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The HIV pandemic spawned a global biomedical research effort which continues today. Because of multinational clinical studies, doctors and health officials possess more tools than ever before for the effective prevention and treatment of HIV/AIDS. The relationship between the United States and Sub-Saharan African nations features prominently within this global

The HIV pandemic spawned a global biomedical research effort which continues today. Because of multinational clinical studies, doctors and health officials possess more tools than ever before for the effective prevention and treatment of HIV/AIDS. The relationship between the United States and Sub-Saharan African nations features prominently within this global research effort. More specifically, many of the most significant HIV-related research findings emanate from clinical trials with a unique multinational configuration: the study protocol is largely designed and funded by American sources but executed at clinical research sites in Sub-Saharan African countries like South Africa and Zimbabwe. This thesis investigates the context and ethics of this configuration, with a focus on US-backed trials conducted in South Africa specifically. Using data collected from semi-structured interviews conducted at South African HIV clinical research sites, this thesis uncovers two significant ethical problems: insufficient benefits delivered to South African clinical trial participants, and informal processes occurring alongside formal protocol. By examining scope, effects, and implications of these problems, it becomes clear that although this research system delivers powerful results, there exists room for improvement.
ContributorsGill, Kohinoor Singh (Author) / Hurlbut, Ben (Thesis director) / Ripley, Charles (Committee member) / Vanig, Thanes (Committee member) / School of Politics and Global Studies (Contributor) / WPC Graduate Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description
Since the Acquired Immune Deficiency Syndrome (AIDS) crisis began in the early 1980s, there has been a significant amount of stigma attached to the disease and the virus that causes it, Human Immunodeficiency Virus (HIV). At the time, HIV/AIDS was viewed as a death sentence. A large part of the

Since the Acquired Immune Deficiency Syndrome (AIDS) crisis began in the early 1980s, there has been a significant amount of stigma attached to the disease and the virus that causes it, Human Immunodeficiency Virus (HIV). At the time, HIV/AIDS was viewed as a death sentence. A large part of the stigma came from the fact that in the early days of the crisis, AIDS patients were predominantly part of the LGBTQ+ community. With the discovery of effective antiretroviral therapies, today HIV can be thought of as a preventable, yet manageable, chronic illness, although it remains a huge public health concern (About HIV/AIDS, 2018). While the virus is now rarely viewed as a death sentence, there is still considerable stigma that surrounds people living with HIV/AIDS (PLWHA). Research shows that the shows and movies people watch can affect their attitudes on a variety of issues, and HIV is no exception. Because HIV is such a big threat to public health, and because people often adopt views they see in media, analyzing the ways shows and movies portray PLWHA is an important aspect in understanding where stigma surrounding HIV/AIDS comes from. The writers behind today's HIV+ characters on television and in movies all seemingly made an effort to decrease stigma, but they went about it in different ways, and with varying amounts of success. A common method to dispel stigma was to use the entertainment-education method (Singhal & Rogers, 1999), which in these cases means characters had discussions about topics like safe sex, Pre-Exposure Prophylaxis (PrEP), and the importance of getting tested. A few shows showed serodiscordant couples, which was also effective at fighting stigma. In contrast, by trying to be representative of PLWHA, some shows actually contributed to the stereotypes behind the stigma, or had characters be openly stigmatizing towards PLWHA. After analyzing what I found the shows and movies did well and what they did poorly, I'll analyze why it is important that shows maintained historical accuracy, and how doing so appeared to fight the stigma associated with HIV/AIDS. I will also evaluate what's missing \u2014 such as which high-risk groups are not represented. Ultimately, this thesis will argue that shows and movies made in the last 12 years all aimed to decrease stigma, through a variety of techniques.
ContributorsEvans, Celia Grace (Author) / Hurlbut, Ben (Thesis director) / Berkel, Cady (Committee member) / Blattman, Joseph (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
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Description
Viral protein U (Vpu) is a type-III integral membrane protein encoded by the Human Immunodeficiency Virus-1 (HIV- 1). It is expressed in infected host cells and plays vital roles in down-regulation of CD4 receptors in T cells and also in the budding of virions. But, there remain key structure/function questions

Viral protein U (Vpu) is a type-III integral membrane protein encoded by the Human Immunodeficiency Virus-1 (HIV- 1). It is expressed in infected host cells and plays vital roles in down-regulation of CD4 receptors in T cells and also in the budding of virions. But, there remain key structure/function questions regarding the mechanisms by which the Vpu protein contributes to HIV-1 pathogenesis and thus, it makes for an attractive target to study the structural attributes of this protein by elucidating a structural model with X-ray crystallography. This study describes a multi-pronged approach of heterologous over-expression of Vpu. The strategies of purification and biophysical/ biochemical characterization of the different versions of the protein to evaluate their potential for crystallization are also detailed. Furthermore, various strategies employed for the crystallization of Vpu by both in surfo and in cubo techniques, and the challenges faced towards the structural studies of this membrane protein by characterization with solution Nuclear magnetic resonance (NMR) spectroscopy are also described.
ContributorsDeb, Arpan (Author) / Leket-Mor, Tsafrir S (Thesis advisor) / Fromme, Petra (Committee member) / Mason, Hugh (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2016
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In 1996, President Clinton ordered the formation of the Advisory Committee on Human Radiation Experiments (ACHRE), which undertook to evaluate the morality of a myriad of secret and publicized radiation experiments ranging from 1944 to 1974. The goal of this thesis is to analyze the ways in which that committee

