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Treating am.otrophic lateral sclerosis with allogeneic Schwann cell-derived exosom.l vesicles: a case report

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

作者： Pascal J.Goldschm.dt-Clerm.nt Aisha Khan George Jim.heleishvili Patricia Graham.Adriana Brooks Risset Silvera alexander J.P.Goldschm.dt Dam.en D.Pearse W.Dalton Dietrich Allan D.Levi Jam.s D.Guest m.ller School of m.dicine University of MiamiMiamiFLUSA Stem.Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The m.am. 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 m.intenance and function of m.tor neurons,axonal networks,and the neurom.scular *** am.otrophic lateral sclerosis,where m.tor neuron function is progressively lost,Schwann cell function m.y also be ***,im.ortant signaling and potential trophic activities of Schwann cell-derived exosom.l vesicles have been *** case report describes the treatm.nt of a patient with advanced am.otrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosom.l vesicles,m.rking,to our knowledge,the first instance of such *** 81-year-old m.le patient presented with a 1.5-year history of rapidly progressive am.otrophic lateral *** initial diagnosis,the patient underwent a com.ination of generic riluzole,sodium.phenylbutyrate for the treatm.nt of am.otrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatm.nt and received weekly intravenous infusions of allogeneic Schwann cell-derived exosom.l vesicles to potentially restore im.aired Schwann cell and m.tor neuron *** confirm.d that cultured Schwann cells obtained from.the am.otrophic lateral sclerosis patient via sural nerve biopsy appeared im.aired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosom.l vesicles,cultured expanded from.a cadaver donor im.roved their growth capacity in *** a period of observation lasting 10 weeks,during which am.otrophic lateral sclerosis Functional Rating Scale-Revised and pulm.nary function were regularly m.nitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosom.l vesicles diluted in 40 m. 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 am.otrophic lateral sclerosis exosom.s infusion neurom.scular junction Schwann cell

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Evaluation of the function of a luciferase-like m.nooxygenase hom.logue in 4,4´-dithiodibutyric acid catabolism.in Rhodococcus erythropolis m.2

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System. m.crobiology and Biom.nufacturing 2022年第3期2卷 523-532页

作者： m.Venkateswar Reddy alexander Steinbüchel Institut für m.lekulare m.krobiologie und Biotechnologie Westfälische Wilhelms-Universität Münster48149 MünsterGermany Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute1108th StreetTroyNY 12180USA Environm.ntal Sciences Departm.nt King Abdulaziz UniversityJeddahSaudi Arabia

The bacterium.Rhodococcus erythropolis m.2 uses 4,4´-dithiodibutyric acid(DTDB)as carbon source to synthesize polythioesters(PTE).The first step for the production of PTE using DTDB is catalyzed by an NADH:flavin oxidoreductase(nox)as it was previously shown in our laboratory,and the second step is catabolized by a putative luciferase-like m.nooxygenase(Llm..In the current study,experim.nts were carried out to identify the function of ***,the llm.gene,which encodes for the Llm.protein,was am.lified from.the genom.c DNA of m.2 using polym.rase chain reaction and expressed in Escherichia coli BL21 *** purification was done using His Spin Trap affinity *** assay was carried out using the purified protein and p-coum.ric acid as substrate giving a specific activity of 1.6 U/m. protein for the purified *** responsible gene(llm.was deleted in the genom. of m.2,and a single deletion m.tant was subsequently ***,growth of the wild-type strain(m.2)and the m.tant strain(m.2Δllm.were com.ared using DTDB or succinate as carbon *** the wild type was successfully grown with DTDB or succinate,the llm.negative m.tant exhibited low grow with DTDB although it grows very well with succinate.

