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Low-dose intrapulmonary drug delivery device for studies on next-generation therapeutics in mice

Journal of Controlled Release 2023年第1期359卷 287-301页

作者： Gracioso Martins, Ana Maria Snider, Douglas B. Popowski, Kristen D. Schuchard, Karl G. Tenorio, Matias Akunuri, Sandip Wee, Junghyun Peters, Kara J. Jansson, Anton Shirwaiker, Rohan Cheng, Ke Freytes, Donald O. Cruse, Glenn P. Department of Molecular Biomedical Sciences College of Veterinary Medicine North Carolina State University RaleighNC United States Comparative Medicine and Translational Research Training Program North Carolina State University RaleighNC United States Comparative Medicine Institute North Carolina State University RaleighNC United States Joint Department of Biomedical Engineering College of Engineering North Carolina State University & University of North Carolina-Chapel Hill NC United States Edward P. Fitts Department of Industrial and Systems Engineering North Carolina State University RaleighNC United States Department of Mechanical and Aerospace Engineering North Carolina State University RaleighNC United States Analytical Instrumentation Facility Monteith Research Center North Carolina State University RaleighNC United States

Although nebulizers have been developed for delivery of small molecules in human patients, no tunable device has been purpose-built for targeted delivery of modern large molecule and temperature-sensitive therapeutics to mice. Mice are used most of all species in biomedical research and have the highest number of induced models for human-relevant diseases and transgene models. Regulatory approval of large molecule therapeutics, including antibody therapies and modified RNA highlight the need for quantifiable dose delivery in mice to model human delivery, proof-of-concept studies, efficacy, and dose-response. To this end, we developed and characterized a tunable nebulization system composed of an ultrasonic transducer equipped with a mesh nebulizer fitted with a silicone restrictor plate modification to control the nebulization rate. We have identified the elements of design that influence the most critical factors to targeted delivery to the deep lungs of BALB/c mice. By comparing an in silico model of the mouse lung with experimental data, we were able to optimize and confirm the targeted delivery of over 99% of the initial volume to the deep portions of the mouse lung. The resulting nebulizer system provides targeted lung delivery efficiency far exceeding conventional nebulizers preventing waste of expensive biologics and large molecules during proof-of-concept and pre-clinical experiments involving mice. (Word Count =207). © 2023 Elsevier B.V.

关键词： Molecules

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Long short-Term memory (LSTM) model-based reinforcement learning for nonlinear mass spring damper system control 7

Long short-Term memory (LSTM) model-based reinforcement lear...

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7th International Conference on Computer Science and Computational Intelligence, CSCI 2022

作者： Wijaya, Santo Heryadi, Yaya Arifin, Yulyani Suparta, Wayan Lukas Computer Science Department BINUS Graduate Program-Doctor of Computer Science Bina Nusantara University Jakarta11480 Indonesia Department of Electrical Engineering Faculty of Industrial Technology Institut Teknologi Nasional Yogyakarta Yogyakarta55281 Indonesia Universitas Katolik Indonesia Atma Jaya Jakarta12930 Indonesia

The Neural Networks (NN) model which is incorporated in the control system design has been studied, and the results show better performance than the mathematical model approach. However, some studies consider that only offline NN model learning and does not use the online NN model learning directly on the control system. As a result, the controller's performance decreases due to changes in the system environment from time to time. The Reinforcement Learning (RL) method has been investigated intensively, especially Model-based RL (Mb-RL) to predict system dynamics. It has been investigated and performs well in making the system more robust to environmental changes by enabling online learning. This paper proposes online learning of local dynamics using the Mb-RL method by utilizing Long Short-Term Memory (LSTM) model. We consider Model Predictive Control (MPC) scheme as an agent of the Mb-RL method to control the regulatory trajectory objectives with a random shooting policy to search for the minimum objective function. A nonlinear Mass Spring Damper (NMSD) system with parameter-varying linear inertia is used to demonstrate the effectiveness of the proposed method. The simulation results show that the system can effectively control high-oscillating nonlinear systems with good performance. © 2022 Elsevier B.V.. All rights reserved.

