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Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites

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Neural Regeneration Research 2025年第9期20卷 2645-2654页

作者： Kirsty Goncalves Stefan Przyborski Department of Biosciences Durham UniversityDurhamUK Reprocell Europe ltd. GlasgowUK

Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's *** accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased ***,the precise cellular and molecular mechanisms governing this response remain *** this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture *** utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized ***,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite *** demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite ***,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patie

关键词： Alzheimer's disease induced pluripotent stem cell neurite outgrowth neuron Nogo Rho A ROCK stem cell three-dimensional culture

Tribological properties of Al-GNP composites at elevated temperature

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Friction 2024年第5期12卷 1028-1041页

作者： Sunil POUDEL Rizwan BAJWA Yongde XIA Zakir KHAN Yi ZHANG Yanqiu ZHU College of Engineering Mathematics and Physical SciencesUniversity of ExeterExeterEX44QFUK European Technical Centre Daido Metal Co.Ltd.Iliminster SomersetTA199PHUK

Lighter and more powerful next generation vehicles and other rotary machinery demand bearings to operate in harsher conditions for higher efficiency,and the continuous development of advanced low-wear and friction materials is thus becoming even more important to meet these *** aluminium composites reinforced with high performance lubricate phases such as graphene nanoplatelets(GNPs)are very promising and have been vigorously *** maintaining a low coefficient of friction(COF)and offering great strength against wear due to their self-lubricating capability,the solid lubricant like GNPs protect the bearing surface from wear damage and prevent change in metallurgical properties during temperature *** paper first studies the high-temperature tribological performance of aluminium matrix composites reinforced with GNP,consolidated via powder metallurgy,then elucidates their tribological *** report that the best tribological performance is achieved by the composite containing 2.0 wt%GNP,with an extraordinarily low COF of 0.09 and a specific wear rate of 3.5×10^(−2)mm^(3)·N^(−1)·m^(−1),which represent 75%and 40%reduction respectively,against the plain aluminium consolidated under identical *** in-track and out-of-track Raman analysis have confirmed the role of GNPs in creating a tribofilm on the counterpart surface which contributed to the excellent performance.

关键词： nanocomposite graphene nanoplatelet(GNP) tribology powder metallurgy

Efficiency of a Modular Cleanroom for Space Applications

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Fluid Dynamics & Materials Processing 2024年第3期20卷 547-562页

作者： Matthew R.Coburn Charlie Young Chris Smith Graham Schultz Miguel Robayo Zheng-Tong Xie Faculty of Engineering and Physical Sciences University of SouthamptonSouthamptonSO171BJUK Plastron uk ltd. Westcott Venture ParkWestcottHP180XBUK Renewable Energy Group University of ExeterExeterTR109FEUK

A prototype cleanroom for hazardous testing and handling of satellites prior to launcher encapsulation,satisfying the ISO8 standard has been designed and analyzed in terms of *** Reynolds Averaged Navier-Stokes(URANS)models have been used to study the related flow field and particulate matter(PM)*** outcomes of the URANS models have been validated through comparison with equivalent large-eddy *** attention has been paid to the location and shape of the air intakes and their orientation in space,in order to balance the PM convection and diffusion inside the *** a cyclone-type flow pattern inside the cleanroom is a key to maintaining a high ventilation efficiency.

关键词： Diffuser LES PM RANS unsteady flow exponential decay

Targeting muscle to treat Charcot-Marie-Tooth disease

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Neural Regeneration Research 2024年第8期19卷 1653-1654页

作者： David Villarroel-Campos James N.Sleigh Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre UCL Queen Square Institute of NeurologyUniversity College LondonLondonUK uk Dementia Research Institute University College LondonLondonUK

Charcot-Marie-Tooth disease(CMT)is a hereditary peripheral neuropathy causing muscle weakness/wasting and sensory dysfunction predominantly in limb *** patients display gait abnormalities,foot deformities,loss of sens... 详细信息

关键词： Marie sensation neuropathy

“Flow” Transcranial Direct Current Stimulation (tDCS) for Depression Treatment in a Primary Healthcare General Practice—An Open-Label Cohort Study Measuring Montgomery-Åsberg Depression Rating Scale (MADRS-S) Outcomes

