recently been split by the British Ornithologists' Union but the American Ornithologists' Union and some other taxonomic committees have not yet made any change. Here we examine the phylogenetic relationship between the two forms using sequence data from multiple nuclear and mitochondrial genes and examine breeding biology, body size, morphology, dispersal and other ***: In order to fully compare cyaneus and hudsonius, we carried out a full literature review, measured museum skins and carried out phylogenetic analysis using a number of different mitochondrial genes and compare our findings to other recent ***: We find that these two allopatric taxa form reciprocally monophyletic groups, show substantial mt DNA sequence divergence, and further differ significantly with respect to body size, plumage characters, breeding biology, dispersal and other behavioral ***: Based on an array of consistently divergent characteristics, it is suggested that the two forms are best regarded as separate species, Hen Harrier(Circus cyaneus) and Northern Harrier(Circus hudsonius).

关键词： Circus cyaneus Circus hudsonius Hen Harrier Northern Harrier Phylogenetics Speciation Evolution

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High-resolution two-photon polymerization:the most versatile technique for the fabrication of microneedle arrays

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Microsystems & Nanoengineering 2021年第5期7卷 1-17页

作者： Zahra Faraji Rad Philip D.Prewett graham j.Davies School of Mechanical and Elearical Engineering University of Southern QueenslandSpringfield CentralQLD 4300Australia Department of Mechanical Engineering University of BirminghamBirmingham B152TTUK Oxacus Ltd Dorchester-on-Thames 0X107HNUK Faculty of Engineering UNSW AustraliaKensingtonNSW 2052Australia College of Engineering and Physical Sciences School of EngineeringUniversity of BirminghamBirmingham B152TTUK

Microneedle patches have received much interest in the last two decades as drug/vaccine delivery or fluid sampling systems for diagnostic and monitoring *** are manufactured using a variety of additive and subtractive micromanufacturing *** the last decade,much attention has been paid to using additive manufacturing techniques in both research and industry,such as 3D printing,fused deposition modeling,inkjet printing,and two-photon polymerization(2PP),with 2PP being the most flexible method for the fabrication of microneedle arrays.2PP is one of the most versatile and precise additive manufacturing processes,which enables the fabrication of arbitrary three-dimensional(3D)prototypes directly from computer-aided-design(CAD)models with a resolution down to 100 *** to its unprecedented flexibility and high spatial resolution,the use of this technology has been widespread for the fabrication of bio-microdevices and bio-nanodevices such as microneedles and microfluidic *** is a pioneering transformative technology that facilitates the fabrication of complex miniaturized structures that cannot be fabricated with established multistep manufacturing methods such as injection molding,photolithography,and ***,microstructures are designed according to structural and fluid dynamics considerations rather than the manufacturing constraints imposed by methods such as machining or etching *** article presents the fundamentals of 2PP and the recent development of microneedle array fabrication through 2PP as a precise and unique method for the manufacture of microstructures,which may overcome the shortcomings of conventional manufacturing processes.

关键词： resolution needle additive

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Physical activity and the prevention of chronic illness in the BRICS nations:Issues relating to gender equality

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journal of Sport and Health Science 2019年第6期8卷 507-508页

作者： Gregore I.Mielke wendy j.Brown Centre for Research on Exercise Physical Activity and HealthSchool of Human Movement and Nutrition SciencesThe University of Queensland

*** BRICS is an acronym for an international association of 5countries(Brazil,Russia,India,China,and South Africa),which together represent the world's major emerging economies and almost one-half of the worlds popula... 详细信息

关键词： population. BRICS prevention

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Effectiveness of predicting tunneling-induced ground settlements using machine learning methods with small datasets

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journal of Rock Mechanics and Geotechnical Engineering 2022年第4期14卷 1028-1041页

作者： Linan Liu wendy Zhou Marte Gutierrez Department of Geology and Geological Engineering Colorado School of MinesGoldenCO80401USA Department of Civil and Environmental Engineering Colorado School of MinesGoldenCO80401USA

Prediction of tunneling-induced ground settlements is an essential task,particularly for tunneling in urban *** settlements should be limited within a tolerable threshold to avoid damages to aboveground *** learning(ML)methods are becoming popular in many fields,including tunneling and underground excavations,as a powerful learning and predicting ***,the available datasets collected from a tunneling project are usually small from the perspective of applying ML *** ML algorithms effectively predict tunneling-induced ground settlements when the available datasets are small?In this study,seven ML methods are utilized to predict tunneling-induced ground settlement using 14 contributing factors measured before or during tunnel *** methods include multiple linear regression(MLR),decision tree(DT),random forest(RF),gradient boosting(GB),support vector regression(SVR),back-propagation neural network(BPNN),and permutation importancebased BPNN(PI-BPNN)*** methods except BPNN and PI-BPNN are shallow-structure ML *** effectiveness of these seven ML approaches on small datasets is evaluated using model accuracy and *** model accuracy is measured by the coefficient of determination(R2)of training and testing datasets,and the stability of a learning algorithm indicates robust predictive ***,the quantile error(QE)criterion is introduced to assess model predictive performance considering underpredictions and *** study reveals that the RF algorithm outperforms all the other models with the highest model prediction accuracy(0.9)and stability(3.0210^(-27)).Deep-structure ML models do not perform well for small datasets with relatively low model accuracy(0.59)and stability(5.76).The PI-BPNN architecture is proposed and designed for small datasets,showing better performance than typical *** important contributing factors of ground settlements are identified,including

