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arXiv 2019年

作者： Zhang, Rui Redford, Steven A. Ruijgrok, Paul V. Kumar, Nitin Mozaffari, Ali Zemsky, Sasha Dinner, Aaron R. Vitelli, Vincenzo Bryant, Zev Gardel, Margaret L. de Pablo, Juan J. Pritzker School of Molecular Engineering University of Chicago ChicagoIL60637 United States The graduate program in Biophysical Sciences University of Chicago ChicagoIL60637 United States James Franck Institute University of Chicago ChicagoIL60637 United States Department of Bioengineering Stanford University StanfordCA94305 United States Program in Biophysics Stanford University StanfordCA94305 United States Department of Chemistry University of Chicago ChicagoIL60637 United States Department of Physics University of Chicago ChicagoIL60637 United States Department of Structural Biology Stanford University Medical Center StanfordCA94305 United States Center for Molecular Engineering Argonne National Laboratory LemontIL60439 United States

Active materials are capable of converting free energy into mechanical work to produce autonomous motion, and exhibit striking collective dynamics that biology relies on for essential functions. Controlling those dynamics and transport in synthetic systems has been particularly challenging. Here, we introduce the concept of spatially structured activity as a means to control and manipulate transport in active nematic liquid crystals consisting of actin filaments and light-sensitive myosin motors. Simulations and experiments are used to demonstrate that topological defects can be generated at will, and then constrained to move along specified trajectories, by inducing local stresses in an otherwise passive material. These results provide a foundation for design of autonomous and reconfigurable microfluidic systems where transport is controlled by modulating activity with light. Copyright © 2019, The Authors. All rights reserved.

关键词： Nematic liquid crystals

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Drug Delivery: Injectable Drug‐Releasing Microporous Annealed Particle Scaffolds for Treating Myocardial Infarction (Adv. Funct. Mater. 43/2020)

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Advanced Functional Materials 2020年第43期30卷

作者： Jun Fang Jaekyung Koh Qizhi Fang Huiliang Qiu Maani M. Archang Mohammad Mahdi Hasani‐Sadrabadi Hiromi Miwa Xintong Zhong Richard Sievers Dong‐Wei Gao Randall Lee Dino Di Carlo Song Li Department of Bioengineering University of California Los Angeles CA 90095 USA Department of Medicine University of California Los Angeles CA 90095 USA Department of Medicine Cardiovascular Research Institute and Institute for Regeneration Medicine University of California San Francisco CA 94143 USA California NanoSystems Institute (CNSI) University of California Los Angeles CA 90095 USA UC Berkeley‐UCSF Graduate Program in Bioengineering University of California San Francisco San Francisco CA 94158 USA Department of Mechanical and Aerospace Engineering University of California Los Angeles CA 90095 USA Jonsson Comprehensive Cancer Centre University of California Los Angeles CA 90024 USA

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Utility of plasma GFAP as a secondary endpoint for clinical trials in Alzheimer's disease

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The journal of prevention of Alzheimer's disease 2025年 100205页

作者： Sarah Abbas Pamela C L Ferreira Bruna Bellaver Guilherme Povala Francieli Rohden Cristiano Schaffer Aguzzoli Hussein Zalzale João Pedro Ferrari-Souza Douglas T Leffa Firoza Z Lussier Carolina Soares Guilherme Bauer-Negrini Markley Silva Oliveira-Junior Matheus Scarpatto Rodrigues Pampa Saha Emma Ruppert Marina Scop Medeiros Cécile Tissot Joseph Therriault Nesrine Rahmouni Stijn Servaes Andrea L Benedet Nicholas J Ashton Dana L Tudorascu Serge Gauthier Helmet Karim Chang Hyung Hong Hyun Woong Roh Eduardo R Zimmer Thomas K Karikari Henrik Zetterberg Kaj Blennow Anum Saeed Sang Joon Son Pedro Rosa-Neto Tharick Pascoal Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh PA USA. Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh PA USA Graduate Program in Biological Sciences: Biochemistry Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil. Brain Institute of Rio Grande do Sul PUCRS 6690 Ipiranga Avenue 90610-000 Porto Alegre RS Brazil. Translational Neuroimaging Laboratory McGill University Research Centre for Studies in Aging Alzheimer's Disease Research Unit Douglas Research Institute Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal Canada Department of Neurology and Neurosurgery Psychiatry and Pharmacology and Therapeutics McGill University Montreal QC Canada Department of Molecular Biophysics and Integrated Bioimaging Lawrence Berkeley National Laboratory Berkeley CA USA. Department of Neurology and Neurosurgery Psychiatry and Pharmacology and Therapeutics McGill University Montreal QC Canada. Translational Neuroimaging Laboratory McGill University Research Centre for Studies in Aging Alzheimer's Disease Research Unit Douglas Research Institute Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal Canada. Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Gothenburg Sweden. Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Gothenburg Sweden Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg Gothenburg Sweden Department of Old Age Psychiatry Institute of Psychiatry Psychology & Neuroscience King's College London London UK. Department of Bioengineering University of Pittsburgh Pittsburgh PA USA. Department of Psychiatry Ajou University School of Medicine Suwon Republic of Korea South Korea. Graduate Program