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Open Journal of Psychiatry 2024年第4期14卷 386-399页

作者： Chris Griffiths Harmony Jiang David Smart Azhar Zafar Northamptonshire Healthcare NHS Foundation Trust Northampton UK University of Northampton Northampton UK General Practice Alliance ltd. Northampton UK

Background: Flow FL-100 is a transcranial direct current stimulation (tDCS) device self-administered by a patient at home in combination with a software application delivered wellbeing behaviour therapy training. tDCS has evidence of effectiveness in treating symptoms of depression. Purpose/Aim: This post marketing study evaluated the effect of Flow on depression for primary care general practice patients with depression symptoms. Methods: Open-label patient cohort design with no control group. Inclusion criteria were aged 18 years or over and reporting depression symptoms. Participants self-administered five 30 minute tDCS sessions per week for the first three weeks, and then 3 sessions per week following this. Three, six and ten week assessment with participant self-report measure: Montgomery- Åsberg Depression Rating Scale (MADRS-S). Results: MADRS-S remission rates were between 29% - 30% at three weeks, 33% - 34% at six-weeks and 50% at 10-weeks treatment. There was a significant improvement in MADRS-S with large effect sizes at all time points. Conclusions: Flow tDCS can be delivered through a primary healthcare general practice service and patients will choose to use. Flow tDCS provides an effective depression treatment in addition and as an alternative to antidepressants and psychotherapy. tDCS has evidence as an effective depression treatment, and the widespread availability of tDCS in primary care general practice should be considered.

关键词： Depression Transcranial Direct Current Stimulation Wellbeing General Practice

Deep learning for joint channel estimation and feedback in massive MIMO systems

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Digital Communications and Networks 2024年第1期10卷 83-93页

作者： Jiajia Guo Tong Chen Shi Jin Geoffrey Ye Li Xin Wang Xiaolin Hou National Mobile Communications Research Laboratory Southeast UniversityNanjing210096China Department of Electrical and Electronic Engineering Imperial College LondonLondonSW72AZUK DOCOMO Beijing Communications Laboratories Co. LtdBeijingChina

The great potentials of massive Multiple-Input Multiple-Output(MIMO)in Frequency Division Duplex(FDD)mode can be fully exploited when the downlink Channel State Information(CSI)is available at base ***,the accurate CsI is difficult to obtain due to the large amount of feedback overhead caused by massive *** this paper,we propose a deep learning based joint channel estimation and feedback framework,which comprehensively realizes the estimation,compression,and reconstruction of downlink channels in FDD massive MIMO *** networks are constructed to perform estimation and feedback explicitly and *** explicit network adopts a multi-Signal-to-Noise-Ratios(SNRs)technique to obtain a single trained channel estimation subnet that works well with different SNRs and employs a deep residual network to reconstruct the channels,while the implicit network directly compresses pilots and sends them back to reduce network *** module is also designed to generate data-bearing *** results show that the two proposed networks exhibit excellent performance of reconstruction and are robust to different environments and quantization errors.

关键词： Channel estimation CSI feedback Deep learning Massive MIMO FDD

Stable diffusion gradients in microfluidic conduits bounded by fluid walls

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Microsystems & Nanoengineering 2024年第3期10卷 357-367页

作者： Federico Nebuloni Cyril Deroy Peter R.Cook Edmond J.Walsh Department of Engineering Science Osney Thermo-Fluids InstituteUniversity of OxfordOxford OX20ESUK Sir William Dunn School of Pathology University of OxfordOxford OX13REUK

Assays mimicking in vitro the concentration gradients triggering biological responses like those involved in fighting infections and blood clotting are essential for biomedical *** assays prove especially attractive as they allow precise control of gradient shape allied to a reduction in *** microfluidic devices are fabricated using solid plastics that prevent direct access to responding ***-walled microfluidics allows the manufacture of circuits on standard Petri dishes in seconds,coupled to simple operating methods;cell-culture medium sitting in a standard dish is confined to circuits by fluid walls made of an immiscible *** develop and experimentally validate an analytical model of diffusion between two or more aqueous streams flowing at different rates into a fluid-walled conduit with the cross-section of a circular *** solid walls,fluid walls morph during flows as pressures fall,with wall shape changing down the *** model is validated experimentally for Fourier numbers<0.1 using fluorescein diffusing between laminar *** enables a priori prediction of concentration gradients throughout a conduit,so allowing rapid circuit design as well as providing bioscientists with an accurate way of predicting local concentrations of bioactive molecules around responsive and nonresponsive cells.

