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ExoHCR: a sensitive assay to profile PD-L1 level on tumor exosomes for immunotherapeutic prognosis

Biophysics Reports 2020年第6期6卷 290-298页

作者： Lujun Hu Wenjie Chen Shurong Zhou Guizhi Zhu College of Bioengineering Sichuan University of Science and Engineering Institute for Structural Biology Drug Discovery and DevelopmentVirginia Commonwealth University The Developmental Therapeutics Program Massey Cancer CenterVirginia Commonwealth University Center for Pharmaceutical Engineering and Sciences Department of PharmaceuticsSchool of PharmacyVirginia Commonwealth University

Cancer immunotherapy has made recent breakthrough, including immune checkpoint blockade(ICB)that inhibits immunosuppressive checkpoints such as programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1). However, most cancer patients do not durably respond to ICB. To predict ICB responses for patient stratification, conventional immunostaining has been used to analyze the PD-L1 expression level on biopsied tumor tissues but has limitations of invasiveness and tumor heterogeneity. Recently, PD-L1 levels on tumor cell exosomes showed the potential to predict ICB response. Here, we developed a non-invasive, sensitive, and fast assay, termed as exosome-hybridization chain reaction(ExoHCR), to analyze tumor cell exosomal PD-L1 levels. First, using a CD63-conjugated magnetic beads, we isolated exosomes from B16 F10 melanoma and CT26 colorectal cancer cells that were immunostimulated to generate PD-L1-positive exosomes. Exosomes were then incubated with a conjugate of PD-L1 antibody with an HCR trigger DNA(T), in which one a PD-L1-T conjugate carried multiple copies of T. Next, a pair of metastable fluorophore-labeled hairpin DNA(H1 and H2) were added, allowing T on a PD-L1-T to initiate HCR in situ on bead-conjugated exosome surfaces. By flow cytometric analysis of the resulting beads, relative to a PD-L1-fluorophore conjugates, ExoHCR amplified the fluorescence signal intensities for exosome detection by 3–7 times in B16 F10 cells and CT26 ***, we validated the biostability of ExoHCR in culture medium supplemented with 50% *** results suggest the potential of ExoHCR for non-invasive, sensitive, and fast PD-L1 exosomal profiling in patient stratification of cancer immunotherapy.

关键词： Exosome Hybridization chain reaction Immune checkpoint PD-L1 analysis Immunotherapy

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Tracking fast neural adaptation by globally adaptive point process estimation for brain-machine interface

arXiv

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arXiv 2021年

作者： Chen, Shuhang Zhang, Xiang Shen, Xiang Huang, Yifan Wang, Yiwen The Program of Bioengineering The Hong Kong University of Science and Technology Kowloon Hong Kong The Department of Electronic and Computer Engineering The Hong Kong University of Science and Technology Kowloon Hong Kong The Department of Chemical and Biological Engineering The Hong Kong University of Science and Technology

Brain-machine interfaces (BMIs) help the disabled restore body functions by translating neural activity into digital commands to control external devices. Neural adaptation, where the brain signals change in response to external stimuli or movements, plays an important role in BMIs. When subjects purely use neural activity to brain-control a prosthesis, some neurons will actively explore a new tuning property to accomplish the movement task. The prediction of this neural tuning property can help subjects adapt more efficiently to brain control and maintain good decoding performance. Existing prediction methods track the slow change of the tuning property in the manual control, which is not suitable for the fast neural adaptation in brain control. In order to identify the active neurons in brain control and track their tuning property changes, we propose a globally adaptive point process method (GaPP) to estimate the neural modulation state from spike trains, decompose the states into the hyper preferred direction and reconstruct the kinematics in a dual-model framework. We implement the method on real data from rats performing a two-lever discrimination task under manual control and brain control. The results show our method successfully predicts the neural modulation state and identifies the neurons that become active in brain control. Compared to existing methods, ours tracks the fast changes of the hyper preferred direction from manual control to brain control more accurately and efficiently and reconstructs the kinematics better and faster. Copyright © 2021, The Authors. All rights reserved.

