单分子阶梯事件分析 Single-molecule detection (SMD) and tracking in living cells is becoming a powerful method for the study of protein local environments, the time course of the enzymatic reaction, and the structure fluctuations of macromolecules, etc. Many single molecule studies have offered new insights into their localization, assembly and activation. Perhaps the dominant advantage of single-molecule fluorescence detection is that it can provide information on the spatial and temporal heterogeneity of molecule that underlies the ensemble average in conventional biochemical experiments. These spatial and temporal heterogeneities often appear as step events, for example, the discrete steps of photobleaching of single fluorescent molecules response to the number of subunits in membrane proteins. Hence ， the step events analysis is becoming an important method of stochiometry study. However, SMD is also a difficult task. The most experiments of single-molecule fluorescence detection are approaching the limits of optical detection, and that the raw experimental data are inundated with all kinds of noise, especially, the Poisson distributed photon shot noise. These steps are so dim that it is very difficult to distinguish them. To leach out the useful information from these noisy raw data is still a challenging task. Perhaps the simplest and most commonly used method for the analysis of step events of single molecule inundated in these noisy data is the thresholding method. When a single-molecule trajectory has sufficient contrast between states, thresholds can be applied to distinguish the states of the molecule. These thresholds are typically chosen manually and introduce subjectivity into the analysis inevitablly. Before thresholding, binning of the data is also required, and this limits the temporal resolution of the measurement to be 1 or 2 orders of magnitude lower than the photon count rate to overcome the effects of shot noise. To mitigate the effects of shot noise, some investigators have applied filters to the data prior to applying a threshold. This can substantially improve the time resolution of the experiment by mitigating some of the effects of shot noise, but there is still the difficulty associated with choosing a threshold. Recently, many methods, such as hidden Markov models, applications of information theory, photon statistics in the context of two colors, maximum likelihood and Bayesian inferential estimation of change points using Poisson statistics, wavelet correlation, and wavelet shrinkage have been developed and applied to single molecule data as a means of extracting more accurate information about the system under observation. Although direct, model-independent information theoretical approaches may also work well, especially when a kinetic model is inapplicable. HMM, which uses all the information from the data prior and posterior, has enjoyed wide applicability and success. However, this method needs a long sequence to train the HMM for the parameter extraction. Many important experimental data sets are far too short to satisfy this requirement, so that the algorithm will converge to a local maximum depending on the initialization of the emission probability distribution. Another problem of HMMs is the necessary prior knowledge of the number of the states.
http://www.sciencenet.cn/htmlnews/2009/9/223338.shtm 美国研发出一种抗流感新药 美国一家生物制药公司9月13日宣布，他们研制出一种新药，经动物实验测试发现对目前流行的甲型H1N1流感病毒有效，而且由于它不直接作用于病毒，不容易出现病毒耐药性问题。 美国NexBio生物制药公司13日在旧金山举行的美国抗微生物制剂和化疗会议上报告说，他们研发的试验新药流感酶（Fludase）在实验鼠身上取得了良好的疗效，对于普通季节性流感和目前流行的甲型H1N1流感都有效。接下来，他们还将进行相关的临床试验。 与达菲等神经氨酸酶抑制剂类药物不同，流感酶的主要成分是唾液酸酶融合蛋白。它作用的对象是细胞本身，使宿主细胞表面的唾液酸受体失去活性，流感病毒就无法与受体结合，也就无法附着细胞。而达菲等药物的原理是抑制流感病毒表面的神经氨酸酶，使其无法感染细胞，因此病毒容易发生变异产生耐药性。 NexBio公司在当天发布的新闻公报中说，流感酶在试验中没有表现出任何明显的抗药性。另外，对于已经对达菲药物产生耐药性的流感病毒毒株，流感酶也能抵御其入侵细胞。 流感病毒最大的特点就是易变，在传播过程中容易变得对抗病毒药物产生耐药性。目前甲型H1N1流感病毒在世界多个国家传播，临床中通常使用瑞士罗氏公司的达菲进行治疗。但据罗氏最新的统计，全球已报告23例对达菲产生耐药性的甲型H1N1流感病例。 