HIV neutralization through use of antibodies and pharmacokinetics of topical applications

Thesis (M.A.)--Boston UniversityThe Human Immunodeficiency Virus Type 1 (HIV-1), a sexually transmitted retrovirus that causes the Acquired Immunodeficiency Syndrome (AIDS), infects over two million people a year. Several methods introduced to prevent HIV-1 transmission, such as condoms, circumcision and antiretroviral drugs, have proven to be partially effective, but more effective approaches are being sought. Topical microbicides are being developed to provide a women-controlled method to prevent the transmission of HIV-1. Unfortunately, most of the candidate microbicide compounds tested to date have either elicited undesirable mucosal inflammation and epithelial lesions leading to increased seroconversions, or have been ineffective. One novel approach currently being explored is the use of monoclonal antibodies as components of topical microbicides. Monoclonal antibodies can be produced inexpensively by transfection into Nicotiana plants. We hypothesize that anti-HIV monoclonal antibodies produced in Nicotiana (MAb-N) will be effective in neutralizing HIV- 1 when used as topical microbicides at mucosal sites, and set out to test whether they retain their efficacy under physiological conditions. We tested the pharmacodynamics of anti-HIV MAb-N efficacy in Cynomolgus macaques following application of the antibodies in the vaginal compartment. We further studied the ability of MAb-N to cross through the vaginal epithelium using an EpiVaginal tissue model. To determine the pharmacodynamics of HIV neutralizing activity after the application of anti-HIV MAb-Ns to the vaginal mucosa, we used a neutralization assay based on HIV-expression in the TZM-bl cell line to test the efficacy of various doses of MAbs in a time course after they had been administered intravaginally in gel form to Cynomolgus macaques. To determine the pharmacokinetics of Mab-N transport across the vaginal epithelium, monoclonal antibodies were added to the apical surface, and a human-IgG ELISA was used to detect Mab-N that had crossed the epithelium into the basal supernatant. Immunohistology was used to confirm and validate ELISA data for evidence of transfer of Mabs across the epithelial layer. Our results show that anti-HIV MAb-Ns were effective in neutralizing cell-free HIV in TZM-bl neutralization assays. We found that MAb-Ns retained their anti-viral efficacy in monkeys after 4-hours. However, neutralizing activity was decreased after 24- hours and 72-hours, with wide variability in effectiveness between individual macaques. Mab-ns tested in the EpiVaginal tissue model showed minimal transfer of antibodies across the epithelium, ranging from 0.005% to 0.09%. Immunohistological data showed that antibodies applied apically to tissue models concentrated only in the superficial layers of the stratum corneum and did not penetrate the epithelium. Our data indicate that anti-HIV MAb-Ns are effective in neutralizing HIV-1 following vaginal application for at least 4 hours, and that they do not pass through the vaginal epithelium in significant amounts. Our data support their further development as vaginal microbicides

Understanding the Formation of Software as a Service (Saas) Commitment the Relational Value Creation Perspective

This study focuses on the use of an important IT innovation--software-as-a-service (SaaS), and draw on sensemaking and the dedication-constraint framework to explain the formation of SaaS commitment. Building on and extending prior studies, we posit that managers’ perceived relational value from SaaS consumption transforms their initial sensemaking of SaaS features into commitment. SaaS features are characterized as strength frames and weakness frames. Perceived relational values are conceptualized as process flexibility, task-knowledge coordination, process specificity, and trust. The proposed model and hypotheses are largely supported by the empirical data from 169 SaaS client firms. We discuss theoretical and practical implications

Understanding Knowledge Outcome Improvement in Virtual Communities: an Integrative Model from a Relational Development Perspective

This study seeks to understand how relational virtual communities (RVC) members improve knowledge outcomes, including reuse and new use of knowledge. We propose a model by integrating dedication/constraint mechanisms into social cognitive theory. This model delineates the relationship between members’ self-belief, motivation, and knowledge outcomes. In particular, self-belief is conceptualized as individual factors and environments factors. Motivation is based on one’s evaluation on interpersonal relationship development, in terms of relationship rewards and identity verification. Empirical results from survey data support most proposed hypotheses. We discuss the implications of our results

