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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

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Beginning from the end:the presynaptic terminal as a pathomechanism hub in frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3217-3218页

作者： Laura Huggon Emma L.Clayton uk dementia Research Institute at King’s College London LondonUK department of Basic and Clinical Neuroscience Institute of Psychiatry Psychology&NeuroscienceKing’s College LondonLondonUK

Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(ALS)are neurodegenerative diseases with significant overlapping *** these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and ALS affecting upper and lower motor neurons),these two diseases are complexly *** and ALS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.

关键词： diseases amyotrophic sclerosis

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Experimental Study for Effect of Multi-Site Spark Ignition on dedicated Hybrid Engine Performance under High Dilution Condition

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Journal of Thermal Science 2025年第1期 254-267页

作者： YAN Bowen WATERS Benjamin HAINES Andrew MCGHEE Mike HU Tiegang deNG Wei PU Yongxian MA Tianyu Powertrain Engineering R&D Center Chongqing Changan Automobile Co.Ltd. Changan uk R&D Centre Limited

In this study,a triple spark ignition scheme was first designed on a three-cylinder 1.5-L dedicated hybrid engine（DHE）.On this basis,the effect of different ignition modes on engine combustion and emission characteristics was studied,especially under high dilution *** results tested at 2000 r/min and 0.8 MPa BMEP（brake mean effective pressure） show that with highly increased in-cylinder flow intensity,using only passive prechamber（PPC） has a lower lean limit than that with single central spark plug（CSP）,thereby leading to slightly higher minimum fuel consumption and nitrogen oxides（NOx） *** side spark plugs（SSP）based on PPC can result in improved capability of lean limit extension and engine performance than ***,the improvement level is lower than that with triple spark plugs（TSP）.As the excess air ratio λincreases,the advantage of PPC and PPC with SSP in improving the combustion phasing compared with CSP gradually ***,the increasing tendency of their ignition delay and combustion duration is more *** added SSP based on PPC can effectively shorten the ignition delay of leaner mixture,but the combustion duration can be only slightly *** a result,under extremely lean condition,the advantage of PPC and PPC with SSP in terms of combustion characteristics over CSP becomes much *** contrast,the TSP ignition can achieve much shorter ignition delay and combustion duration simultaneously under this *** to the highest available dilution level,the TSP ignition achieves the lowest raw ***,it can also reduce the raw carbon monoxide（CO） and hydrocarbons（HC） emissions compared to CSP due to a more thorough combustion of the end gas *** on the excellent performance of TSP,the highest engine brake thermal efficiency（BTE） was further *** results show that with normal RON 92 fuel,the engine finally achieved 43.69% and 45.02% BTE under stochiometric mode with exhaust

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The Changing Face of Synthetics in the Diamond Industry-Recent developments and Reliable Identification

The Changing Face of Synthetics in the Diamond Industry-Rece...

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2011中国珠宝首饰学术交流会

作者： David Fisher de beers uk ltd. Diamond Trading Company Research Centre

China is an increasingly important diamond market and as such will inevitably be seen as a potential market for synthetics and treated *** important contribution of the research carried out by de beers was the production of the Diamond Verification Instruments:DiamondSure,DiamondView and *** can be used to screen out diamonds that could potentially be synthetics and DiamondView allows imaging of the fluorescence patterns associated with growth and therefore provides unambiguous identification of *** of typical features of various synthetics are *** technical uses of single crystal diamond are currently expanding and the demands of these technologies for higher crystal qualities and larger sizes have helped drive the development of synthesis methods and these advances have enabled the production of material that could potentially be manufactured into polished *** there have been significant developments both in the synthesis methods themselves and in post-growth treatments,detection capability has kept pace with these developments and continues to provide reliable *** testing supporting full disclosure will ensure that consumers will be properly informed about their diamond purchases and will maintain the integrity of brands such as Forevermark into the future.

关键词： Diamond Synthetics Identification

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Innovation Portfolio Management for Small-medium Enterprises

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Journal of Systems Science and Systems Engineering 2020年第5期29卷 507-524页

作者： Daniel Pashley Theo Tryfonas Andy Crossley Chris Setchell Stylianos Karatzas iMETRUM ltd. BristolUK Civil Engineering department University of BristolUK Civil Engineering department University of PatrasGreece

