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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

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

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： john Mitrofanis Jonathan Stone Michael R.Hamblin Pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

Magnetohydrodynamic‑based Internal Cooling System for a Ceramic Cutting Tool:Concept Design,Numerical Study,and Experimental Evalidation

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Nanomanufacturing and Metrology 2023年第4期6卷 60-80页

作者： john o’Hara Fengzhou Fang Center of Micro/Nano Manufacturing Technology(MNMT-Dublin) University College DublinDublin 4Ireland State Key Laboratory of Precision Measuring Technology and Instruments Laboratory of Micro/Nano Manufacturing Technology(MNMT)Tianjin UniversityTianjin 300072China

The efective removal of the heat generated during mechanical cutting processes is crucial to enhancing tool life and produc-ing workpieces with superior surface *** internal cooling systems used in cutting inserts employ a liquid water-based solvent as the primary medium to transport the excess thermal energy generated during the cutting *** limitations of this approach are the low thermal conductivity of water and the need for a mechanical input to circulate the coolant around the inner chamber of the cutting *** this context,this paper proposes an alternative method in which liquid gallium is used as the coolant in combination with a magnetohydrodynamic(MHD)pump,which avoids the need for an external power *** computational fuid dynamics,we created a numerical model of an internal cooling system and then solved it under conditions in which a magnetic feld was applied to the liquid *** was followed by a simulation study performed to evaluate the efectiveness of liquid gallium over liquid *** results of experiments conducted under non-cooling and liquid gallium cooling conditions were analyzed and compared in terms of the tool wear *** results showed that after six machining cycles at a cutting speed Vc=250 m min−1,the corner wear VBc rate was 75µm with the coolant of and 48µm with the MHD-based coolant on,representing a decrease of 36%in tool *** Vc=900 m min−1,the corner wear VBc rate was 75µm with the coolant of and 246µm with the MHD-based coolant on,representing a decrease of 31%in tool *** external cooling using liquid water was added,the results showed at Vc=250 m min−1,the diference between the tool wear rate reduction with the internal liquid gallium coolant relative to the external coolant was 29%.When the cutting speed was increased to Vc=900 m min−1,the diference observed between the internal liquid gallium coolant relative to the external coolant was 16%.The study proves the feasibility of using liqu

关键词： Internal cooling Heat transfer Liquid metal Magnetic feld Cutting tool

Proportional-integral-derivative control of nonlinear half-car electro-hydraulic suspension systems

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2013年第6期14卷 401-416页

作者： john E. D. EKoRU Jimoh o. PEDRo School of Mechanical Aeronautical and Industrial Engineering University of the Witwatersrand Private Bag 03 WITS 2050 Johannesburg South Africa

This paper presents the development of a proportional-integral-derivative (PID)-based control method for application to active vehicle suspension systems (AVSS). This method uses an inner PID hydraulic actuator force control loop, in combination with an outer PID suspension travel control loop, to control a nonlinear half-car AVSS. Robustness to model uncertainty in the form of variation in suspension damping is tested, comparing performance of the AVSS with a passive vehicle suspension system (PVSS), with similar model parameters. Spectral analysis of suspension system model output data, obtained by performing a road input disturbance frequency sweep, provides frequency response plots for both nonlinear vehicle suspension systems and time domain vehicle responses to a sinusoidal road input disturbance on a smooth road. The results show the greater robustness of the AVSS over the PVSS to parametric uncertainty in the frequency and time domains.