关键词： Ground settlements Tunneling Machine learning Small dataset Model accuracy Model stability Feature importance

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A method to evaluate REE-HFSE mineralised provinces by value creation potential, and an example of application: Gardar REE-HFSE province, Greenland

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Geoscience Frontiers 2020年第6期11卷 2141-2156页

作者： graham j.Banks Símun D.Olsen Antonio Gusak Geological Survey of Denmark and Greenland Øster Voldgade 10DK-1350CopenhagenDenmark Permanent Address:Route to Reserves Ulriksdalvej 13Valby2500CopenhagenDenmark University of Copenhagen Øster Voldgade 10DK-1350CopenhagenDenmark

The rare earth elements and high-field-strength elements(REE-HFSE)exploration sector conducts most evaluations at deposit and smaller *** is not evident how the sector performs a preceding exploration stage—rating and prioritising REE-HFSE mineralised provinces—to determine which provinces are prospective enough to warrant *** we present an objective,repeatable,low-cost method to screen any REE-HFSE province,as a foundation for district-scale investigations or asset *** is original for REE-HFSE screening,and adapted from regional scale copper,cobalt and petroleum exploration,and CO2 storage,screening *** is centred upon a mineralised province’s favourability for potential value creation,and to identify:(a)its main information gaps;(b)its weakest links;(c)its exploration maturity and remaining potential category;(d)how it compares against other REE-HFSE provinces;and(e)if further investigation is *** method incorporates geoscience,strategy,economic and socio-environmental factors in a way that is understandable and directly usable across stakeholder *** workflow is systematic,yet flexible enough to accommodate organisationspecific criteria,and usable for other *** provides the platform to build a global REE-HFSE province map and database consistently across national boundaries and *** for the extent of province exploration maturity and remaining mineral potential are *** illustrate the applicability of these methods using the Gardar REE-HFSE Province(GRHP)of south *** conclude that it is a moderate size,frontier province that is currently of questionable favourability for value *** move GRHP into a positive favourability class,its current weak links need strengthening by research,government policy and industry stakeholders:evaluate the mineral system;integrate all information geospatially and place it in the public domain;help the region improve some communi

关键词： REE HFSE Province Screening Favourability Value

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ABNORMAL PROTEIN TYROSINE KINASES ASSOCIATED WITH HUMAN HAEMATOLOGICAL MALIGNANCIES

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Chinese journal of Cancer Research 2002年第2期14卷 79-83页

作者：孙雪梅 graham j Lieschke The Affiliated Drum Tower Hospital Nanjing University Nanjing 210008 ChinaLudwig Institute for Cancer Research The Royal Melbourne Hospital Victoria 3050 Australia Ludwig Institute for Cancer Research The Royal Melbourne Hospital Victoria 3050 Australia

Objective: To survey the role of protein tyrosine kinases (PTKs) in the pathogenesis of several hematopoietic malignancies. Methods: By reviewing the published laboratory and clinical studies on PTK-related oncoproteins and their causative role in some leukemias and lymphomas. Results: Protein tyrosine kinases are key participants in signal transduction pathways that regulate cellular growth, activation and differentiations. Aberrant PTK activity resulting from gene mutation (often accompanying chromosome translocation) plays an etiologic role in several clonal hematopoietic malignancies. For example, the PTK product of the BCR-ABL fusion gene resulting from the t (9; 22) translocation exhibits several fold higher tyrosine kinase activity than the product of the ABL gene. Evidence suggests that the BCR-ABL oncoprotein alone is sufficient to case chronic myelogenous leukemia (CML) and other Ph positive acute leukemia. PTK over-activity resulting from chromosomal translocations creating TEL-ABL, TEL-jAK2 and TEL-PDGFRβ fusion proteins plays an important role in the pathogenesis of other types of leukemia. Another example occurs in anaplastic large cell lymphoma (ALCL). Experimental and clinical evidences indicate that translocations involving ALK gene on chromosome 2p23, most commonly resulting in an NPM-ALK fusion oncogene, result in constitutive activation of ALK and cause ALCL. This group of lymphomas is now named ALK positive lymphoma or ALKoma. Conclusion: Genetic lesions creating aberrant fusion proteins that result in excessive PTK activity are increasingly being recognized as central to the pathogenesis of hemotopoietic malignancies. These chimeric PTK molecules represent attractive disease-specific targets against which new classes therapeutic agents are being developed.

关键词： Protein tyrosine kinase (PTK) Hematopoietic malignancy BCR-ABL Chronic myelogenous leukemia (CML) Anaplastic large cell lymphoma (ALCL) STI 571 Protein tyrosine kinase inhibitor

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Comments on ‘Enhanced piezoresistivity in Ni-silicone rubber composites’

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Chinese Physics B 2010年第1期19卷 431-432页

作者： D.Bloor A.graham P.j. Laughlin D.Lussey Department of Physics Durham University Peratech Ltd Old Repeater StationBrompton-on-SwaleDL10 7JHUK

This paper describes the accepted meaning of the term ＇negative resistance＇ and its use in the literature, and discusses the features in the previously published data on QTC^TM （market name of a metal-polymer composite） that show that the non-linear, hysteretic current voltage characteristics are not caused by joule heating. The benefit of the high metal filler loading in QTC^TM and other unique features of this composite are reviewed.

关键词： I V characteristics quantum tunnelling oiezoresitivity

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