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

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 *** 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 *** soluble intermediate aggregated species of Aβ,termed oligomers and protofbrils,are believed to be key pathogenic forms,responsible for synaptic and neuronal degeneration in ***,antibodies that can strongly and selectively bind to these soluble intermediate aggregates are of great diagnostic and therapeutic ***:We designed and recombinantly produced a hexavalent antibody based on mAb158,an Aβprotofbrilselective *** humanized version of mAb158,lecanemab(BAN2401),is currently in phase 3 clinical trials for the treatment of *** new designs involved recombinantly fusing single-chain fragment variables to the N-terminal ends of mAb158 ***-time interaction analysis with LigandTracer and surface plasmon resonance were used to evaluate the kinetic binding properties of the generated antibodies to Aβ*** ELISA setups were applied to demonstrate the binding strength of the hexavalent antibody to Aβaggregates of diferent ***,the ability of the antibodies to protect cells from Aβ-induced efects was evaluated by MTT ***: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 ***,ELISA experiments demonstrated that the hexavalent design also had strong binding to small oligomers,while retaining weak and intermediate binding to monomers and insoluble *** hexavalent antibody also reduced cell death induced by a mixture of soluble Aβ***:We provide a new antibody design with i

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

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Minimum-Time and Minimum-Jerk Gait Planning in Joint Space for Assistive Lower Limb Exoskeleton

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Journal of Bionic Engineering 2023年第5期20卷 2164-2178页

作者： Habib Mohamad Sadjaad Ozgoli fadi Motawej Department of Electrical and Computer Engineering Tarbiat Modares UniversityTehran14117-13116Iran Department of Mechatronics Engineering Tishreen UniversityLattakia0096341Syria

Assistive lower limb exoskeleton robot has been developed to help paraplegic patients walk again.A gait planning method of this robot must be able to plan a gait based on gait parameters,which can be changed during the stride according to human intention or walking *** gait is usually planned in cartesian space,which has shortcomings such as singularities that may occur in inverse kinematics equations,and the angular velocity of the joints cannot be entered into the ***,it is vital to have a gait planning method in the joint *** this paper,a minimum-time and minimum-jerk planner is proposed for the robot *** do so,a third-order system is defined,and the cost function is introduced to minimize the jerk of the joints throughout the *** minimum time required is calculated to keep the angular velocity trajectory within the range specified by the motor’s maximum *** conditions of the joints are determined to secure backward balance and fulfill gait ***,the proposed gait planning method is tested by its implementation on the Exoped®exoskeleton.

关键词： Bionic robot Gait planning Optimization Complete paraplegic Lower limb exoskeleton

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Maximizing aged photovoltaic array power:a computer modelling study

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Clean Energy 2024年第1期8卷 171-187页

作者： fadi N.Sibai Electrical&Computer Engineering Department Gulf University for Science and TechnologyMishrefKuwait

Photovoltaic(PV)modules age with time for various reasons such as corroded joints and terminals and glass coating defects,and their ageing degrades the PV array *** the help of the PV array numerical model,this paper explores the effects of PV module ageing on the PV array power,and the power gains and costs of rearranging and recabling aged PV modules in a PV *** numerical PV array model is first revised to account for module ageing,rearrangement and recabling,with the relevant equations presented *** updated numerical model is then used to obtain the array powers for seven different PV *** power results are then analysed in view of the attributes of the seven PV array examples.A guiding method to recommend recabling after rearranging aged modules is then proposed,leading to further significant power gains,while eliminating intra-row *** certain conditions are met,it was shown that recabling PV modules after rearranging them may lead to further significant power gains,reaching 57%and 98%in two considered PV array *** gains are possible in other arrays.A cost-benefit analysis weighing annual power gains versus estimated recabling costs is also given for the seven considered PV array examples to guide recabling decisions based on technical and economic *** the considered examples,recabling costs can be recovered in<4 *** with the powers of the aged arrays,power gains due to our proposed rearranging and recabling the PV arrays ranged between 73%and 131%in the considered examples—well over the gains reported in the ***,the cost of our static module rearrangement and recabling method outshines the costs of dynamic reconfiguration methods recently published in the literature.

