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targeting trkB–PSD-95 coupling to mitigate neurological disorders

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

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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

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Assessing impacts of energy storage on resilience of distribution systems against hurricanes

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Journal of Modern Power Systems and Clean Energy 2019年第4期7卷 731-740页

作者： Hieu t.NgUYEN john w.MUHS Masood PARVANIA Department of Electrical and Computer Engineering University of UtahSalt Lake CityUT 84112USA

this paper develops a comprehensive framework to analyze the impact of energy storage on improving the resilience of distribution systems against *** paper first develops a spatio-temporal model of progressing hurricane when making landfall that can be used to anticipate outage scenarios caused by the gust-wind *** optimization model is then developed for optimizing the operation of distribution systems during hurricane that captures both pre-outage and post-outage network operation *** simulations are performed on the modified IEEE 33-bus distribution system with real hurricane data in Houston to demonstrate the effectiveness of the proposed model.

关键词： Resilience Hurricane Energy storage Distribution system

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A Review on the Management of Biliary Complications after Orthotopic Liver transplantation

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Journal of Clinical and translational Hepatology 2019年第1期7卷 61-71页

作者： Brian t.Moy john w.Birk Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Orthotopic liver transplantation is the definitive treatment for end-stage liver disease and hepatocellular *** complications are the most common complications seen after transplantation,with an incidence of 10-25%.these complications are seen both in deceased donor liver transplant and living donor liver *** treatment of biliary complications with endoscopic retrograde cholangiopancreatography(commonly known as ERCP)has become a mainstay in the management *** success rate has reached 80%in an experienced endoscopist's *** unsuccessful with ERCP,percutaneous transhepatic cholangiography can be an alternative *** recognition and treatment has been shown to improve morbidity and mortality in post-liver transplant *** focus of this review will be a learned discussion on the types,diagnosis,and treatment of biliary complications post-orthotopic liver transplantation.

关键词： Biliary tract complication Orthotropic liver transplantation Stricture Bile leak

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Capacitive micromachined ultrasound transducers for intravascular ultrasound imaging

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Microsystems & Nanoengineering 2020年第1期6卷 565-577页

作者： Jiaqi wang Zhou Zheng Jasmine Chan john t.w.Yeow Department of Systems Design Engineering Faculty of EngineeringUniversity of WaterlooWaterlooON N2L 3G1Canada

Intravascular ultrasound(IVUS)is a burgeoning imaging technology that provides vital information for the diagnosis of coronary arterial diseases.A significant constituent that enables the IVUS system to attain high-resolution images is the ultrasound transducer,which acts as both a transmitter that sends acoustic waves and a detector that receives the returning *** the most mature form of ultrasound transducer available in the market,piezoelectric transducers have dominated the field of biomedical ***,there are some drawbacks associated with using the traditional piezoelectric ultrasound transducers such as difficulties in the fabrication of high-density arrays,which would aid in the acceleration of the imaging speed and alleviate motion *** advent of microelectromechanical system(MEMS)technology has brought about the development of micromachined ultrasound transducers that would help to address this *** from the advantage of being able to be fabricated into arrays with lesser complications,the image quality of IVUS can be further enhanced with the easy integration of micromachined ultrasound transducers with complementary metal-oxide-semiconductor(CMOS).this would aid in the mitigation of parasitic capacitance,thereby improving the ***,there are two commonly investigated micromachined ultrasound transducers,piezoelectric micromachined ultrasound transducers(PMUts)and capacitive micromachined ultrasound transducers(CMUts).Currently,PMUts face a significant challenge where the fabricated PMUts do not function as per their ***,CMUts with different array configurations have been developed for *** this paper,the different ultrasound transducers,including conventional-piezoelectric transducers,PMUts and CMUts,are reviewed,and a summary of the recent progress of CMUts for IVUS is presented.

关键词： piezoelectric transducers thereby

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An infrared photothermoelectric detector enabled by MXene and PEDOt:PSS composite for noncontact fingertip tracking

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Microsystems & Nanoengineering 2023年第1期9卷 229-239页

作者： Jiaqi wang Zhemiao Xie guanxuan Lu Jiayu Alexander Liu john t.w.Yeow Advanced Micro-/Nano-Devices Lab Department of Systems Design EngineeringUniversity of Waterloo200 University Ave WestWaterlooONN2L 3G1Canada

Photothermoelectric(PtE)detectors functioning on the infrared spectrum show much potential for use in many fields,such as energy harvesting,nondestructive monitoring,and imaging *** advances in low-dimensional and semiconductor materials research have facilitated new opportunities for PtE detectors to be applied in material and structural ***,these materials applied in PtE detectors face some challenges,such as unstable properties,high infrared reflection,and miniaturization ***,we report our fabrication of scalable bias-free PtE detectors based on ti3C2 and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate(PEDOt:PSS)composites and characterization of their composite morphology and broadband *** also discuss various PtE engineering strategies,including substrate choices,electrode types,deposition methods,and vacuum ***,we simulate metamaterials using different materials and hole sizes and fabricated a gold metamaterial with a bottom-up configuration by simultaneously combining MXene and polymer,which achieved an infrared photoresponse ***,we demonstrate a fingertip gesture response using the metamaterial-integrated PtE *** research proposes numerous implications of MXene and its related composites for wearable devices and Internet of things(Iot)applications,such as the continuous biomedical tracking of human health conditions.

