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        Proteolytic Activation of the 1918 Influenza Virus Hemagglutinin

        Chaipan, Chawaree,Kobasa, Darwyn,Bertram, Stephanie,Glowacka, Ilona,Steffen, Imke,Solomon Tsegaye, Theodros,Takeda, Makoto,Bugge, Thomas H.,Kim, Semi,Park, Youngwoo,Marzi, Andrea,Pö,hlmann, Stef American Society for Microbiology 2009 Journal of virology Vol.83 No.7

        <B>ABSTRACT</B><P>Proteolytic activation of the hemagglutinin (HA) protein is indispensable for influenza virus infectivity, and the tissue expression of the responsible cellular proteases impacts viral tropism and pathogenicity. The HA protein critically contributes to the exceptionally high pathogenicity of the 1918 influenza virus, but the mechanisms underlying cleavage activation of the 1918 HA have not been characterized. The neuraminidase (NA) protein of the 1918 influenza virus allows trypsin-independent growth in canine kidney cells (MDCK). However, it is at present unknown if the 1918 NA, like the NA of the closely related strain A/WSN/33, facilitates HA cleavage activation by recruiting the proprotease plasminogen. Moreover, it is not known which pulmonary proteases activate the 1918 HA. We provide evidence that NA-dependent, trypsin-independent cleavage activation of the 1918 HA is cell line dependent and most likely plasminogen independent since the 1918 NA failed to recruit plasminogen and neither exogenous plasminogen nor the presence of the A/WSN/33 NA promoted efficient cleavage of the 1918 HA. The transmembrane serine protease TMPRSS4 was found to be expressed in lung tissue and was shown to cleave the 1918 HA. Accordingly, coexpression of the 1918 HA with TMPRSS4 or the previously identified HA-processing protease TMPRSS2 allowed trypsin-independent infection by pseuodotypes bearing the 1918 HA, indicating that these proteases might support 1918 influenza virus spread in the lung. In summary, we show that the previously reported 1918 NA-dependent spread of the 1918 influenza virus is a cell line-dependent phenomenon and is not due to plasminogen recruitment by the 1918 NA. Moreover, we provide evidence that TMPRSS2 and TMPRSS4 activate the 1918 HA by cleavage and therefore may promote viral spread in lung tissue.</P>

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        The Benefits of Sales Force Automation Explored: An Empirical Examination of SFA Usage on Relationship Quality and Performance

        Park, Jeong Eun,Holloway, Betsy Bugg,Lee, Sungho Korean Marketing Association 2013 ASIA MARKETING JOURNAL Vol.14 No.4

        Sales force automation (SFA) technologies are increasingly used to support customer relationship management (CRM) strategies. However, the popular press reports mixed results among companies incorporating SFA technologies and the previous studies have less interested in relationship quality between sales person and customer as an outcome of SFA. Actually the improved quality of the salesperson-customer relationship may be the most important outcome of SFA usage. This outcome is especially meaningful in today's marketplace given the increasing focus placed on customer retention and other customer related performance such as customer lifetime value. Therefore, this study seeks to further examine the impact of SFA usage within two different firms using SFA technologies to examine the impact of SFA usage on both customer relationship quality and sales performance. Additionally, the moderating roles of perceived managerial support and salesperson experience on the outcomes of SFA usage are examined. The results shows that direct effect of SFA usage on performance was not significant but highlight the mediating role of customer relationship quality in the SFA usage - sales performance relationship. Also, this research examines a number of moderating effects of both management supports for SFA and salesperson's sales work experience. The results indicate that management support has a significant direct influence on relationship quality and salesperson performance, but not a significant moderating effect on the relationship between SFA usage and the outcomes (relationship quality and performance). Thus moderating effects were not supported but find significant main effects. First of all, finding of this study suggest that a formula for successful SFA implementation must be one that highlights a SFA usage → relationship quality → sales performance sequence. This means when sales person use SFA they must build relationship with customer first then will return some long term performance. Second, the implications of not considering the introduction of big technology initiatives in terms of fit within the company's culture, strategy, structure, and environment may in many cases be quite noteworthy. Therefore, the launching of a new technology in the firm, such as SFA, may have a nonlinear impact upon overall firm performance, depending on the presence of other complimentary resources and capabilities. Finally the authors offer a number of implications for research and practice, and suggest directions for future SFA research that may further improve our understanding of this increasingly relevant topic.

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