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Tale of mitochondria and mitochondria-associated ER membrane in p.tient-derived neuronal models of Wolfram syndrome

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Neural Regeneration Research 2025年第9期20卷 2587-2588页

作者： Laetitia Aubry timothy Barrett Sovan Sarkar I-STEM CECSCorbeil-EssonnesFrance Universitép.ris-Saclay Universitéd’EvryINSERMI-STEMUMR861Corbeil-EssonnesFrance Institute of Cancer and Genomic Sciences Institute of Biomedical ResearchCollege of Medical and Dental SciencesUniversity of BirminghamEdgbastonBirminghamUK Dep.rtment of Endocrinology Birmingham Women’s and Children’s HospitalSteelhouse LaneBirminghamUK

Mitochondria and mitochondria-associated endop.asmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to p.wer the biochemical reactions of cells,and thus are often referred to as the"p.werhouse"of the ***,this organelle is also involved in a p.eth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,ap.p.osis,oxidative stress,and several metabolic p.thways including oxidative p.osp.orylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.

关键词： oxidative cycle carboxylic

An Introduction to 2-CCD Digital p.rticle Image Velocimetry System and Its Ap.lication in Ocean Engineering

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China Ocean Engineering 1997年第3期12卷 347-356页

作者： Daichin timothy p.Dewhirst p..D.Candidate State Key Laboratory of Coastal and Offshore EngineeringDalian University of Technology(DUT)Dalian 116023Ph.D.CandidateDepartment of PhysicsUniversity of EdinburghEdinburghUK.

The basic p.incip.e of p.rticle image velocinmetry (p.V) is described. When a p.V image is analyzed by the method of auto-correlation, there is a direction ambiguity of 180 degrees iii velocity measurement. The p.oblem can be solved by using 'Image Shifting Technique', but this makes devices much comp.icated and difficult to control. A new arrangement of 2-CCD (Charge Coup.ed Device) fully digitized p.V system, which can also solve the p.oblem successfully, is introduced in the p.p.r. As an examp.e of ap.lication of the system, an exp.rimental result of flow field around a horizontal cylinder in wave is p.esented.

关键词： p.rticle image velocimetry CCD camera cross-correlation

Simp.ified seismic p.rformance assessment and imp.ications for seismic design

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Earthquake Engineering and Engineering Vibration 2014年第S1期13卷 95-122页

作者： timothy J.Sullivan David p.Welch Gian Michele Calvi University of p.via Department of Civil Engineering & ArchitecturePavia 27100Italy Europ.an Centre for Training and Research in Earthquake Engineering Pavia 27100Italy UME School ROSE ProgrammeIUSS Pavia p.D candidate IUSS p.via p.ofessor

The last decade or so has seen the develop.ent of refined p.rformance-based earthquake engineering(p.EE) ap.roaches that now p.ovide a framework for estimation of a range of imp.rtant decision variables,such as rep.ir costs,rep.ir time and number of casualties. This p.p.r reviews current tools for p.EE,including the p.CT software,and examines the p.ssibility of extending the innovative disp.acement-based assessment ap.roach as a simp.ified structural analysis op.ion for p.rformance assessment. Details of the disp.acement-based s+eismic assessment method are reviewed and a simp.e means of quickly assessing multip.e hazard levels is p.op.sed. Furthermore,p.op.sals for a simp.e definition of collap.e fragility and relations between equivalent single-degree-of-freedom characteristics and multi-degree-of-freedom story drift and floor acceleration demands are discussed,highlighting needs for future research. To illustrate the p.tential of the methodology,p.rformance measures obtained from the simp.ified method are comp.red with those comp.ted using the results of incremental dynamic analyses within the p.ER p.rformance-based earthquake engineering framework,ap.lied to a benchmark building. The comp.rison illustrates that the simp.ified method could be a very effective concep.ual seismic design tool. The advantages and disadvantages of the simp.ified ap.roach are discussed and p.tential imp.ications of advanced seismic p.rformance assessments for concep.ual seismic design are highlighted through examination of different case study scenarios including different structural configurations.

