DOCSLIB.ORG

High-Throughput Tandem-Microwell Assay for Ammonia Repositions FDA-Approved Drugs to Helicobacter Pylori Infection

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
High-Throughput Tandem-Microwell Assay for Ammonia Repositions FDA-Approved Drugs to Helicobacter Pylori Infection bioRxiv preprint doi: https://doi.org/10.1101/2021.01.05.425432; this version posted March 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 High-throughput tandem-microwell assay for ammonia repositions 2 FDA-Approved drugs to Helicobacter pylori infection 3 Fan Liu,a,b,# Jing Yu,b,# Yan-Xia Zhang,c Fangzheng Li,a, d Qi Liu,e Yueyang Zhou,a 4 Shengshuo Huang,b Houqin Fang,f Zhuping Xiao,e Lujian Liao,f Jinyi Xu,d Xin-Yan Wu,c 5 Fang Wu a,* 6 7 aKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for 8 Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China 9 bState Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology 10 and Immunology, School of Life Science and Biotechnology, Shanghai Jiao Tong 11 University, Shanghai, 200240, China 12 cSchool of Chemistry & Molecular Engineering, East China University of Science and 13 Technology, Shanghai, 200237, China. 14 dState Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, 15 China Pharmaceutical University, Nanjing, 210009, China 16 eHunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine 17 in Wuling Mountains, Jishou University, Hunan, 416000, China 18 fShanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China 19 Normal University, Shanghai, 200241, China. 20 #These authors contributed equally to this work. 21 *To whom correspondence may be addressed. Email: [email protected] 22 23 Abbreviations: AHA, acetohydroxamic acid; CBS, cystathionine beta-synthase; CSE, cystathionine 24 -lyase; DTT, dithiothreitol; EBS, ebselen; FAD, Foreign Approved Drugs; FDA, U.S. Food and Drug 25 Administration; H. pylori, Helicobacter pylori; HPU, H. pylori urease; HTS, high-throughput 26 screening; JBU, jack bean urease; KD, equilibrium dissociation constant; LB, Luria-Bertani liquid 27 medium; MICs, minimum inhibitory concentrations; O. anthropi, Ochrobactrum anthropi; OAU, 28 Ochrobactrum anthropic urease; P. mirabilis, Proteus mirabilis; SPR, surface plasmon resonance. 29 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.05.425432; this version posted March 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 30 Abstract 31 To date, little attempt has been made to develop new treatments for Helicobacter 32 pylori (H. pylori), although the community is aware of the shortage of treatments for H. 33 pylori. In this study, we developed a 192-tandem-microwell-based high-throughput-assay 34 for ammonia that is a known virulence factor of H. pylori and a product of urease. We 35 could identify few drugs, i.e. panobinostat, dacinostat, ebselen, captan and disulfiram, to 36 potently inhibit the activity of ureases from bacterial or plant species. These inhibitors 37 suppress the activity of urease via substrate-competitive or covalent-allosteric mechanism, 38 but all except captan prevent the antibiotic-resistant H. pylori strain from infecting human 39 gastric cells, with a more pronounced effect than acetohydroxamic acid, a well-known 40 urease inhibitor and clinically used drug for the treatment of bacterial infection. This 41 study offers several bases for the development of new treatments for urease-containing 42 pathogens and to study the mechanism responsible for the regulation of urease activity. 43 44 45 46 47 Keywords: Ammonia, High-throughput screening, Antibiotic resistance, Urease, 48 Mechanism of action, Helicobacter pylori 49 50 2 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.05.425432; this version posted March 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 51 1. Introduction 52 Bacteria, fungi and plants, with the exception of animals, contain urease[1]. Urease (EC 53 3.5.1.5) is a class of nickel metalloenzyme that hydrolyzes amino acid metabolites to 54 produce ammonia (NH3) and carbon dioxide[2, 3]. The active catalytic site of urease 55 consists of two nickel ions, a carbamylated lysine residue, two histidines and an aspartic 56 acid. In addition to the consistent catalytic mechanism, the amino acid sequence of urease 57 has been reported to be highly conserved between different species[4]. 