关键词： walls diffusion attractive

Nondestructive and active interrogation system for special nuclear material:proof of principle and initial results

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Nuclear Science and Techniques 2024年第5期35卷 216-225页

作者： Mahmoud Bakr Kai Masuda Yoshiyuki Takahashi Tsuyoshi Misawa Norio Yamakawa Tomas Scott Institute of Advanced Energy Kyoto UniversityGokashoUjiKyoto 611‑0011Japan School of Physics University of BristolBs81TL Tyndall AvenueBristolUK Physics Department Faculty of ScienceAssiut UniversityAssiut 71516Egypt Research Reactor Institute Kyoto University2 Asashiro‑NishiKumatoriOsaka 590‑0494Japan Pony Industry Co.ltd. 2‑3‑6 Kitakyuhoji‑MachiChuo‑KuOsaka 541‑0057Japan Astral Neutronics ltd Unit H5HallenBristol BS107SBUK

Herein,we employ the threshold energy neutron analysis(TENA)technique to introduce the world's first active interrogation system to detect special nuclear materials(SNMs),including U-235 and *** system utilizes a DD neutron generator based on inertial electrostatic confinement(IEC)to interrogate suspicious *** detect secondary neutrons produced during fission reactions induced in SNMs,a tensioned metastable fluid detector(TMFD)is *** current status of the system's development is reported in this paper,accompanied by the results from experiments conducted to detect 10 g of highly enriched uranium(HEU).Notably,the experimental findings demonstrate a distinct difference in the count rates of measurements with and without *** difference in count rates surpasses two times the standard deviation,indicating a confidence level of more than 96% for identifying the presence of *** paper presents and extensively discusses the proof-of-principle experimental results,along with the system's planned trajectory.

关键词： Special nuclear materials Uranium detection Inertial electrostatic confinement fusion TENA HEU CTMFD

Bimetallic reduced graphene oxide/zeolitic imidazolate framework hybrid aerogels for efficient heavy metals removal

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Frontiers of Chemical Science and Engineering 2024年第8期18卷 49-66页

作者： Nurul A.Mazlan Allana Lewis Fraz Saeed Butt Rajakumari Krishnamoorthi Siyu Chen Yi Huang School of Engineering Institute for Materials&ProcessesThe University of EdinburghEdinburgh EH93FBUK

Graphene oxide is a promising adsorption ***,it has been difficult to recycle and separate graphene oxide in the *** alleviate this problem,graphene oxide was thermally reduced to produce porous hydrogel which was then functionalized with *** functional groups act as not only adsorption sites but also nucleation sites for in situ crystallization of cobalt-doped zeolitic-imidazolate-framework-8 *** effects of cobalt-doping contents on the physicochemical and adsorption properties of the resulting aerogel were also evaluated by varying the cobalt *** instance,the reduced graphene oxide-polydopamine/50cobalt-zeolitic-imidazolate-framework-8 aerogel exhibited a high surface area of 900 m^(2)·g^(-1)and maintained the structure in water after ten *** as-synthesized aerogels showed an ultrahigh adsorption capacity of 1217±24.35 mg·g^(-1)with a removal efficiency of>99%of lead,as well as excellent adsorption performance toward other heavy metals,such as copper and cadmium with adsorption capacity of 1163±34.91 and 1059±31.77 mg·g^(-1),*** importantly,the lead adsorption stabilized at 1023±20.5 mg·g^(-1)with a removal efficiency of>80%after seven cycles,indicating their potential in heavy metal removal from industrial wastewater.

关键词： rGO Co-doped ZIF-8 heavy metals adsorption aerogel