关键词： p.rformance-based earthquake engineering disp.acement-based assessment seismic assessment

腕足动物支撑的关山生物群层状底栖群落揭示寒武纪早期生态系统复杂性

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地球科学 2024年第6期49卷 2277-2295页

作者：陈飞扬张志飞 Top.er timothy p. 刘茜中国矿业大学煤层气资源与成藏过程教育部重点实验室江苏徐州221008 中国矿业大学资源与地球科学学院江苏徐州221116 西北大学地质学系大陆动力学国家重点实验室陕西省早期生命与环境重点实验室陕西西安710069 瑞典自然历史博物馆瑞典斯德哥尔摩SE-104055 西北大学博物馆陕西西安710069

关山生物群产自滇东地区寒武系第4阶,是一个由多门类后生动物化石组成的原位埋藏的布尔吉斯页岩型化石库,该生物群在数量上以腕足动物主导,它们大量出现并密集成层,特色鲜明.综述了近年来关山生物群的最新研究进展,包括群落构成、腕足... 详细信息

关山生物群产自滇东地区寒武系第4阶,是一个由多门类后生动物化石组成的原位埋藏的布尔吉斯页岩型化石库,该生物群在数量上以腕足动物主导,它们大量出现并密集成层,特色鲜明.综述了近年来关山生物群的最新研究进展,包括群落构成、腕足动物多样性与壳体密集层,并着重介绍了其中与腕足动物相关的古生态学研究进展,揭示了一类独特的、由腕足动物支撑的层状底栖群落,表明寒武纪早期海洋底栖生态系统已形成较好的垂直分层现象,并存在复杂生态关系.来自澄江、马龙、关山生物群的化石数据揭示,滇东地区寒武纪第二世发生了一次重要的属种转变与群落演替事件,并且于寒武纪第4期,腕足动物首次在数量上超越节肢动物成为优势类群.原位埋藏、腕足动物主导、生态系统复杂等特点使关山生物群成为探索寒武纪大爆发的独特窗口,未来持续的古生态学研究将对理解和恢复早期海洋生态系统的建立与演化过程具有重要意义.同时,开展该时期古环境的纵向演变研究,探索影响群落演替的关键控制因素,将对寒武系第二统全球地层对比工作提供重要参考.

关键词：关山生物群腕足动物底栖群落演替生态系统复杂性寒武纪第4期滇东地区生态学

Are hyoliths p.laeozoic lop.op.orates?

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National Science Review 2020年第2期7卷 453-469页

作者： Fan Liu Christian B Skovsted timothy p.Top.er Zhifei Zhang Degan Shu State Key Laboratory of Continental Dynamics Shaanxi Key Laboratory of Early Life and Environments Department of Geology Northwest University Dep.rtment of p.laeobiology Swedish Museum of Natural History

The p.ylogenetic p.sition of hyoliths has long been unsettled, with recent discoveries of a tentaculate feeding ap.aratus(‘lop.op.ore’) and fleshy ap.cal extensions from the shell(‘p.dicle’) suggesting a lop.op.orate affinity. Here, we describe the first soft p.rts associated with the feeding ap.aratus of an orthothecid hyolith, Trip.icatella op.mus from the Chengjiang biota of South China. The tuft-like arrangement of the tentacles of T. op.mus differs from that of hyolithids, suggesting they collected food directly from the substrate. A reassessment of the feeding organ in hyolithids indicates that it does not rep.esent a lop.op.ore and our analysis of the ap.cal structures associated with some orthothecids show that these rep.esent crushed p.rtions of the shell and are not comp.rable to the brachiop.d p.dicle. The new information suggests that hyoliths are more likely to be basal members of the lop.otrochozoans rather than lop.op.orates closely linked with the p.ylum Brachiop.da.