http://www.bio-medicine.org/medicine-technology-1/NexBio-28R-29-Presents-DAS181--28Fludase-28R-29--29-Potently-Inhibits-Novel-Swine-Origin-A-28H1N1-29-and-NAI-Resistant-Influenza-Viruses--at-ICAAC-200-4982-1/ NexBio(R) Presents DAS181 (Fludase(R)*) Potently Inhibits Novel Swine-Origin A(H1N1) and NAI-Resistant Influenza Viruses, at ICAAC 2009 hcocgle("Outline") ... ... ...SAN DIEGO Sept. 13 /- NexBio Inc. announced today the p... ... hrss("RSS & Subscription") http://www.bio-medicine.org/inc/biomed/medicine-technology.asp http://feeds.bio-medicine.org/latest-medical-technology document.write(" Email Subscription: Get Latest Medical Technology delivered by email "); Email Subscription: Get Latest Medical Technology delivered by email DAS181 (Fludase(R)) is an investigational broad spectrum drug candidate being evaluated in human clinical development for treatment and prevention of Influenza-Like Illness caused by all strains of influenza and parainfluenza. Unlike neuraminidase inhibitors (NAI), e.g. Tamiflu(R), which directly target the influenza virus (pathogen target), DAS181 works by inactivating the human receptor (host target) for these viruses; thus, it may be less likely to encounter acquired resistance compared with currently-available antiviral drugs. Extensive, prolonged nonclinical influenza studies have not shown the development of any meaningful resistance. This approach may have advantages over mono-therapy or combination therapy which directly target the pathogen. Previously announced preclinical studies conducted in collaboration with the CDC and others have shown DAS181 to have significant therapeutic and prophylactic activity in in vivo animal models and in human ex vivo lung tissue for a highly virulent H5N1 (A/VN/1203/04) strain of influenza. A Late Breaker presentation, entitled Novel Swine-Origin A (H1N1) Influenza Viruses are Potently Inhibited by DAS181, a Sialidase Fusion Protein examined i n vitro , ex vivo , and in vivo models to evaluate the activity of DAS181 against multiple human novel 2009 influenza A/H1N1 viruses (Novel H1N1 or Swine Flu). The data presented '// 信息分析平台： http://www.gopubmed.org/web/gopubmed/1?WEB01dvvul63ftcj4I32I2I00d000j10040001rl 检索策略： Fludase or DAS181 相关文献计量分析结果： Top Years Publications 2009 3 2007 2 2006 1 Top Countries Publications USA 2 Hong Kong S.A.R., China 1 Switzerland 1 United Kingdom 1 Top Cities Publications Hong Kong 1 Geneva 1 London 1 Atlanta 1 San Diego 1 Top Journals Publications J Infect Dis 2 Antimicrob Agents Chemother 1 Clin Infect Dis 1 Idrugs 1 Antimicrob Agents Ch 1 1 2 Top Authors Publications Hayden F 2 Aschenbrenner L 2 Malakhov M 2 Fang F 2 Nicholls J 1 Chan R 1 Chan M 1 Wong A 1 Karamanska R 1 Dell A 1 Haslam S 1 Sihoe A 1 Chui W 1 Triana-Baltzer G 1 Li Q 1 Peiris J 1 Fang F 1 Zhang H 1 Al-Shamahi A 1 Bright J 1 1 2 1 2 3 4 Top Terms Publications Viruses 5 Recombinant Fusion Proteins 5 Influenza A Virus, H5N1 Subtype 4 Orthomyxoviridae 4 Influenza in Birds 4 viral reproduction 4 Mice 4 Influenza, Human 4 Antiviral Agents 4 Animals 4 Humans 4 sialic acid binding 3 Sialic Acids 3 Virulence 3 Neuraminidase 3 Cell Line 2 Therapeutics 2 Receptors, Virus 2 Lung 2 Virus Replication 2 1 2 3 4 相关研究报道： Title: DAS181 inhibits H5N1 influenza virus infection of human lung tissues. PMID: 19596886 Related Articles Authors: Chan, R W , Chan, M C , Wong, A C , Karamanska, R , Dell, A , Haslam, S M , Sihoe, A D , Chui, W H , Triana-Baltzer, G , Li, Q , Peiris, J S , Fang, F , Nicholls, J M Journal: Antimicrob Agents Chemother , Vol. 53 (9): 3935-41 , 2009 Abstract: DAS181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing the virus receptor, sialic acid (Sia), from the adjacent glycan structures. DAS181 and its analogues have previously been shown to be potently active against multiple strains of seasonal and avian influenza virus strains in several experimental models, including cell lines, mice, and ferrets. Here we demonstrate