检索结果-内蒙古大学图书馆

SSRN 2019年

作者： Ng, Katharine M. Aranda-Diaz, Andrés Tropini, Carolina Frankel, Matthew Ryan van Treuren, William W. O’Laughlin, Colleen Merrill, Bryan D. Yu, Feiqiao Brian Pruss, Kali M. Oliveira, Rita Almeida Higginbottom, Steven K. Neff, Norma Fischbach, Michael Xavier, Karina B. Sonnenburg, Justin L. Huang, Kerwyn Casey Department of Bioengineering Stanford University School of Medicine StanfordCA94305 United States Department of Microbiology & Immunology Stanford University School of Medicine StanfordCA94305 United States Chan Zuckerberg Biohub San FranciscoCA94158 United States Instituto Gulbenkian de Ciência Oeiras Portugal Biophysics Graduate Program

That antibiotics alter microbiota composition and increase infection susceptibility is well known, but their generalizable effects on the gut commensal community and dependence on environmental variables remain open questions. Here, we systematically compared antibiotic responses in gnotobiotic and conventional mice across antibiotics, microbiotas, diets, and housing status. We identify remarkable resilience, whereby a humanized microbiota recovers before drug administration ends, with transient oligodominance and taxa-asymmetric reduction in diversity. In general, in vitro sensitivities were not predictive of in vivo responses, underscoring the significance of community context. A fiber-deficient diet exacerbated collapse of the microbiota. We also observed response reprogramming, in which species replacement after ciprofloxacin treatment established resilience to a second treatment, as did transmission through cross-housing. Single-housing drastically disrupted recovery, highlighting the importance of sanitation and environmental reservoirs. Our findings highlight the ability of the commensal microbiota to deterministically adapt to large perturbations, and the translational potential for modulating diet, sanitation, and microbiota composition during antibiotics. © 2019, The Authors. All rights reserved.

关键词： Antibiotics

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Novel techniques for large-scale manipulations of cortical networks in non-human primates

Novel techniques for large-scale manipulations of cortical n...

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Annual International Conference of the IEEE Engineering in Medicine and Biology Society

作者： Azadeh Yazdan-Shahmorad Daniel B. Silversmith Philip N. Sabes University of California San Francisco San Francisco CA US UC Berkeley – UCSF Graduate Program in Bioengineering San Francisco CA 94158 USA

Optogenetics is a powerful tool that enables millisecond-level control of the activity of specific groups of neurons. Furthermore, it has the great advantage of artifact free recordings. These characteristics make this technique ideal for relating brain function to behavior in animals with great behavioral capabilities such as non-human primates (NHPs). We recently introduced a practical, stable interface for optogenetic stimulation and recording of large-scale cortical circuits in NHPs. Here we present the various potentials of this interface for studying circuits and connectivity at a large-scale and for relating it to behavior.

关键词： Frequency modulation Oscillators Time series analysis Couplings Electrical stimulation

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Mitigation of Chromosome Loss in Clinical CRISPR-Cas9-Engineered T Cells

SSRN

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SSRN 2023年

作者： Tsuchida, Connor A. Brandes, Nadav Bueno, Raymund Trinidad, Marena Mazumder, Thomas Yu, Bingfei Hwang, Byungjin Chang, Christopher Liu, Jamin Sun, Yang Hopkins, Caitlin R. Parker, Kevin R. Qi, Yanyan Satpathy, Ansuman T. Stadtmauer, Edward A. Cate, Jamie H.D. Eyquem, Justin Fraietta, Joseph A. June, Carl H. Chang, Howard Y. Ye, Chun Jimmie Doudna, Jennifer A. University of California Berkeley - University of California San Francisco Graduate Program in Bioengineering University of California Berkeley BerkeleyCA United States Innovative Genomics Institute University of California Berkeley BerkeleyCA United States Division of Rheumatology Department of Medicine University of California San Francisco San FranciscoCA United States Center for Personal Dynamic Regulomes Stanford University StanfordCA United States Parker Institute for Cancer Immunotherapy Stanford University School of Medicine StanfordCA United States Biomedical Sciences Graduate Program University of California San Francisco San FranciscoCA United States Medical Scientist Training Program University of California San Francisco San FranciscoCA United States Department of Medicine University of California San Francisco San FranciscoCA United States Parker Institute for Cancer Immunotherapy San FranciscoCA United States Gladstone-UCSF Institute of Genomic Immunology San FranciscoCA United States Department of Biochemistry and Biophysics University of California San Francisco San FranciscoCA United States Abramson Cancer Center Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Parker Institute for Cancer Immunotherapy Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Center for Cellular Immunotherapies Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department of Microbiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department of Pathology Stanford University School of Medicine StanfordCA United States Division of Hematology-Oncology Department of Medicine Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department o

