Digital Commons Network^™

Metabolic Alterations And Cardiovascular Risk After Hepatitis C Cure In Subjects With Or At Risk For Hiv, Christophe Maxime Fokoua Dongmo

Legacy Theses & Dissertations (2009 - 2024)

Background. Hepatitis C virus (HCV) infection engenders substantial metabolic changes. These changes are altered when the virus is cleared after successful treatment. We measured these metabolic alterations that occur after HCV cure; further, we assessed whether these alterations differed in subgroups defined by patients’ characteristics.

Decision-Analytic Models Using Reinforcement Learning To Inform Dynamic Sequential Decisions In Public Policy, Seyedeh Nazanin Khatami

Doctoral Dissertations

We developed decision-analytic models specifically suited for long-term sequential decision-making in the context of large-scale dynamic stochastic systems, focusing on public policy investment decisions. We found that while machine learning and artificial intelligence algorithms provide the most suitable frameworks for such analyses, multiple challenges arise in its successful adaptation. We address three specific challenges in two public sectors, public health and climate policy, through the following three essays. In Essay I, we developed a reinforcement learning (RL) model to identify optimal sequence of testing and retention-in-care interventions to inform the national strategic plan “Ending the HIV Epidemic in the US”. …

Neural Oscillatory Activity Serving Sensorimotor Control Is Regulated By The Mitochondrial Redox Environment In Health And Disease, Rachel Spooner

Theses & Dissertations

Despite effective regimens of combination antiretroviral therapy, individuals with HIV are still at higher risk for developing forms of cognitive impairment, with one of the most common behavioral abnormalities to manifest being motor dysfunction. This is an important consideration, as deficits in motor control likely contribute to higher-order cognitive impairments, which together, lead to functional dependencies in the ever-growing aging population of HIV-infected adults. While the neuroanatomical bases of motor dysfunction have recently been illuminated in people living with HIV (PLWH), there remains an open question regarding the molecular processes supporting the circuit-level neuronal dynamics that potentially serve these behavioral …

Std Prevention: An Educational Intervention For Exotic Dancers, Maria Delurdes Dehoyos

Electronic Theses and Dissertations

The Centers for Disease Control and prevention reported nearly 2.3 million STD cases diagnosed in 2017, and the number is continuing to rise. San Antonio, Texas, is ranked third in the state of Texas with the highest STD rates and leading in the state with congenital syphilis. There is an increased risk for contracting STDs working in the sex industry. There are little to no studies pertaining to any educational interventions offered to exotic dancers to increase personal knowledge on STDs. This research has focused on an educational intervention offered by a nurse practitioner to exotic dancers in two adults-only …

Sexual Behaviors Associated With Online Partner-Seeking Among Men Who Have Sex With Men From Small/Midsized Towns Or Rural Areas In Kentucky, Vira Pravosud

Theses and Dissertations--Epidemiology and Biostatistics

The HIV epidemic remains one of the most significant public health issues in the United States, particularly among men who have sex with men (MSM). New avenues for partner-seeking have emerged over the past three decades, including through the Internet, social media, and geosocial networking applications. Consisting of three cross-sectional studies, this dissertation research aimed to determine associations between the use of various online tools for partner-seeking (hereafter collectively referred to as “apps”) and HIV-related sexual behaviors among 252 young adult MSM residing in small/midsized towns or rural areas in Central Kentucky, a group that has been under-represented in the …

The Use Of Heterocycles As Important Structures In Medicinal Chemistry, Sayre Weast

Honors Theses

Heterocycles have many applications in the discipline of medicinal chemistry. These structures are found in various natural products with relevant biological activity. Our research group, in collaboration with two others, is particularly interested in one heterocycle, quinoline, as a scaffold for HIV-1 integrase inhibitors. A synthetic route has been developed to produce a derivatized structure on small scale. One goal of this thesis was to expand the scale of this route to provide increased quantities of the quinoline scaffold. Procedures were adapted to accommodate the increase in scale to convert commercially available anthranilic acids to quinolines via the isatoic anhydride. …

Hiv/Aids In The Latino Community Of San Francisco: Past And Present, Jessica Da Silva

School of Professional Studies

There are approximately 122,000 people of Latino origin in San Francisco, which account for 15% of the total population (Census, 2010). Historically, Latinos have and still face several barriers to access healthcare and improvements in health (Aguirre-Molina, Molina & Zambrana, 2001). When the world was exposed to the spread of a new and unknown virus, the broader population suffered from the epidemic. The Latino community in San Francisco was and still is one of the hardest hit by the virus.