that DAS181 treatment leads to desialylation of both alpha2-6-linked and alpha2-3-linked Sia in ex vivo human lung tissue culture and primary pneumocytes. DAS181 treatment also effectively protects human lung tissue and pneumocytes against the highly pathogenic avian influenza virus H5N1 (A/Vietnam/3046/2004). Two doses of DAS181 treatment given 12 h apart were sufficient to block H5N1 infection in the ex vivo lung tissue culture. These findings support the potential value of DAS181 as a broad-spectrum therapeutic agent against influenza viruses, especially H5N1. Affiliation: Department of Microbiology, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR. Wikipedia: Animal virus , Avian Flu , Avian Influenza , Cell line , Glycans , Grippe , House Mouse , House mice , Human flu , Human influenza , Influenza , Influenza, human , Influenza Virus , Influenza in birds , Laboratory mice , Laboratory mouse , Lung , Mathematical model , Mice , Mouse , Mus , Mus domesticus , Mus musculus , Mus musculus domesticus , Orthomyxoviridae , Orthomyxovirus , Pathogenicity , Polysaccharides , Sialic acids , Therapeutic , Tissue , Treatment , Virulence , Virus Title: DAS181 and H5N1 virus infection. PMID: 19302014 Related Articles Authors: Zhang, H Journal: J Infect Dis , Vol. 199 (8): 1250, author reply 1250-1 , 2009 No abstract given. Pubmed MeSH: Animals , Antiviral Agents , Mice , Orthomyxoviridae Infections , Recombinant Fusion Proteins Wikipedia: Animal virus , Virus Title: Developing new antiviral agents for influenza treatment: what does the future hold? PMID: 19067613 Related Articles Authors: Hayden, F G Journal: Clin Infect Dis , Vol. 48 Suppl 1 , 2009 Abstract: Antiviral agents for the treatment of influenza are urgently needed to circumvent the limitations of current drugs in several critical areas: high frequencies of resistance to M2 inhibitors among currently circulating strains and variable frequencies of resistance to oseltamivir among A(H1N1) strains, limited efficacy of treatment and treatment-emergent antiviral resistance in cases of avian influenza A(H5N1) illness in humans, and lack of parenteral agents for seriously ill patients. Two neuraminidase inhibitors (NAIs), zanamivir and peramivir, have undergone or are undergoing clinical trials for use by intravenous or intramuscular administration, and one long-acting NAI , designated CS-8958, is under study for use by inhalation. Advances in understanding the mechanisms involved in influenza virus replication have revealed a number of potential targets that might be exploited in the development of new agents. Among these agents are T-705, a polymerase inhibitor, and DAS181 , an attachment inhibitor. Combination therapy with currently available agents is supported by data from animal models but has received limited clinical study to date. Affiliation: Global Influenza Programme, World Health Organization, Geneva , Switzerland . fgh@virginia.edu Pubmed MeSH: Amides , Cyclopentanes , Drug Resistance, Viral , Drug Therapy, Combination , Guanidines , Humans , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H5N1 Subtype , Pyrazines , Recombinant Fusion Proteins Wikipedia: Animal , Animal model , Animal virus , Animalia , Antiviral agents , Antiviral drugs , Antivirals , Avian Flu , Avian Influenza , Blood circulation , Client , Drugs , Grippe , Human flu , Human influenza , Influenza , Influenza, human , Influenza Virus , Influenza in birds , Inhalation , Inhaling , Models, animal , Neuraminidase , Orthomyxoviridae , Orthomyxovirus , Oseltamivir , Patient , Relenza , Sialidase , TamiFlu , Viral replication , Virus , Zanamivir Title: BioPartnering Europe--15th Annual Conference. Highlights from open house and emerging company presentations--Part 1. PMID: 18041679 Related Articles Authors: Bright, J , Al-Shamahi, A Journal: IDrugs , Vol. 10 (12): 855-7 , 2007 No abstract given. Affiliation: Thomson Scientific, 77 Hatton Garden, London , EC1N 8JS, UK . jonathan.bright@thomson.com Pubmed MeSH: Cytokines , Drug Industry , Humans , Interpersonal Relations , Nanotechnology , Nebulizers and Vaporizers , Recombinant Fusion Proteins Title: DAS181 , a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection. PMID: 18008229 Related Articles Authors: Belser, J A , Lu, X H , Szretter, K J , Jin, X , Aschenbrenner, L M , Lee, A , Hawley, S , Kim, D H , Malakhov, M P , Yu, M , Fang, F D , Katz, J M Journal: J Infect Dis , Vol. 196 (10): 1493-9 , 2007 Abstract: Increasing resistance to currently available influenza antivirals highlights the need to develop alternate approaches for the prevention and/or treatment of influenza. DAS181 ( Fludase ), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against influenza A and B viruses. Here, we use a mouse model to evaluate the efficacy of DAS181 treatment against a highly pathogenic avian influenza H5N1 virus. When used to treat mice daily beginning 1 day before infection with A/Vietnam/1203/2004(H5N1) virus, DAS181 treatment at 1 mg/kg/day protected 100% of mice from fatal disease, prevented viral dissemination to the brain, and effectively blocked infection in 70% of mice. DAS181 at 1 mg/kg/day was also effective therapeutically, conferring enhanced survival of H5N1 virus-challenged mice when treatment was begun 72 h after infection. This notable antiviral activity underscores the potential utility of DAS181 as a new class of drug that is effective against influenza viruses with pandemic potential. Affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta , GA 30333, USA . Pubmed MeSH: Animals , Brain , Disease Models, Animal , Humans , Lung , Mice, Inbred BALB C , Recombinant Fusion Proteins , Viral Fusion Proteins Wikipedia: Animal virus , Antiviral agents , Antiviral drugs , Antivirals , Avian Flu , Avian Influenza , Critique , Disease outbreak , Drugs , Epidemic , Epithelium , Evaluation , Evaluation research , Grippe , Herpes B Virus , House Mouse , House mice , Human flu , Human influenza , Influenza , Influenza, human , Influenza Virus , Influenza in birds , Laboratory mice , Laboratory mouse , Mesothelium , Mice , Monkey B virus , Mouse , Mus , Mus domesticus , Mus musculus , Mus musculus domesticus , N-acetylneuraminate lyase , NPL , Neuraminidase , Orthomyxoviridae , Orthomyxovirus , Pandemic , Pathogenicity , Proteins , Respiratory epithelium , Sialic acids , Sialidase , Therapeutic , Treatment , Virulence , Virus Title: Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection. PMID: 16569867 Related Articles Authors: Malakhov, M P , Aschenbrenner, L M , Smee, D F , Wandersee, M K , Sidwell, R W , Gubareva, L V , Mishin, V P , Hayden, F G , Kim, D H , Ing, A , Campbell, E R , Yu, M , Fang, F D Journal: Antimicrob Agents Chemother , Vol. 50 (4): 1470-9 , 2006 Abstract: Influenza is a highly infectious disease characterized by recurrent annual epidemics and unpredictable major worldwide pandemics. Rapid spread of the highly pathogenic avian H5N1 strain and escalating human infections by the virus have set off the alarm for a global pandemic. To provide an urgently needed alternative treatment modality for influenza, we have generated a recombinant fusion protein composed of a sialidase catalytic domain derived from Actinomyces viscosus fused with a cell surface-anchoring sequence. The sialidase fusion protein is to be applied topically as an inhalant to remove the influenza viral receptors, sialic acids, from the airway epithelium. We demonstrate that a sialidase fusion construct, DAS181 , effectively cleaves sialic acid receptors used by both human and avian influenza viruses. The treatment provides long-lasting effect and is nontoxic to the cells. DAS181 demonstrated potent antiviral and cell protective efficacies against a panel of laboratory strains and clinical isolates of IFV A and IFV B, with virus replication inhibition 50% effective concentrations in the range