CRISPR-Cas9 genome editing has enabled advanced T cell therapies, but occasional loss of the targeted chromosome could be a safety concern. To investigate whether Cas9-induced chromosome loss is a universal phenomenon and evaluate its clinical significance, we conducted a systematic analysis in primary human T cells. Arrayed and pooled CRISPR screens revealed that partial or entire chromosome loss after Cas9-induced DNA cutting is a rare but generalized phenomenon, occurring also in pre-clinical chimeric antigen receptor T cells. T cells with chromosome loss persist for weeks in culture, implying potential interference with clinical use. A modified cell manufacturing process, employed in our first-in-human clinical trial of Cas9-engineered T cells, dramatically reduced chromosome loss while largely preserving genome editing efficacy. Expression of p53 correlated with the protection from chromosome loss observed with this protocol, suggesting both a mechanism and a strategy for T cell engineering that mitigates genotoxicity in the clinic. © 2023, The Authors. All rights reserved.

关键词： T-cells

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Toward Quantification and Visualization of Active Stress Waves for Myocardial Biomechanical Function Assessment

Toward Quantification and Visualization of Active Stress Wav...

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Computers in Cardiology (CinC)

作者： Niels F Otani Dylan Dang Christopher Beam Fariba Mohammadi Brian Wentz S M Kamrul Hasan Suzanne M Shontz Karl Q Schwarz Sabu Thomas Cristian A Linte School of Mathematical Sciences Rochester Institute of Technology Rochester NY Mechanical Engineering University of Kansas Lawrence KS Bioengineering Graduate Program University of Kansas Lawrence KS Center for Imaging Science Rochester Institute of Technology Rochester NY Electrical Engineering and Computer Science University of Kansas Lawrence KS Division of Cardiology University of Rochester Medical Center Rochester NY

ISBN: (数字)9781728169361

ISBN: (纸本)9781728159423

Estimating and visualizing myocardial active stress wave patterns is crucial to understanding the mechanical activity of the heart and provides a potential non-invasive method to assess myocardial function. These patterns can be reconstructed by analyzing 2D and/or 3D tissue displacement data acquired using medical imaging. Here we describe an application that utilizes a 3D finite element formulation to reconstruct active stress from displacement data. As a proof of concept, a simple cubic mesh was used to represent a myocardial tissue "sample" consisting of a 10 x 10 x 10 lattice of nodes featuring different fiber directions that rotate with depth, mimicking cardiac transverse isotropy. In the forward model, tissue deformation was generated using a test wave with active stresses that mimic the myocardial contractile forces. The generated deformation field was used as input to an inverse model designed to reconstruct the original active stress distribution. We numerically simulated malfunctioning tissue regions (experiencing limited contractility and hence active stress) within the healthy tissue. We also assessed model sensitivity by adding noise to the deformation field generated using the forward model. The difference image between the original and reconstructed active stress distribution suggests that the model accurately estimates active stress from tissue deformation data with a high signal-to-noise ratio.

关键词： Stress Myocardium Strain Biomechanics Image reconstruction Imaging Deformable models

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Spatiotemporal development of expanding bacterial colonies driven by emergent mechanical constraints and nutrient gradients

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Nature communications 2025年第1期16卷 4878页

作者： Harish Kannan Hui Sun Mya Warren Tolga Çağlar Pantong Yao Brian R Taylor Kinshuk Sahu Daotong Ge Matteo Mori David Kleinfeld JiaJia Dong Bo Li Terence Hwa Department of Mathematics University of California San Diego La Jolla CA USA. Department of Mathematics and Statistics California State University Long Beach CA USA. paul.sun@csulb.edu. Department of Physics University of California San Diego La Jolla CA USA. San Diego Supercomputer Center University of California San Diego La Jolla CA USA. Neurosciences Graduate Program University of California San Diego La Jolla CA USA. Joint BioEnergy Institute Emeryville CA USA and Systems Biology Department Sandia National Laboratories Livermore CA USA. Department of Bioengineering University of California San Diego La Jolla CA USA. Department of Biomedical Engineering Duke University Durham NC USA. Department of Neurobiology University of California San Diego La Jolla CA USA. Department of Physics & Astronomy Bucknell University Lewisburg PA USA. jiajia.dong@bucknell.edu. Department of Mathematics and Ph.D. Program in Quantitative Biology University of California San Diego La Jolla CA USA. bli@ucsd.edu. Department of Physics University of California San Diego La Jolla CA USA. hwa@ucsd.edu.