In 1996, President Clinton ordered the formation of the Advisory Committee on Human Radiation Experiments (ACHRE), which undertook to evaluate the morality of a myriad of secret and publicized radiation experiments ranging from 1944 to 1974. The goal of this thesis is to analyze the ways in which that committee formed moral evaluations and the extent to which its strategies related to a broader historical and philosophical discourse. Here I attempt to describe two specific techniques of simplification the committee deploys in order to make a retrospective moral analysis possible. Although the techniques comprise specific problems, frameworks, subjective perspectives, and conceptual links, their unifying principle is the field of choices the techniques produce. In the first technique I outline, I argue that by focusing on the problem of historical relativism, the committee gains a platform through which it would be granted flexibility in making a distinction between moral wrongdoing and blameworthiness. In the second technique of simplification I outline, I argue that the committee's incorporation of a principle to reduce uncertainty as an ethical aim allow it to establish new ways to reconcile scientific aims with moral responsibility. In addition to describing the structure of these techniques, I also demonstrate how they relate to the specific experiments the analysts aim to evaluate, using both the ACHRE experiments as well as the Nuremberg Trial experiments as my examples. My hope is not to show why a given committee made a particular moral evaluation, or to say whether a decision was right or wrong, but rather to illustrate how certain techniques open up a field of choices that allow moral analysts to form retrospective moral judgments.
ContributorsCirjan, Cristian (Author) / Hurlbut, Ben (Thesis director) / Humphrey, Ted (Committee member) / Zachary, Gregg (Committee member) / Barrett, The Honors College (Contributor)
Created2015-05
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Description
HIV continues to remain a global health issue, in particular in many low and middle-income countries. The World Health Organization (WHO) estimates that of the nearly 38 million HIV-1 positive individuals, 25% are unaware they are infected. Despite decades of research, a safe and effective preventative vaccine has yet to

HIV continues to remain a global health issue, in particular in many low and middle-income countries. The World Health Organization (WHO) estimates that of the nearly 38 million HIV-1 positive individuals, 25% are unaware they are infected. Despite decades of research, a safe and effective preventative vaccine has yet to be produced. The HIV-1 envelope glycoprotein41 and the Gag structural protein have been identified to be particularly important in HIV-1 transcytosis and cytotoxic lymphocyte response, respectively. Enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of glycoprotein (dgp41) comprising the membrane proximal external region (MPER), transmembrane domain and cytoplasmic tail may present a unique and safe way of presenting these proteins in a state mimicking their natural formation. Another form of presenting the immunogenic glycoprotein41, particularly the MPER component, is by presenting it onto the N-terminal of an IgG molecule, thereby creating an IgG fusion molecule. In our lab, both VLPs and IgG fusion molecules are highly expressed and purified within GnGn Nicotiana benthamiana. The results indicated that these recombinant proteins can be assembled properly within plants and can elicit an immune response in mice. This provides a preliminary step in using such Gag/dpg41 VLPs and RIC as present a safe, effective, and inexpensive HIV vaccine.
ContributorsGarcia, Izamar (Author) / Mor, Tsafrir (Thesis director) / Mason, Hugh (Committee member) / Kamzina, Aigerim (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Description

Plant-made virus-like particles (VLPs), composed of HIV-1 Gag and deconstructed gp41 proteins, have been shown to be safe and immunogenic in mice. Here, we report the successful production of HIV-1 Gag/dgp41 VLPs in Nicotiana benthamiana, using an enhanced geminivirus-based expression vector. This novel vector results in unique expression kinetics, with

Plant-made virus-like particles (VLPs), composed of HIV-1 Gag and deconstructed gp41 proteins, have been shown to be safe and immunogenic in mice. Here, we report the successful production of HIV-1 Gag/dgp41 VLPs in Nicotiana benthamiana, using an enhanced geminivirus-based expression vector. This novel vector results in unique expression kinetics, with peak protein accumulation and minimal necrosis achieved on day 4 post-infiltration. In comparing various purification strategies, it was determined that a 20% ammonium sulfate precipitation is an effective and efficient method for removing plant proteins and purifying the recombinant VLPs of interest. If further purification is required, this may be achieved through ultracentrifugation. VLPs are a useful platform for a variety of biomedical applications and developing the technology to efficiently produce VLPs in the plant expression system is of critical importance.

ContributorsFleming, Claire (Author) / Mor, Tsafrir (Thesis director) / Mason, Hugh (Committee member) / Kamzina, Aigerim (Committee member) / Barrett, The Honors College (Contributor) / Department of Physics (Contributor) / School of Life Sciences (Contributor)
Created2022-05