Characterization And Quantification Of Covalent Modification Of Proteins Using Mass Spectrometry, Pratikkumar N. Rathod

Dissertations, Theses, and Capstone Projects

Identification and characterization of various post-translational modifications of protein is a key to understanding many unknown cellular processes. In the last few decades, mass spectrometry has evolved as an essential and effective analytical tool for qualitative and quantitative analysis of proteins. In this research, we have developed a novel MALDI-MS² based quantification method for Desmosine and Isodesmosine, which served as cross-linking amino acids of elastin, in order to measure the elastin degradation in the body. This is the first quantification method that not only illustrates the potential of MALDI-Ion Trap MS², but also improvement over the current …

Capacity Of Human Immunodeficiency Virus Targeting Chimeric Antigen Receptor T Cells To Eliminate Follicular Dendritic Cells Bearing Human Immunodeficiency Virus Immune Complexes, Matthew T. Ollerton

Theses and Dissertations

An important obstacle to a functional cure for HIV/AIDS is the persistence of viral reservoirs found throughout the body in various cells and tissues. Reservoirs can be latently infected cells, or in the case of follicular dendritic cells (FDC), non-infected cells that trap infectious virus on their surface through immune complexes (HIV-IC). Although several strategies have been employed to target and eliminate viral reservoirs, they are short-lived and ineffective. In an attempt to provide a long-term approach, chimeric antigen receptor T (CAR-T) cells were designed to eliminate native HIV on FDCs. Although effective at eliminating HIV-infected cells, and halting spreading …

Capacity Of Human Immunodeficiency Virus Targeting Chimeric Antigen Receptor T Cells To Eliminate Follicular Dendritic Cells Bearing Human Immunodeficiency Virus Immune Complexes, Matthew T. Ollerton

Theses and Dissertations

An important obstacle to a functional cure for HIV/AIDS is the persistence of viral reservoirs found throughout the body in various cells and tissues. Reservoirs can be latently infected cells, or in the case of follicular dendritic cells (FDC), non-infected cells that trap infectious virus on their surface through immune complexes (HIV-IC). Although several strategies have been employed to target and eliminate viral reservoirs, they are short-lived and ineffective. In an attempt to provide a long-term approach, chimeric antigen receptor T (CAR-T) cells were designed to eliminate native HIV on FDCs. Although effective at eliminating HIV-infected cells, and halting spreading …

Association Between Hiv And Violence Among Female Commercial Sex Workers In Ukraine : Analysis Of Bio-Behavioral Surveillance Conducted In 2015-2016, Ganna Momotyuk

Legacy Theses & Dissertations (2009 - 2024)

A cross-sectional analysis investigated the association between HIV and violence in female commercial sex workers (FCSW) in Ukraine between 10/2015 and 01/2016. Methods: 3,885 FCSW from a total of 4,300 were questioned about behavioral and social demographics and tested for HIV in mobile testing van. Results: of the 3,885 respondents, 5.89% were HIV positive, and 47.00% had experienced violence. We tested for and found that drug use was an effect modifier for the association between HIV and violence. Analyses were stratified by injecting drug use and no injecting drug use. High risk for HIV was found in the non-IDU stratum …

The Utility Of Mobile Phones For Health Among Women Living With Hiv In Urban Malawi, Linda Marie Dietrich

Theses and Dissertations

The use of mobile phones are becoming ubiquitous with growing interest by healthcare providers to utilize mobile phone technology for various health-related applications, called mHealth. This is especially true in low-income countries such as those in sub-Saharan Africa. When implementing mHealth applications, it is important to understand the dynamic social, cultural and environmental factors where mHealth will be implemented to ensure that interventions developed are effective. A qualitative study to explore the sociotechnical factors experienced by women participating in an HIV support group in urban Malawi was conducted to enhance our understanding of women’s experience with mobile phone use and …

Multilevel Analysis Of Individual, Neighborhood, And Health Care Facility Characteristics Associated With Achievement And Maintenance Of Hiv Viral Suppression Among Persons Newly Diagnosed With Hiv In New York City, Ellen W. Wiewel

Dissertations, Theses, and Capstone Projects

Objective

To investigate the effect of individual, health care facility, and neighborhood characteristics on achievement and maintenance of HIV viral suppression, among New York City residents aged 13 years and older diagnosed with HIV between 2006 and 2012.

Methods

I used individual-level data from the New York City HIV surveillance registry and Case Surveillance-Based Sampling, facility-level data from the surveillance registry, and neighborhood-level data from the U.S. Census and American Community Survey. The outcomes of interest were first viral suppression after diagnosis (Aims 1 and 3; ≤400 copies/mL) and virologic failure after first suppression among persons who achieved suppression (Aim …

Study Of Infectious Diseases By Mathematical Models: Predictions And Controls, Sm Ashrafur Rahman

Electronic Thesis and Dissertation Repository

The aim of this thesis is to understand the spread, persistence and prevention mechanisms of infectious diseases by mathematical models. Microorganisms that rapidly evolve pose a constant threat to public health. Proper understanding of the transmission machinery of these existing and new pathogens may facilitate devising prevention tools. Prevention tools against transmissions, including vaccines and drugs, are evolving at a similar pace. Efficient implementation of these new tools is a fundamental issue of public health. We primarily focus on this issue and explore some theoretical frameworks.

