Doctor of Philosophy

dissertationThe FDA antiviral drug, Tamiflu (oseltamivir) is the front-line antiviral drug for the fight against 2003 avian flu (H5N1) as well as, more recently, for the 2009 swine flu (H1N1pdm). The drug functions as a neuraminidase inhibitor that prevents the release of new virions. Unfortunately, there is emerging evidence that the neuraminidase mutations H274Y and N294S render oseltamivir ineffective against the H5N1 virus. Of greater concern is the growing likelihood of the emergence of similar oseltamivir-resistant strains of H1N1pdm. It is therefore critical to understand the mechanisms for mutation-induced drug resistance in the H5N1 and H1N1pdm flu viruses in order to develop new and effective therapies. As molecular dynamics (MD) simulations have become an important tool for the study of biological systems, this dissertation aims to employ MD simulations for computer-aided rational drug design. Specifically, different MD simulation techniques were utilized in the investigation of oseltamivir-resistant mechanisms of H5N1/H1N1pdm and for the development of new antiviral drugs. Chapter 1 is simply a general introduction to the whole thesis. Chapter 2 presents top-hits for H1N1pdm neuraminidase identified by virtual screening using ensemblebased docking technique, which incorporates protein flexibility into molecular docking. Next in Chapter 3, progress in the development of two related methodologies for calculation of solvation free energy, one called the Coupled Reference Interaction Site model-hyper-netted chain/molecular dynamics (RISM/MD) approach, and another called Molecular Mechanics Poisson?Boltzmann linear response approximation and surface area contributions (MMPB-LRA-SA), are presented. The methods are expected to be applicable to the lead refinement process since they provide more reliable results than the continuum model but are less computationally expensive than conventional MD methods. In Chapter 4, we discuss our observations based on drug-protein endpoint interactions on how the mutations H274Y and N294S induce oseltamivir resistance in neuraminidase N1 subtypes. However, since the two mutations are non-active-site, endpoint interactions alone cannot fully account for the drug resistance. In Chapter 5, we present our finding of the drug binding pathway through electrostatic surface potential and steered MD simulation. The results reveal a novel oseltamivir-resistant mechanism in which the mutations rupture the drug binding funnel, in conjuction with the findings reported in Chapter 4. Our study not only assists understanding of oseltamivir-resistance in neuraminidase N1 subtypes, but also bears several important consequences for the intelligent design of new inhibitors that can overcome the established resistance strain

Willingness to Pay for the Preservation of Lo Go - Xa Mat National Park in Vietnam

Lo Go - Xa Mat National Park has great value in terms of biodiversity but preserving the park is a great challenge for the Vietnamese government. This study estimated the willingness to pay of households to preserve Lo Go - Xa Mat National Park, using the contingent valuation method. We employed the single-bounded dichotomous choice question format to estimate how much households in Ho Chi Minh City were willing to contribute towards a preservation plan for the park. This plan comprised twelve preservation activities and compensating the local communities for their foregone income. The study found that households in Ho Chi Minh City were willing to pay at least VND 6,209 per month for three years for the preservation of Lo Go - Xa Mat National Park. With protest votes included, factors strongly affecting households' willingness to pay were bid amount and the amount of their monthly electricity bill. The education level of the respondents and the number of working people in the household had significant but lesser impact on their willingness to pay. Without protest votes, the bid amount, monthly electricity bill amount and education level of respondents significantly affected willingness to pay. We found that the annualized benefit value of the project was larger than its annualized cost. This indicated that the preservation plan was economically viable. This study does not provide the total value of Lo Go - Xa Mat National Park, but it shows the great value of the park in terms of local households' willingness to pay for its preservation and this is important information for policy-makers in deciding how to protect the park efficiently.willingness to pay, Vietnam

Government Crisis Assessment and Reputation Management. A case study of the Vietnam Health Minister’s crises in 2013-2014

