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ATP-binding cassette transporters at the zebrafish blood-brain barrier and the potential utility of the zebrafish as an in vivo model

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Cancer Drug Resistance 2021年第3期4卷 620-633页

作者： Jordan m.Hotz Joanna R.Thomas Emily N.Katz Robert W.Robey Sachi Horibata michael m.gottesman Laboratory of Cell Biology Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Zebrafish Core Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentBethesdaMD 20892USA

The brain is protected from toxins by a tightly regulated network of specialized cells,including endothelial cells,pericytes,astrocyes,and neurons,known collectively as the blood-brain barrier(BBB).This selectively permeable barrier permits only the most crucial molecules essential for brain function to enter and employs a number of different mechanisms to prevent the entry of potentially harmful toxins and *** addition to a physical barrier comprised of endothelial cells that form tight junctions to restrict paracellular transport,there is an active protective mechanism made up of energy-dependent transporters that efflux compounds back into the *** of these ATP-binding cassette(ABC)transporters are highly expressed at the BBB:P-glycoprotein(P-gp,encoded by the ABCB1 gene)and ABCG2(encoded by the ABCG2 gene).Although a number of in vitro and in vivo systems have been developed to examine the role that ABC transporters play in keeping compounds out of the brain,all have inherent advantages and ***(Danio rerio)have become a model of interest for studies of the BBB due to the similarities between the zebrafish and mammalian BBB *** this review,we discuss what is known about ABC transporters in zebrafish and what information is still needed before the zebrafish can be recommended as a model to elucidate the role of ABC transporters at the BBB.

关键词： ABC transporters blood-brain barrier ABCG2 P-glycoprotein zebrafish

The multidrug resistance transporter P-glycoprotein confers resistance to ferroptosis inducers

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Cancer Drug Resistance 2023年第3期6卷 468-480页

作者： William J.E.Frye Lyn m.Huff Josém.González Dalmasy Paula Salazar Rachel m.Carter Ryan T.Gensler Dominic Esposito Robert W.Robey Suresh V.Ambudkar michael m.gottesman Laboratory of Cell Biology Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Protein Expression Laboratory Frederick National Laboratory for Cancer ResearchLeidos Biomedical ResearchIncFrederickMD 21704USA

Aim:Ferroptosis is a non-apoptotic form of cell death caused by lethal lipid *** small molecule ferroptosis inducers(FINs)have been reported,yet little information is available regarding their interaction with the ATP-binding cassette(ABC)transporters P-glycoprotein(P-gp,ABCB1)and *** thus sought to characterize the interactions of FINs with P-gp and ABCG2,which may provide information regarding oral bioavailability and brain penetration and predict drug-drug ***:Cytotoxicity assays with ferroptosis-sensitive A673 cells transfected to express P-gp or ABCG2 were used to determine the ability of the transporters to confer resistance to FINs;confirmatory studies were performed in OVCAR8 and NCI/ADR-RES *** ability of FINs to inhibit P-gp or ABCG2 was determined using the fluorescent substrates rhodamine 123 or purpuin-18,***:P-gp overexpression conferred resistance to FIN56 and the erastin derivatives imidazole ketone erastin and piperazine erastin.P-gp-mediated resistance to imidazole ketone erastin and piperazine erastin was also reversed in UO-31 renal cancer cells by CRISPR-mediated knockout of *** FINs mL-162,GPX inhibitor 26a,and PACmA31 at 10µm were able to increase intracellular rhodamine 123 fluorescence over 10-fold in P-gp-expressing mDR-19 *** inhibitor 26a was able to increase intracellular purpurin-18 fluorescence over 4-fold in ABCG2-expressing R-5 ***:Expression of P-gp may reduce the efficacy of these FINs in cancers that express the transporter and may prevent access to sanctuary sites such as the *** ability of some FINs to inhibit P-gp and ABCG2 suggests potential drug-drug interactions.

关键词： Ferroptosis drug resistance P-glycoprotein ABCG2

Improved Quantile Convolutional and Recurrent Neural Networks for Electric Vehicle Battery Temperature Prediction

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Big Data mining and Analytics 2024年第2期7卷 512-530页

作者： Andreas m.Billert Runyao Yu Stefan Erschen michael Frey Frank Gauterin Karlsruhe Institute of Technology(KIT) Institute of Vehicle System TechnologyKarlsruhe 76131Germanyand also with Bayerische Motoren Werke(BMW)AGMunich 80788Germany Technical University of munich(TUm) Munich 80333Germany BmW AG Munich 80788Germany KIT Institute of Vehicle System TechnologyKarlsruhe 76131Germany

The battery thermal management of electric vehicles can be improved using neural networks predicting quantile sequences of the battery *** work extends a method for the development of Quantile Convolutional and Quantile Recurrent Neural Networks(namely Q*NN).Fleet data of 225629 drives are clustered and balanced,simulation data from 971 simulations are augmented before they are combined for training and *** Q*NN hyperparameters are optimized using an efficient Bayesian optimization,before the Q*NN models are compared with regression and quantile regression models for four *** analysis of point-forecast and quantile-related metrics shows the superior performance of the novel Q*NN *** median predictions of the best performing model achieve an average RmSE of 0.66°C and R^(2) of *** predicted 0.99 quantile covers 98.87%of the true values in the test *** conclusion,this work proposes an extended development and comparison of Q*NN models for accurate battery temperature prediction.

关键词： deep learning battery temperature convolutional and recurrent neural network quantile forecasting

A review of control strategies used for morphing aircraft applications

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Chinese Journal of Aeronautics 2024年第4期37卷 436-463页

作者： muhammed S.PARANCHEERIVILAKKATHIL Jafar S.PILAKKADAN Rafic m.AJAJ mohammadreza AmOOZGAR Davood ASADI Yahya ZWEIRI michael I.FRISWELL Department of Aerospace Engineering Khalifa University of Science and TechnologyAbu DhabiUnited Arab Emirates Department of Aerospace Engineering Advanced Research and Innovation Center(ARIC)Khalifa University of Science and TechnologyAbu DhabiUnited Arab Emirates Department of mechanical Materials&Manufacturing EngineeringUniversity of NottinghamNottingham NG72RDUK Department of Aerospace Engineering Adana Alparslan Turkes Science and Technology UniversityTurkey College of Engineering Swansea UniversitySwansea SA18ENUK

This paper reviews the various control algorithms and strategies used for fixed-wing morphing aircraft applications. It is evident from the literature that the development of control algorithms for morphing aircraft technologies focused on three main areas. The first area is related to precise control of the shape of morphing concepts for various flight conditions. The second area is mainly related to the flight dynamics, stability, and control aspects of morphing aircraft. The third area deals mainly with aeroelastic control using morphing concepts either for load alleviation purposes and/or to control the instability boundaries. The design of controllers for morphing aircraft/wings is very challenging due to the large changes that can occur in the structural, aerodynamic, and inertial characteristics. In addition, the type of actuation system and actuation rate/speed can have a significant effect on the design of such controllers. The aerospace community is in strong need of such a critical review especially as morphing aircraft technologies move from fundamental research at a low Technology Readiness Level(TRL) to real-life applications. This critical review aims to identify research gaps and propose future directions. In this paper, research activities/papers are categorized according to the control strategy used. This ranges from simple Proportional Integral Derivative(PID) controllers at one end to complex robust adaptive controllers and deep learning algorithms at the other end. This includes analytical, computational, and experimental studies. In addition, the various dynamic models used and their fidelities are highlighted and discussed.

关键词： Control strategies morphing aircraft Shape morphing Flight dynamics Aeroelasticity