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ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer’s disease with a bispecific,brain-penetrating fusion protein

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Translational Neurodegeneration 2022年第1期11卷 70-83页

作者： Gillian Bonvicini Stina Syvänen Ken G.Andersson Merja Haaparanta-Solin Francisco López-Picón dag sehlin Department of Public Health and Caring Sciences Uppsala University75185 UppsalaSweden BioArctic AB 11251 StockholmSweden Preclinical Imaging Laboratory Turku PET CentreUniversity of Turku20520 TurkuFin-land MediCity Research Laboratory University of Turku20520 TurkuFinland.

Background:Hijacking the transferrin receptor(TfR)is an effective strategy to transport amyloid-beta(Aβ)immuno-positron emission tomography(immunoPET)ligands across the blood-brain barrier(BBB).Such ligands are more sensitive and specific than small-molecule ligands at detecting Aβpathology in mouse models of Alzheimer’s disease(AD).This study aimed to determine if this strategy would be as sensitive in rats and to assess how TfR affinity affects BBB transport of bispecific immunoPET radioligands.Methods:Two affinity variants of the rat TfR antibody,OX26,were chemically conjugated to a F(ab′)2 fragment of the anti-Aβantibody,bapineuzumab(Bapi),to generate two bispecific fusion proteins:OX265-F(ab′)2-Bapi and OX2676-F(ab′)2-Bapi.Pharmacokinetic analyses were performed 4 h and 70 h post-injection of radioiodinated fusion proteins in wild-type(WT)rats.[124I]I-OX265-F(ab′)2-Bapi was administered to TgF344-AD and WT rats for in vivo PET imaging.Ex vivo distribution of injected[124I]I-OX265-F(ab′)2-Bapi and Aβpathology were assessed.Results:More[125I]I-OX265-F(ab′)2-Bapi was taken up into the brain 4 h post-administration than[124I]I-OX2676-F(ab′)2-Bapi.[124I]I-OX265-F(ab′)2-Bapi PET visualized Aβpathology with significantly higher signals in the TgF344-AD rats than in the WT littermates without Aβpathology.The PET signals significantly correlated with Aβlevels in AD animals.Conclusion:Affinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB,such that the higher-affinity bispecific fusion protein crossed the BBB more efficiently.Furthermore,bispecific immunoPET imaging of brain Aβpathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats,suggesting that this immunoPET strategy has the potential to be translated to higher species.

关键词： ImmunoPET Transferrin receptor Alzheimer’s disease Amyloid-beta

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SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-β antibody in a mouse model of Alzheimer's disease

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Translational Neurodegeneration 2020年第3期9卷 473-483页

作者： Tobias Gustavsson Stina Syvänen Paul O'Callaghan dag sehlin Department of Public Health and Caring Sciences Uppsala UniversityUppsalaSweden Department of Medical Cell Biology Uppsala UniversityUppsalaSweden

Background:Alzheimer's disease(AD)immunotherapy with antibodies targeting amyloid-B(AB)has been extensively explored in clinical trials.The aim of this study was to study the long-term brain distribution of two radiolabeled monoclonal Aβ antibody variants-RmAb158,the recombinant murine version of BAN2401,which has recently demonstrated amyloid removal and reduced cognitive decline in AD patients,and the bispecific RmAb158-scFv8D3,which has been engineered for enhanced brain uptake via transferrin receptor-mediated transcytosis.Methods:A single intravenous injection of iodine-125(251)-labeled RmAb158-scFv8D3 or RmAb158 was administered to AD transgenic mice(tg-ArcSwe).In vivo single photon emission computed tomography was used to investigate brain retention and intrabrain distribution of the antibodies over a period of 4 weeks.Activity in blood and brain tissue was measured ex vivo and autoradiography was performed in combination with Aβand CD31 immunostaining to investigate the intrabrain distribution of the antibodies and their interactions with AB.Results:Despite faster blood clearance,[125]RmAb158-scFv8D3 displayed higher brain exposure than[25]RmAb158 throughout the study.The brain distribution of[l25]RmAb158-scFv8D3 was more uniform and coincided with parenchymal Aβ pathology,while[2 I]RmAb158 displayed a more scattered distribution pattern and accumulated in central parts of the brain at later times.Ex vivo autoradiography indicated greater vascular escape and parenchymal Aβ interactions for[25]RmAb158-scFv8D3,whereas[25]RmAb158 displayed retention and Aβ interactions in lateral ventricles.Conclusions:The high brain uptake and uniform intrabrain distribution of RmAb158-scFv8D3 highlight the benefits of receptor-mediated transcytosis for antibody-based brain imaging.Moreover,it suggests that the alternative transport route of the bispecific antibody contributes to improved efficacy of brain-directed immunotherapy.