BACKGROUND:Clinical trials have recently incorporated plasma glial fibrillary acidic protein (GFAP) as an exploratory endpoint. To include plasma GFAP as a secondary endpoint, it is essential to characterize its longitudinal progression in target populations. OBJECTIVE:To evaluate the potential use of plasma GFAP changes as a secondary endpoint in Alzheimer's disease trials. METHODS:We longitudinally evaluated plasma GFAP in individuals with amyloid-beta (Aβ)-PET scans at baseline in three well-characterized cohorts. Cox proportional hazards regression tested the association between changes in plasma GFAP and cognitive function. Analysis of the 95 % confidence interval of annualized change in plasma GFAP provided statistical inference for a significant longitudinal change. Effect size was calculated as the group mean divided by the standard deviation (SD). We estimated the sample size needed to test a 25% drug effect with 80% power on reducing changes in GFAP. RESULTS:We assessed 487 individuals [176 cognitively unimpaired (CU; 29% Aβ positive) and 311 cognitively impaired (CI; 51% Aβ positive)] with some degree of cerebrovascular disease (Fazekas 1-3), over a mean (SD) follow-up of 1.84 (0.46) years. Changes in plasma GFAP were significantly associated with worsening in Clinical Dementia Rating sum of boxes (CDR-SB) score across the population (p < 0.0001). In CU, only Aβ positive individuals showed significant changes in GFAP (p < 0.001). On the other hand, both CI Aβ positive and negative individuals showed longitudinal progression in GFAP levels (p < 0.0001). The effect size of changes in plasma GFAP was higher in CU Aβ positive (0.44), followed by CI Aβ positive (0.42) and CI Aβ negative (0.38). Clinical trials focusing on CU Aβ positive would require 1320 individuals per study arm, while focusing on CI Aβ positive would require 1440 individuals per study arm. CONCLUSION:Plasma GFAP increased in parallel with cognitive decline, making it a candidate for monitor

关键词： Biomarker Clinical trial Plasma GFAP

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Obesity alters pathology and treatment response in inflammatory disease

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四川生理科学杂志 2022年第3期44卷 446-446页

作者： Sagar P Bapat NOMIS Center for Immunobiology and Microbial Pathogenesis The Salk Institute for Biological Studies La Jolla CA USA Gene Expression Laboratory The Salk Institute for Biological Studies La Jolla CA USA Medical Scientist Training Program University of California San Diego La Jolla CA USA Department of Laboratory Medicine University of California San Francisco San Francisco CA USA Department of Microbiology and Immunology University of California San Francisco San Francisco CA USA Diabetes Center University of California San Francisco San Francisco CA USA Medical Scientist Training Program University of California San Francisco CA USA Division of Pulmonary Critical Care Allergy and Sleep Department of Medicine University of California San Francisco San Francisco CA USA School of Pharmaceutical Sciences Xiamen University Xiamen China Department of Dermatology University of California San Diego La Jolla CA USA Department of Surgery University of California San Francisco San Francisco CA USA Department of Medicine University of California San Francisco San Francisco CA USA Sandler Asthma Basic Research Center University of California San Francisco San Francisco CA USA School of Medicine Wake Forest University Winston–Salem NC USA Department of Dermatology Icahn School of Medicine at Mount Sinai New York NY USA Lung Biology Center Department of Medicine University of California San Francisco San Francisco CA USA Department of Biomedical Science Graduate School Kyungpook National University Kyungpook National University Hospital Daegu South Korea Department of Dermatology University of California San Francisco San Francisco CA USA Department of Pathology University of California San Francisco San Francisco CA USA Department of Internal Medicine Division of Pulmonary Critical Care and Sleep Medicine University of Kentucky Lexington KY USA Pulmonary Critical Care Section Department of Medicine Veterans Affairs San Diego Hea

Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune,allergic and inflammatory *** evidence indicates that obesity and metabolic disease can also influence the immune system1-7,although the mechanisms and effects on immunotherapy outcomes remain largely ***,using two models of atopic dermatitis,we show that lean and obese mice mount markedly different immune *** converted the classical type 2 T helper(TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 *** also observed divergent responses to biologic therapies targeting TH2 cytokines,which robustly protected lean mice but exacerbated disease in obese ***-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ(PPARγ)in TH2 cells from obese mice relative to lean mice.

关键词： dermatitis inflammatory allergic

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SARS-CoV-2 identified through crystallographic screening and computational docking

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Science Advances 2021年第16期7卷

作者： Schuller, Marion Correy, Galen J. Gahbauer, Stefan Fearon, Daren Wu, Taiasean Díaz, Roberto Efraín Young, Iris D. Martins, Luan Carvalho Smith, Dominique H. Schulze-Gahmen, Ursula Owens, Tristan W. Deshpande, Ishan Merz, Gregory E. Thwin, Aye C. Biel, Justin T. Peters, Jessica K. Moritz, Michelle Herrera, Nadia Kratochvil, Huong T. Aimon, Anthony Bennett, James M. Neto, Jose Brandao Cohen, Aina E. Dias, Alexandre Douangamath, Alice Dunnett, Louise Fedorov, Oleg Ferla, Matteo P. Fuchs, Martin R. Gorrie-Stone, Tyler J. Holton, James M. Johnson, Michael G. Krojer, Tobias Meigs, George Powell, Ailsa J. Rack, Johannes Gregor Matthias Rangel, Victor L. Russi, Silvia Skyner, Rachael E. Smith, Clyde A. Soares, Alexei S. Wierman, Jennifer L. Zhu, Kang O Brien, Peter Jura, Natalia Ashworth, Alan Irwin, John J. Thompson, Michael C. Gestwicki, Jason E. Von Delft, Frank Shoichet, Brian K. Fraser, James S. Ahel, Ivan Sir William Dunn School of Pathology University of Oxford South Parks Road OxfordOX1 3RE United Kingdom Department of Bioengineering and Therapeutic Sciences University of California San Francisco San FranciscoCA94158 United States Department of Pharmaceutical Chemistry University of California San Francisco San FranciscoCA94158 United States Diamond Light Source Ltd. Harwell Science and Innovation Campus DidcotOX11 0DE United Kingdom Institute for Neurodegenerative Disease University of California San Francisco San FranciscoCA94158 United States Chemistry and Chemical Biology Graduate Program University of California San Francisco San FranciscoCA94158 United States Tetrad Graduate Program University of California San Francisco San FranciscoCA94158 United States Coronavirus Research Group Structural Biology Consortium University of California San Francisco San FranciscoCA94158 United States Biochemistry Department Institute for Biological Sciences Federal University of Minas Gerais Belo Horizonte Brazil Helen Diller Family Comprehensive Cancer University of California San Francisco San FranciscoCA94158 United States Centre for Medicines Discovery University of Oxford South Parks Road HeadingtonOX3 7DQ United Kingdom Stanford Synchrotron Radiation Lightsource Slac National Accelerator Center Menlo ParkCA94025 United States Wellcome Centre for Human Genetics University of Oxford Old Road Campus OxfordOX3 7BN United Kingdom National Synchrotron Light Source Ii Brookhaven National Laboratory UptonNY11973 United States Department of Biochemistry and Biophysics University of California San Francisco San FranciscoCA94158 United States Department of Molecular Biophysics and Integrated Bioimaging Lawrence Berkeley National Laboratory BerkeleyCA94720 United States ChemPartner Corporation South San FranciscoCA94080 United States Structural Genomics Consortium University of Oxford Old Road Campus HeadingtonOX3 7DQ United Kingdom School of

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors. © 2021 American Association for the Advancement of Science. All rights reserved.