Bacterial colonies growing on solid surfaces can exhibit robust expansion kinetics, with constant radial growth and saturating vertical expansion, suggesting a common developmental program. Here, we study this process for Escherichia coli cells using a combination of modeling and experiments. We show that linear radial colony expansion is set by the verticalization of interior cells due to mechanical constraints rather than radial nutrient gradients as commonly assumed. In contrast, vertical expansion slows down from an initial linear regime even while radial expansion continues linearly. This vertical slowdown is due to limitation of cell growth caused by vertical nutrient gradients, exacerbated by concurrent oxygen depletion. Starvation in the colony interior results in a distinct death zone which sets in as vertical expansion slows down, with the death zone increasing in size along with the expanding colony. Thus, our study reveals complex heterogeneity within simple monoclonal bacterial colonies, especially along the vertical dimension. The intricate dynamics of such emergent behavior can be understood quantitatively from an interplay of mechanical constraints and nutrient gradients arising from obligatory metabolic processes.

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The mechanism of action of T-705 as a unique delayed chain terminator on influenza viral polymerase transcription

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Biophysical Chemistry 2021年 277卷 106652-106652页

作者： Wang, Yuqing Yuan, Congmin Xu, Xinzhou Chong, Tin Hang Zhang, Lu Cheung, Peter Pak-Hang Huang, Xuhui The Hong Kong University of Science and Technology-Shenzhen Research Institute Hi-Tech Park Nanshan Shenzhen 518057 China Bioengineering Graduate Program Department of Biological and Chemical Engineering The Hong Kong University of Science and Technology Clear Water Bay Hong Kong Department of Chemistry State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and Technology Kowloon Hong Kong State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences Fuzhou 350002 Fujian China University of Chinese Academy of Sciences Beijing 100049 China Department of Chemical Pathology The Chinese University of Hong Kong Prince of Wales Hospital Shatin New Territories Hong Kong Li Ka Shing Institute of Health Sciences Li Ka Shing Medical Sciences Building The Chinese University of Hong Kong Shatin New Territories Hong Kong

Favipiravir (T-705) has been developed as a potent anti-influenza drug and exhibited a strong inhibition effect against a broad spectrum of RNA viruses. Its active form, ribofuranosyl-triphosphate (T-705-RTP), functions as a competitive substrate for the RNA-dependent RNA polymerase (RdRp) of the influenza A virus (IAV). However, the exact inhibitory mechanisms of T-705 remain elusive and subject to a long-standing debate. Although T-705 has been proposed to inhibit transcription by acting as a chain terminator, it is also paradoxically suggested to be a mutagen towards IAV RdRp by inducing mutations due to its ambiguous base pairing of C and U. Here, we combined biochemical assay with molecular dynamics (MD) simulations to elucidate the molecular mechanism underlying the inhibitory functions exerted by T-705 in IAV RdRp. Our in vitro transcription assay illustrated that IAV RdRp could recognize T-705 as a purine analogue and incorporate it into the nascent RNA strand. Incorporating a single T-705 is incapable of inhibiting transcription as extra natural nucleotides can be progressively added. However, when two consecutive T-705 are incorporated, viral transcription is completely terminated. MD simulations reveal that the sequential appearance of two T-705 in the nascent strand destabilizes the active site and disrupts the base stacking of the nascent RNA. Altogether, our results provide a plausible explanation for the inhibitory roles of T-705 targeting IAV RdRp by integrating the computational and experimental methods. Our study also offers a comprehensive platform to investigate the inhibition effect of antivirals and a novel explanation for the designing of anti-flu drugs. © 2021