关键词： Neurons

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Bok's equi-volume principle: Translation, historical context, and a modern perspective

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Brain Multiphysics 2022年 3卷

作者： Consolini, Jack Demirci, Nagehan Fulwider, Andrew Hutsler, Jeffrey J. Holland, Maria A. Department of Aerospace and Mechanical Engineering University of Notre Dame Notre Dame 46556 IN United States Bioengineering Graduate Program University of Notre Dame Notre Dame 46556 IN United States Department of Chemical and Biomolecular Engineering University of Notre Dame Notre Dame 46556 IN United States Department of German and Russian Languages and Literatures University of Notre Dame Notre Dame 46556 IN United States Program in Neuroscience University of Nevada Reno 89557 NV United States

The human brain has a complex and unique structure, characterized by intricate three-dimensional folds. These folds, and the mechanisms for their formation, have been studied for over a hundred years. Here we offer a full translation of the pivotal (1929) work by Siegfried Bok, “Der Einflußder in den Furchen und Windungen auftretenden Krümmungen der Großhirnrinde auf die Rindenarchitektur” (“The Influence of the Curvature Occurring in the Folds and Turns of the Cerebral Cortex on Cortical Architecture”). This paper established the influential equi-volume principle, which stated that cortical and laminar thicknesses, along with neuronal shape and fiber orientation, change in order to preserve relative volume throughout the folds of the cortex. We also offer a commentary on the main points of the work, looking at Bok's observations and predictions regarding the structure of neurons, cortical laminae, and the cortex itself, throughout the folds and curves of the brain. His equi-volume principle has held up to decades of experimentation and, even today, has important implications for the analysis of brain structure and function. Statement of Significance: This manuscript presents, for the first time, a full English translation of the foundational neuroanatomy article, “Der Einflußder in den Furchen und Windungen auftretenden Krümmungen der Großhirnrinde auf die Rindenarchitektur” (“The Influence of the Curvature Occurring in the Folds and Turns of the Cerebral Cortex on Cortical Architecture”), written over 90 years ago by Siegfried T. Bok and heavily cited since then. In addition, we provide an assessment of Bok's main points, in light of his contemporaries in research at the time, as well as more recent work during the intervening decades. © 2022 The Author(s)

关键词： Cortical folding Cortical laminae Cortical thickness Neuroanatomy

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A comprehensive review of solid-state lithium batteries: Fast Charging characteristics and in-operando diagnostics

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Nano Energy 2025年 142卷

作者： Ruoxu Shang Talyah Nelson Thanh Vy Nguyen Charlotte Nelson Harsha Antony Brian Abaoag Mihrimah Ozkan Cengiz S. Ozkan Materials Science and Engineering Program University of California Riverside CA USA Department of Mechanical Engineering University of California Riverside CA USA Department of Bioengineering University of California Riverside CA USA Department of Electrical and Computer Engineering University of California Riverside CA USA

This comprehensive review article delves into the evolving landscape of solid-state batteries (SSBs), presenting a critical evaluation beyond the conventional lithium-ion technology. It meticulously explores the performance analysis, fast-charging capabilities, and in-operando characterization of SSBs. Amid growing demands for safer, higher energy density, and more sustainable energy storage solutions, SSBs emerge as a compelling alternative, promising to revolutionize applications from portable electronics to electric vehicles. This review begins with a detailed examination of the fundamental principles underpinning SSBs, including their unique architecture and the roles of solid electrolytes in enhancing safety and energy density. It then shifts focus to the pivotal aspect of fast charging – a critical parameter for consumer acceptance and market penetration of electric vehicles. The analysis extends to the intricacies of in-operando characterization techniques, which are essential for understanding the dynamic processes within SSBs during operation, thus offering insights into optimizing performance and longevity. By juxtaposing SSBs with conventional lithium-ion batteries, the review highlights the technological strides and hurdles ahead. Furthermore, it discusses the latest advancements in materials science, engineering strategies, and characterization methods that potentially address the current limitations of SSBs. Conclusively, this review not only underscores the significant progress in SSB technology but also outlines the roadmap and future directions for researchers and industry stakeholders aiming to harness the full potential of SSBs in next-generation energy storage systems.