关键词： solar energy optimizing array power photovoltaic array modelling photovoltaic modules ageing photovoltaic module rearrangement module recabling and reconfiguration PV array mismatch

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Application of Machine Learning for Online Reputation Systems

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International Journal of Automation and computing 2021年第3期18卷 492-502页

作者： Ahmad Alqwadri Mohammad Azzeh fadi Almasalha Department of Computer Science Applied Science Private UniversityAmman 11931Jordan Department of Software Engineering Applied Science Private UniversityAmman 11931Jordan

Users on the Internet usually require venues to provide better purchasing *** can be provided by a reputation system that processes ratings to provide *** rating aggregation process is a main part of reputation systems to produce global opinions about the product *** methods that are frequently used do not consider consumer profiles in their calculations and cannot discover unfair ratings and trends emerging in new *** sophisticated rating aggregation methods that use a weighted average technique focus on one or a few aspects of consumers′profile *** paper proposes a new reputation system using machine learning to predict reliability of consumers from their *** particular,we construct a new consumer profile dataset by extracting a set of factors that have a great impact on consumer reliability,which serve as an input to machine learning *** predicted weight is then integrated with a weighted average method to compute product reputation *** proposed model has been evaluated over three Movie Lens benchmarking datasets,using 10-folds cross ***,the performance of the proposed model has been compared to previous published rating aggregation *** obtained results were promising which suggest that the proposed approach could be a potential solution for reputation *** results of the comparison demonstrated the accuracy of our ***,the proposed approach can be integrated with online recommendation systems to provide better purchasing recommendations and facilitate user experience on online shopping markets.

关键词： Reputation system rating aggregation machine learning consumer reliability user trust

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IoMT-Cloud Task Scheduling Using AI

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Computer Modeling in Engineering & Sciences 2023年第5期135卷 1345-1369页

作者： Adedoyin A.Hussain fadi Al-Turjman Computer Engineering Department and Research Centre for AI and IoT Near East UniversityNicosiaTurkey Computer Engineering Department CyprusWest UniversityGazimagusaTurkey Artificial Intelligence Engineering Department and AI and Robotics Institutes Near East UniversityNicosiaTurkey Research Centre for AI and IoT Faculty of EngineeringUniversity of KyreniaKyreniaTurkey

The internet of medical things(IoMT)empowers patients to get adaptable,and virtualized gear over the *** scheduling is the most fundamental problem in the IoMT-cloud since cloud execution commonly relies on ***,a proposition is being made for a distinct scheduling technique to suitably meet these *** manage the scheduling issue,an artificial intelligence(AI)method known as a hybrid genetic algorithm(HGA)is *** proposed AI method will be justified by contrasting it with other traditional optimization and AI scheduling *** CloudSim is utilized to quantify its effect on various parameters like time,resource utilization,cost,and *** proposed AI technique enhanced the viability of task scheduling with a better execution rate of 32.47ms and a reduced time of ***,the experimented outcomes show that the HGA reduces cost as well as time profoundly.

关键词： Artificial intelligence IoMT hybrid genetic algorithm cloud

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A frequency and velocity-dependent impedance method for prediction of rail/foundation dynamics

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Earthquake Engineering and Engineering Vibration 2021年第1期20卷 101-111页

作者： Reda Mezeh Marwan Sadek fadi Hage Chehade Isam Shahrour Laboratory of Civil Engineering and GeoEnvironment University of LilleSciences and TechnologiesPolytech’LilleVilleneuve d’AscqHauts-de-France 59655France Doctoral School of Science and Technology Lebanese UniversityBeirut 0000Lebanon

This paper presents an efficient numerical tool for the prediction of railway dynamic response.A behavior calibration of the infinite Euler-Bernoulli beam resting on continuous viscoelastic foundation is *** laws of the discrete elements are determined for a rectilinear ballasted track.A three-dimensional model coupled with an adaptive meshing scheme is employed to calibrate the beam model impedances by finding the similarity between the output signals using the genetic *** model shows an important performance with significant reduction in computational *** study emphasizes the major impact of the excitation characteristics on the parameters of the discrete models.

关键词： moving loads rail vibrations rail/foundation interaction dynamic impedances genetic algorithm

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Toward a New Algorithm for Nonlinear Fractional Differential Equations

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Advances in Applied Mathematics and Mechanics 2013年第2期5卷 222-234页

作者： fadi Awawdeh S.Abbasbandy Department of Mathematics Hashemite UniversityJordan Department of Mathematics Imam Khomeini International UniversityGhazvin 34149-16818Iran

This paper is concerned with the development of an efficient algorithm for the analytic solutions of nonlinear fractional differential *** proposed algorithm Laplace homotopy analysis method(LHAM)is a combined form of the Laplace transform method with the homotopy analysis *** biggest advantage the LHAM has over the existing standard analytical techniques is that it overcomes the difficulty arising in calculating complicated ***,the solution procedure is easier,more effective and *** examples are examined to demonstrate the accuracy and efficiency of the proposed algorithm.