关键词： Coronavirus

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Publisher Correction: Modular and tunable biological feedback control using a de novo protein switch

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Nature 2020年第7798期579卷 E8页

作者： Andrew H Ng Taylor H Nguyen Mariana Gómez-Schiavon Galen Dods Robert A Langan Scott E Boyken Jennifer A Samson Lucas M Waldburger John E Dueber David Baker Hana El-Samad Department of Biochemistry and Biophysics University of California San Francisco San Francisco CA USA. Department of Bioengineering University of California Berkeley Berkeley CA USA. The UC Berkeley-UCSF Graduate Program in Bioengineering UC Berkeley Berkeley CA USA. Cell Design Initiative University of California San Francisco CA USA. Department of Biochemistry University of Washington Seattle WA USA. Institute for Protein Design University of Washington Seattle WA USA. Graduate Program in Biological Physics Structure and Design University of Washington Seattle WA USA. Howard Hughes Medical Institute University of Washington Seattle WA USA. Department of Biochemistry and Biophysics University of California San Francisco San Francisco CA USA. hana.el-samad@ucsf.edu. Cell Design Initiative University of California San Francisco CA USA. hana.el-samad@ucsf.edu. Chan-Zuckerberg Biohub San Francisco CA USA. hana.el-samad@ucsf.edu.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Erratum: “Effects of calibration methods on quantitative material decomposition in photon-counting spectral computed tomography using a maximuma posterioriestimator” [Med. Phys., 44(10): 5187-5197 (2017)]

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Medical Physics 2018年第9期45卷 4323-4323页

作者： Tyler E. Curtis Ryan K. Roeder Department of Aerospace and Mechanical Engineering Bioengineering Graduate Program University of Notre Dame Notre Dame IN46556 USA

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Interdependence theory of tissue failure: Bulk and boundary effects

arXiv

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arXiv 2017年

作者： Suma, Daniel Acun, Aylin Zorlutuna, Pinar Vural, Dervis Can Department of Bioengineering University of Minnesota Bioengineering Graduate Program University of Notre Dame Department of Aerospace and Mechanical Engineering University of Notre Dame Department of Physics University of Notre Dame United States

The mortality rate of many complex multicellular organisms increase with age, which suggests that net aging damage is accumulative, despite remodeling processes. But how exactly do little mishaps in the cellular level accumulate and spread to become a systemic catastrophe? To address this question we present experiments with synthetic tissues, an analytical model consistent with experiments, and a number of implications that follow the analytical model. Our theoretical framework describes how shape, curvature and density influences the propagation of failure in a tissue subject to oxidative damage. We propose that aging is an emergent property governed by interaction between cells, and that intercellular processes play a role that are at least as important as intracellular ones. Copyright © 2017, The Authors. All rights reserved.

关键词： Analytical models

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The Multi-modality Cell Segmentation Challenge: Towards Universal Solutions

