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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

Aseismic smart building isolation systems under multi-level earthquake excitations： Part II, energy-dissipation and damage reduction

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Frontiers of Structural and Civil Engineering 2015年第3期9卷 297-306页

作者： Min-Ho CHEY J. Geoffrey CHASE john B. MANDER Athol J. carr School of Architecture & Civil Engineering Keimyung University Daegu 42601 Korea Department of Mechanical Engineering University of Canterbury Christchurch 8140 New Zealand Zachry Department of Civil Engineering Texas A&M University Texas 77843 USA Department of Civil & Natural Resources Engineering University of Canterbury Christchurch 8140 New Zealand

Based on the performance results of the previously suggested smart building isolation systems （lst companion paper）, this following study verifies the control effects of the systems from the view point of energy dissipation and damage level metrics. Several different model cases of the strategically isolated multi-story building structures utilizing passive dampers and semi-active resettable devices are analyzed and the energy-based target indices are compared. Performance comparisons are conducted on statistically calculated story/structural hysteretic energy and story/structural damage demands over realistic suites of earthquake ground motion records, representing seismic excitations of specific return period probability. Again, the semi-active solutions show significant promise for applications ofresettable device, offering advantages over passive systems in the consistent damage reductions. The specific results of this study include the identification of differences in the mechanisms by which smart building isolation systems remove energy, based on the differences in the devices used. Less variability is also seen for the semi-active isolation systems, indicating an increased robustness.

关键词： smart building isolation story and structural energy-dissipation damage assessment

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Dynamic expression of Slit1–3 and Robo1–2 in the mouse peripheral nervous system after injury

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Neural Regeneration Research 2020年第5期15卷 948-958页

作者： Bing Chen Lauren carr Xin-Peng Dun Department of Neurology The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical UniversityHuai’anJiangsu ProvinceChina Plymouth University Peninsula Schools of Medicine and Dentistry PlymouthUK The Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

The Slit family of axon guidance cues act as repulsive molecules for precise axon pathfinding and neuronal migration during nervous system development through interactions with specific Robo *** we previously reported that Slit1–3 and their receptors Robo1 and Robo2 are highly expressed in the adult mouse peripheral nervous system,how this expression changes after injury has not been well ***,we constructed a peripheral nerve injury mouse model by transecting the right sciatic *** 14 days after injury,quantitative real-time polymerase chain reaction was used to detect mRNA expression of Slit1–3 and Robo1–2 in L4–5 spinal cord and dorsal root ganglia,as well as the sciatic *** analysis was performed to examine Slit1–3,Robo1–2,neurofilament heavy chain,F4/80,and vimentin in L4–5 spinal cord,L4 dorsal root ganglia,and the sciatic ***-expression of Slit1–3 and Robo1–2 in L4 dorsal root ganglia was detected by in situ *** addition,Slit1–3 and Robo1–2 protein expression in L4–5 spinal cord,L4 dorsal root ganglia,and sciatic nerve were detected by western blot *** results showed no significant changes of Slit1–3 or Robo1–2 mRNA expression in the spinal cord within 14 days after *** the dorsal root ganglion,Slit1–3 and Robo1–2 mRNA expression were initially downregulated within 4 days after injury;however,Robo1–2 mRNA expression returned to the control level,while Slit1–3 mRNA expression remained upregulated during regeneration from 4–14 days after *** the sciatic nerve,Slit1–3 and their receptors Robo1–2 were all expressed in the proximal nerve stump;however,Slit1,Slit2,and Robo2 were barely detectable in the nerve bridge and distal nerve stump within 14 days after ***3 was highly ex-pressed in macrophages surrounding the nerve bridge and slightly downregulated in the distal nerve stump within 14 days after ***1 was upregulated in vimentin-positive cells and migrating S

关键词： dorsal root ganglion nerve regeneration neural regeneration peripheral nerve Robo 1 Robo 2 sciatic nerve Slit1 Slit2 Slit3

Innovative seismic retrofitting strategy of added stories isolation system

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Frontiers of Structural and Civil Engineering 2013年第1期7卷 13-23页

作者： Min-Ho CHEY J.Geoffrey CHASE john B.MANDER Athol J.carr School of Architecture&Art Yanbian University of Science&TechnologyYanji 133000China Department of Mechanical Engineering University of CanterburyChristchurch 8140New Zealand Zachry Department of Civil Engineering Texas A&M UniversityTexas 77843USA Department of Civil&Natural Resources Engineering University of CanterburyChristchurch 8140New Zealand

The seismic performance of“added stories isolation”(ASI)systems are investigated for 12-story moment resisting *** newly added and isolated upper stories on the top of the existing structure are rolled to act as a large tuned mass damper(TMD)to overcome the limitation of the size of tuned mass,resulting to“12+2”and“12+4”stories building *** isolation layer,as a core design strategy,is optimally designed based on optimal TMD design principle,entailing the insertion of passive flexible laminated rubber bearings to segregate two or four upper stories from a conventionally constructed lower superstructure *** performance metrics are presented for 30 earthquake records from the 3 suites of the SAC *** history analyses are used to compute various response performances and reduction factors across a wide range of seismic hazard *** show that ASI systems can effectively manage seismic response for multi-degree-of freedom(MDOF)systems across a broader range of ground motions without requiring burdensome extra *** results include the identification of differences in the number of added story by which the suggested isolation systems remove energy.