58 Bacterial urease is known to be a key virulence factor of some pathogens for a number of 59 diseases[5], e.g., Helicobacter pylori (H. pylori) for gastritis or gastric cancer, and 60 Proteus mirabilis (P. m i ra b i li s ) for urinary tract infections and urinary stones[6] . The 61 pathogens can hydrolyze urea substrates to produce NH3. The released NH3 not only 62 helps H. pylori to survive in the low pH environment of the stomach but also causes 63 damage to the gastric mucosa, triggering the infection[7]. Additionally, NH3 generated by 64 P. mirabilis urease has been demonstrated to form urinary stones and destroy the urinary 65 epithelium in the urinary system[8]. Because the human body does not contain urease, 66 bacterial urease has been thought to be an important and specific drug target for 67 combating these pathogens[9]. 68 A number of studies have been performed to identify inhibitors of urease[10-13], but only 69 one urease inhibitor, acetohydroxamic acid (AHA), was approved for the treatment of 70 urinary infections and urinary stones in 1983 by the US Food and Drug Administration 71 (FDA)[14, 15]. Severe side effects, low stability in gastric juice, and a lack of direct 3 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.05.425432; this version posted March 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 72 evidence for suppressing the growth of pathogens seem to be the limiting factors for the 73 low success rate of these urease inhibitors. Adverse side effects of AHA, including 74 teratogenic effects[16], a low efficiency indicated by the required high dose for the 75 patient (~ 1000 mg/day for adults), and the assumed drug resistance of bacteria, further 76 imply that potent and bioactive inhibitors with new chemical moieties are urgently 77 needed to combat these pathogens. Indeed, the current clinical first-line regimen for the 78 treatment of H. pylori [proton-pump inhibitor, clarithromycin, amoxicillin or 79 metronidazole (sometimes tinidazole)][17, 18], is unable to completely eradicate H. 80 pylori due to the increased antibiotic resistance[17, 19]. 81 To date, few validated high-throughput assay has been constructed to quantitatively 82 analyze NH3 and the activity of NH3-generating enzyme urease, but no high-throughput 83 screening approach has been employed to systematically extend the chemical moiety of 84 urease inhibitors. The current assay to determine the activity of urease mainly relies on 85 colorimetric reactions to determine the concentration of NH3 using indophenol or 86 Nessler’s reaction[20]. Recently, a microfluidic chip-based fluorometric assay has been 87 developed to monitor the activity of urease[21, 22]. In addition, a cell-based assay for H. 88 pylori urease has been reported lately, and validated by known inhibitors of urease, but it 89 has not been employed to screen new inhibitors for urease yet[23]. Overall, the current 90 assay setting and procedures are relatively time-consuming and vulnerable to 91 interference. 92 In this study, we established and validated a new tandem-well-based HTS assay for NH3 4 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.05.425432; this version posted March 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 93 and NH3-generating urease and performed an HTS screening campaign to identify 94 druggable chemical entities from 3,904 FDA or Foreign Approved Drugs (FAD) 95 -approved drugs for jack bean and bacterial ureases. Five clinically used drugs, i.e., 96 panobinostat, dacinostat, ebselen (EBS), captan and disulfiram, were found to be 97 submicromolar inhibitors of H. pylori urease (HPU), jack bean urease (JBU), or urease 98 from Ochrobactrum anthropi (O. anthropi), a newly identified pathogen with resistance 99 to -lactam antibiotics[24]. Moreover, panobinostat, dacinostat, EBS and disulfiram 100 potently inhibited the infection of H. pylori, suggesting that these pharmacologically 101 active moieties or drugs could serve as bases for the development of new treatments for 102 urease-positive pathogens. 5 bioRxiv preprint doi: https://doi.org/10.1101/2021.01.05.425432; this version posted March 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 103 2. Material and methods 104 2.1 Materials 105 Jack bean urease (JBU), DMSO, and dithiothreitol (DTT) were purchased from Sigma 106 (Steinheim, Germany). Hypochlorous acid, sodium nitroprusside, salicylate, potassium 107 sodium tartrate, urea, sodium hydroxide, bovine serum albumin, Triton X-100, 108 L-histidine and L-cysteine were purchased from Sangon (Shanghai, China).