关键词： Alzheimer's disease Amyloid beta SPECT Immunotherapy Bispecific antibody Transferrin receptor

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Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta

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Translational Neurodegeneration 2021年第3期10卷 502-517页

作者： Fadi Rofo Jos Buijs Ronny Falk Ken Honek Lars Lannfelt Anna M.Lilja Nicole G.Metzendorf Tobias Gustavsson dag sehlin Linda Söderberg Greta Hultqvist Protein Drug Design Faculty of PharmacyUppsala University75124 UppsalaSweden Department of Immunology Genetics and PathologyUppsala University75185 UppsalaSweden Ridgeview Instruments 75237 UppsalaSweden BioArctic AB 11251 StockholmSweden Department of Public Health and Caring Sciences Uppsala University75185 UppsalaSweden

Background:Amyloid-β(Aβ)immunotherapy is a promising therapeutic strategy in the fght against Alzheimer’s disease(AD).A number of monoclonal antibodies have entered clinical trials for AD.Some of them have failed due to the lack of efcacy or side-efects,two antibodies are currently in phase 3,and one has been approved by FDA.The soluble intermediate aggregated species of Aβ,termed oligomers and protofbrils,are believed to be key pathogenic forms,responsible for synaptic and neuronal degeneration in AD.Therefore,antibodies that can strongly and selectively bind to these soluble intermediate aggregates are of great diagnostic and therapeutic interest.Methods:We designed and recombinantly produced a hexavalent antibody based on mAb158,an Aβprotofbrilselective antibody.The humanized version of mAb158,lecanemab(BAN2401),is currently in phase 3 clinical trials for the treatment of AD.The new designs involved recombinantly fusing single-chain fragment variables to the N-terminal ends of mAb158 antibody.Real-time interaction analysis with LigandTracer and surface plasmon resonance were used to evaluate the kinetic binding properties of the generated antibodies to Aβprotofbrils.Diferent ELISA setups were applied to demonstrate the binding strength of the hexavalent antibody to Aβaggregates of diferent sizes.Finally,the ability of the antibodies to protect cells from Aβ-induced efects was evaluated by MTT assay.Results:Using real-time interaction analysis with LigandTracer,the hexavalent design promoted a 40-times enhanced binding with avidity to protofbrils,and most of the added binding strength was attributed to the reduced rate of dissociation.Furthermore,ELISA experiments demonstrated that the hexavalent design also had strong binding to small oligomers,while retaining weak and intermediate binding to monomers and insoluble fbrils.The hexavalent antibody also reduced cell death induced by a mixture of soluble Aβaggregates.Conclusion:We provide a new antibody design with increased valency to promote binding avidity to a

关键词： Multivalent antibodies Alzheimer’s disease Aβ Avidity Oligomers Protofbrils

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变废为宝:“蓝色循环”海洋塑料废物管理新策略

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Science Bulletin 2024年第8期69卷 993-996页

作者：余灏轩 Izni Zahidi Chow Ming Fai 梁东方 dagØivind Madsen Department of Civil Engineering School of EngineeringMonash University MalaysiaBandar Sunway 47500Malaysia Monash Climate-Resilient Infrastructure Research Hub(M-CRInfra) School of EngineeringMonash University MalaysiaBandar Sunway 47500Malaysia Department of Engineering University of CambridgeCambridge CB21PZUK Davis School of Business Colorado Mesa UniversityGrand Junction 81501-3122USA

The"Blue Circle"vision,initiated by Zhejiang Province in China,represents a groundbreaking advancement in addressing marine plastic waste.Far more than just an innovative concept,it embodies a future-forward approach to managing marine plastic waste,revealing the untapped potential in what was previously considered mere debris.This initiative,marrying scientific innovation with advanced technology,has been rightfully acknowledged with the prestigious2023 United Nations"Champions of the Earth"award,recognizing its innovative strategy in environmental stewardship(https://***/a/202310/31/WS65406475a31090682a5eb9ee.html).

关键词： breaking debris initiated

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Investigation of Hexavalent Chromium Reduction in Strong Saline and Acidic Nitro-Phosphate Solutions

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Journal of Analytical Sciences, Methods and Instrumentation 2024年第1期14卷 1-13页

作者： Deniz Avsar Niels Højmark Andersen dag Øistein Eriksen Jon Petter Omtvedt Department of Chemistry University of Oslo Oslo Norway

Phosphorus fertilizers from less pure sedimentary sources become increasingly important, due to depletion of phosphorus from igneous rock of high quality. Consequently, robust methods with potential to remove various types of hazardous elements are required. Among such impurities, hexavalent chromium (Cr(VI)) is very likely to become a future challenge. Different industrial ways to treat phosphate rock are currently being practised, and we have here studied how chromium behaves when using the nitro-phosphate process. The reduction mechanism of Cr (VI) in nitric acid and phosphoric acid solutions was investigated by measuring redox potential and UV-VIS spectra. The results show that Cr (VI) is not stable in strong nitric acid solutions. Reduction of Cr (VI) species decreased with decreasing temperature, NO2 concentration, ionic strength and absence of light. These findings support the proposed reduction reaction:The reduction rate was observed proportional to the nitric acid decomposition: .