关键词： Chain terminator Influenza Mutagen RNA polymerase T-705

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Current Methods for Hyperpolarized [1-13C]pyruvate MRI Human Studies

arXiv

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arXiv 2023年

作者： Larson, Peder E.Z. Bernard, Jenna M.L. Bankson, James A. Bøgh, Nikolaj Bok, Robert A. Chen, Albert P. Cunningham, Charles H. Gordon, Jeremy Hövener, Jan-Bernd Laustsen, Christoffer Mayer, Dirk McLean, Mary A. Schilling, Franz Slater, James Vanderheyden, Jean-Luc von Morze, Cornelius Vigneron, Daniel B. Xu, Duan Hansen, Esben Søvsø Szocska Miller, Jack Bertelsen, Lotte Bonde Vaeggemose, Michael Lin, Gigin Capozzi, Andrea Fuetterer, Max Chen, Albert Leftin, Avi Schulte, Rolf Rius, Irene Marco Booth, Thomas C. Mishkovsky, Mor Walker, Christopher Michael Keshari, Kayvan Woitek, Ramona Takado, Yuhei Vasquez, Crystal Müller, Christoph Floyd, Joel Grashei, Martin Topping, Geoff van Heijster, Frits Che, Jenny Kim, Yaewon Kurhanewicz, John Ohliger, Michael Sriram, Renuka Chaumeil, Myriam Bock, Michael Schmidt, Andreas Gallagher, Ferdia Chowdhury, Rafat Gong, Yangcan Punwani, Shonit Merritt, Matthew Grist, James Tyler, Damian Khashami, Fatemeh Malloy, Craig Park, Jae Mo Zaha, Vlad Department of Radiology and Biomedical Imaging University of California San FranciscoCA94143 United States UC Berkeley-UCSF Graduate Program in Bioengineering University of California San Francisco United States University of California BerkeleyCA94143 United States Department of Imaging Physics MD Anderson Medical Center HoustonTX United States The MR Research Center Department of Clinical Medicine Aarhus University Aarhus Denmark GE Healthcare Menlo ParkCA United States Sunnybrook Research Institute TorontoON Canada Department of Medical Biophysics University of Toronto TorontoON Canada Kiel University Am Botanischen Garten 14 Kiel24118 Germany Department of Diagnostic Radiology and Nuclear Medicine University of Maryland School of Medicine BaltimoreMD United States Greenebaum Cancer Center University of Maryland School of Medicine BaltimoreMD United States Department of Radiology University of Cambridge Cambridge United Kingdom Cancer Research UK Cambridge Institute University of Cambridge Li Ka Shing Center Cambridge United Kingdom Department of Nuclear Medicine School of Medicine Klinikum Rechts der Isar Technical University of Munich Munich81675 Germany JLVMI Consulting LLC DousmanWI United States Department of Radiology Washington University St. LouisMO United States Aarhus University Aarhus Denmark Chang Gung Memorial Hospital Taoyuan Taiwan Technical University of Denmark Copenhagen Denmark ETH Zurich Zurich Switzerland GE Healthcare WaukeshaWI United States Institute for Bioengineering of Catalonia Barcelona Spain Kings College London London United Kingdom École Polytechnique Fédérale de Lausanne Lausanne Switzerland MD Anderson Cancer Center HoustonTX United States Memorial Sloan Kettering Cancer Center New YorkNY United States Danube Private University Kerns-Stein an der Donau Austria National Institutes for Quantum Science and Technology Chiba Japan National Institutes Health National Cancer Institute Bethe

MRI with hyperpolarized (HP) 13C agents, also known as HP 13C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-13C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP 13C-pyruvate preparation, (2) MRI system setup and calibrations, (3) data acquisition and image reconstruction, and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the "HP 13C MRI Consensus Group" as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods & Equipment study groups. It further aims to provide a comprehensive reference for future consensus building as the field continues to advance human studies with this metabolic imaging modality. © 2023, CC BY.

关键词： Magnetic resonance imaging

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Development of Virtual Reality-Vision System in Robot-Assisted Laparoscopic Surgery

Development of Virtual Reality-Vision System in Robot-Assist...