of 0.04 to 0.9 nM. Mouse and ferret studies confirmed significant in vivo efficacy of the sialidase fusion in both prophylactic and treatment modes. Affiliation: NexBio, Inc., 6330 Nancy Ridge Dr., Suite 105, San Diego , CA 92121, USA . Pubmed MeSH: Animals , Bacterial Adhesion , Cell Line , Dogs , Ferrets , Glycoproteins , Humans , Intercellular Signaling Peptides and Proteins , Mice, Inbred BALB C , Peptide Fragments Wikipedia: Actinomyces , Animal virus , Antiviral agents , Antiviral drugs , Antivirals , Avian Flu , Avian Influenza , Catalytic domain , Catalytic site , Communicable disease , Disease outbreak , Epidemic , Epithelium , Grippe , House Mouse , House mice , Human flu , Human influenza , Infectious Disease , Influenza , Influenza, human , Influenza Virus , Influenza in birds , Laboratories , Laboratory , Laboratory mice , Laboratory mouse , Mesothelium , Mice , Mouse , Mus , Mus domesticus , Mus musculus , Mus musculus domesticus , Neuraminidase , Orthomyxoviridae , Orthomyxovirus , Pandemic , Pathogenicity , Proteins , Recombinant fusion proteins , Recombinant proteins , Recrudescence , Recurrence , Relapse , Sialic acids , Sialidase , Virulence , Virus 对该研究主题的追踪信息分析： 1: J Infect Dis. 2007 Nov 15;196(10):1493-9. Epub 2007 Oct 31. Related Articles , Links Comment in: J Infect Dis. 2009 Apr 15;199(8):1250, author reply 1250-1. DAS181, a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection. Belser JA , Lu X , Szretter KJ , Jin X , Aschenbrenner LM , Lee A , Hawley S , Kim do H , Malakhov MP , Yu M , Fang F , Katz JM . Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. Increasing resistance to currently available influenza antivirals highlights the need to develop alternate approaches for the prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against influenza A and B viruses. Here, we use a mouse model to evaluate the efficacy of DAS181 treatment against a highly pathogenic avian influenza H5N1 virus. When used to treat mice daily beginning 1 day before infection with A/Vietnam/1203/2004(H5N1) virus, DAS181 treatment at 1 mg/kg/day protected 100% of mice from fatal disease, prevented viral dissemination to the brain, and effectively blocked infection in 70% of mice. DAS181 at 1 mg/kg/day was also effective therapeutically, conferring enhanced survival of H5N1 virus-challenged mice when treatment was begun 72 h after infection. This notable antiviral activity underscores the potential utility of DAS181 as a new class of drug that is effective against influenza viruses with pandemic potential. Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. http://www.journals.uchicago.edu/doi/abs/10.1086/522609?url_ver=Z39.88-2003rfr_id=ori:rid:crossref.orgrfr_dat=cr_pub%3dncbi.nlm.nih.gov The Journal of Infectious Diseases 2007;196:14931499 2007 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2007/19610-0012$15.00 DOI: 10.1086/522609 MAJOR ARTICLE DAS181, A Novel Sialidase Fusion Protein, Protects Mice from Lethal Avian Influenza H5N1 Virus Infection JessicaA.Belser, 1,2, a XiuhuaLu, 1, a KristyJ.Szretter, 1,2 XiaopingJin, 1 LauraM.Aschenbrenner, 3 AliceLee, 3 StephenHawley, 3 DoHyongKim, 3 MichaelP.Malakhov, 3 MangYu, 3 FangFang, 3 and JacquelineM.Katz 1 1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, and 2 Emory University, Atlanta, Georgia; 3 NexBio, Inc., San Diego, California Increasing resistance to currently available influenza antivirals highlights the need to develop alternate approaches for the prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against influenza A and B viruses. Here, we use a mouse model to evaluate the efficacy of DAS181 treatment against a highly pathogenic avian influenza H5N1 virus. When used to treat mice daily beginning 1 day before infection with A/Vietnam/1203/2004(H5N1) virus, DAS181 treatment at 1 mg/kg/day protected 100% of mice from fatal disease, prevented viral dissemination to the brain, and effectively blocked