Load more

Recommended publications
  • People's Republic of China: Hunan Roads Development III Project
    Completion Report Project Number: 37494 Loan Number: 2219 September 2014 People’s Republic of China: Hunan Roads Development III Project This document is being disclosed to the public in accordance with ADB's Public Communications Policy 2011. CURRENCY EQUIVALENTS Currency unit – yuan (CNY) At Appraisal At Project Completion (15 June 2005) (31 Dec 2012) CNY1.00 = $0.1210 $0.1587 $1.00 = CNY8.2700 CNY6.3026 ABBREVIATIONS ADB – Asian Development Bank EIRR – economic internal rate of return EMDP – ethnic minority development plan EMP – environmental management plan FIRR – financial internal rate of return GDP – gross domestic product HPTD – Hunan provincial transportation department ICB – international competitive bidding JECC – Hunan Jicha Expressway Construction and Development Co. O&M – operation and maintenance PRC – People’s Republic of China SEIA – summary environmental impact assessment TA – technical assistance WEIGHTS AND MEASURES ha – hectare km – kilometer m2 – square meter m3 – cubic meter mu – Chinese unit of measurement (1 mu = 666.67 m2) pcu – passenger car unit NOTE In this report, “$” refers to US dollars, unless otherwise stated. Vice-President S. Groff, Operations 2 Director General A. Konishi, East Asia Department (EARD) Director H. Sharif, People’s Republic of China Resident Mission (PRCM), EARD Team leader G. Xiao, Senior Project Officer (Transport), PRCM, EARD Team members H. Hao, Project Analyst, PRCM, EARD F. Wang, Senior Project Officer (Financial Management), PRCM, EARD W. Zhu, Senior Project Officer (Resettlement), PRCM, EARD Z. Ciwang, Associate Social Development Officer, PRCM, EARD N. Li, Environment Consultant, PRCM, EARD In preparing any country program or strategy, financing any project, or by making any designation of or reference to a particular territory or geographic area in this document, the Asian Development Bank does not intend to make any judgments as to the legal or other status of any territory or area.
    [Show full text]
  • Photoinduced Floquet Topological Magnons in a Ferromagnetic
    Photoinduced Floquet topological magnons in a ferromagnetic checkerboard lattice Zhiqin Zhang1,a, Wenhui Feng1,a, Yingbo Yao3, Bing Tang1,2* 1 Department of Physics, Jishou University, Jishou 416000, China 2The Collaborative Innovation Center of Manganese-Zinc-Vanadium Industrial Technology, Jishou University, Jishou 416000, China 3 College of Information and Electronic Engineering, Hunan City University, Yiyang 413000,China Keywords: Floquet topological magnons; Topological phase transitions; The Floquet-Bloch theory; Irradiated checkerboard ferromagnets ABSTRACT This theoretical work is devoted to investigating laser-irradiated Floquet topological magnon insulators on a two-dimensional checkerboard ferromagnet and corresponding topological phase transitions. It is shown that the checkerboard Floquet topological magnon insulator is able to be transformed from a topological magnon insulator into another one possessing various Berry curvatures and Chern numbers by changing the light intensity. Especially, we also show that both Tamm-like and topologically protected Floquet magnon edge states can exist when a nontrivial gap opens. In addition, our results display that the sign of the Floquet thermal Hall conductivity is also tunable via varying the light intensity of the laser field. * Corresponding author. E-mail addresses: [email protected] a These authors contributed equally to this work. 1. Introduction Up to now, topological insulators have received more and more attention from both theoretical and experimental researchers[1]. Such nontrivial insulators have been realized in a lot of electronic systems, which possess a bulk energy band gap like a common insulator but possess the topologically protected edge (or surface) states because of the bulk-boundary correspondence[2]. Theoretically, the idea of the topological band structure does not depend on the statistical characteristic of the quasiparticle (boson or fermion ) excitations.