关键词： Model predictive control

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Numerical investigation on the thermal-nanofluidic flow induced transverse and longitudinal vibrations of single and multi-walled branched nanotubes resting on nonlinear elastic foundations in a magnetic environment

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Partial Differential Equations in Applied Mathematics 2024年 9卷

作者： Yinusa, A.A. Sobamowo, M.G. Adelaja, A.O. Ojolo, S.J. Waheed, M.A. Usman, M.A. Siqueira, Antonio Marcos de Oliveira Campos, Júlio César Costa Ola-Gbadamosi, Ridwan Department of Mechanical Engineering University of Lagos Nigeria Department of Mathematics University of Lagos Nigeria Department of Mechanical Engineering Federal University of Agriculture Abeokuta Nigeria Department of Chemical Engineering University of Lagos Nigeria Chemical Engineering Graduate Program Department of Chemistry Federal University of Viçosa Brazil Universidade Federal de Viçosa Brazil Department of Mechanical Engineering Lagos State University Nigeria

Carbon nanotubes (CNTs) have attracted great attention due to their tremendous mechanical, thermal, structural and electrical properties leading to many promising applications. The unique and interesting properties of CNTs, such as their mechanical and electrical features, have fascinated industries and researchers to implement CNTs for production of different electromechanical devices. However, it is established that the phenomenon of buckling often occurs when CNTs are subjected to compressive loads and their frequencies under vibration are in order of Tera-Hz and Giga-Hz. Moreover, the profound dynamic behaviours of nanotube under the influences of slip when conveying fluid and magnetic field require a serious and meticulous study. Therefore, this study focuses on the vibration analysis of nanofluid-conveying embedded multi-walled branched nanotubes resting on Winkler-Pasternak foundation in a thermal-magnetic environment. Using Euler-Bernoulli theory, Hamilton's principle and nonlocal elasticity theory, fully coupled equations of motion governing the transverse and longitudinal vibrations of the nanotube are developed. Also, the equation of the deformation of the nanotubes as well as the pressure variation in the tubes are developed. Additionally, Navier-Stoke's equation and energy equation for the fluid and nanotube are coupled with the vibration models. The dynamics of the multi-walled carbon nanotubes when coupled with Navier-Stokes and energy equations require meticulous study as it is different from the usual assumption of plug flow. Therefore, in this present work, the developed coupled systems of nonlinear partial differential equations are solved using multi-dimensional numerical PDEs solvers coupled with PDE-tools in MATLAB. With the aids of the solutions, parametric studies were performed. The results indicate that increasing the downstream angle decreases the stability of the system. Also, the results obtained from the dynamic behaviour of the system

关键词： Branched nanotubes Navier-Stokes equation Numerical methods Transverse and longitudinal vibration

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DROPLET DIGITAL IMMUNO-PCR FOR PROFILING PROTEIN-SPECIFIC EXTRACELLULAR VESICLES 26

DROPLET DIGITAL IMMUNO-PCR FOR PROFILING PROTEIN-SPECIFIC EX...

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26th International Conference on Miniaturized systems for Chemistry and Life Sciences, MicroTAS 2022

作者： Lix, Chxnchen Lin, Hxixian Yao, Shxhxai Department of Laboratory Medicine Nanfang Hospital Southern Medical University Guangzhou China Department of Mechanical and Aerospace Engineering The Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong Bioengineering Graduate Program Department of Chemical and Biological Engineering The Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong

ISBN: (纸本)9781733419048

We construct a versatile droplet digital immuno-PCR ddiPCR assay which integrates immuno-PCR and droplet digital PCR ddPCR for quantifying protein-specific extracellular vesicle EV subpopulations at the single-vesicle level. We applied the ddiPCR assays for profiling the EV proteins of CD/CD63/CD81, HER2, EpCAM in a breast cancer cohort. The results demonstrated that the counting of multi-subpopulation EVs could significantly distinguish patients with breast tumor at different stages or hepatocellular carcinoma from healthy controls. This study provides a promising strategy to count multi-subpopulation EVs at the single-vesicle level for cancer diagnosis. © 2022 MicroTAS 2022 - 26th International Conference on Miniaturized systems for Chemistry and Life Sciences. All rights reserved.

关键词： Drops

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Portfolio Selection Using Mean Variance Theory Based on the 30-year Historical Returns of Selected Subsectors of the Philippine industrial Sector

Portfolio Selection Using Mean Variance Theory Based on the ...