关键词： Solid-state batteries (SSBs) Fast charging Operando Lithium-ion Batteries

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Verification of Geant4-DNA step-by-step-reaction-diffusion master equation model for long-term radiolysis simulation

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Physica Medica 2025年 133卷 104983-104983页

作者： Yoon, Euntaek Tran, Ngoc Hoang Incerti, Sebastien Choi, Chang Heon Interdisciplinary Program in Bioengineering Seoul National University Seoul 08826 Cuba Biomedical Research Institute Seoul National University Hospital Seoul 03080 Cuba Univ. Bordeaux CNRS LP2I UMR 5797 Gradignan F-33170 France Department of Radiation Oncology Seoul National University Hospital Seoul 03080 Cuba Institute of Radiation Medicine Seoul National University Medical Research Center Seoul 03080 Cuba Department of Radiation Oncology Seoul National University College of Medicine Seoul 03080 Cuba

Purpose: This paper describes the verification of the step-by-step-reaction-diffusion Master Equation (SBS-RDME) model, implemented in Geant4-DNA, for long-term radiolysis simulations in the Fricke dosimeter. Methods: Scaling for reaction rate constants due to the high acidity of the Fricke solution was applied. The secondary electrons generated by gamma irradiation from Co-60 were used as the radiation source for the simulations. Model parameters were optimized by observing changes in output and computation time in response to variations in the starting time t and initial voxel resolution ℎ of the compartment-based simulation. The yields of ferric ion G(Fe³⁺) and chemical species influencing its formation were calculated using the SBS-RDME model and using the IRT method for comparison. The time evolution of the yields of Fe³⁺, ^[rad]OH, H^[rad], HO₂^[rad], H₂O₂, and H₂ were compared, and the reactions affecting the yield of each chemical species were analyzed. Results: The model parameters were set to t = 5 ns and h = 12.5 nm. The yield trends over time for chemical species were consistent between the SBS-RDME model and the IRT method. At 50 s, the G(Fe³⁺) from the two calculations agreed within 3.2 %. Contribution analysis of the reactions affecting the generation/removal of each chemical species indicated that the main reason for this discrepancy between the two calculations might be the inability of the SBS method to consider specific reaction types during simulation. Conclusions: The SBS-RDME model was verified for long-term simulations by comparing its results to those obtained from the IRT method. © 2025 Associazione Italiana di Fisica Medica e Sanitaria

关键词： Fricke dosimetry Geant4-DNA RDME Water radiolysis

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Radiation tolerance study of scintillation properties with 6 MeV electron beam on inorganic scintillators

Radiation tolerance study of scintillation properties with 6...

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IEEE Symposium on Nuclear Science (NSS/MIC)

作者： C. Park S. Kim J. Seo M. Alima H. Kim H. Park K. Lee S. Cho J.-Y. Yeom Global Health Technology Research Center Korea University Seongbuk-Gu Republic of Korea Interdisciplinary Program in Precision Public Health Korea University Seongbuk-Gu Republic of Korea Department of Health and Safety Convergence Science Korea University Seongbuk-Gu Republic of Korea Department of Bioengineering Korea University Seongbuk-Gu Republic of Korea Department of Radiation Oncology Chonnam National University Medical School Dong-Gu Republic of Korea School of Biomedical Engineering Korea University Seongbuk-Gu Republic of Korea

The radiation tolerance of several inorganic scintillators was investigated to ensure their reproducibility in electron beam exposure. LuAG:Pr, GPS:Ce, LYSO:Ce, GAGG:Ce single, and GAGG:Ce ceramic scintillators were prepared with all faces polished mechanically and thermally annealed. Electron beam exposures at 50, 100, 500, 1000, and 3000 Gy were conducted using a 6 MeV clinical electron beam from a Varian Novalis Tx linear accelerator with a 270-degree bending magnet. Energy spectra were acquired by exciting a 137 Cs source coupled to a photomultiplier tube (PMT) kept in the dark box with a biased high voltage of -900 V. The relative light output of GPS:Ce and LuAG:Pr compared to the baseline decreased steadily after electron beam exposure, recording 66.2% and 56.9%, respectively, at a dose of 3 kGy. The transmittance and photoluminescence of these scintillators also deteriorated with increasing crystallographic defects. In contrast, LYSO:Ce and GAGG:Ce scintillators demonstrated high tolerance to electron beams. Thermal annealing was shown to restore the scintillation properties of the degraded scintillators. These findings provide valuable insights into the radiation tolerance of inorganic scintillators and have implications for the design of radiation detectors for various applications, including radiation therapy and aerospace. Using inorganic scintillators in radiation therapy is particularly critical for estimating radiation exposure. The potential of these scintillators in aerospace applications will also be explored based on the promising results of this study.