    [Show full text]
  • A Probe Into the EFL Learning Style Preferences of Minority College Students: an Empirical Study of Tujia EFL Learners in Jishou University
    ISSN 1799-2591 Theory and Practice in Language Studies, Vol. 2, No. 8, pp. 1662-1667, August 2012 © 2012 ACADEMY PUBLISHER Manufactured in Finland. doi:10.4304/tpls.2.8.1662-1667 A Probe into the EFL Learning Style Preferences of Minority College Students: An Empirical Study of Tujia EFL Learners in Jishou University Feng Liu Faculty of English, College of Literature and Law, Sichuan Agricultural University, Ya'an, China Email: [email protected] Abstract—The purpose of this study is to find out the learning style preferences of Tujia EFL learners in Tujia-Miao Autonomous Prefecture of Xiangxi1 and provide some suggestions for improving effectiveness of College English teaching in Tujia-Miao Autonomous Prefecture of Xiangxi based on the findings. The findings of the study have both theoretical and practical significance. Theoretically, first, the feasibility of the multidimensional questionnaire of learning styles is proved in this empirical study. At the same time, the successful application of the multidimensional learning-styles instrument will help researchers to draw a complete picture of students’ learning style preferences. Second, the present study also found “the ethnic culture and socialization are the most important factors that influence the Tujia EFL learning style preferences”. Practically, the results help the Tujia EFL learners understand their own learning style preferences and instructors in making decisions about course design and improving the methods of the Tujia EFL classroom teaching. Methodologically, the successful application of both quantitative and qualitative approach and the use of a multidimensional learning-styles instrument expand the methodology of learning styles research. Index Terms—Tujia EFL learners, learning style preferences, ethnic culture, socialization I.
    [Show full text]
  • A Complete Collection of Chinese Institutes and Universities For
    Study in China——All China Universities All China Universities 2019.12 Please download WeChat app and follow our official account (scan QR code below or add WeChat ID: A15810086985), to start your application journey. Study in China——All China Universities Anhui 安徽 【www.studyinanhui.com】 1. Anhui University 安徽大学 http://ahu.admissions.cn 2. University of Science and Technology of China 中国科学技术大学 http://ustc.admissions.cn 3. Hefei University of Technology 合肥工业大学 http://hfut.admissions.cn 4. Anhui University of Technology 安徽工业大学 http://ahut.admissions.cn 5. Anhui University of Science and Technology 安徽理工大学 http://aust.admissions.cn 6. Anhui Engineering University 安徽工程大学 http://ahpu.admissions.cn 7. Anhui Agricultural University 安徽农业大学 http://ahau.admissions.cn 8. Anhui Medical University 安徽医科大学 http://ahmu.admissions.cn 9. Bengbu Medical College 蚌埠医学院 http://bbmc.admissions.cn 10. Wannan Medical College 皖南医学院 http://wnmc.admissions.cn 11. Anhui University of Chinese Medicine 安徽中医药大学 http://ahtcm.admissions.cn 12. Anhui Normal University 安徽师范大学 http://ahnu.admissions.cn 13. Fuyang Normal University 阜阳师范大学 http://fynu.admissions.cn 14. Anqing Teachers College 安庆师范大学 http://aqtc.admissions.cn 15. Huaibei Normal University 淮北师范大学 http://chnu.admissions.cn Please download WeChat app and follow our official account (scan QR code below or add WeChat ID: A15810086985), to start your application journey. Study in China——All China Universities 16. Huangshan University 黄山学院 http://hsu.admissions.cn 17. Western Anhui University 皖西学院 http://wxc.admissions.cn 18. Chuzhou University 滁州学院 http://chzu.admissions.cn 19. Anhui University of Finance & Economics 安徽财经大学 http://aufe.admissions.cn 20. Suzhou University 宿州学院 http://ahszu.admissions.cn 21.