arXiv

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arXiv 2023年

作者： Ma, Jun Xie, Ronald Ayyadhury, Shamini Ge, Cheng Gupta, Anubha Gupta, Ritu Gu, Song Zhang, Yao Lee, Gihun Kim, Joonkee Lou, Wei Li, Haofeng Upschulte, Eric Dickscheid, Timo de Almeida, José Guilherme Wang, Yixin Han, Lin Yang, Xin Labagnara, Marco Gligorovski, Vojislav Scheder, Maxime Rahi, Sahand Jamal Kempster, Carly Pollitt, Alice Espinosa, Leon Mignot, Tâm Middeke, Jan Moritz Eckardt, Jan-Niklas Li, Wangkai Li, Zhaoyang Cai, Xiaochen Bai, Bizhe Greenwald, Noah F. Van Valen, David Weisbart, Erin Cimini, Beth A. Cheung, Trevor Brück, Oscar Bader, Gary D. Wang, Bo Peter Munk Cardiac Centre University Health Network TorontoON Canada Department of Laboratory Medicine and Pathobiology University of Toronto TorontoON Canada Vector Institute TorontoON Canada Department of Molecular Genetics University of Toronto TorontoON Canada Donnelly Centre University of Toronto TorontoON Canada Princess Margaret Cancer Centre University Health Network TorontoON Canada School of Medicine and Pharmacy Ocean University of China Qingdao China New Delhi India Laboratory Oncology Dr. BRA-IRCH All India Institute of Medical Sciences New Delhi India Department of Image Reconstruction Nanjing Anke Medical Technology Co. Ltd. Nanjing China Shanghai Artificial Intelligence Laboratory Shanghai China Graduate School of AI KAIST Seoul Korea Republic of Shenzhen Research Institute of Big Data Shenzhen China Shenzhen China Helmholtz AI Research Center Jülich Jülich Germany Faculty of Mathematics and Natural Sciences Institute of Computer Science Heinrich Heine University Düsseldorf Düsseldorf Germany Hinxton United Kingdom Champalimaud Foundation - Centre for the Unknown Lisbon Portugal Department of Bioengineering Stanford University Palo AltoCA United States Tandon School of Engineering New York University New YorkNY United States School of Biomedical Engineering Health Science Center Shenzhen University Shenzhen China Lausanne Switzerland School of Biological Sciences University of Reading Reading United Kingdom Laboratoire de Chimie Bactérienne CNRS Université Aix Marseille UMR Institut de Microbiologie de la Méditerranée Marseille France Department of Internal Medicine I University Hospital Dresden Technical University Dresden Dresden Germany Else Kroener Fresenius Center for Digital Health Technical University Dresden Dresden Germany Department of Automation University of Science and Technology of China Hefei China Institute of Advanced Technology University of Science and Technology of China Hefei Chi

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multi-modality cell segmentation benchmark, comprising over 1500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging. © 2023, CC BY-NC-ND.

关键词： Deep learning

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Cytocompatible magnetostrictive microstructures for nano- A nd microparticle manipulation on linear strain response piezoelectrics

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Multifunctional Materials 2018年第1期1卷

作者： Xiao, Zhuyun Khojah, Reem Chooljian, Marc Conte, Roberto Lo Schneider, Joseph D. Fitzell, Kevin Chopdekar, Rajesh V. Wang, Yilian Scholl, Andreas Chang, Jane Carman, Gregory P. Bokor, Jeffrey Carlo, Dino Di Candler, Rob N. Department of Electrical and Computer Engineering University of California Los Angeles United States Department of Bioengineering University of California Los Angeles United States University of California Berkeley UCSF Graduate Program in Bioengineering Berkeley United States Department of Electrical Engineering and Computer Sciences University of California Berkeley United States Department of Mechanical and Aerospace Engineering University of California Los Angeles United States Department of Chemical and Biomolecular Engineering University of California Los Angeles United States Advanced Light Source Lawrence Berkeley National Laboratory Berkeley United States California Nanosystems Institute Los Angeles United States

In this work, we investigate polycrystalline Ni and FeGamagnetostrictivemicrostructures on prepoled (011)-cut single crystal [Pb(Mg1/3Nb2/3)O3]1-x-[PbTiO3]x (PMN-PT, x ≈ 0.31) with linear strain profile versus applied electric field. Magnetostrictive microstructure arrays with various geometries are patterned on PMN-PT. Functionalizedmagnetic beads are trapped by localized stray fields originating fromthe microstructures. With an applied electric field, themagnetic domains are actuated, inducing the motion of the coupled particles with sub-micrometer precision. This work shows promise of using energy-efficient electric-field-controlled magnetostrictivemicro- A nd nanostructures formanipulatingmagnetic beads via a linear strain response. The work also demonstrates the viability of cells suspended in solution on these structures when subject to applied electric fields, proving the cytocompatibility of the platform for live cell sorting applications. © 2018 IOP Publishing Ltd.

关键词： Electric fields

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