Knowledge-Based Clubhouse Adoption Intention in the Post-COVID-19 Era in the Hospitality Industry

The COVID-19 pandemic has affected the digital transformation of the hospitality industry and triggered Clubhouse knowledge adoption behavior. Clubhouse engagement in the COVID-19 era has gradually changed the forms of communication. Hospitality industry owners can communicate about their interactions and trades through Clubhouse, and members can share their operating and management experiences. Therefore, hospitality industry owners can learn from and support each other. This study aims to bridge the gap between professional knowledge and management adoption in the community of hospitality industry owners. We treat members’ self-regulated and socially regulated learning styles as variables in our analysis of members’ behaviors after acquiring knowledge from the community. This study contributes to our understanding of knowledge-based digital transformation processes in the hospitality industry in the post-COVID-19 era. It has implications for both Clubhouse users and hosts

Understanding Clients’ Intentions to Explore Software-as-a-Service (SaaS) Features: A Social Capital Theory Perspective

The pervasive post-adoption of on-demand software-as-a-service (SaaS) products via the Internet has provided clients with sufficient convenience and functional flexibility to rent and build the multifunctional services they require. Prior research has called for a deeper understanding of how client firms encourage the exploration of SaaS applications in the workplace. However, exploring the best service combinations depends on the clients’ socially related motivation. Hence, we draw on social capital theory in this study to examine clients’ intentions to explore new SaaS service features. We use service quality to complement structural capital as an indicator, as it is more suitable for assessing the service structure of systems. Drawing on a sample of 246 employees in the IT service departments of small- and medium-sized companies in Taiwan, we generate the following empirical results. First, most of the main effect paths only show significant positive signs for the effect of relational capital on the intention to explore, and the effect of environmental quality on social capital is not supported. Second, we rebuild the mediation model to test the non-supported hypotheses and find that relational capital partially mediates the relationship between service quality and the intention to explore. The theoretical and practical implications of these findings are discusse

UNDERSTANDING POST-ADOPTION OF ONLINE SHOPPING CONTINUANCE USAGE THROUGH THE SOCIAL EXCHANGE THEORY

Electronic commerce researchers have retention of Consumers post-adoption continuance behavior attendees induce deep trust and service quality of online shopping behavior, thereby contributing to higher revenue and marketing strategy based on social exchange theory. This study provides additional information about the path from the service quality and trust to continuous usage. Also, this study investigates the different tendencies to continuance behavior by habit as a moderating effect within the conceptual model. According to the structural invariance test across moderating effect, it showed that: First, most of main effect paths showed significant positive signs only habit as moderator on trust in service provider is negative support. Second, the habit was supported as a moderator except for the trust in shopping-site to online shopping continuance interaction path. Unexpectedly, the positive moderating effect of habit tendency towards the path of trust in shopping-site to online shopping continuance in not significant. The theoretical and practical implications are discussed

Pentacene-Based Thin-Film Transistors With a Solution-Process Hafnium Oxide Insulator

Abstract—Pentacene-based organic thin-film transistors with solution-process hafnium oxide (HfOx) as gate insulating layer have been demonstrated. The solution-process HfOx could not only exhibit a high-permittivity (κ = 11) dielectric constant but also has good dielectric strength. Moreover, the root-mean-square surface roughness and surface energy (γs) on the surface of the HfOx layer were 1.304 nm and 34.24 mJ/cm2, respectively. The smooth, as well as hydrophobic, surface of HfOx could facilitate the direct deposition of the pentacene film without an additional polymer treatment layer, leading to a high field-effect mobility of 3.8 cm2/(V · s). Index Terms—Hafnium oxide, high permittivity, organic thinfilm transistor (OTFT), solution process, surface energy