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IEEE International Conference on industrial engineering and engineering Management

作者： A. D. Yamanaka M.N. Young T.N. Chuahay Y. Pratseyo S. Persada R. Nadlifatin School of Graduate Studies Mapua University Manila Philippines School of Industrial Engineering and Engineering Management Mapua University Manila Philippines Department of Finance Chung Yuan University Taoyuan City Taiwan Department of Industrial Engineering and Management Yuan Ze University Taoyuan City Taiwan International Bachelor Program in Engineering Yuan Ze University Taoyuan City Taiwan Entrepreneurship Business Creation Business School Binus University West Jakarta Indonesia Department of Information Systems Institut Teknologi Sepuluh Nopember Surabaya Indonesia

ISBN: (数字)9798350386097

ISBN: (纸本)9798350386103

Portfolio selection is an important part of investment management that aims to select the right combination of assets to achieve an optimal risk-return ratio. This study integrates the Mean-Variance Theory utilizing the 30-year historical returns of the Philippine Stock Exchange. Three subsectors of the industrial Sector were used as the investment pool. The back-test results showed that the MeanVariance portfolios of selected subsectors can outperform the industrial sector and not the market. Stakeholders must be cautious when investing in these three subsectors, considering the values obtained from the simulations. There are recommended portfolio selections wherein companies have a specific allocation that investors and financial managers can use whenever they decide to invest in these subsectors. Overall, this study offers a framework for investors to use as a guide in diversifying their stakes in the Philippine Stock Exchange.

关键词： Companies Benchmark testing industrial engineering Market research Stakeholders Resource management Stock markets Portfolios Optimization Investment

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Mean Variance Portfolio Selection Utilizing Services Subsector’s (Media, Telecommunications, and Information Technology) 30-Year Philippine Stock Exchange Trading Data

Mean Variance Portfolio Selection Utilizing Services Subsect...

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IEEE International Conference on industrial engineering and engineering Management

作者： E.D. Salazar M.N. Young T.N. Chuahay Y. Pratseyo S. Persada R. Nadilfatin Myra F. Contreras School of Industrial Engineering and Engineering Management Mapúa University Intramuros School of Graduate Studies Mapúa University Intramuros Department of Finance Chung Yuan Christian University Taoyuan City Taiwan Department of Industrial Engineering and Management Yuan Ze University Taoyuan City Taiwan International Bachelor Program in Engineering Yuan Ze University Taoyuan City Taiwan Entrepreneurship Business Creation Business School Binus University West Jakarta Indonesia Department of Information Systems Institur Teknologi Sepuluh Nopember Surabaya Indonesia

ISBN: (数字)9798350386097

ISBN: (纸本)9798350386103

The Philippine Stock Exchange (PSE), established in 1927, has significantly evolved, especially since the 1980s with major reforms and technological advancements. This paper analyzes the performance of portfolios in the Media, Telecommunications, and Information Technology sectors listed on the PSE over a 30year span. Using mean-variance analysis, it evaluates portfolio optimization by balancing risk and return. Drawing on data from 1993 to 2022, the study examines portfolios across various risk-return frontiers (RRFs) and compares the service sector’s performance. The results highlight varying portfolio metrics across RRFs, with some showing outperformance and higher RRFs leading to diminishing returns. The study also identifies key companies with significant stock allocations, providing strategic insights for portfolio construction. These findings offer investors guidance on optimizing portfolio strategies within the PSE for better decision-making and investment outcomes.

关键词： Measurement Decision making Companies Media Telecommunications Resource management Stock markets Portfolios Optimization Investment

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engineering FRET biosensor for H3K9 acetylation imaging in single living cells

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Med-X 2024年第1期2卷 1-16页

作者： Li, Shitian Sun, Chang Harrison, Reed E. S. Cheng, Leonardo Gao, Li Liu, Longwei Wang, Yingxiao Peng, Qin Department of Bioengineering Institute of Engineering in Medicine University of California San Diego USA Biological Sciences Graduate Program University of California San Diego USA Institute of Systems and Physical Biology Shenzhen Bay Laboratory Shenzhen China School of Chemical Engineering and Technology North University of China Taiyuan China Alfred E. Mann Department of Biomedical Engineering University of Southern California Los Angeles USA

Histone acetylation is an important epigenetic modification that governs gene expression, chromatin changes in stress response, and cell fate transition. FRET biosensors have been developed for various epigenetic events to enable spatiotemporal tracking of sub-cellular signaling events. Previously reported histone H3 acetylation biosensor recognizing two acetyl residues lacked specificity. In this study, using a single bromodomain of the BRD4, we have developed a genetically encoded H3K9ac biosensor. We systematically investigated different combinations of the BET family protein as binding domains and performed site-saturated mutagenesis to optimize the biosensor, achieving a dynamic FRET change up to 30% under TSA treatment. With the application of the optimized H3K9ac biosensor, we revealed different basal active chromatin architectures in invasive tumor cells compared to benign tumor cells. Furthermore, we found that H3K9ac level increased dramatically when cancer cells passed through microchannels, which models the physical constraints and mechanical microenvironmental conditions that cancer cells encounter when passing through narrow spaces within the body. This result highlights the chromatin plasticity in response to external mechanical stresses. In summary, our H3K9ac biosensor provides a versatile tool for mechanistic investigation of cell fate transition in cancer and mechanotransduction.