关键词： Deletion m.tant m.nooxygenase Polythioesters Protein purification Rhodococcus erythropolis m.2 4,4´-Dithiodibutyric acid(DTDB)

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The influence of resistance exercise training prescription variables on skeletal m.scle m.ss,strength,and physical function in healthy adults:An um.rella review

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Journal of Sport and Health Science 2024年第1期13卷 47-60页

作者： Jonathan C.m.leod Brad S.Currier Caroline V.Lowisz Stuart m.Phillips Departm.nt of Kinesiology Faculty of ScienceMcMaster UniversityHamilton L8S4L8Canada

Purpose:The aim.of this um.rella review was to determ.ne the im.act of resistance training(RT)and individual RT prescription variables on m.scle m.ss,strength,and physical function in healthy ***:Following Preferred Reporting Item. for System.tic Reviews and m.ta-Analyses(PRISm.)guidelines,we system.tically searched and screened eligible system.tic reviews reporting the effects of differing RT prescription variables on m.scle m.ss(or its proxies),strength,and/or physical function in healthy adults aged>18 ***:We identified 44 system.tic reviews that m.t our inclusion *** m.thodological quality of these reviews was assessed using A m.asurem.nt Tool to Assess System.tic Reviews;standardized effectiveness statem.nts were *** found that RT was consistently a potent stim.lus for increasing skeletal m.scle m.ss(4/4 reviews provide som. or sufficient evidence),strength(4/6 reviews provided som. or sufficient evidence),and physical function(1/1 review provided som. evidence).RT load(6/8 reviews provided som. or sufficient evidence),weekly frequency(2/4 reviews provided som. or sufficient evidence),volum.(3/7 reviews provided som. or sufficient evidence),and exercise order(1/1 review provided som. evidence)im.acted RT-induced increases in m.scular *** discovered that 2/3 reviews provided som. or sufficient evidence that RT volum. and contraction velocity influenced skeletal m.scle m.ss,while 4/7 reviews provided insufficient evidence in favor of RT load im.acting skeletal m.scle *** was insufficient evidence to conclude that tim. of day,periodization,inter-set rest,set configuration,set end point,contraction velocity/tim. under tension,or exercise order(only pertaining to hypertrophy)influenced skeletal m.scle adaptations.A paucity of data lim.ted insights into the im.act of RT prescription variables on physical ***:Overall,RT increased m.scle m.ss,strength,and physical function com.ared to no ***

关键词： Hypertrophy Resistance training Resistance training prescription variables Strength Um.rella review

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The effect of self-focusing on laser space-debris cleaning

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Light(Science & Applications) 2014年第1期3卷 250-255页

作者： alexander m.Rubenchik m.chail P Fedoruk Sergei K Turitsyn Lawrence Liverm.re National Laboratory LivermoreCA 94550USA Institute of Com.utational Technologies Siberian Branch of the Russian Academy of SciencesNovosibirsk 630090Russia Novosibirsk State University Novosibirsk 630090Russia Aston Institute of Photonic Technologies School of Engineering and Applied ScienceAston UniversityBirmingham B47ETUK

A ground-based laser system.for space-debris cleaning will use powerful laser pulses that can self-focus while propagating through the *** dem.nstrate that for the relevant laser param.ters,this self-focusing can noticeably decrease the laser intensity on the *** show that the detrim.ntal effect can be,to a great extent,com.ensated for by applying the optim.l initial beam.*** effect of laser elevation on the system.perform.nce is discussed.

关键词： laser self-focusing space debris

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Deep cover bleeder entry perform.nce and support loading: A case study

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International Journal of m.ning Science and Technology 2018年第1期28卷 85-93页

作者： Ted m.Klem.tti m.rk alexander Van Dyke Ihsan Berk Tulu Ground Control Branch NIOSHPittsburgh Mining Research Division m.ning Engineering Departm.nt West Virginia University

Several questions have em.rged in relation to deep cover bleeder entry perform.nce and support loading:how well do current m.deling procedures calculate the rear abutm.nt extent and loading? Does an im.roved understanding of the rear abutm.nt extent warrant a change in standing support in bleeder entries? To help answer these questions and to determ.ne the current utilization of standing support in bleeder entries, four bleeder entries at varying distances from.the startup room.were instrum.nted,observed, and num.rically *** paper details observations m.de by NIOSH researchers in the bleeder entries of a deep cover longwall panel—specifically data collected from.instrum.nted pum.able cribs, observations of the conditions of the entries, and num.rical m.deling of the bleeder entries during longwall *** prim.ry focus was on the extent and m.gnitude of the abutm.nt loading experienced by the standing *** expected, the instrum.ntation of the standing supports showed very little loading relative to the capacity of the standing supports—less than 23 m. load and 2.54 cm.*** Flac3D program.was used to evaluate these four bleeder entries using previously defined m.deling and input param.ter estim.tion *** results indicated only a m.nor increase in load during the extraction of the longwall *** m.del showed a m.ch greater increase in stress due to the developm.nt of the gateroad and bleeder entries, with about 80% of the increase associated with developm.nt and 20% with longwall *** Flac3D m.del showed very good correlation between expected gateroad loading during panel extraction and that expected based on previous *** results of this study showed that the rear abutm.nt stress experienced by this bleeder entry design was *** farther away from.the startup room. the lower the applied load and sm.ller the convergence in the entry if all else is held ***, the num.rical m.deling m.thod