    [Show full text]
  • University of Leeds Chinese Accepted Institution List 2021
    University of Leeds Chinese accepted Institution List 2021 This list applies to courses in: All Engineering and Computing courses School of Mathematics School of Education School of Politics and International Studies School of Sociology and Social Policy GPA Requirements 2:1 = 75-85% 2:2 = 70-80% Please visit https://courses.leeds.ac.uk to find out which courses require a 2:1 and a 2:2. Please note: This document is to be used as a guide only. Final decisions will be made by the University of Leeds admissions teams.
    [Show full text]
  • On Lyapunov-Type Inequalities for Nonlinear Dynamic Systems on Time Scales✩
    Computers and Mathematics with Applications 62 (2011) 4028–4038 Contents lists available at SciVerse ScienceDirect Computers and Mathematics with Applications journal homepage: www.elsevier.com/locate/camwa On Lyapunov-type inequalities for nonlinear dynamic systems on time scalesI Qi-Ming Zhang a,∗, Xiaofei He b, Jianchu Jiang c a College of Science, Hunan University of Technology, Zhuzhou 412007, Hunan, PR China b College of Mathematics and Computer Science, Jishou University, Jishou, 416000, Hunan, PR China c Department of Mathematics, Humanities Science and Technology, University of Hunan, Loudi, 417000, Hunan, PR China article info a b s t r a c t Article history: In this paper, by using elementary analysis, we establish several new Lyapunov type Received 25 April 2011 inequalities for the following nonlinear dynamic system on an arbitrary time scale T Received in revised form 16 September − 2011 x1.t/ D α.t/x(σ .t// C β.t/jy.t/jp 2y.t/; − Accepted 19 September 2011 y1.t/ D −γ .t/jx(σ .t//jq 2x(σ .t// − α.t/y.t/; Keywords: when the end-points are not necessarily usual zeros, but rather, generalized zeros, which Nonlinear dynamic system generalize and improve all related existing ones including the continuous and discrete Lyapunov inequality cases. Generalized zero ' 2011 Elsevier Ltd. All rights reserved. Time scales 1. Introduction In recent years, the theory of time scales (or measure chains) has been developed by several authors with one goal being the unified treatment of differential equations (the continuous case) and difference equations (the discrete case). A time scale is an arbitrary nonempty closed subset of the real numbers R.
    [Show full text]
  • 2021 ICM Contest
    2021 Interdisciplinary Contest in Modeling® Press Release—April 23, 2021 COMAP is pleased to announce the results of the 23nd annual influence between artists, and to identify revolutionaries. The E Interdisciplinary Contest in Modeling (ICM). This year 16,059 teams Problem asked teams to create a more equitable and sustainable food representing institutions from sixteen countries/regions participated in system. Students were also required to consider the timeline of the contest. Nineteen teams were designated as OUTSTANDING implementation and the obstacles to change for a region. The F representing the following schools: Problem considered the future of higher education by asking students to create a model to measure the health and sustainability of a national Beijing Normal University, China system of higher education. This problem required actionable policies Northwestern Polytechnical University, China to move a country to a healthier and more sustainable system based on Fudan University, China (AMS Award) the components they chose to include in their model and the country Shenzhen University, China (AMS Award) being considered. For all three problems, teams used pertinent data and South China University of Technology, China grappled with how phenomena internal and external to the system Shanghai Jiao Tong University, China (2) needed to be considered and measured. The student teams produced (INFORMS Award 2103649, INFORMS Award 2106028) creative and relevant solutions to these complex questions and built China University of Petroleum (East China), China models to handle the tasks assigned in the problems. The problems (Vilfredo Pareto Award) also required data analysis, creative modeling, and scientific Xidian University, China methodology, along with effective writing and visualization to Renmin University, China (SIAM Award) communicate their teams' results in a 25-page report.
