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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

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 Survey of Language-Based Approaches to Cyber-Physical and Embedded System Development

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Tsinghua Science and Technology 2015年第2期20卷 130-141页

作者： Paul Soulier Depeng Li john.r. williams University of Hawaii Massachusetts Institute of Technology(MIT)

As computers continue to advance, they are becoming more capable of sensing, interacting, and communicating with the physical and cyber world. Medical devices, electronic braking systems in automotive applications, and industrial control systems are examples of the many Cyber-Physical Systems （CPS） that utilize these computing capabilities. Given the potential consequences of software related failures in such systems, a high degree of safety, security, and reliability is often required. Programming languages are important tools used by programmers to develop CPS. They provide a programmer with the ability to transform designs into machine code. Of equal importance is their ability to detect and avoid programming mistakes. The development of CPS has predominantly been accomplished using the C programming language. Although C is a powerful language, it lacks features present in other languages that facilitate the development of reliable systems. This has prompted research into language-based alternatives for improving program quality through the use of programming languages. This paper presents an overview of the characteristics of embedded and cyber-physical systems and the associated requirements imposed on programming languages. This is followed by a survey of relevant research into language- based methods for creating safe, reliable, and robust software for CPS.

关键词： cyber-physical systems embedded systems programming languages type systems

reconstructing seafloor age distributions in lost ocean basins

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Geoscience Frontiers 2021年第2期12卷 769-780页

作者： Simon williams Nicky M.Wright john Cannon Nicolas Flament r.Dietmar Müller Department of Geology Northwest UniversityXi’an710069China State Key Laboratory of Continental Dynamics Northwest UniversityXi’an710069China research School of Earth Sciences The Australian National UniversityACT2601Australia ArC Centre of Excellence for Climate Extremes The Australian National UniversityACT2601Australia EarthByte Group School of GeosciencesUniversity of SydneyAustralia GeoQuEST research Centre School of EarthAtmospheric and Life SciencesUniversity of WollongongNorthfields AvenueNSW2522Australia

reconstructions of past seafloor age make it possible to quantify how plate tectonic forces,surface heat flow,ocean basin volume and global sea level have varied through geological ***,past ocean basins that have now been subducted cannot be uniquely reconstructed,and a significant challenge is how to explore a wide range of possible ***,we investigate possible distributions of seafloor ages from the late Paleozoic to present using published full-plate reconstructions and a new,efficient seafloor age reconstruction workflow,all developed using the open-source software *** test alternative reconstruction models and examine the influence of assumed spreading rates within the Panthalassa Ocean on the reconstructed history of mean seafloor age,oceanic heat flow,and the contribution of ocean basin volume to global sea *** reconstructions suggest variations in mean seafloor age of~15 Myr during the late Paleozoic,similar to the amplitude of variations previously proposed for the Cretaceous to *** reconstructed oceanic age-area distributions are broadly compatible with a scenario in which the long-period fluctuations in global sea level since the late Paleozoic are largely driven by changes in mean seafloor *** suggestions of a constant rate of seafloor production through time can be modelled using our workflow,but require that oceanic plates in the Paleozoic move slower than continents based on current reconstructions of continental motion,which is difficult to reconcile with geodynamic studies.

关键词： Plate reconstructions Sea level Seafloor spreading

Distribution characteristics of inertial sediment particles in the turbulent boundary layer of an open channel flow determined using Voronoi analysis

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International Journal of Sediment research 2017年第3期32卷 401-409页

作者： Xin Liu Chunning Ji Xiaoli Xu Dong Xu john J.r.williams State Key Laboratory of Hydraulic Engineering Simulation and Safety Tianjin University Tianjin research Institute for Water Transport Engineering M.O.T. State Key Laboratory of Hydraulics and Mountain river Engineering Sichuan University School of Engineering and Materials Science Queen Mary University of London

This paper presents the numerical investigation of the distribution of inertial sediment particles in the turbulent boundary layer of an open channel flow with the particle Stokes number ranging from 0.6 to 20.4. The methodology is a combination of three numerical approaches, i.e. direct numerical simulation of turbulent flow, the point-particle immersed boundary method, and the discrete particle method. By applying the Vorono analysis, the preferential concentration characteristics of sediment particles were investigated quantitatively. It was found that the normalized area of the Voronoi cells follows a lognormal particle distribution. The inertial sediment particles distributed unevenly in the turbulent boundary layer and the unevenness, governed by the particle Stokes number, was more significant as the particle Stokes number approaches unity. The inertial sediment particles in the turbulent boundary layer accumulated preferentially in streamwise-aligned streaky structures and this pattern was less significant with increasing particle Stokes number.

关键词： Inertial sediment particles Turbulent boundary layers Voronoi analysis Direct numerical simulation

A Couple Nagging Interpretive Difficulties in Zhuangzi Studies vis-à-vis William James on the Ethics and Psychology of Belief

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Frontiers of Philosophy in China 2019年第4期14卷 593-611页

作者： john.r.bert williams Department of Philosophy National University of SingaporeSingapore 117570Singapore

The present article addresses two lingering questions in the interpretation of the Zhuangzi莊子—(a)How can one reconcile the scepticism of the Zhuangzi with its positive project(s)?and(b)Who can become a sagely person?The questions are addressed with reference to aspects of William James’accounts of the ethics and psychology of belief.