For small and medium sized enterprises,portfolio management can be a difficult exercise;especially when the available paths forwards are shrouded in *** overcome this,they are required to research and decide upon the path to follow,but this can be difficult when the information to gather is unclear,leading to ad-hoc processes and *** motivation for this project originated from a small and medium sized enterprise experiencing this problem of unknown critical information and a technological portfolio with significant *** no procedure or method in place,they conducted the research in an ad-hoc way resulting in uncertainty and low repeatability of *** tackle this problem,innovation structuring frameworks were synthesised with appropriate risks and context to pose a new structure for information *** resulting structure was tested within the small and medium sized enterprise to investigate the repeatability of the information capture and the subsequent *** proposed structure was also analysed by-process experts for its wider *** the small and medium sized enterprise,this led to a consistent and repeatable method that delivered increased confidence about selecting a path forwards for its *** addition,it was found to be applicable to external organisations increasing the moders worth and *** implications of this work have led to a change in the operational procedure of the small and medium sized enterprise to utilise the defined process for researching new ideas for their portfolio which can lead to repeatable and trustworthy *** also has applicability to other similar companies and could lead them through a repeatable process as presented here.

关键词： Portfolio management directed research decision support small-medium enterprise

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Acceptor doping and actuation mechanisms in Sr-doped BiFeO_(3)-BaTiO_(3)ceramics

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Journal of Materiomics 2024年第1期10卷 57-69页

作者： Ziqi Yang Yizhe Li Bing Wang Juncheng Pan Annette K.Kleppe David A.Hall department of Materials University of ManchesterM139PLManchesterUK Diamond Light Source ltd. Harwell Science and Innovation CampusOX110DEDidcotUK

BiFeO_(3)-BaTiO_(3)(BF-BT)ceramics are important multiferroic materials,which are attracting significant attention for potential applications in high temperature lead-free piezoelectric *** the present study,the effects of Sr^(2+)as an acceptor dopant for Bi^(3+),in the range from 0 to 1.0%(in mole),on the structure and ferroelectric/piezoelectric properties of 0.7BiFeO_(3)-0.3BaTiO_(3)ceramics were *** use of a post-sintering Ar annealing process was found to be an effective approach to reduce electrical conductivity induced by the presence of electron holes associated with reoxidation during cooling.A low Sr dopant concentration(0.3%,in mole)yielded enhanced ferroelectric(P_(max)∼0.37 C/m^(2),P_(r)∼0.30 C/m^(2))and piezoelectric(d_(33)∼178 pC/N,k_(p)∼0.27)properties,whereas higher levels led to chemically heterogeneous core-shell structures and secondary phases with an associated decline in *** electric field-induced strain of the Sr-doped BF-BT ceramics was investigated using a combination of digital image correlation macroscopic strain measurements and in-situ synchrotron X-ray *** of the intrinsic(lattice strain)and extrinsic(domain switching)contributions to the electric field induced strain indicated that the intrinsic contribution dominated during the poling process.

关键词： Bismuth ferrite-barium titanate Acceptor doping Electroceramics Piezoelectricity In-situ X-ray diffraction

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Optimal Offering of Energy Storage in uk Day-Ahead Energy and Frequency Response Markets

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Journal of Modern Power Systems and Clean Energy 2024年第2期12卷 415-426页

作者： Makedon Karasavvidis Andreas Stratis Dimitrios Papadaskalopoulos Goran Strbac department of Electrical and Electronic Engineering Imperial College LondonLondonUK Statkraft uk ltd. LondonUK department of Electrical and Computer Engineering University of PatrasPatrasGreece IEEE

The offering strategy of energy storage in energy and frequency response(FR) markets needs to account for country-specific market regulations around FR products as well as FR utilization factors, which are highly uncertain. To this end, a novel optimal offering model is proposed for stand-alone price-taking storage participants, which accounts for recent FR market design developments in the uk, namely the trade of FR products in time blocks, and the mutual exclusivity among the multiple FR products. The model consists of a day-ahead stage, devising optimal offers under uncertainty, and a real-time stage, representing the storage operation after uncertainty is materialized. Furthermore, a concrete methodological framework is developed for comparing different approaches around the anticipation of uncertain FR utilization factors(deterministic one based on expected values, deterministic one based on worst-case values, stochastic one, and robust one), by providing four alternative formulations for the real-time stage of the proposed offering model, and carrying out an out-of-sample validation of the four model instances. Finally, case studies employing real data from uk energy and FR markets compare these four instances against achieved profits, FR delivery violations, and computational scalability.