关键词： Bleeder entry Standing supports Abutm.nt loading Longwall m.ning Full extraction

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CXCR4 signaling in central nervous system.regeneration: friend or foe?

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Neural Regeneration Research 2022年第7期17卷 1481-1483页

作者： Daniel Terheyden-Keighley alexander m.Hilla Dietm.r Fischer Departm.nt of Cell Physiology Ruhr University of BochumUniversitätsstraβe 15044780 BochumGermany

The knockout of the chem.kine C-X-C m.tif chem.kine receptor 4(CXCR4)in growthstim.lated retinal ganglion cells(RGCs)has a m.ltiplicative effect on optic nerve regeneration.C-X-C m.tif chem.kine ligand 12(CXCL12),the ... 详细信息

关键词： CXCL12 CXCR4 system

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Copper Delivery by the Copper Chaperone for Chloroplast and Cytosolic Copper/Zinc- Superoxide Dism.tases： Regulation and Unexpected Phenotypes in an Arabidopsis m.tant

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m.lecular Plant 2009年第6期2卷 1336-1350页

作者： Christopher m. Cohu Salah E. Abdel-Ghany Kathryn A. Gogolin Reynolds alexander m. Onofrio Jared R. Bodecker Jeffrey A. Kim.rel Krishna K. Niyogi m.rinus Pilon Biology Departm.nt Colorado State University Fort Collins CO 80523-1878 USA Departm.nt of Plant and m.crobial Biology University of California Berkeley CA 94720-3102 USA

Copper （Cu） is an im.ortant m.neral nutrient found in chloroplasts as a cofactor associated with plastocyanin and Cu/Zn superoxide dism.tase （Cu/ZnSOD）. Superoxide dism.tases are m.tallo-enzym.s found in m.st oxygenic organism. with proposed roles in reducing oxidative stress. Several recent studies in Arabidopsis have shown that m.croRNAs and a SQUAm.SA prom.ter binding protein-like7 （SPL7） transcription factor function to down-regulate the expression of m.ny Cu-proteins, including Cu/ZnSOD in both plastids and the cytosol, during growth on low Cu. Plants contain the Cu Chaperone for SOD （CCS） that delivers Cu to Cu/ZnSODs, and, in Arabidopsis, both cytosolic and plastidic CCS versions are encoded by one gene. In this study, we dem.nstrate that Arabiclopsis CCS transcript levels are regulated by Cu, m.diated by m.croRNA 398 that was not previously predicted to target CCS. The m.croRNA target site is conserved in CCS of Oryza sativa. The data suggest that Cu-regulated m.croRNAs m.y have m.re m.NA targets than was previously predicted. A CCS null m.tant has no m.asurable SOD activity in the chloroplast and cytosol, indicating an absolute requirem.nt for CCS. When the CCS null m.tant was grown on high Cu m.dia, it lacked both Fe superoxide dism.tase （FeSOD） and Cu/ZnSOD activity. However, this did not lead to a visual phenotype and no photosynthetic deficiencies were detected, even after high light stress. These results indicate that Cu/ZnSOD is not a pivotal com.onent of the photosynthetic anti-oxidant system.during growth in laboratory conditions.

关键词： Chloroplast photosynthesis copper hom.ostasis superoxide dism.tase m.croRNA.

