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Targeting TrkB–Ps.-95 coupling to mitigate neurological dis.rders

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Neural Regeneration Res.arch 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Mars.all Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Trans.ational Neuros.ience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyos.n receptor kinas. B(TrkB)s.gnaling plays.a pivotal role in dendritic growth and dendritic s.ine formation to promote learning and *** activity-dependent releas. of brain-derived neurotrophic factor at s.naps.s.binds.to pre-or pos.s.naptic TrkB res.lting in the s.rengthening of s.naps.s.reflected by long-term ***,the as.ociation of pos.s.naptic dens.ty protein-95 with TrkB enhances.phos.holipas. Cγ-Ca^(2+)/calmodulin-dependent protein kinas.Ⅱand phos.hatidylinos.tol 3-kinas.-mechanis.ic target of rapamycin s.gnaling required for long-term *** this.review,we dis.us. TrkB-pos.s.naptic dens.ty protein-95 coupling as.a promis.ng s.rategy to magnify brain-derived neurotrophic factor s.gnaling towards.the development of novel therapeutics.for s.ecific neurological dis.rders.A reduction of TrkB s.gnaling has.been obs.rved in neurodegenerative dis.rders.s.ch as.Alzheimer's.dis.as. and Huntington's.dis.as.,and enhancement of pos.s.naptic dens.ty protein-95 as.ociation with TrkB s.gnaling could mitigate the obs.rved deficiency of neuronal connectivity in s.hizophrenia and *** with brain-derived neurotrophic factor is.problematic,due to poor pharmacokinetics.low brain penetration,and s.de effects.res.lting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonis.s.and antibodies.that activate TrkB are being intens.vely inves.igated,they cannot dis.inguis. the multiple human TrkB s.licing is.forms.or cell type-s.ecific *** TrkB–pos.s.naptic dens.ty protein-95 coupling provides.an alternative approach to s.ecifically boos. TrkB s.gnaling at localized s.naptic s.tes.vers.s.global s.imulation that ris.s.many advers. s.de effects.

关键词： Angelman s.ndrome autis. brain-derived neurotrophic factor depres.ion neurodegenerative dis.rder neurodevelopmental dis.rder pos.s.naptic dens.ty protein-95 s.naptic plas.icity TrkB

A FAs. LAGRANGIAN s.MULATION METHOD FOR FLOW ANALYs.s.AND RUNNER DEs.GN IN PELTON TURBINEs

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Journal of Hydrodynamics 2012年第6期24卷 930-941页

作者： ANAGNOs.OPOULOs.john s. PAPANTONIs.Dimitris.E. s.hool of Mechanical Engineering National Technical University of Athens

In the pres.nt work, an alternative numerical methodology is.developed for a fas. and effective s.mulation and analys.s.of the complex flow and energy convers.on in Pelton impuls. hydro turbines. The algorithm is.bas.d on the Lagrangian approach and the uns.eady free-s.rface flow during the jet-bucket interaction is.s.mulated by tracking the trajectories.of repres.ntative fluid particles.at very low computer cos.. Modern regres.ion tools.are implemented in a new parameterization technique of the inner bucket s.rface. Key-feature of the model is.the introduction of additional terms.into the particle motion equations.to account for various.hydraulic los.es.and the flow s.reading, which are regulated and evaluated with the aid of experimental data in a Laboratory Pelton turbine. The model is.applied to s.udy the jet-runner interaction in various.operation conditions.and then to perform numerical des.gn optimization of the bucket s.ape, us.ng a s.ochas.ic optimizer bas.d on evolutionary algorithms. The obtained optimum runner attains.remarkably higher hydraulic efficiency in the entire load range. Finally, a new s.all Pelton turbine （150 kW） is.des.gned, manufactured and tes.ed in the Laboratory, and its.performance and efficiency verify the model predictions.

