178 research outputs found

    The Moderating Effect of Switching Barriers: Online Stock and Derivatives Trading

    Get PDF
    This study attempts to develop a researchmodel that examines the direct effects of customersatisfaction and switching barriers on customer retention aswell as the moderating effect of switching barriers on therelationship between customer satisfaction and customerretention in retail online stock and derivatives tradingindustry in Hong Kong. An online questionnaire wasemployed as the means of data collection. The significantpositive effects of customer satisfaction and switchingbarriers on customer retention are confirmed. In addition,the significant negative moderating effect of switchingbarriers on the relationship between customer satisfactionand customer retention are also confirmed

    Perceived Usefulness of Internet for Adopters and Non-adopters: An Empirical Analysis of Retired Senior Citizens in Hong Kong

    Get PDF
    Intense competition in Hong Kong Internetservice market has resulted in increasingly sophisticatedmarketing practices by service providers, such as marketsegmentation and targeting. Senior citizens have nowbecome a focus of attention of Internet businesscompanies. However, perceived usefulness of Internet onpart of retired senior citizens has not been studiedadequately. The present study is intended to fill thisimportant gap. Survey questionnaire was employed as themeans of data collection. The main results revealed thatadopters perceive Internet services significantly moreuseful than non-adopters. However, there is no significantdifference between perceptions of male and femaleadopters

    Mainland Chinese Tourists’ Expectations, Perceived Performance of and Satisfaction towards Shopping Malls in Hong Kong

    Get PDF
    Tourists from mainland China constitute one of the world's biggest and fastest-growing travel markets. The Hong Kong Tourism Board expects the frequency of the mainland Chinese tourists to grow steadily. One of the beneficiaries of this phenomenon is Hong Kong’s shopping malls. However, understanding of tourists from mainland China’s expectations from, perceived performance of and satisfaction with the shopping malls’ attributes in Hong Kong is inadequate. This study intends to fill this important gap. A survey questionnaire was employed for data collection. The main results reveal the mainland Chinese tourists’ levels of satisfaction, indifference and dissatisfaction as well as the relationship between shopping malls’ attributes and customer satisfaction

    Use of switching barriers to retain customers: Online retail stock traders in Hong Kong

    Get PDF
    Why some customers decide to stay withexisting service provider after having thought of switchinghas apparently not been examined adequately in extantresearch. The purpose of this research is to identifyfactors relevant to building constructs to representswitching barriers in online retail stock trading industryin Hong Kong. Review of extant literature, development ofa questionnaire and focus group interviews are the threeprincipal methods used for this research. Four factors thatare relevant for measuring switching barriers areidentified: two positive barriers involve service recoveryand trust and two negative barriers relate to higherswitching costs and lack of attractive alternatives

    Electrostatic Contribution of Surface Charge Residues to the Stability of a Thermophilic Protein: Benchmarking Experimental and Predicted pKa Values

    Get PDF
    Optimization of the surface charges is a promising strategy for increasing thermostability of proteins. Electrostatic contribution of ionizable groups to the protein stability can be estimated from the differences between the pKa values in the folded and unfolded states of a protein. Using this pKa-shift approach, we experimentally measured the electrostatic contribution of all aspartate and glutamate residues to the stability of a thermophilic ribosomal protein L30e from Thermococcus celer. The pKa values in the unfolded state were found to be similar to model compound pKas. The pKa values in both the folded and unfolded states obtained at 298 and 333 K were similar, suggesting that electrostatic contribution of ionizable groups to the protein stability were insensitive to temperature changes. The experimental pKa values for the L30e protein in the folded state were used as a benchmark to test the robustness of pKa prediction by various computational methods such as H++, MCCE, MEAD, pKD, PropKa, and UHBD. Although the predicted pKa values were affected by crystal contacts that may alter the side-chain conformation of surface charged residues, most computational methods performed well, with correlation coefficients between experimental and calculated pKa values ranging from 0.49 to 0.91 (p<0.01). The changes in protein stability derived from the experimental pKa-shift approach correlate well (rβ€Š=β€Š0.81) with those obtained from stability measurements of charge-to-alanine substituted variants of the L30e protein. Our results demonstrate that the knowledge of the pKa values in the folded state provides sufficient rationale for the redesign of protein surface charges leading to improved protein stability

    Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses

    Get PDF
    BACKGROUND: Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL(pro)), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: Here, we profiled the substrate specificities of 3CL(pro) from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19 Γ— 8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CL(pro) prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CL(pro) from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CL(pro) prefers P4-Pro and SARS-CoV 3CL(pro) prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences 'VARLQ↓SGF' that can be cleaved efficiently by all 3CL(pro) with relative activity of 1.7 to 3.2, and 'VPRLQ↓SGF' that can be cleaved specifically by IBV 3CL(pro) with relative activity of 4.3. CONCLUSIONS/SIGNIFICANCE: The comprehensive substrate specificities of 3CL(pro) from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases

    Profiling of Substrate Specificity of SARS-CoV 3CLpro

    Get PDF
    BACKGROUND: The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-coronavirus is required for autoprocessing of the polyprotein, and is a potential target for treating coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a thorough understanding of substrate specificity of the protease, a substrate library of 198 variants was created by performing saturation mutagenesis on the autocleavage sequence at P5 to P3' positions. The substrate sequences were inserted between cyan and yellow fluorescent proteins so that the cleavage rates were monitored by in vitro fluorescence resonance energy transfer. The relative cleavage rate for different substrate sequences was correlated with various structural properties. P5 and P3 positions prefer residues with high Ξ²-sheet propensity; P4 prefers small hydrophobic residues; P2 prefers hydrophobic residues without Ξ²-branch. Gln is the best residue at P1 position, but observable cleavage can be detected with His and Met substitutions. P1' position prefers small residues, while P2' and P3' positions have no strong preference on residue substitutions. Noteworthy, solvent exposed sites such as P5, P3 and P3' positions favour positively charged residues over negatively charged one, suggesting that electrostatic interactions may play a role in catalysis. A super-active substrate, which combined the preferred residues at P5 to P1 positions, was found to have 2.8 fold higher activity than the wild-type sequence. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated a strong structure-activity relationship between the 3CL(pro) and its substrate. The substrate specificity profiled in this study may provide insights into a rational design of peptidomimetic inhibitors

    Coverage versus supply cost in facility location:physics of frustrated spin systems

    Get PDF
    A comprehensive coverage is crucial for communication, supply, and transportation networks, yet it is limited by the requirement of extensive infrastructure and heavy energy consumption. Here, we draw an analogy between spins in antiferromagnet and outlets in supply networks, and apply techniques from the studies of disordered systems to elucidate the effects of balancing the coverage and supply costs on the network behavior. A readily applicable, coverage optimization algorithm is derived. Simulation results show that magnetized and antiferromagnetic domains emerge and coexist to balance the need for coverage and energy saving. The scaling of parameters with system size agrees with the continuum approximation in two dimensions and the tree approximation in random graphs. Due to frustration caused by the competition between coverage and supply cost, a transition between easy and hard computation regimes is observed. We further suggest a local expansion approach to greatly simplify the message updates which shed light on simplifications in other problems

    A Preliminary Analysis of Combined Liver Resection With New Chemotherapy for Synchronous and Metachronous Colorectal Liver Metastasis

    Get PDF
    ObjectiveTo compare the survival between patients with synchronous and metachronous colorectal liver metastases after hepatectomy with new generation of perioperative chemotherapy.MethodsFrom October 2002 to January 2008, patients receiving hepatectomy for synchronous or metachronous colorectal liver metastasis were studied retrospectively.ResultsFifty-five patients (synchronous group = 35, metachronous group = 20) underwent hepatectomy for colorectal liver metastases. Besides younger age with male predominance, patients in the synchronous group had more tumour multinodularity and bilobe liver involvement. They had received less hepatic curative hepatectomy (81.1% vs. 100%) with a higher rate of peri-operative chemotherapy (91.4% vs. 50%) and postoperative morbidity (25.7% vs. 0%). However both groups had no statistical significant difference in median overall survival (OS) and disease free survival (DFS). Inferior OS and DFS were observed in the synchronous group for patients who had no peri-operative chemotherapy or those showing poor response to chemotherapy. The most favourable OS is observed in both groups after performing globally curative hepatectomy.ConclusionSynchronous colorectal liver metastasis is not a poor prognostic factor for survival when compared with the metachronous metastasis. Globally curative hepatectomy in combination of new generation of chemotherapy is recommended for the management of resectable colorectal liver metastasis
    • …
    corecore