    [Show full text]
  • Advances in Decision Science and Management
    Advances in Intelligent Systems and Computing Volume 1391 Series Editor Janusz Kacprzyk, Systems Research Institute, Polish Academy of Sciences, Warsaw, Poland Advisory Editors Nikhil R. Pal, Indian Statistical Institute, Kolkata, India Rafael Bello Perez, Faculty of Mathematics, Physics and Computing, Universidad Central de Las Villas, Santa Clara, Cuba Emilio S. Corchado, University of Salamanca, Salamanca, Spain Hani Hagras, School of Computer Science and Electronic Engineering, University of Essex, Colchester, UK László T. Kóczy, Department of Automation, Széchenyi István University, Gyor, Hungary Vladik Kreinovich, Department of Computer Science, University of Texas at El Paso, El Paso, TX, USA Chin-Teng Lin, Department of Electrical Engineering, National Chiao Tung University, Hsinchu, Taiwan Jie Lu, Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, NSW, Australia Patricia Melin, Graduate Program of Computer Science, Tijuana Institute of Technology, Tijuana, Mexico Nadia Nedjah, Department of Electronics Engineering, University of Rio de Janeiro, Rio de Janeiro, Brazil Ngoc Thanh Nguyen , Faculty of Computer Science and Management, Wrocław University of Technology, Wrocław, Poland Jun Wang, Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong The series “Advances in Intelligent Systems and Computing” contains publications on theory, applications, and design methods of Intelligent Systems and Intelligent Computing. Virtually all disciplines
    [Show full text]
  • Arxiv:2007.08278V3 [Astro-Ph.CO] 15 Feb 2021 Non-Gaussianity in MSSM Curvaton Model
    Revised fNL parameter in a curvaton scenario Lei-Hua Liu1, Bin Liang2, Ya-Chen Zhou1, Xiao-Dan Liu1,∗ Wu-Long Xu3, and Ai-Chen Li3;4 1. Department of Physics, College of Physics, Mechanical and Electrical Engineering, Jishou University, Jishou 416000, China 2. College of Civil Engineering, Hunan University of Technology, Zhuzhou, 412007, China 3. Institute of Theoretical Physics, Beijing University of Technology, Beijing 100124, China 4. Departamento de matematica da Universidade de Aveiro and CIDMA, Campus de Santiago, 3810-183 Aveiro, Portugal We revise the Non-Gaussianity of canonical curvaton scenario with a generalized δN formalism, in which it could handle the generic potentials. In various curva- ton models, the energy density is dominant in different period including the sec- ondary inflation of curvaton, matter domination and radiation domination. Our method could unify to deal with these periods since the non-linearity parameter fNL associated with Non-Gaussianity is a function of equation of state w. We firstly investigate the most simple curvaton scenario, namely the chaotic curvaton with quadratic potential. Our study shows that most parameter space satisfies with ob- servational constraints. And our formula will nicely recover the well-known value of fNL in the absence of non-linear evolution. From the micro origin of curvaton, we also investigate the Pseudo-Nambu-Goldstone curvaton. Our result clearly indicates that the second short inflationary process for Pseudo-Nambu-Goldstone curvaton is ruled out in light of observations. Finally, our method sheds a new way for inves- tigating the Non-Gaussianity of curvaton mechanism, espeically for exploring the arXiv:2007.08278v3 [astro-ph.CO] 15 Feb 2021 Non-Gaussianity in MSSM curvaton model.
    [Show full text]
  • ANTHEMS of DEFEAT Crackdown in Hunan
    ANTHEMS OF DEFEAT Crackdown in Hunan Province, 19891989----9292 May 1992 An Asia Watch Report A Division of Human Rights Watch 485 Fifth Avenue 1522 K Street, NW, Suite 910 New York, NY 10017 Washington, DC 20005 Tel: (212) 974974----84008400 Tel: (202) 371371----65926592 Fax: (212) 972972----09050905 Tel: (202) 371371----01240124 888 1992 by Human Rights Watch All rights reserved Printed in the United States of America ISBN 1-56432-074-X Library of Congress Catalog No. 92-72352 Cover Design by Patti Lacobee Photo: AP/ Wide World Photos The cover photograph shows the huge portrait of Mao Zedong which hangs above Tiananmen Gate at the north end of Tiananmen Square, just after it had been defaced on May 23, 1989 by three pro-democracy demonstrators from Hunan Province. The three men, Yu Zhijian, Yu Dongyue and Lu Decheng, threw ink and paint at the portrait as a protest against China's one-party dictatorship and the Maoist system. They later received sentences of between 16 years and life imprisonment. THE ASIA WATCH COMMITTEE The Asia Watch Committee was established in 1985 to monitor and promote in Asia observance of internationally recognized human rights. The chair is Jack Greenberg and the vice-chairs are Harriet Rabb and Orville Schell. Sidney Jones is Executive Director. Mike Jendrzejczyk is Washington Representative. Patricia Gossman, Robin Munro, Dinah PoKempner and Therese Caouette are Research Associates. Jeannine Guthrie, Vicki Shu and Alisha Hill are Associates. Mickey Spiegel is a Consultant. Introduction 1. The 1989 Democracy Movement in Hunan Province.................................................................................... 1 Student activism: a Hunan tradition..................................................................................................