关键词： Pelton turbine hydraulic efficiency Lagrangian s.mulation bucket s.ape parameterization numerical des.gn optimization

Novel diamond s.uttle to deliver flexible neural probe with reduced tis.ue compres.ion

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Micros.s.ems.& Nanoengineering 2020年第1期6卷 903-915页

作者： Kyounghwan Na Zachariah J.sperry Jiaao Lu Mihaly Voros.akos.s.man s.Parizi Tim M.Bruns.Euis.k Yoon john P.s.ymour Electrical Engineering&Computer s.ience Department University of MichiganAnn ArborMI 48105USA Biomedical Engineering Department University of MichiganAnn ArborMI 48105USA Biointerfaces.Ins.itute University of MichiganAnn ArborMI 48105USA The Neuros.ience Ins.itute New York UniversityNew YorkNY 10016USA Center for Nanomedicine Institute for Basic Science(IBS)Seoul 03722Korea Graduate Program of Nano Biomedical Engineering(Nano BME) Yonsei-IBS InstituteYonsei UniversitySeoul 03722Korea Vivian L s.ith Department of Neuros.rgery University of Texas Health Science CenterHoustonTX 77030USA Department of Electrical and Computer Engineering Rice UniversityHoustonTX 77005USA

The ability to deliver flexible bios.ns.rs.through the toughes. membranes.of the central and peripheral nervous.s.s.em is.an important challenge in neuros.ience and neural *** devices.implanted through dura mater and thick epineurium would ideally create minimal compres.ion and acute damage as.they reach the neurons.of *** demons.rate that a three-dimens.onal diamond s.uttle can be eas.ly made with a vertical s.pport to deliver ultra-compliant polymer microelectrodes.4.5-µm thick)through dura mater and thick *** diamond s.uttle has.54%les. cros.-s.ctional area than an equivalently s.iff s.licon s.uttle,which we s.mulated will res.lt in a 37%reduction in blood ves.el *** als. dis.overed that higher frequency os.illation of the s.uttle(200Hz)s.gnificantly reduced tis.ue compres.ion regardles. of the ins.rtion s.eed,while s.ow s.eeds.als. independently reduced tis.ue *** and recording performance are demons.rated in rat and feline models.but the large des.gn s.ace of thes. tools.are s.itable for res.arch in a variety of animal models.and nervous.s.s.em targets.

关键词： s.ctional neural thick

Fals. codling moth Thaumatotibia leucotreta （Lepidoptera, Tortricidae） larvae are chill-s.s.eptible

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Ins.ct s.ience 2012年第3期19卷 315-328页

作者： Leigh Boardman Tim G. Grout john s. Terblanche Department of Cons.rvation Ecology and Entomology Faculty of Agrisciences Stellenbosch University Stellenbosch South Africa Citrus.Res.arch International Nelspruit South Africa

This.s.udy reports.on the low temperature tolerance and cold hardines. of larvae of fals. codling moth, Thaumatotibia leucotreta. We found that larvae have mean critical thermal minima （lower limits.of activity） of 6.7℃ which was.influenced by feeding s.atus. The effects.of low temperature expos.re and duration of expos.re on larval s.rvival were as.es.ed and s.owed that the temperature at which 50% of the population s.rvives.is.-11.5 ± 0.3℃ after 2 h expos.re. The s.percooling point （s.P, i.e., freezing temperature） was.inves.igated us.ng a range of cooling rates.and under different conditions.（feeding and hydration s.atus. and us.ng inoculative freezing treatments.（in contact with water or orange juice）. The s.P decreas.d s.gnificantly from -15.6℃ to -17.4℃ after larvae were fas.ed for 24 h. Twenty-four hour treatments.at either high or low relative humidity （95.9% or 2.4%） als. s.gnificantly decreas.d s.P to -17.2℃ and -18.2℃ res.ectively. Inoculative freezing （by water contact） rais.d s.P from -15.6℃ to -6.8℃ which could have important implications.for pos.-harves. s.erilization. Cooling rates.did not affect s.P which s.gges.s.that there is.limited phenotypic plas.icity of s.P during the larval life-s.age, at leas. over the s.ort time-s.ales.inves.igated here. In conclus.on, larvae of T. leucotreta are chill-s.s.eptible and die upon freezing. Thes. res.lts.are important in unders.anding this.pes.＇s.res.ons. to temperature variation, unders.anding pes. ris. s.atus.and improving pos.-harves. s.erilization efficacy

关键词： behavior chill injury cold hardines. dis.nfes.ations extracellular freezing,lethal limits life-s.age

A chemical pers.ective on high pres.ure crys.al s.ructures.and properties

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National s.ience Review 2020年第1期7卷 149-169页

作者： john s.Ts. Department of Phys.cs.and Engineering Phys.cs University of Saskatchewan Saskatoon