关键词： Zhuangzi William James scepticism ethics of belief psychology of belief sagely person

Numerical investigation of particle saltation in the bed-load regime

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Science China(Technological Sciences) 2014年第8期57卷 1500-1511页

作者： JI ChunNing ANTE Munjiza ELDAD Avital XU Dong john williams State Key Laboratory of Hydraulic Engineering Simulation and Safety Tianjin University School of Engineering & Materials Science Queen MaryUniversity of London

This paper numerically investigates particle saltation in a turbulent channel flow having a rough bed consisting of 2–3 layers of densely packed *** this study,we combined three the state-of-the-art technologies,i.e.,the direct numerical simulation of turbulent flow,the combined finite-discrete element modelling of the deformation,movement and collision of the particles,and the immersed boundary method for the fluid-solid *** we verify our code by comparing the flow and particle statistical features with the published data and then present the hydrodynamic forces acting on a particle together with the particle coordinates and velocities,during a typical *** found strong correlation between the abruptly decreasing particle stream-wise velocity and the increasing vertical velocity at collision,which indicates that the continuous saltation of large grain-size particles is controlled by collision parameters such as particle incident angle,local rough bed packing arrangement,and particle density,*** physical process is different from that of particle entrainment in which turbulence coherence structures play an important *** distribution functions of several important saltation parameters and the relationships between them are *** results show that the saltating particles hitting the windward side of the bed particles are more likely to bounce off the rough bed than those hitting the *** on the above findings,saltation mechanisms of large grain-size particles in turbulent channel flow are presented.

关键词： particle saltation bed-load regime hydrodynamic forces turbulent channel flow

Effects of local compositional and structural disorder on vacancy formation in entropy-stabilized oxides from first-principles

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npj Computational Materials 2022年第1期8卷 909-915页

作者： Sieun Chae Logan williams Jihang Lee john T.Heron Emmanouil Kioupakis Department of Materials Science and Engineering University of MichiganAnn ArborMIUSA

Entropic stabilization has evolved into a strategy to create new oxide materials and realize novel functional properties engineered through the alloy *** an atomistic understanding of these properties to enable their design,however,has been challenging due to the local compositional and structural disorder that underlies their fundamental structure-property ***,we combine high-throughput atomistic calculations and linear regression algorithms to investigate the role of local configurational and structural disorder on the thermodynamics of vacancy formation in (MgCoNiCuZn)O-based entropy-stabilized oxides (ESOs) and their influence on the electrical *** find that the cation-vacancy formation energies decrease with increasing local tensile strain caused by the deviation of the bond lengths in ESOs from the equilibrium bond length in the binary *** oxygen-vacancy formation strongly depends on structural distortions associated with the local configuration of chemical *** in ESOs exhibit deep thermodynamic transition levels that inhibit electrical *** applying the charge-neutrality condition,we determine that the equilibrium concentrations of both oxygen and cation vacancies increase with increasing Cu mole *** results demonstrate that tuning the local chemistry and associated structural distortions by varying alloy composition acts an engineering principle that enables controlled defect formation in multi-component alloys.

关键词： alloy structural vacancy

Why does caloric restriction increase life and healthspan? The ‘clean cupboards’ hypothesis

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National Science review 2020年第7期7卷 1153-1156页

作者： john.r.Speakman State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Institute of Biological and EnvironmentalSciences University of Aberdeen CAS Center of Excellence in Animal Evolution and Genetics Kunming Institute of Zoology Chinese Academy of Sciences

The disposable soma hypothesis explanation of the effects of caloric restriction(Cr) on lifespan fails to explain why Cr generates negative impacts alongside the positive effects and does not work in all species. I pr...

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Different Performances of H_2O_2 to Oxidise Aldicarb and Hexazinone in the Advanced Oxidation Process of Ozone/Hydrogen Peroxide

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Journal of Donghua University(English Edition) 2014年第3期31卷 348-353页

作者：冉治霖孙楚李绍峰 CrAIG Denver williams TrEVOr john Hocking School of Transportation and Environment Shenzhen Institute of Information Technology College of resources and Environment Northeast Agricultural University Shenzhen Key Lab of Industrial Water Saving&Municipal Sewage reclamation Technology Shenzhen Polytechnic Institute School of Applied Science University of WolverhamptonWolverhampton WV1 1LYUK

The degradations of hexazinone and aldicarb by direct ozonation combined an advanced oxidation process( AOP) of O3/H2O2 were investigated in this study focusing on the oxidation mechanism by identifying the hydrogen peroxide consumption during the oxidation process of the two chemicals. The results showed that H2O2 could enhance the removal rate of the triazine herbicide hexazinone,and it was consumed along with the variation of removal rate in the light of different pH levels. The addition of H2O2 contributed little to the removal of the thiocarbamate herbicide aldicarb and H2O2 content kept constantly throughout the degradation process. Tert-butyl alcohol( TBA) effectively scavenged the ·OH radical for hexazinone,but had no effect on the removal rate of aldicarb. Aldicarb removal was mainly attributed to direct ozonation molecule in both O3( 97.00%) and O3/H2O2( 96.76%)systems. Moreover,sole O3 could hardly oxidize hexazinone whereas·OH radicals contribute respective 74.70% and 97.50% of removal in O3 system and O3/H2O2 AOP. All of these findings suggest that the mechanism of ·OH radical generation and the chain reaction in O3/H2O2 AOP should be further discussed.

关键词： hexazinone aldicarb O3/H2O2 direct and indirect oxidation H2O2consumption