关键词： Nitro-Phosphate Fertilizers Chromium (VI) Reduction Chromium Speciation Ultraviolet-Visible Spectroscopy

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Global trends in international research collaboration, 1980-2021

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数据与情报科学学报:英文版 2023年第2期8卷 26-42页

作者： dag W.Aksnes Gunnar Sivertsen NIFU-Nordic Institute for studies in Innovation Research and EducationØkernveien 90653 OsloNorway

Purpose:The aim of this study is to analyze the evolution of international research collaboration from 1980 to 2021.The study examines the main global patterns as well as those specific to individual countries,country groups,and different areas of research.Design/methodology/approach:The study is based on the Web of Science Core collection database.More than 50 million publications are analyzed using co-authorship data.International collaboration is defined as publications having authors affiliated with institutions located in more than one country.Findings:At the global level,the share of publications representing international collaboration has gradually increased from 4.7%in 1980 to 25.7%in 2021.The proportion of such publications within each country is higher and,in 2021,varied from less than 30%to more than 90%.There are notable disparities in the temporal trends,indicating that the process of internationalization has impacted countries in different ways.Several factors such as country size,income level,and geopolitics may explain the variance.Research limitations:Not all international research collaboration results in joint co-authored scientific publications.International co-authorship is a partial indicator of such collaboration.Another limitation is that the applied full counting method does not take into account the number of authors representing in each country in the publication.Practical implications:The study provides global averages,indicators,and concepts that can provide a useful framework of reference for further comparative studies of international research collaboration.Originality/value:Long-term macro-level studies of international collaboration are rare,and as a novelty,this study includes an analysis by the World Bank’s division of countries into four income groups.

关键词： International collaboration Research collaboration Team science Co-authorship Internationalization Globalization

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The Impact of Hydrogen Energy Storage on the Electricity Harvesting

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Intelligent Automation & Soft Computing 2023年第5期36卷 1963-1978页

作者： Ghassan Mousa Ayman A.Aly Imran Khan dagØivind Madsen Department of Mechanical Engineering Faculty of EngineeringK.C.KARE Energy Research and Innovation CentreKing Abdulaziz UniversityJeddah21589Saudi Arabia Department of Mechanical Engineering College of EngineeringTaif UniversityP.O.Box 11099Taif21944Saudi Arabia Department of Electrical Engineering University of Engineering&Technology PeshawarPakistan University of South-Eastern Norway Bredalsveien 143511 HønefossNorway

The economics,infrastructure,transportation,and level of living of a country are all inﬂuenced by energy.The gap between energy usage and availabil-ity is a global issue.Currently,all countries rely on fossil fuels for energy genera-tion,and these fossil fuels are not sustainable.The hydrogen proton exchange membrane fuel cell(PEMFC)power system is both clean and efﬁcient.The fuel delivery system and the PEMFC make up the majority of the PEMFC power sys-tem.The lack of an efﬁcient,safe,and cost-effective hydrogen storage system is still a major barrier to its widespread use.Solid hydrogen storage has the large capacity,safety and good reversibility.As a hydrogen source system,the hydro-gen supply characteristics affect the characteristics of the PEMFC at the output.In this paper,a mathematical model of a hydrogen source reactor and PEMFC based on chemical absorption/desorption of solid hydrogen storage is established,and a simulation model of a PEMFC power system coupled with solid hydrogen storage is established using MATLAB/SIMULINK software,and the hydrogen supply of the reactor is analyzed in detail.The inﬂuence of prominent factors is evaluated.The research results show that the proposed method improved the system perfor-mance.At the same time,increasing the PEMFC temperature,increasing the area of the proton exchange membrane and the oxygen supply pressure can increase the output power of the power system.