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MR-Compatibility of Detector Modules for a Second-Generation RF-Penetrable Brain TOF-PET Insert for Simultaneous PET/MRI

MR-Compatibility of Detector Modules for a Second-Generation...

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IEEE Symposium on Nuclear Science (NSS/MIC)

作者： Qian Dong Zander Adams Ronald D. Watkins Salar Sajedi Chen-Ming Chang Ilaria Sacco Craig S. Levin Departments of Electrical Engineering and Radiology Stanford University Stanford CA USA Departments of Radiology Stanford University Stanford CA USA Department of Radiology Electrical Engineering Bioengineering and Physics Stanford University and Molecular Imaging Program at Stanford (MIPS) Stanford CA USA

ISBN: (数字)9781665421133

ISBN: (纸本)9781665421140

Simultaneous positron emission tomography / magnetic resonance imaging (PET/MRI) acquires fused anatomical and molecular information of diseases. However, this diagnostically attractive idea is highly technically challenging due to the mutual interference between PET and MRI. Currently, clinical integrated PET/MRI systems are available, but only three support simultaneous PET/MRI and only two support time-of-flight (ToF). For small brain structures, a brain-dedicated PET insert provides better spatial resolution and sensitivity performances at a more affordable cost since it can be inserted into any existing MR system. Our first generation RF-penetrable brain PET insert has proven RF-penetrability and MR-compatibility. In the second generation system, SiPM signals are digitized inside detectors which results in better PET performance but presents a greater technical challenge for achieving MR-compatibility. In this paper, we report our initial MR-compatibility results for two fully assembled TOF PET detector modules. We studied the MR noise spectrum and MR image quality change with PET detectors present. With the presence of PET detectors, no noise peaks were induced in the MR acquisition, but the average noise level was increased by 15%, which led to a -3.1 to -4.2 dB degradation in MR image SNR. The uniformity of MR images was influenced by less than 2%. No ghosting artifacts were detected (ghosting intensity level (GIL) < 2%). The changes seen with just two detectors may not exist once we scale up to the full PET ring.

关键词： Image quality Sensitivity Magnetic resonance imaging Detectors Interference Positron emission tomography Spatial resolution

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The Pull of Tissue Engineering: A STEM Outreach program with a Modular Cyclic Stretch Device to Engage High School Students

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Biomedical Engineering Education 2021年第1期2卷 31-39页

作者： Ozdemir, Tugba Senocak, Erdal Gerber, Gene Tayhan, Secil Erden Brown, Justin L. Biomedical Engineering Program Chemical and Biological Engineering Department South Dakota School of Mines and Technology Rapid City USA Department of Science Education Tokat Gaziosmanpasa University Tokat Turkey Department of Biomedical Engineering The Pennsylvania State University State College USA Department of Genetics and Bioengineering Tokat Gaziosmanpasa University Tokat Turkey

In this paper we designed a STEM outreach program with a modular tissue engineering education tool (we refer to as “modular cyclic-stretch device”) to engage high school students in STEM hands-on activities. Using simple machines such as gears and rotating cams, students were able to build a custom device to apply cyclic stretch to biomaterials. With the help of this hands-on activity, our outreach program helped students grasp tendon tissue biomechanics and understand the importance of applying biomechanical force to regenerate tendon tissue in a laboratory setting. The two-day outreach program comprised: 1. pre- and post-tests; 2. lectures; 3. laboratory sessions, including the microscopic examination of stained tissue sections and a hands-on group activity employing the modular cyclic-stretch device; and 4. homework. Assessment results suggest that our program supports improved student awareness and interest in tissue engineering as a future profession. The program elevated students’ confidence in their ability to apply engineering principles to tasks such as building a modular cyclic-stretch device and measuring the mechanical properties of biological tissues. Building an educational bioreactor improved students’ understanding of the dynamic nature of the human body and the importance of tissue engineering as an emerging discipline towards replacing or regenerating damaged organs. We propose that our modular device has great outreach potential to introduce tissue engineering concepts to high school and potentially college freshmen engineering students.