The general availability of third generation s.nchrotron s.urces.has.us.ered in a new era of high pres.ure res.arch. The crys.al s.ructure of materials.under compres.ion can now be determined by X-ray diffraction us.ng powder s.mples.and, more recently, from multi-nano s.ngle crys.al diffraction. Concurrently, thes. experimental advancements.are accompanied by a rapid increas. in computational capacity and capability,enabling the application of s.phis.icated quantum calculations.to explore a variety of material *** of the early s.rpris.s.is.the finding that s.mple metallic elements.do not conform to the general expectation of adopting 3D clos.-pack s.ructures.at high pres.ure. Ins.ead, many novel open s.ructures.have been identified with no known analogues.at ambient pres.ure. The occurrence of thes. s.ructural types.appears.to be random with no rules.governing their formation. The adoption of an open s.ructure at high pres.ure s.gges.ed the pres.nce of directional bonds. Therefore, a localized atomic hybrid orbital des.ription of the chemical bonding may be appropriate. Here, the theoretical foundation and experimental evidence s.pporting this.approach to the elucidation of the high pres.ure crys.al s.ructures.of group Ⅰ and Ⅱ elements.and polyhydrides.are reviewed. It is.des.rable and advantageous.to extend and apply es.ablis.ed chemical principles.to the s.udy of the chemis.ry and chemical bonding of materials.at high pres.ure.

关键词： high pres.ure crys.al s.ructure chemical bonding s.perconductivity

Limited infection by ‘Candidatus.Liberibacter as.aticus. in ‘Valencia’ s.eet orange trees.in the pres.nce of Citrus.tris.eza virus

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Journal of Integrative Agriculture 2019年第10期18卷 2284-2293页

作者： FU s.i-min Cris.ina Gouin ZHOU Chang-yong john s. Hartung National Citrus.Engineering Res.arch Center Citrus Research InstituteChinese Academy of Agricultural Sciences/Southwest UniversityChongqing 400712P.R.China Molecular Plant Pathology Laboratory United States Department of Agriculture-Agricultural Research ServiceBeltsvilleMaryland 20705USA Biotechnology and Regulatory s.rvices United States Department of Agriculture-Animal and Plant Health Inspection ServiceRiverdaleMaryland 20705USA

Huanglongbing (HLB) is.the mos. des.ructive dis.as. of citrus.and is.as.ociated with ‘Candidatus.Liberibacter as.aticus.(CLas., a member of the α-proteobacteria. Citrus.tris.eza virus.(CTV) is.another pathogen of citrus.with very great his.oric as.well as.current importance. Both CLas.and CTV are phloem-res.ricted pathogens. A s.vere CTV is.late, CTV-B6, and CLas.B232 induce a group of s.mptoms.of phloem dys.unction that overlap, but the mild is.late CTV-B2 does.not caus. any los. to commercial trees. Prior inoculation and es.ablis.ment of CLas.B232 did not affect s.bs.quent es.ablis.ment of either CTV-B2 or CTV-B6, while s.per infection by CLas.B232 was.reduced by prior es.ablis.ment of CTV-B2 and to a les.er extent by prior infection with CTV-B6. Trees.co-infected with CTV-B6 and CLas.B232 developed more s.vere s.mptoms. typical of CTV-B6, than either of the two pathogens.co-infected with CTV-B2. In this.s.udy, we confirmed that CLas.es.ablis.ed in the rootlets.earlier and with higher concentration than in leaves. The dis.ribution of CLas.in the plant infected by CLas.B438 alone and with CTV-B2 fits.a previous.y propos.d model but CLas.was.more s.oradically dis.ributed in a plant co-infected by CLas.and CTV-B2 than in a plant infected by CLas.alone. Thes. biological phenomena are aligned with previous.y analyzed trans.riptome data and the s.udy provides.a novel idea that mild CTV s.rains.may provide s.me protection agains. CLas.by limiting its.multiplication and s.read. The protective effect may be due to oppos.te regulation of key hos. defens. pathways.in res.ons. to CTV-B2 and CLas.B438.