关键词： added stories seismic isolation tuned mass damper parametric optimization statistical method

Feature-aligned segmentation using correlation clustering

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Computational Visual Media 2017年第2期3卷 147-160页

作者： Yixin Zhuang Hang Dou Nathan carr Tao Ju National Digital Switching System Engineering & Technological Research Center Washington University in St. Louis Adobe

We present an algorithm for segmenting a mesh into patches whose boundaries are aligned with prominent ridge and valley lines of the shape. Our key insight is that this problem can be formulated as correlation clustering(CC), a graph partitioning problem originating from the data mining *** formulation lends two unique advantages to our method over existing segmentation methods. First,since CC is non-parametric, our method has few parameters to tune. Second, as CC is governed by edge weights in the graph, our method offers users direct and local control over the segmentation result. Our technical contributions include the construction of the weighted graph on which CC is defined, a strategy for rapidly computing CC on this graph, and an interactive tool for editing the segmentation. Our experiments show that our method produces qualitatively better segmentations than existing methods on a wide range of inputs.

关键词： mesh segmentation correlation clustering(CC) feature lines

Review of therapies for intermediate and advanced stage hepatocellular carcinoma, not suitable for curative therapies: a rapidly changing landscape

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Hepatoma Research 2019年第1期5卷 26-35页

作者： Brian I.carr Liver Transplantation Institute Inonu UniversityMalatyaTurkey and Izmir Biomedicine and Genome CenterDokuz Eylul UniversityIzmir 35340Turkey

Recent clinical trials and new agents have permitted greater clarity in the choice of effective agents for that majority of patients with hepatocellular carcinoma who have advanced disease at diagnosis and thus cannot be offered potentially curative resection,ablation or liver *** main treatment for these patients remains chemoembolization,although evidence for selective internal radiation therapy(SIRT)with SIR-Spheres or Theraphere,is beginning to suggest that the results with this may be comparable with less *** who have failed chemoembolization or SIRT or have metastatic disease at presentation are suitable for the multikinase inhibitor sorafenib(nexavar)or newly-approved lenvatinib(lenvima)as first line *** choice between which of them to use first is not currently *** who have failed sorafenib can be offered a choice of FDA-approved regorafenib(stivarga)or immune checkpoint inhibitor nivolumab(opdivo)as second line *** that considerable percent of patients presenting with macroscopic portal vein thrombosis,the choice appears to be between multikinase inhibitor or SIRT,given the potential toxicity of chemoembolization in this ***,considering the potency of both nivolumab and regorafenib and the pipeline of new agents such as atezolizumab(tecentriq)in current clinical trials,including new immune checkpoint inhibitors,this landscape may change within a couple of years,especially if new evidence arises for the superior effectiveness of combinations of any of these agents over single agents.

关键词： Hepatocellular carcinoma advanced kinase inhibitors immune checkpoint inhibitors transarterial chemoembolization selective internal radiation therapy

Pressureless sintering behavior and properties of Ag-SnO_2

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Rare Metals 2019年第1期38卷 35-41页

作者： Henri Desplats Elodie Brisson Philippe Rogeon Patrick carré Alexandre Bonhomme Department of Materials Engineering IRDL FRE CNRS 3744University of South Brittany Schneider Electric-Electropole 31 rue Pierre Mendes France

In this study, the results of measurements on pressureless sintering behavior of Ag-SnO_2(88%wt Ag,12%wt SnO_2) pellets were reported. Dilatometric measurements, relative densities, hardness values, rupture transverse strength and electrical conductivities function of sintering temperatures were presented. A constant thermal expansion coefficient was determined, and a threshold temperature of densification(T_d) was exhibited. Sintering kinetics were reported for different temperatures. Hardness values were measured, and no increase in hardness is found under Td. Three-points bending tests were used to determine the transverse rupture strength whose evolution appears importantly well under Td. In the same manner, the increase in initial electrical conductivities begins well under Td. Under the threshold temperature, the relative increase in electrical conductivity is found to be independent of initial density of green compact pellets. This work highlights different evolutions in function of sintering temperature for the electrical conductivity and transverse rupture strength on the one hand, and for the densification and hardness on the other hand.

关键词： Ag-SnO2 Pressureless sintering Dilatometry Mechanical properties Electrical conductivity

SMALL WIND POWER CONSIDERATIONS

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Journal of Green Building 2009年第2期4卷 3-22页

作者： David carr Kenneth Starcher West Texas A&M University the Alternative Energy Institute MS ET

INTRODUCTION Wind energy can be a supplemental source of energy to an electric grid or the complete power supply for an isolated *** produces no waste particulate matter,uses no water for cooling,and contributes no green house gasses to the environment.A short description of the Alternative Energy Institute,at West Texas A&M University,and the basics of wind energy as well as some discussion of home scale wind systems are presented *** uses of wind energy and many of the basic concerns and considerations of placing wind energy conversion systems on or near primary structures are *** basic plan for a renewable energy system inclusion into a home or building is shown;it is always preferable to reduce the energy load and ensure that the structure will use energy as efficiently as possible before a system is *** federal support for renewables is at a new high,and the source for local and regional description of programs is shown.

关键词： environment SIDE system