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International Conference on Control, Automation and Systems

作者： Yeeun Jo Yoon Jae Kim Hye-Min Moon Sungwan Kim Interdisciplinary Program for Bioengineering Graduate School Seoul National University Seoul Korea Institute of Medical and Biological Engineering Medical Research Center Seoul National University Seoul Korea

ISBN: (纸本)9781538670804;9788993215168

The robot-assisted surgical systems that allow minimally invasive surgery have diverse advantages compared to conventional open surgery. However, there still remain some drawbacks to be improved such as the discontinuous surgical operation flow that occurs during switching control between the endoscope system and the patient side manipulator (PSM). It can lead to collision between surgical instruments, possibility of injury to patients, and increased operation time. Thus, a virtual reality-vision system is proposed to enable continuous surgical operation flow and inruitive control of endoscopic system. As a preliminary study, 6 types of motion capture data, pitch down, pitch up, roll left, roll right, yaw left, and yaw right, were collected from two subjects. Signal-to-noise ratio (SNR) is high enough to avoid classification issue, so available ranges of threshold for each motion could be suggested. Based on the provided thresholds, intuitive velocity control strategy of endoscope system will be implemented. Furthermore, collision avoidance system using Oriented Bounded Box (OBB) was designed to suppress user mistakes caused by unintended head motion. The simulation results show motion trajectory of endoscope without any collision with other instruments.

关键词： Robot-assisted surgery Endoscopic system Virtual reality (VR) Vision system Oculus Collision avoidance

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Recent advances in quantum dots for biomedical applications

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Journal of Pharmaceutical Investigation 2018年第2期48卷 209-214页

作者： Lee, Jae Seo Youn, Yun Hee Kwon, Il Keun Ko, Na Re Department of Dentistry Graduate School Kyung Hee University 26 Kyungheedae-ro Dongdaemun-gu Seoul 02447 South Korea Department of Dental Materials School of Dentistry Kyung Hee University 26 Kyungheedae-ro Dongdaemun-gu Seoul 02447 South Korea Interdisciplinary Program for Bioengineering Seoul National University 1 Gwanak-ro Gwanak-gu Seoul 08826 South Korea

Quantum dots (QDs) have been widely used for fluorescent nanoprobes as bioimaging agents. However, QD can have toxic side-effects as they include heavy metals. Many researchers suggest graphene quantum dots (GQDs) as an alternative material with low toxicity and good biocompatibility. GQDs have many attractive features due to their structure. These include outstanding mechanical properties, optical properties, and good physicochemical stability. These exceptional properties can be exploited for biomedical applications, especially in the fields of drug-delivery, bioimaging, and tissue-engineering. This article presents a comprehensive review of GQDs. The primary focus is on their unique properties as they relate to the biomedical field and recently reported applications. © 2018, The Korean Society of Pharmaceutical Sciences and Technology.

关键词： Bio-sensing agents Biomedical application Drug delivery system Graphene quantum dots Quantum dots Tissue engineering

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Physics-based learned design: Optimized coded-illumination for quantitative phase imaging

arXiv

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arXiv 2018年

作者： Kellman, Michael R. Bostan, Emrah Repina, Nicole Waller, Laura Department of Electrical Engineering and Computer Sciences University of California BerkeleyCA94720 United States Graduate Program in Bioengineering University of California BerkeleyCA94720 United States

Coded-illumination can enable quantitative phase microscopy of transparent samples with minimal hardware requirements. Intensity images are captured with different source patterns and a non-linear phase retrieval optimization reconstructs the image. The non-linear nature of the processing makes optimizing the illumination pattern designs complicated. Traditional techniques for experimental design (e.g. condition number optimization, spectral analysis) consider only linear measurement formation models and linear reconstructions. Deep neural networks (DNNs) can efficiently represent the non-linear process and can be optimized over via training in an end-to-end framework. However, DNNs typically require a large amount of training examples and parameters to properly learn the phase retrieval process, without making use of the known physical models. Here, we aim to use both our knowledge of the physics and the power of machine learning together. We develop a new data-driven approach to optimizing coded-illumination patterns for a LED array microscope for a given phase reconstruction algorithm. Our method incorporates both the physics of the measurement scheme and the non-linearity of the reconstruction algorithm into the design problem. This enables efficient parameterization, which allows us to use only a small number of training examples to learn designs that generalize well in the experimental setting without retraining. We show experimental results for both a well-characterized phase target and mouse fibroblast cells using coded-illumination patterns optimized for a sparsity-based phase reconstruction algorithm. Our learned design results using 2 measurements demonstrate similar accuracy to Fourier Ptychography with 69 measurements. Copyright © 2018, The Authors. All rights reserved.

关键词： Statistics

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