infection in 70% of mice. DAS181 at 1 mg/kg/day was also effective therapeutically, conferring enhanced survival of H5N1 viruschallenged mice when treatment was begun 72 h after infection. This notable antiviral activity underscores the potential utility of DAS181 as a new class of drug that is effective against influenza viruses with pandemic potential. Received 24 April 2007; accepted 29 May 2007; electronically published 31 October 2007. Reprints or correspondence: Dr. Jacqueline M. Katz, Influenza Division MS G‐16, 1600 Clifton Rd. NE, Atlanta, GA 30333 ( JKatz@cdc.gov ); or, Fang Fang, NexBio, Inc., 10665 Sorrento Valley Rd., San Diego, CA 92121 ( ffang@nexbio.com ). 该研究论文被引用情况（Cited by） HongZhang. (2009) DAS181 and H5N1 Virus Infection. The Journal of Infectious Diseases 199:8, 1250-1250 Online publication date: 15-Apr-2009. Citation - Full Text - PDF Version (39 kB) JessicaA.Belser, XiuhuaLu, JacquelineM.Katz, DavidF.Wurtman, MangYu, and FangFang. (2009) Reply to Zhang. The Journal of Infectious Diseases 199:8, 1250-1251 Online publication date: 15-Apr-2009. Citation - Full Text - PDF Version (39 kB) FrederickHayden. (2009) Developing New Antiviral Agents for Influenza Treatment: What Does the Future Hold?. Clinical Infectious Diseases 48:s1, S3-S13 Online publication date: 1-Jan-2009. Abstract - Full Text - PDF Version (565 kB) Potential conflicts of interest: L.M.A., A.L., S.H., D.H.K., M.P.M., M.Y., and F.F. declare that they have competing financial interests. J.M.K. received funding from NexBio, Inc., to cover the cost of this research. J.A.B., X.L., K.J.S., and X.J. declare that they have no potential conflicts. Present in part: IX International Symposium on Respiratory Viral Infections, Hong Kong, March 2007 (abstract VII-3); Options for the Control of Influenza VI, Toronto, June 2007 (abstract 071). Financial support: Oak Ridge Institute for Science and Education (support to J.A.B. and K.J.S.); National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant RAI056786‐03, grant U01AI070281‐01, and contract HHSN266200600015C); Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention. J.A.B. and X.L. contributed equally to this work. 原始研究论文请见： DAS181, a novel sialidase fusion protein, protects 对该论文的相关文献计量分析结果（111篇）： Top Years Publications 2007 26 2008 23 2009 19 2006 14 2005 8 2000 7 2001 4 1998 3 1999 3 2003 3 2002 1 Top Countries Publications USA 61 China 15 Japan 6 Netherlands 4 Singapore 3 Hong Kong S.A.R., China 2 Vietnam 2 Russia 2 United Kingdom 2 Canada 2 Switzerland 1 Belgium 1 Australia 1 Germany 1 Italy 1 Turkey 1 India 1 1 2 3 Top Cities Publications Memphis 19 Atlanta 16 Logan 5 Rotterdam 4 Athens, USA 4 Tokyo 4 Singapur 3 Wuhan 3 Guangzhou 3 Hong Kong 2 Ho Chi Minh City 2 San Diego 1 Foster City 1 Harbin 1 Changchun 1 Geneva 1 Yangzhou 1 Tottori 1 Madison 1 Saint Petersburg 1 1 2 3 1 2 3 Top Journals Publications J Virol 19 J Infect Dis 9 Vaccine 8 Antimicrob Agents Ch 7 Antivir Res 7 Antivir Ther 5 Antiviral Res 5 Plos Pathog 4 Antimicrob Agents Chemother 3 Plos Med 2 Clin Infect Dis 2 J Med Virol 2 J Gen Virol 2 Lancet Infect Dis 2 J Med Chem 2 Antivir Chem Chemother 1 Bing Du Xue Bao 1 J Vet Med Sci 1 Dermatology 1 Lancet 1 1 2 3 1 2 3 ... 32 Top Authors Publications Webster R 18 Katz J 17 Lu X 11 Tumpey T 9 Govorkova E 7 Sidwell R 5 Zaki S 5 Cox N 5 Swayne D 5 Leneva I 4 Hayden F 4 Barnard D 4 Wong M 4 Ilyushina N 4 Hoffmann E 4 Salomon R 4 Yen H 4 Morken T 4 Kawaoka Y 4 Ninomiya A 4 1 2 3 ... 32 1 2 3 ... 40 Top Terms Publications Viruses 110 Influenza, Human 110 Animals 102 Influenza A Virus, H5N1 Subtype 98 Orthomyxoviridae 95 Influenza in Birds 83 Mice 82 Virulence 76 Humans 75 Influenza A virus 62 Disease Outbreaks 60 Mice, Inbred BALB C 59 Antiviral Agents 59 viral reproduction 49 Lung 48 Orthomyxoviridae Infections 43 Virus Replication 39 Neuraminidase 36 Immunization 35 Immunity 34 1 2 3 ... 40
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