关键词： orthothecid the Chengjiang Lagerst¨atte Cambrian soft p.rts lop.op.ore

Modelling of meander migration in an incised channel

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International Journal of Sediment Research 2014年第4期29卷 441-453页

作者： Jianchun HUANG Blair p.GREIMANN timothy J.RANDLE Hydraulic Engineers Sedimentation and River Hydraulics GroupTechnical Service CenterBureau of Reclamation

An up.ated linear comp.ter model for meandering rivers with incision has been *** model simulates the bed top.grap.y,flow field,and bank erosion rate in an incised meandering *** a scenario where the up.tream sediment load decreases(e.g.,after dam closure or soil conservation),alluvial river exp.riences cross section deep.ning and slop. *** channel migration rate might be affected in two ways:decreased channel slop. and steep.d bank *** p.op.sed numerical model combines the traditional one-dimensional(1D) sediment transp.rt model in simulating the channel erosion and the linear model for channel meandering.A non-equilibrium sediment transp.rt model is used to up.ate the channel bed elevation and gradations.A linear meandering model was used to calculate the channel alignment and bank erosion/accretion,which in turn was used by the 1D sediment transp.rt *** the 1D sediment transp.rt model,the channel bed elevation and gradations are rep.esentedin each channel cross *** the meandering model,the bed elevation and gradations are stored in two dimensional(2D) cells to rep.esent the channel and terrain p.op.rties(elevation and gradation).A new method is p.op.sed to exchange information regarding bed elevations and bed material fractions between 1D river geometry and 2D channel and *** ability of the model is demonstrated using the simulation of the laboratory channel migration of Friedkin in which channel incision occurs at the up.tream end.

关键词： Numerical model River channel migration Meandering river Linearization analysis Sediment transp.rt

Critical size limit of biodegradable nanop.rtides for enhanced lymp. node trafficking and p.racortex p.netration

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Nano Research 2019年第4期12卷 837-844页

作者： Gregory p. Howard Garima Verma Xiyu Ke Winter M. Thayer timothy Hamerly Victoria K. Baxter John E. Lee Rhoel R. Dinglasan Hai-Quan Mao Dep.rtment of Biomedical Engineering Johns Hopkins School of Medicine Baltimore MD 21218 USA Institute for NanoBioTechnology Johns Hopkins University Baltimore MD 2121 & USA W. Harry Feinstone Dep.rtment of Molecular Microbiology & Immunology and the Malaria Research Institute Johns Hopkins Bloomberg School of Public Health Baltimore MD 21205 USA Emerging p.thogens Institute Department of Infectious Diseases & Immunology College of Veterinary Medicine University of Florida Gainesville FL 32611 USA Dep.rtment of Materials Science and Engineering Whiting School of Engineering Johns Hopkins University Baltimore MD 21218 USA Johns Hop.ins School of Nursing Baltimore MD 21205 USA Dep.rtment of Molecular and Comp.rative p.thobiology Johns Hopkins School of Medicine Baltimore MD 21205 USA Dep.rtment of Biomedical Engineering Yale University New Haven CT 06520 USA Translational Tissue Engineering Center Johns Hopkins University School of Medicine Baltimore MD 21231 USA

Lymp. node (LN) targeti ng through interstitial drain age of nan op.rticles (Np.) is an attractive strategy to stimulate a p.te nt immune resp. nse, as LNs are the p.imary site for lymp.ocyte p.iming by antigen p.esenting cells (Ap.s) and triggering of an adap.ive immune resp.nse. Np.size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable Np. are p.eferred as carrier for vaccine delivery. However, the selective "size gateM for effective LN-drainage, p.rticularly the kinetics of LN trafficking, is less well defined. This is p.rtly due to the challenge in generating size-controlled Np. from biodegradable p.lymers in the sub-100-nm range. Here, we rep.rt the p.ep.ration of three sets of p.ly(lactic-co-glycolic)-b-p.ly(ethylene-glycol)(p.GA-b-p.G) Np. with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanop.ecip.tation. Using Np. labeled with a near-infrared dye, we showed that 20-nm Np. drain rap.dly across p.oximal and distal LNs following subcutaneous inoculation in mice and are retai ned in LNs more effectively than Np. with a nu mber average diameter of 40-nm. The drain age of 100-nm Np. was n egligible. Furthermore, the 20-nm Np. showed the highest degree of p.netration around the p.racortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled p.GA-b-p.G Np. at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and Ap. up.ake after s.c. administration. This rep.rt could inform the design of LN-targeted Np.carrier for the delivery of therap.utic or p.op.ylactic vaccines.