关键词： Force control Proportional-integral-derivative (PID) control Nonlinear half-car Active vehicle suspension system (AVSS) Hydraulic actuator dynamics Model uncertainty

Interactive influence of rainfall manipulation and livestock grazing on species diversity of the herbaceous layer community in a humid savannah in Kenya

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Plant Diversity 2019年第3期41卷 198-205页

作者： Joseph o.ondier Daniel o.okach john C.onyango Dennis o.otieno Department of Botany Maseno University Private Bag Maseno Kenya Department of Biological Sciences Jaramogi Oginga Odinga University of Science and Technology P.O Box 210-40601 Bondo Kenya Department of Plant Ecology University of Bayreuth D-95440 Bayreuth Germany

Changes in rainfall regime and grazing pressure affect vegetation composition and diversity with ecological implications for savannahs. The savannah in East Africa has experienced increased livestock grazing and rainfall variability but the impacts associated with those changes on the herbaceous layer have rarely been documented. We investigated the effect of livestock grazing, rainfall manipulation and their interaction on the composition and diversity of the herbaceous community in the savannah for two years in Lambwe, Kenya. Rainfall manipulation plots were set up for vegetation sampling;these plots received either 50% more or 50% less rainfall than control plots. Simpson’s diversity and Bergere Parker indices were used to determine diversity changes and dominance respectively. The frequency of species was used to compute their abundance and their life forms as determined from the literature. Grazing significantly increased species diversity through suppression of dominant species. Rainfall manipulation had no significant impact on plant diversity in fenced plots, but rainfall reduction significantly reduced diversity in grazed plots. In contrast, rainfall manipulation had no impact on dominance in either fenced or grazed plots. The interaction of grazing and rainfall manipulation is complex and will require additional survey campaigns to create a complete picture of the implications for savannah structure and composition.

关键词： Plant diversity Grazing Rainfall Moist savannah

New moon from an old hand

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Chinese Science Bulletin 2004年第17期49卷 1788-1800页

作者： Michael john o’Hara Institute of Geography and Earth Sciences University of WalesAber- ystwyth SY23 3DBWalesUK

The outcome of the Apollo lunar exploration program 1969—1974 was a model of lunar petrogenesis which ignored the probability of selective volatilisation of gases and alkalis from fire-fountaining lunar basalts. It overlooked the fact that the average compositions of the erupted basalts were those of plagioclase-saturated and low-pressure cotectic liquids on eruption, clearly indicating that they were not primary magmas. The basalts may have undergone evolution by gabbro fractionation within the lu- nar crust, perhaps in large lava lakes now solidified as the lunar maria. The existing model involving a global magma ocean and plagioclase flotation to form the lunar crust arises solely from the incorrect assumption that the basalts are primary magmas. The plagioclase flotation hypothesis re- quires the presence of a significant positive europium anom- aly in the lunar highland crust, and was founded upon its alleged presence. However, that positive anomaly is neither established by the original data set nor by the much broader current data set. Critical observations, and experiments which will advance the debate are suggested, and alternative interpretations outlined.

关键词：阿波罗飞行月球标本挥发性斜长岩饱和度铕可选择解释

Secure data networks for electrical distribution applications

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Journal of Modern Power Systems and Clean Energy 2015年第3期3卷 447-455页

作者： David M.LAVERTY john B.o’RAW Kang LI D.john MoRRoW School of EEECS Queen’s University Belfast125 Stransmillis RoadBelfast BT95AHUK

Smart Grids are characterized by the application of information communication technology(ICT)to solve electrical energy *** power networks span large geographical areas,thus a necessary component of many Smart Grid applications is a wide area network(WAN).For the Smart Grid to be successful,utilities must be confident that the communications infrastructure is *** paper describes how a WAN can be deployed using WiMAX radio technology to provide high bandwidth communications to areas not commonly served by utility communications,such as generators embedded in the distribution network.A planning exercise is described,using Northern Ireland as a case *** suitability of the technology for real-time applications is assessed using experimentally obtained latency data.