关键词： Homotopy analysis method Laplace transform fractional differential equations

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Chimeric Antigen Receptors and Regulatory T Cells:The Potential for HLA-Specific Immunosuppression in Transplantation

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Engineering 2022年第3期8卷 30-43页

作者： Sabrina Wright Conor Hennessy Joanna Hester fadi Issa Nuffield Department of Surgical Sciences University of OxfordOxford OX39DUUK

Chimeric antigen receptors(CARs)are a breakthrough in genetic engineering that have revolutio nized the field of adoptive cellular therapy(ACT).Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic CAR *** advantage of cells with programmed specificity has been demonstrated clinically in the field of oncology,and it is clear that such cells have greater accuracy,potency,and reduced off-target therapeutic effects compared with their unmodified *** contrast to conventional T cells(Tconvs),regulatory T cells(Tregs)play a major role in suppressing immune activation and regulating the host immune *** expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases,graft-versus-host disease(GVHD),and organ transplant rejectio *** the latter,they hold immense potential as mediators of immune tolerance for recipients of ***,current research into CAR-Treg engineering is extremely limited,and there is uncertainty regarding optimal design for therapeutic *** review examines the rationale behind the development of CAR-Tregs,their significance for human transplantation,potential designs,safety considerations,and comparisons of CAR-Tregs in transplantation models to date.

关键词： Chimeric antigen receptors T cell Treg Alloimmunity Bioengineering Transplant Autoimmunity

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Virtual Element Formulation for Finite Strain Elastodynamics Dedicated to Professor Karl Stark Pister for his 95th birthday

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Computer Modeling in Engineering & Sciences 2021年第12期129卷 1151-1180页

作者： Mertcan Cihan Blaz Hudobivnik fadi Aldakheel Peter Wriggers Institute for Continuum Mechanics Leibniz Universitat HannoverHannover30419Germany

The virtual element method(VEM)can be seen as an extension of the classical finite element method(FEM)based on Galerkin *** allows meshes with highly irregular shaped elements,including concave *** far the virtual element method has been applied to various engineering problems such as elasto-plasticity,multiphysics,damage and fracture *** work focuses on the extension of the virtual element method to efficient modeling of nonlinear elasto-dynamics undergoing large *** this framework,we employ low-order ansatz functions in two and three dimensions for elements that can have arbitrary polygonal *** formulations considered in this contribution are based on minimization of potential function for both the static and the dynamic *** the construction of a virtual element is based on a projection part and a stabilization *** the stiffness matrix needs a suitable stabilization,the mass matrix can be calculated using only the projection *** the implicit time integration scheme,Newmark-Method is *** show the performance of the method,various two-and three-dimensional numerical examples in are presented.

关键词： Virtual element method three-dimensional dynamics finite strains

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Microstructure and texture evolution of AZ31 Mg alloy after uniaxial compression and annealing

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Journal of Magnesium and Alloys 2019年第1期7卷 124-133页

作者： fadi Abouhilou Abdelkader Hanna Hiba Azzeddine Djamel Bradai Faculty of Physics USTHBBP32 El-AliaDar El-BeidaAlgiersAlgeria Physics and Chemistry of Materials Laboratory Department of PhysicsUniversity Mohamed BoudiafM’Sila 28000Algeria Department of Physics University Mohamed BoudiafM’sila 28000Algeria

The effect of initial texture on the microstructure and texture evolution of as extruded AZ31 alloy after hot uniaxial compression at 430°C and subsequent annealing at 450°C for 72h has been investigated using electron backscatter *** were machined from the extruded block in such orientations that the compression axis,CD,was parallel(CD0ED)or perpendicular(CD90ED)to the initial extrusion direction,ED,*** show that the deformation microstructure for both samples was characterized by equiaxed grains that resulted from dynamic *** at 450°C for 72 h led to the increase of grains size to 28 and 25μm for CD0ED and CD90ED samples,respectively.A random deformation texture was developed in CD0ED sample while the deformation of CD90ED developed typical(0002)basal *** deformation textures of both samples were retained after subsequent annealing at 450°C for 72 *** flow behavior was affected by the initial *** CD0ED sample showed the highest work *** evolutions were explained in term of the activation and suppression of basal,non-basal slip and mechanical twinning.©2018 Published by Elsevier *** behalf of Chongqing *** is an open access article under the CC BY-NC-ND license.

关键词： Magnesium alloys Schmid factor Texture Deformation Annealing Microstructure

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