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Investigation of a Novel Approach for RF Shielding of PET Detectors in PET/MR Imaging

Investigation of a Novel Approach for RF Shielding of PET De...

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IEEE Symposium on Nuclear Science (NSS/MIC)

作者： Zander Adams Qian Dong Ronald D. Watkins Craig S. Levin Department of Radiology Stanford University Stanford CA USA Departments of Electrical Engineering and Radiology Stanford University Stanford CA USA Departments of Radiology Electrical Engineering Bioengineering and Physics Stanford University and Molecular Imaging Program at Stanford (MIPS) Stanford CA USA

ISBN: (数字)9781665421133

ISBN: (纸本)9781665421140

Simultaneous PET/MRI is a promising advancement that combines functional and structural molecular imaging to improve diagnostic capabilities. Achieving this integration, however, has proven challenging due to the propensity for mutual interference between MRI and other electronics. Powerful magnetic fields and RF signals from the MR system interfere with PET detector electronics in the bore, and the PET detectors may radiate extraneous signals which impact MR image quality. Specialized shielding is required to achieve electromagnetic compatibility without introducing additional artifacts into images. In this work, we evaluate the suitability of a metallic shielding paint for our application. We establish an acceptable lower bound on shielding effectiveness of −28.7 dB near the MRI center frequency of 127.74 MHz and show that the shielding material is less prone to eddy currents than comparable alternatives.

关键词： Radio frequency Molecular imaging Image quality Magnetic resonance imaging RF signals Detectors Interference

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Methodological Properties of Transcutaneous Electrical Nerve Stimulation (TENS) Equipment Used for Analgesia in Humans: a Systematic Review

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SN Comprehensive Clinical Medicine 2021年第6期3卷 1363-1372页

作者： Guimarães, Igor Batista Volpini Lana, Mariana Ribeiro de Aquino, Mariana Rodrigues Carvalho Cavalheiro, Jessé Mendonça Alves, Davi Neiva Vimieiro, Claysson Bruno Santos Associação Mineira de Reabilitação Orthotics for Humans Laboratory (OhLab) Child Rehabilitation Center Belo Horizonte Brazil Graduate Program in Mechanical Engineering Bioengineering Laboratory Labbio Universidade Federal de Minas Gerais Belo Horizonte Brazil Faculty of Engineering and Architecture Biomedical Engineering Department Universidade FUMEC Belo Horizonte Brazil Graduate Program in Mechanical Engineering Pontifícia Universidade Católica de Minas Gerais Belo Horizonte Brazil

Pain is considered a public health problem due to its high economic cost, high prevalence, and great impact on the quality of life of patients and their families. Transcutaneous electrical nerve stimulation (TENS) has been shown to be a safe, inexpensive option with satisfactory results in improving pain control. However, the success of this therapy presents as key factors the parameters used, among them the intensity and duration of treatment. However, little is known about the validation of such equipment. To perform a systematic review of the equipment available for the application of electrostimulation as a therapeutic resource for analgesia, which had their methodological properties tested. A systematic literature search was conducted for all relevant scientific articles in the SCIELO, Medline/PubMed, PEDRo, and EBSCO databases. A total of 318 articles were found. Sixty-six were duplicate studies, 252 were selected by title, 72 by abstract, 5 by text full reading, and finally only 2 were included, since the others did not meet the pre-established inclusion criteria. The evidence gathered in this study shows that the performance evaluation of commercially available electrostimulation equipment may be a responsibility of the national regulatory agency. Our findings reinforce the importance of greater availability of information about the regulatory processes of these devices and the verification of the parameters of the regulated devices, so that the achievement of therapeutic goals is not compromised.

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