关键词： Telecoms Latency WiMAX Security

Hybrid q-Rung orthopair Fuzzy Sets Based CoCoSo Model for Floating offshore Wind Farm Site Selection in Norway

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CSEE Journal of Power and Energy Systems 2022年第5期8卷 1261-1280页

作者： Muhammet Deveci Dragan Pamucar Umit Cali Emre Kantar Konstanze Kolle john o.Tande Department of Industrial Engineering Turkish Naval AcademyNational Defence UniversityIstanbul 34940Turkey Department of operations Research and Statistics Faculty of Organizational SciencesUniversity of BelgradeBelgradeSerbia Department of Electric Power Engineering Norwegian University of Science and TechnologyTrondheim NO-7491Norway Department of Electric Power Technology SINTEF Energy ResearchTrondheim NO-7491Norway Department of Energy Systems SINTEF Energy ResearchTrondheim NO-7034Norway

Unlocking offshore wind farms’high energy generation potential requires a comprehensive multi-disciplinary analysis that consists of intensive technical,economic,logistical,and environmental *** wind energy projects have high investment volumes that make it essential to conduct extensive site selection to ensure feasible investment decisions that reduce the potential financial *** on the scenario and circumstances,a ranking of alternative offshore wind energy projects helps to prioritise the investment *** algorithms based on expert knowledge can support the prioritisation and thus alleviate the work load for investment decisions in the *** case study considered here is to find the best site for a floating offshore wind farm in Norway from four pre-selected alternatives:Utsira Nord,Stadthavet,Froyabanken,and Trana *** propose a hybrid decisionmaking model as a combined compromised solution(CoCoSo)based on the q-rung orthopair fuzzy sets(q-RoFSs)including the weighted q-rung orthopair fuzzy Hamacher average(Wq-RoFHA)and the weighted q-rung orthopair fuzzy Hamacher geometric mean(Wq-RoFHGM)*** this model,the q-RoFSs based full consistency method(FUCoM)is introduced as a new methodology to determine the weights of the decision *** results of the proposed model show that the best site among the investigated four alternatives is A1:Utsira Nord.A sensitivity analysis has verified the stability of the proposed decision-making model.

关键词： Decision-making q-rung orthopair fuzzy sets Fuzzy hamacher site selection offshore wind farm FUCoM

Inclusion of forestry offsets in emission trading schemes:insights from global experts

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Journal of Forestry Research 2022年第1期33卷 279-287页

作者： Anil Shrestha Sarah Eshpeter Nuyun Li Jinliang Li john o.Nile Guangyu Wang Asia Forest Research Centre Faculty of ForestryUniversity of British ColumbiaVancouverBC V6T 1Z4Canada China Green Carbon Foundation Beijing 100714People’s Republic of China Chinese Institute Green Carbon Beijing 100029People’s Republic of China The Carbon Institute San DiegoCA 92103USA

Emissions trading schemes(ETSs)have been a central component of international climate change policies,as a carbon pricing tool to achieve emissions reduction *** carbon offset credits have been leveraged in many ETSs to efficiently meet emission reduction targets,yet there is little knowledge about the perceptions,experiences,and challenges associated with the forest carbon offsetting in existing and pilot *** that the future inclusion of forest carbon offset in ETS management activities and policies will require strong support and acceptability among the institutions and experts involved in ETS,this study explores the experiences and lessons learned with 16 globally engaging experts representing major existing ETSs(North America,Europe,and New Zealand)and Chinese pilot ETSs towards the inclusion of forestry offsets,major concerns and challenges with existing implementation *** revealed that many respondents particularly from North America,New Zealand,and Chinese pilot systems portrayed positive attitudes toward the inclusion of forestry carbon offsets and its role in contributing to a viable ETS,while European experts were not *** cited leakage,permanence,additionality,and monitoring design features as the major challenges and concerns that inhibit the expansion and inclusion of forest carbon *** from Chinese pilot schemes referenced a unique set of challenges related to implementation,including the increasing cost of afforestation and reforestation projects,the uncertainty in the future supply and demand for their national Certified Emissions Reduction(CER)scheme and landowner *** and future ETSs should learn from and address the challenges experienced by global experts and carbon pricing mechanisms to design,evaluate,or enhance their forest carbon offset programs for an effective and viable system that successfully contributes to GHG mitigation practices *** recommend inclu

关键词： Emission trading scheme Forest carbon offsets Climate change Cap and trade Carbon