In Vietnam, many government announcements have gathered negative receptions from the public. Among them, Ms. Nguyen Thi Kim Tien, Vietnam Minister of Health, has received more of it. Through the case study of Ms. Kim Tien’s many scandals during the 2013-2014 period, this study is interested to see if the health scandals eventually elevated into a government crisis, how they affected the minister’s reputation, and what she could have done to better respond to the public. This study examined news articles on such health scandals to confirm whether the health scandals indeed escalated to be a government crisis. It also identified the advantages and disadvantages of Ms. Kim Tien’s responses in restoring her reputation to the public to understand what factors contributed to public dissatisfaction toward the minister. This study concluded that poorly-managed health scandals eventually elevated into a government crisis and greatly affected the minister’s reputation. It is suggested that PR is what the government needs to deal with such situations. The research also leaves room for a quantitative approach to the case to increase the result’s validity and representativeness. Until now, as the health issues and the resignation appeals are still needed, the crisis management effort should get more attention from the government, and such study is needed to better understand the situation

Struggles for Women-Inclusive Leadership in Toraja Church in Indonesia and the Evangelical Church of Vietnam

Traditionally, women in Vietnam have been seen as the sole nurturer and care-taker of the family. Similarly, recent reports show that both men and women in Vietnam expect women to behave in a socially constrained way. Women’s struggle for leadership in religious organizations in Southeast Asia has been particularly characterized with various levels of accomplishment. This study takes the Toraja Church in Indonesia and the Evangelical Church of Vietnam as two cross-cultural case studies. As the main causes of change in the churches, the author discusses (1) the degree of destabilizing forces from external context and institutional structure; (2) the degree of support and identification with the struggle by male leaders; and (3) the dominant existence of women’s feminist projects and their success in turning their feminist projects into collective effort

Truth Telling in Peacebuilding: A Buddhist Contribution

Truth telling has been recognized as important in the process of trauma healing and reconciliation according to modern peacebuilding theories. Studies have shown that truth telling is not a simple issue but involves problems and challenges that need research and solutions. This study contributes to this problem-solution or the question “How should difficult and painful truth be told in a way that minimizes harm and maximizes benefit for all?†by offering an alternative knowledge and method rooted in the Buddhist tradition. Based on textual study of the Majjhima Nikaya and Anguttara Nikaya, the paper argues that the Buddha’s teachings can widen the understanding and minimize potential problems with the work of truth telling whether in the collective or interpersonal context by providing a concrete systematic framework and criteria for reflection, making decision and communication of truth

How Vietnamese Organizations Perceive the Use of Social Media in Crisis Communication

Social media has proliferated into the everyday life of Vietnamese people. As a result, in the past years, Vietnam has seen many organizational crises that started on this platform. Social media has proven to be able to foster crises, thanks to open platforms that allow for relatively free discussion among strangers with common interests.  Nonetheless, Vietnamese organizations have often ignored or underutilized these channels in their crisis communication efforts. Organizations prioritize using traditional media in their crisis communication efforts and paid little to no attention to social media outlets, even if the crisis had started on social media channels. Through a survey with experienced Vietnamese PR practitioners, this research aims to understand this trend of crisis management and explore the perception of Vietnamese organizations toward the use of social media in crisis communication.Bahasa Indonesia Abstrak: Media sosial telah menjamur ke dalam kehidupan sehari-hari rakyat di Vietnam. Akibatnya, dalam beberapa tahun terakhir, Vietnam telah melihat banyak krisis organisasi yang dimulai pada platform ini. Media sosial telah terbukti mampu menumbuhkan krisis, berkat platform terbuka yang memungkinkan diskusi bebas  untuk kepentingan bersama. Meskipun demikian, organisasi di Vietnam sering mengabaikan atau kurang memanfaatkan saluran-saluran ini dalam upaya krisis komunikasi yang mereka alami. Organisasi lebih memprioritaskan menggunakan media tradisional dalam upaya menanggulangi krisis komunikasi mereka dan sedikit memberikan perhatian kepada outlet media sosial, bahkan jika krisis telah dimulai pada saluran media sosial. Melalui survei yang dilakukan oleh praktisi PR di Vietnam yang berpengalaman, penelitian ini bertujuan untuk memahami tren manajemen krisis ini dan mengeksplorasi persepsi organisasi di Vietnam terhadap penggunaan media sosial dalam komunikasi krisis.