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Development of a VS ultrasound diagnostic system with image evaluation functions 11

Development of a VS ultrasound diagnostic system with image ...

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11th IEEE Global Conference on Consumer Electronics, GCCE 2022

作者： Zhou, Jiayi Koizumi, Norihiro Nishiyama, Yu Tsumura, Ryosuke Tsukihara, Hiroyuki Matsumoto, Naoki The University of Electro-Communications Department of Mechanical and Intelligent Systems Tokyo Japan The University of Electro-Communications Department of Computer and Network Engineering Tokyo Japan Health and Medical Research Institute National Institute of Advanced Industrial Science and Technology Tokyo Japan The University of Tokyo Graduate School of Engineering Tokyo Japan Nihon University Department of Gastroenterology and Hepatology Tokyo Japan

ISBN: (纸本)9781665492324

An inevitable feature of ultrasound-based diagnoses is that the quality of the ultrasound images produced depends directly on the skill of the physician operating the probe. This is because physicians have to constantly adjust the probe position to obtain a cross-section of the target organ, which is constantly shifting due to patient respiratory motions. Therefore, we developed an ultrasound diagnostic robot that works in cooperation with a visual servo system based on deep learning that will help alleviate the burdens imposed on physicians. Two different image processing methods (BiSeNet V2) were used to detect the target kidney location, as well as to evaluate the appropriateness of the obtained ultrasound images (ResNet 50) in developed system. © 2022 IEEE.

关键词： Visual servoing

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Running Cooperative Tasks in a Multi-Robot System with Cyber-Physical Features

Running Cooperative Tasks in a Multi-Robot System with Cyber...

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IEEE Latin American Robotics Symposium, LARS

作者： Héber Renato Fadel de Morais João Paulo Lima Silva de Almeida Lúcia Valéria Ramos de Arruda Graduate Program in Electrical Engineering and Industrial Informatics (CPGEI) Federal University of Technology - Paraná Curitiba Brazil Federal Institute of Paraná Jacarezinho Brazil

ISBN: (数字)9781665462808

ISBN: (纸本)9781665462815

This paper develops a system based on cyber-physical concepts to support robots in tasks that require cooperative work and information sharing. The work's inspiration is the need of the 4.0 industry for cobots visiting different workstations to assist human workers, for tools and raw material transportation, and other tasks. As in any industrial environment, unexpected events may occur, and the cobots must face them, reducing their effects on the production line. In this work, multiple robots (MR) managed by a system with cyber-physical (CP) features cooperate in an experimental dynamic environment to safely accomplish several tasks. For this, the robots must visit targets (analogous to workstations) in an orderly way, while one support robot must deal with oil stains on the environment's floor detected along the robots' navigation (unexpected event). The proposed CP-MR system is evaluated through experimental results allowing a performance analysis.

关键词： Visualization Service robots Federated learning Information sharing Robot sensing systems Workstations Multi-robot systems

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Time Stacking Decision Tree for Oscillatory Failure Case Detection in a Flight Control System

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IFAC-PapersOnLine 2023年第2期56卷 354-359页

作者： Giberto Reynoso-Meza Victor Henrique Alves Ribeiro Marcelo Feliciano Filho Bianca Zavadisk de Abreu Industrial and Systems Engineering Graduate Program (PPGEPS) Pontifícia Universidade Católica do Paraná (PUCPR) Rua Imaculada Conceição 1155 Zip code 80215-901 Curitiba PR Brazil Silex Curitiba PR Brazil Colégio Estadual da Polícia Militar Curitiba PR Brazil

Flight control systems are an essential part of aircraft, consisting of all elements between the pilot and the movable parts, such as actuators, controllers, and sensors, to control the aircraft's attitude, trajectory and speed. In this context, oscillatory failure cases are problems that can occur in any part of the flight control system, causing undesired oscillatory behavior that affects the aircraft's structural load. On the one hand, correctly detecting such failures enables weight saving to improve aircraft performance in different aspects; on the other hand, such detection enables reconfiguring the control law to keep the aircraft in its path. This work describes a data-driven oscillatory fault detection model and the control law reconfiguration for a fight control system for the Aerospace industrial Benchmark. Preliminary results indicate that the developed system can accurately detect faults in several scenarios and properly reconfigure the control loop.

关键词： Aerospace Guidance, navigation and control of vehicles Fault detection and diagnosis Machine learning

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