关键词： Hydrogen energy fuel cell power system optimization electrical energy harvesting

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An Optimal Method for Speech Recognition Based on Neural Network

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Intelligent Automation & Soft Computing 2023年第5期36卷 1951-1961页

作者： Mohamad Khairi Ishak dagØivind Madsen Fahad Ahmed Al-Zahrani School of Electrical and Electronic Engineering Universiti Sains MalaysiaNibong Tebal14300Malaysia University of South-Eastern Norway Bredalsveien 143511HønefossNorway Computer Engineering Department Umm Al-Qura UniversityMecca24381Saudi Arabia

Natural language processing technologies have become more widely available in recent years,making them more useful in everyday situations.Machine learning systems that employ accessible datasets and corporate work to serve the whole spectrum of problems addressed in computational linguistics have lately yielded a number of promising breakthroughs.These methods were particularly advantageous for regional languages,as they were provided with cut-ting-edge language processing tools as soon as the requisite corporate information was generated.The bulk of modern people are unconcerned about the importance of reading.Reading aloud,on the other hand,is an effective technique for nour-ishing feelings as well as a necessary skill in the learning process.This paper pro-posed a novel approach for speech recognition based on neural networks.The attention mechanism isﬁrst utilized to determine the speech accuracy andﬂuency assessments,with the spectrum map as the feature extraction input.To increase phoneme identiﬁcation accuracy,reading precision,for example,employs a new type of deep speech.It makes use of the exportchapter tool,which provides a corpus,as well as the TensorFlow framework in the experimental setting.The experimentalﬁndings reveal that the suggested model can more effectively assess spoken speech accuracy and readingﬂuency than the old model,and its evalua-tion model’s score outcomes are more accurate.

关键词： Machine learning neural networks speech recognition signal processing learning process ﬂuency and accuracy

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Determining the degree of saturation of rocks as a function of time:A case study from mountainous area of Turkey

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Journal of Mountain Science 2018年第10期15卷 2307-2319页

作者： Serhat dag Department of Geological Engineering Gümüshane University 29100Turkey

The aim of this study is to scrutinize whether, in terms of saturation, the 48 hour duration suggested by ISRM(International Society for Rock Mechanics) methods and ASTM(American Society for Testing and Materials) standard in rocks is sufficient or not, and to examine how the degree of saturation of rocks may be determined as a function of time. For this purpose, samples from five different rock groups including igneous(andesite, granite, andesitic tuff) and sedimentary(limestone, sandstone) exposed in Gümü?hane city which is from mountainous area of north-eastern Turkey, have been compiled. Measurements were taken on the samples left for saturation under laboratory conditions as a result of which the degree of saturation values at the end of these time periods were determined. Similarly, at the end of 48 hours, the samples were left to dry under atmospheric conditions in the laboratory environment and their time dependent degree of saturation were also calculated at different times. The changes as a function of time in the degree of saturation were then examined mathematically using non-linear, exponential and logarithmic functions. Graphs and equations related with the acquired time-degree of saturation values and the correlation coefficient(r) values for these equalities have indicated a high accordance between time and degree of saturation for the studied rock groups. The applied methodology will be beneficial for determining the degree of saturation based on time for engineering studies that will be carried out in similar lithologies.

关键词：持续时间岩石力学土耳其浸透实验室环境案例国际社会 ASTM

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Industrial Recycling Process of Batteries for EVs

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Computers, Materials & Continua 2023年第2期74卷 4571-4586页

作者： Abdallah Abdallah Muhamed Dauwed Ayman A.Aly Bassem F.Felemban Imran Khan dagФivind Madsen School of Engineering Technology Al Hussein Technical University(HTU)Amman11831Jordan Department of Medical Instrumentation Techniques Engineering Dijlah University CollegeBaghdadIraq Department of Mechanical Engineering College of EngineeringTaif UniversityTaif21944Saudi Arabia Department of Electrical Engineering University of Engineering and TechnologyPeshawar814Pakistan University of South-Eastern Norway Bredalsveien 143511 H?nefossNorway

The growing number of decarbonization standards in the transportation sector has resulted in an increase in demand for electric cars.Renewable energy sources have the ability to bring the fossil fuel age to an end.Electrochemical storage devices,particularly lithium-ion batteries,are critical for this transition’s success.This is owing to a combination of favorable characteristics such as high energy density and minimal self-discharge.Given the environmental degradation caused by hazardous wastes and the scarcity of some resources,recycling used lithium-ion batteries has significant economic and practical importance.Many efforts have been undertaken in recent years to recover cathode materials(such as high-value metals like cobalt,nickel,and lithium).Regrettably,the regeneration of lower-value-added anode materials(mostly graphite)has received little attention.However,given the widespread use of carbon-based materials and the higher concentration of lithium in the anode than in the environment,anode recycling has gotten a lot of attention.As a result,this article provides the most recent research progress in the recovery of graphite anode materials from spent lithium ion batteries,analyzing the strengths and weaknesses of various recovery routes such as direct physical recovery,heat treatment recovery,hydrometallurgy recovery,heat treatment-hydrometallurgy recovery,extraction,and electrochemical methods from the perspectives of energy,environment,and economy;additionally,the reuse of recycled anode mats is discussed.Finally,the problems and future possibilities of anode recycling are discussed.To enable the green recycling of wasted lithium ion batteries,a low energy-consuming and ecologically friendly solution should be investigated.

关键词： Industrial recycling process lithium ion batteries electro-chemical process remanufacturing

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