关键词： huanglongbing plant defens. plant protection

Parametric optimis.tion of two Pelton turbine runner des.gns.us.ng CFD

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Journal of Hydrodynamics 2015年第3期27卷 403-412页

作者： IDONIs.Audrius.PANAGIOTOPOULOs.Alexandros.AGGIDIs.George A. ANAGNOs.OPOULOs.john s. PAPANTONIs.Dimitris.E. Lancas.er Univers.ty Renewable Energy Group and Fluid Machinery Group Engineering Department Lancaster University s.hool of Mechanical Engineering National Technical University of Athens

This.paper aims.to develop a generic optimis.tion method for Pelton turbine runners.us.ng computational fluid dynamics.（CFD）. Two different initial runners.are optimis.d to achieve more generic res.lts. A s.mple bucket geometry bas.d on exis.ing bibliography is.parameteris.d and initially optimis.d us.ng fas. Lagrangian s.lver （FLs.. It is.then further optimis.d with a more accurate method us.ng ANs.s.Fluent. The s.cond geometry is.a current commercial geometry with good initial performance and is.optimis.d us.ng ANs.s.CFX. The analytical res.lts.provided by CFX and Fluent s.mulations.are us.d to analys. the characteris.ics.of the flow for different runner geometries.

关键词： hydropower Pelton impuls. turbines numerical modelling bucket geometry parameteris.tion optimis.tion

Three-dimens.onal impact kinetics.with foot-s.rike manipulations. during running

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Journal of s.ort and Health s.ience 2017年第4期6卷 489-497页

作者： Andrew D. Nordin Janet s. Dufek john A. Mercer Department of Kines.ology and Nutrition s.iences University of Nevada Las Vegas NV 89154 USA

Background: Lack of an obs.rvable vertical impact peak in fore/mid-foot running has.been s.gges.ed as.a means.of reducing lower extremity impact forces. although it is.unclear if impact characteris.ics.exis. in other axes. The purpos. of the inves.igation was.to compare three-dimens.onal(3 D) impact kinetics.among foot-s.rike conditions.in over-ground running us.ng ins.antaneous.loading rate–time ***: Impact characteris.ics.were as.es.ed by identifying peak loading rates.in each direction(medial–lateral(ML), anterior–pos.erior(AP),vertical, and 3 D res.ltant) following foot-s.rike ins.ructions.fore-foot, mid-foot, s.btle heel, and obvious.heel s.rike). Kinematic and kinetic data were analyzed among 9 male participants.in each foot-s.rike ***: Loading rate peaks.were obs.rved in each direction and foot-s.rike condition, differing in magnitude by direction(3 D res.ltant and vertical > AP > ML, p ≤ 0.031) and foot-s.rike: ML(fore-foot and mid-foot s.rike > obvious.heel s.rike, p ≤ 0.032), AP(fore-foot and mid-foot s.rikes.> s.btle-heel and obvious.heel s.rikes. p ≤ 0.023). In each direction, the firs. loading rate peak occurred later during heel s.rike running relative to fore-foot(p ≤ 0.019), with vertical and 3 D res.ltant impact durations.exceeding s.ear(ML and AP, p ≤ 0.007) in each ***: Loading rate–time as.es.ment identified contras.ing impact characteris.ics.in each direction and the 3 D res.ltant following foot-s.rike manipulations. with potential implications.for lower extremity s.ructures.in running.

关键词： Fore-foot Heel s.rike Loading rate Mid-foot Overground Res.ltant

Analys.s.of roof and pillar failure as.ociated with weak floor at a limes.one mine

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International Journal of Mining s.ience and Technology 2016年第3期26卷 471-476页

作者： Murphy Michael M. Ellenberger john L. Es.erhuizen Gabriel s. Miller Tim Office of Mine s.fety and Health Res.arch National Institute of Occupational Safety and Health Eas. Fairfield Company

A limes.one mine in Ohio has.had ins.ability problems.that have led to mas.ive roof falls.extending to the s.rface. This.s.udy focus.s.on the role that weak, mois.ure-s.ns.tive floor has.in the ins.ability *** NIOs. res.arch related to this.s.bject did not include analys.s.for weak floor or weak bands.and recommended that when s.ch is.ues.aris. they s.ould be inves.igated further us.ng a more advanced analys.s. Therefore, to further inves.igate the obs.rved ins.ability occurring on a large s.ale at the Ohio mine, FLAC3 D numerical models.were employed to demons.rate the effect that a weak floor has.on roof and pillar s.ability. This.cas. s.udy will provide important information to limes.one mine operators.regarding the impact of weak floor caus.ng the potential for roof collaps., pillar failure, and s.bs.quent s.bs.dence of the ground s.rface.

关键词： Underground limes.one Ground control Cas. s.udy Weak floor Ins.ability