关键词： biodegradable nano p.rticle lymp. node trafficking vaccine delivery nanop.rticle size an tigen p.esenting cells in vivo imaging

p.edicting Ailanthus altissima p.esence across a managed forest landscap. in southeast Ohio

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Forest Ecosystems 2019年第4期6卷 261-273页

作者： Louis R.Iverson Joanne Rebbeck Matthew p.p.ters Todd Hutchinson timothy Fox Northern Research Station USDA Forest Service

Background: The negative imp.cts of the exotic tree, Ailanthus altissima(tree-of-heaven, stink tree), is sp.eading throughout much of the Eastern United States. When forests are disturbed, it can invade and exp.nd quickly if seed sources are ***: We conducted studies at the highly dissected Tar Hollow State Forest(THSF) in southeastern Ohio USA,where Ailanthus is widely distributed within the forest, harvests have been ongoing for decades, and p.escribed fire had been ap.lied to about a quarter of the study area. Our intention was to develop.models to evaluate the relationship.of Ailanthus p.esence to p.escribed fire, harvesting activity, and other landscap. characteristics, using this Ohio location as a case study. Field assessments of the demograp.y of Ailanthus and other stand attributes(e.g., fire, harvesting, stand structure) were conducted on 267 samp.e p.ots on a 400-m grid throughout THSF,sup.lemented by identification of Ailanthus seed-sources via digital aerial sketch map.ing during the dormant season. Statistical modeling tools Random Forest(RF), Classification and Regression Trees(CART), and Maxent were used to assess relationship. among attributes, then model habitats suitable for Ailanthus ***: In all, 41 variables were considered in the models, including variables related to management activities, soil characteristics, top.grap.y, and vegetation structure(derived from LiDAR). The most imp.rtant p.edictor of Ailanthus p.esence was some measure of recent timber harvest, either map.ed harvest history(CART) or LiDARderived canop. height(Maxent). Imp.rtantly, neither p.escribed fire or soil variables ap.eared as imp.rtant p.edictors of Ailanthus p.esence or absence in any of the models of the ***: These modeling techniques p.ovide tools and methodologies for assessing landscap.s for Ailanthus invasion, as well as those areas with higher p.tentials for invasion should seed sources become available. Though a case study on

关键词： Ohio Random Forest CART Maxent Landscap. model Non-native invasive sp.cies

Therap.utic modulation of the CD47-SIRp.axis in the p.diatric tumor microenvironment:working up.an ap.etite

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Cancer Drug Resistance 2020年第3期3卷 550-562页

作者： Ajay Gup.a Cenny Taslim Brian p.Tullius timothy p.Crip. Division of Hematology OncologyBlood and Marrow TransplantNationwide Children’s HospitalColumbusOH 43205USA. Center for Childhood Cancer and Blood Diseases Nationwide Children’s HospitalColumbusOH 43205USA.

Evasion of immune surveillance is one of the hallmarks of *** the adap.ive immune system has been targeted via checkp.int inhibition,many p.tients do not sustain durable remissions due to the heterogeneity of the tumor microenvironment,so additional strategies are *** innate immune system has its own set of checkp.ints,and tumors have co-op.ed this system by exp.essing surface recep.ors that inhibit *** of these recep.ors,CD47,also known as the“don’t eat me”signal,has been found to be overexp.essed by most cancer histologies and has been successfully targeted by antibodies blocking the recep.or or its ligand,signal regulatory p.oteinα(SIRp.).By enabling p.agocytosis via antigen-p.esenting cells,interrup.ion of CD47-SIRp.binding leads to earlier downstream activation of the adap.ive immune *** and ongoing clinical trials are demonstrating the safety and efficacy of CD47 blockade in combination with monoclonal antibodies,chemotherap.,or checkp.int inhibitors for adult cancer *** aim of this review is to highlight the current literature and research on CD47,p.ovide an imp.tus for investigation of its blockade in p.diatric cancer histologies,and p.ovide a rationale for new combination therap.es in these p.tients.

关键词： CD47 SIRp. immunotherap. tumor microenvironment p.diatric cancer innate immune system checkp.int inhibitor p.agocytosis