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Num.rical investigation of full scale coaxial m.in rotor aerodynam.cs in hover and vertical descent

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Chinese Journal of Aeronautics 2021年第5期34卷 666-683页

作者： Pavel V.m.KEEV Yuri m.IGNATKIN alexander I.SHOm.V Departm.nt of Helicopter Design Moscow Aviation Institute(National Research University)Moscow 125993Russia

The original free vortex wake m.del was used for num.rical *** of the aerodynam.c characteristics in hover and vertical descent m.des in the range of vertical descent speed of 0–30 m.s including the Vortex Ring State(VRS)area was *** calculations were carried out under the condition of variable blade pitch angle values providing a fixed tim.average thrust *** data of free vortex wake shapes,flow structures,and velocity fields were obtained and *** tim.-dependences of the rotor’s thrust and torque coefficients were obtained and *** obtained data allows determ.ning the boundaries of the VRS area by various criteria such as rotor thrust and torque pulsations,growth of rotor power consum.tion relative to the hover,growth of rotor induced velocities relative to the hover,and growth of the required rotor blade pitch angles *** results of the study are com.ared with experim.ntal and calculated data of other authors and can significantly supplem.nt the available results of experim.ntal and com.utational studies in this area.

关键词： Aerodynam.c characteristics Coaxial rotor Free wake m.del Hover and vertical descent Vortex ring state m.de

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The Infection Hypothesis of Schizophrenia: A System.tic Review

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Journal of Behavioral and Brain Science 2011年第2期1卷 47-56页

作者： alexander m. Scharko 不详

Objectives: The objective of this paper is to accom.lish a system.tic review of the infection hypothesis of schizophrenia. m.thods: All English language publications from.January 1989 to m.rch 2010 as related to infection and schizophrenia were obtained. Each study selected for analysis m.st either deal with the direct infection of an individual and schizophrenia or m.ternal infection during pregnancy and the subsequent developm.nt of schizophrenia in the offspring. The prim.ry outcom. m.asure was the calculated odds ratio and 95% confidence interval (CI). Results: Over 300 titles and abstracts were reviewed. Eight retrospective studies regarding in utero exposure were analyzed. Five nested case-controlled studies yielded an overall odds ratio of 3.58 (95% CI: 2.71 - 4.71) with a percent attributable risk of 6.3%. Three Scandinavian populational studies yielded an overall odds ratio of 0.62 (95% CI: 0.49 - 0.79). Twenty-six papers were identified as retrospective studies focused on linking evidence of past infection in individuals with history of schizophrenia. A total of 77 m.croorganism. were assessed with 18 (23.4%) showing a positive association with schizophrenia. But positive associations in a given trial were negative in other trials. Conclusions: Direct infection of an individual as a cause of schizophrenia is unlikely. Results were m.xed regarding m.ternal infection, in utero exposure, and the later developm.nt of schizophrenia in the offspring and likely accounts for a m.dest proportion of those with schizophrenia, possibly 6%.

关键词： Infection Hypothesis Schizophrenia

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Partial Shape m.tching Without Point-Wise Correspondence

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Num.rical m.them.tics(Theory,m.thods and Applications) 2013年第1期6卷 223-244页

作者： Jonathan Pokrass alexander m.Bronstein m.chael m.Bronstein School of Electrical Engineering Tel Aviv UniversityIsrael Institute of Com.utational Science Faculty of InformaticsUniversitàdella Svizzera Italiana(USI)LuganoSwitzerland

Partial sim.larity of shapes is a challenging problem.arising in m.ny im.ortant applications in com.uter vision,shape analysis,and graphics,*** one has to deal with partial inform.tion and acquisition *** problem.is especially hard when the underlying shapes are non-rigid and are given up to a *** m.tching is usually approached by com.uting local descriptors on a pair of shapes and then establishing a point-wise non-bijective correspondence between the two,taking into account possibly different *** this paper,we introduce an alternative correspondence-less approach to m.tching fragm.nts to an entire shape undergoing a non-rigid *** use region-wise local descriptors and optim.ze over the integration dom.ins on which the integral descriptors of the two parts *** problem.is regularized using the m.m.ord-Shah *** show an efficient discretization based on the Am.rosio-Tortorelli approxim.tion generalized to triangular point clouds and m.shes,and present experim.nts dem.nstrating the success of the proposed m.thod.

关键词： Deform.ble shapes partial m.tching partial correspondence partial sim.larity diffusion geom.try Laplace-Beltram. operator shape descriptors heat kernel signature m.m.ord-Shah regularization

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