关键词： unstable composite sizes

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Integral sliding mode based optimal composite nonlinear feedback control for a class of systems

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Control theory and technology 2014年第2期12卷 139-146页

作者： Zhou ZHENg weijie SUN Hui CHEN john t. w. YEOw College of Automation Science and Engineering South China University of Technology

this paper presents an optimization method of designing the integral sliding mode （ISM） based composite nonlinear feedback （CNF） controller for a class of low order linear systems with input saturation. the optimal CNF control is first designed as a nominal control to yield high tracking speed and low overshoot. the selection of all the tuning parameters for the CNF control law is turned into a minimization problem and solved automatically by particle swarm optimization （PSO） algorithm. Subsequently, the discontinuous control law is introduced to reject matched disturbances. then, the optimal ISM-CNF control law is achieved as the sum of the optimal CNF control law and the discontinuous control law. the effectiveness of the optimal ISM-CNF controller is verified by comparing with a step by step designed one. High tracking performance is achieved by applying the optimal ISM-CNF controller to the tracking control of the micromirror.

关键词： Composite nonlinear feedback Integral sliding mode Input saturation PSO Micromirror

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the petrogenesis of modern and ophiolitic lavas reconsidered:ti-V and Nb-th

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geoscience Frontiers 2022年第2期13卷 90-109页

作者： john w.Shervais Department of geosciences Utah State UniversityLoganUT 84322-4500United States

tectonic discrimination diagrams are a key tool for understanding ancient volcanic rock *** this contribution we compile over 15,000 whole rock compositions to re-evaluate the ti-V discrimination diagram and compare it to another commonly used tool,the Nb/Yb-th/Yb *** have reformulated the ti-V diagram into a log-log plot to distinguish samples more clearly at lower *** compilation shows that MORB are dominated by ti/V=20-43,whereas juvenile arc tholeiites and boninites are characterized by ti/Vgenerally,although there is minor overlap at the boundary(ti/V=20-22).Plume-related volcanic rocks(ocean island basalts,oceanic plateaux,and continental flood basalts)generally have ti/V>43,although there may be significant overlap with MORB-like ratios for ridgecentered OIB and for some oceanic *** 56%of alkaline OIB have ti/V>***-arc basins are dominantly *** models show that MORB and juvenile arc volcanics most likely formed under different fO;conditions,but are permissive of similar fO_(2)if the arc rocks form by much higher melt *** Nb/Yb ***/Yb plot clearly distinguishes most oceanic basalts(MORB,plateaux,OIB)from subduction-related volcanic rocks(boninite,juvenile arc tholeiite,calc-alkaline)and from flood *** propose here a new two-proxy diagram of ti/V ***/Nb,which incorporates the advantages of both.

关键词： Ophiolite Discrimination diagrams trace element geochemistry Vanadium

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PRESSURE-VELOCItY EQUILIBRIUM HYDRODYNAMIC MODELS

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Acta Mathematica Scientia 2010年第2期30卷 563-594页

作者： john w.grove Computational Physics group Computer Computationaland Statistical Sciences DivisionCCS-2 MS D413Los Alamos National Laboratory

this article describes mathematical models for phase separated mixtures of materials that are in pressure and velocity equilibrium but not necessarily temperature equilibrium. general conditions for constitutive model... 详细信息

关键词： Euler equations multiple phase mixtures non-equilibrium temperature mixtures

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An Update to Hepatobiliary Stents

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Journal of Clinical and translational Hepatology 2015年第1期3卷 67-77页

作者： Brian t.Moy john w.Birk Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT USA

Endoscopic stent placement is a common primary management therapy for benign and malignant biliary ***,continuous use of stents is limited by occlusion and *** technology has evolved significantly over the past two decades to reduce these *** purpose of this article is to review current guidelines in managing malignant and benign biliary obstructions,current endoscopic techniques for stent placement,and emerging stent *** began as a simple plastic stent technology has evolved significantly to include uncovered,partially covered,and fully covered self-expanding metal stents (SEMS) as well as magnetic,bioabsorbable,drug-eluting,and antireflux stents.

关键词： Biliary obstruction Stent Hepatobiliary malignancy Liver hilum

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