关键词： Energy markets energy storage frequency response optimal offering robust optimization stochastic programming

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Overview of Future Antenna design for Mobile Terminals

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Engineering 2022年第4期8卷 12-14页

作者： Hanyang Wang Huawei Technologies(uk)Co. Ltd.Reading RG26UFUK

*** Over the years,antenna design for mobile terminals has become increasingly *** is mainly attributed to the limited space available in such devices for the housing of multiple antennas with wide and multi-frequency band *** coming fifth generation(5G)of wireless communications makes this issue even more challenging for mobile terminal antenna designers,since it requires a very large number of multiple input/multiple output(MIMO)antennas at sub-6 GHz frequency bands,as well as two or three antenna-in-package(AiP)modules at millimeter-wave frequency *** these antenna designs,the antennas must be small,compact,low profile,and lightweight,while maintaining wideband and multiband ***,for MIMO antenna design,although the antennas are placed very close together,a high degree of isolation between antennas must be satisfied,even within the same frequency *** article presents an overview of future antenna design for mobile terminals.

关键词： antenna millimeter bands

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An interferometric ex vivo study of corneal biomechanics under physiologically representative loading,highlighting the role of the limbus in pressure compensation

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Eye and Vision 2020年第5期7卷 412-422页

作者： Abby Wilson John Jones John RTyrer John Marshall Wolfson School of Mechanical Manufacturing and Electrical EngineeringLoughborough UniversityLoughboroughUK Laser Optical Engineering ltd. DerbyshireUK Institute of Ophthalmology UCLLondonUK

Background:The mechanical properties of the cornea are complex and regionally *** paper uses an original method to investigate the biomechanics of the cornea in response to hydrostatic loading over the typical physiological range of intra-ocular pressure(IOP)fluctuations thereby increasing understanding of clinically relevant corneal biomechanical properties and their contributions to the refractive properties of the ***:Displacement speckle pattern interferometry(DSPI)was used to measure the total surface displacement of 40 porcine and 6 human corneal-scleral specimens in response to pressure variations up to 1 mmHg from a baseline of 16.5 *** specimens were mounted in a modified artificial anterior chamber(AAC)and loaded *** of high strain in response to loading were identified by comparing the displacements across different ***:The nature of the response of the corneal surface to loading demonstrated high regional topographic *** properties were shown to be asymmetrical,and deformation of the limbal and pre-limbal regions dominated these responses respectively with over 90%(N-T)and 60%(S-I)of the total maximum displacement occurring in these regions indicating *** contrast,the curvature of the central cornea remained relatively unchanged merely translating in ***:The limbal and pre-limbal regions of the cornea appear to be fundamental to the absorption of small pressure fluctuations facilitating the curvature of the central cornea to remain relatively *** differential mechanical properties of this region could have important implications for the application of corneal surgery and corneal crosslinking,warranting further investigation.

关键词： Cornea Biomechanics Interferometry Limbus Topography

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Clinical impact of an anti-biofilm Hydrofiber dressing in hard-to-heal wounds previously managed with traditional antimicrobial products and systemic antibiotics

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Burns & Trauma 2020年第1期8卷 388-396页

作者： Daniel G.Metcalf Philip G.Bowler Science&Technology Research&DevelopmentConvaTec Ltd.DeesideFlintshireUK

Background:Hard-to-heal wounds are often compromised by the presence of *** presents an infection risk,yet traditional antimicrobial wound care products and systemic antibiotics are often used despite the uncertainty of therapeutic success and wound *** aim of this study was to investigate the clinical impact of a next-generation anti-biofilm Hydrofiber wound dressing(AQUACEL Ag+Extra[AQAg+E])in hard-to-heal wounds that had previously been treated unsuccessfully with traditional silver-,iodine-or polyhexamethylene biguanide(PHMB)-containing dressings and products and/or systemic ***:Clinical case study evaluations of the anti-biofilm dressing were conducted,where deteriorating or stagnant wounds were selected by clinicians and primary dressings were replaced by the anti-biofilm dressing for up to 4 weeks,or as deemed clinically appropriate,with monitoring via case report *** data was stratified for cases where traditional silver-,iodine-or PHMBcontaining products,or systemic antibiotics,had been used prior to the introduction of the antibiofilm ***:Sixty-five cases were identified for inclusion,wounds ranging in duration from 1 week to 20 years(median:12 months).In 47(72%)cases the wounds were stagnant,while 15(23%)were deteriorating;3 wounds were not *** an average of 4.2 weeks of management with the anti-biofilm dressing(range:1–11 weeks),in 11(17%)cases the wounds had healed(*** wound closure),40(62%)wounds improved,9(14%)wounds remained the same and 5(8%)wounds ***:The introduction of this anti-biofilm dressing into protocols of care that had previously involved wound management with traditional antimicrobial products and/or antibiotics was shown to facilitate improvements in the healing status of most of these hard-to-heal *** containing proven anti-biofilm technology,in combination with antimicrobial silver and exudate management technology,appear to b

关键词： Antibiotics Antimicrobials AQUACEL Ag+Extra Biofilm Dressings Iodine Hard-to-heal wounds Polyhexamethylene biguanide Silver

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