    [Show full text]
  • The 10Th IEEE International Conference on Trust, Security And
    The 9th International Conference on Security, Privacy and Anonymity in Computation, Communication and Storage (SpaCCS 2016) FINAL PROGRAM 16 – 18 November 2016 Zhangjiajie, Hunan Province, China Copyright © Trusted Computing Institute, Central South University, China http://trust.csu.edu.cn Introduction to Central South University Central South University (CSU) is a comprehensive and national key university under the direct administration of the Ministry of Education in China. CSU is among the first group of top universities in China admitted into “Project 211”, which is a project of building national key universities and colleges for the 21st century, and “Project 985”, which is a joint constructive project of building world-class universities co-sponsored by the Chinese central government and the local governments, and “Project 2011”, which is targeted for promoting the capability and capacity of cooperative creativity in top universities in China. Mr. Zhang Yaoxue, a member of the Chinese Academy of Engineering, and the inventor of Transparent Computing (TC), is the President of CSU. Approved by the State Council, CSU was established on April 29, 2000, by merging three separate universities, including Hunan Medical University (HMU), Changsha Railway University (CRU), and Central South University of Technology (CSUT). CSU covers an area of around 5,117 mu (341 hectares). CSU boasts a high-quality group of faculty, comprising of many famous scholars and experts with great influence both at home and abroad. Among them, there are 2 members of the Chinese Academy of Sciences, 15 academicians who are members of Chinese Academy of Engineering, 9 are members of the Discipline Assessment Group of the Academic Degrees Committee of the State Council, 23 scientific and technological experts have been recognized at a national level for their outstanding achievements, 545 experts have been awarded special subsidies from the Government, more than 1000 are doctorate supervisors and 33 are Special-term Professors funded by the Changjiang Scholar Program.
    [Show full text]
  • Pathways to Higher Education
    The Ford Foundation Pathways to Higher Education A Ford Foundation global initiative for promoting inclusiveness in higher education. DESPITE A MASSIVE INCREASE IN HIGHER EDUCATION ENROLLMENTS AROUND THE WORLD, the student body in most higher education institutions does not begin to represent the demographics of their countries. In 2001 The Ford Foundation launched a $50 million, ten-year global initiative, Pathways to Higher Education, to support efforts that transform higher education institutions outside the United States to enable greater numbers of poor, minority, or oth- erwise underrepresented students to obtain a university degree. Pathways supports more than 125 higher education institutions across the world that are working to transform their policies, classroom practices, missions, curricula, and daily operations so that more students from marginalized groups enter and graduate from universities. Higher education institutions and research groups are also supported through Pathways to build knowledge about the numbers and characteristics of under- represented populations, and the nature of the barriers they face to pursuing higher education degrees. Because the social and political contexts of marginalized peoples, while linked by the common experiences of exclu- sion, are distinct, Pathways takes a unique shape in each of the countries. Pathways requires a rigorous process of demonstrating commitment to traditionally excluded students on the part of the higher education institution. Each institution seeks: 1. Increases in their admission, matriculation and graduation rates 2. Broader higher education admission policies and practices 3. Better academic and social supports 4. Changes in the institutional climate to foster inclusiveness 5. Faculty diversity and faculty training in culturally competent teaching methods 6.
    [Show full text]