Pre-exposure prophylaxis (PrEP) is considered one of the promising interventions against HIV infection as …

Mathematical Modeling Of Communicable Imported Diseases Screening In The United Arab Emirates, Lahbib Ben Ahmadi

Theses

The United Arab Emirates (UAE), as one of the countries with high numbers of expatriates in the world, is expected to face public health challenges. The reason for this situation is that the majority of those expatriates belong to regions where health issues are usually left behind. This may create the possibility of having imported communicable diseases. However, screening policy should be tested and adapted to protect the population from any imported communicable disease. This study aims at identifying an approach and method to deal with these imported diseases via a set of differential equations. The spread of a communicable …

Platinum Complexes And Zinc Finger Proteins: From Target Recognition To Fixation, Samantha Tsotsoros

Theses and Dissertations

Bioinorganic chemistry strives to understand the roles of metals in biological systems, whether in the form of naturally occurring or addition of non-essential metals to natural systems. Metal ions play vital roles in many cellular functions such as gene expression/regulation and DNA transcription and repair. The study of metal-protein-DNA/RNA interactions has been relatively unexplored. It is important to understand the role of metalloprotein interactions with DNA/RNA as this enhanced knowledge may lead to better understanding of diseases and therefore more effective treatments. A major milestone in the development of this field was the discovery of the cytotoxic properties of cisplatin …

Design And Synthesis Of Novel Sultams As Non-Nucleoside Inhibitors Of Hiv Reverse Transcriptase, Brian Chadwick Lecroix

Doctoral Dissertations

The compound 2-methyl-3-phenyl-2,3-dihydro-1,2-benzisothiazole 1,1-dioxide (NSC 108406) was identified as an HIV-1 reverse transcriptase inhibitor by the National Cancer Institute. Using this lead, the Baker group has developed a series of analogues with various groups at the 3-position that show a spectrum of biological activities. In the end, the substituents used could not compare to the biological activity of the inhibitor efavirenz (Sustiva^® [trademark]), and so it was decided to synthesize sultams with alkylethynyl substituents at the 3-position of the sultams in an attempt to mimic the activity of efavirenz.

Previous research analyzed the proposed novel sultams in the modeling …

Comparison Of Methodologies For Synthesis Of 3-(Cyclopropylethynyl)Benzisothiazole 1,1-Dioxide, Rachel Lee Naramore

Chancellor’s Honors Program Projects

No abstract provided.

Interactions Of The Human Immunodeficiency Virus Type 1 Nucleocapsid Protein With Non-Hiv-Derived Nucleic Acids : Implications For The Viral Replication Cycle, Abhijit Padmakar Jadhav

Legacy Theses & Dissertations (2009 - 2024)

During attempts to develop aptamers that bind to the nucleocapsid protein of HIV-1 (i.e. NCp7) with high affinity, a heretofore unreported property of the protein--the ability to mediate degradation of nucleic acids, was discovered. Using λ DNA as a model nucleic acid system, it was shown that NCp7-mediated degradation of nucleic acids is non-specific, depends on incubation time, the concentration of NCp7, and the presence of divalent and monovalent cations. It was further demonstrated that degradation can be abrogated if NCp7 is pre-incubated with NCp7-inhibitors. Lyophilization of NCp7 can induce irreversible changes in its secondary structure that result in loss …

Follicular Dendritic Cells, Resting Cd4+ T Cells And Human Immunodeficiency Virus Expression, Changna Wang

Theses and Dissertations

Many events associated with Human Immunodeficiency Virus (HIV) infection/replication occur in and around the germinal centers (GCs) of secondary lymphoid tissues where follicular dendritic cells (FDCs) reside, suggesting that this microenvironment may contribute unique signaling that is important to viral progression. My research focused on characterizing signaling, both positive and negative, contributed by FDCs that affects HIV infection and replication. Specifically, I determined if FDC signals could induce the expression of latent HIV in T cells and if so, to characterize the signaling pathways involved. Moreover, I also examined the ability of FDCs to produce inhibitory signals that might block …

Sonication Assisted Synthesis Of Oligomannosides, Christabel Tomla Tanifum

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Oligomannosides prevalently exist as cell surface antigens. They play important roles in diseases such as viral infection and cancer, and they have been shown to be useful as candidates for vaccines. HIV, one of the most devastating modern diseases, has a high content of mannose sugars on its envelope glycoprotein gp120. Oligomannosides of the HIV virus, also called Man9, which are found on the glycoprotein gp120, have been shown to play a protective role for the HIV virus, shielding highly conserved protein domains of gp120 from proteolytic attacks. Thus gp120 plays an important role in HIV infection of cells, being …

Modeling Hiv Drug Resistance, Mingfu Zhu

All Dissertations

Despite the development of antiviral drugs and the optimization of therapies, the emergence of drug resistance remains one of the most challenging issues for successful treatments of HIV-infected patients. The availability of massive HIV drug resistance data provides us not only exciting opportunities for HIV research, but also the curse of high dimensionality.
We provide several statistical learning methods in this thesis to analyze sequence data from different perspectives. We propose a hierarchical random graph approach to identify possible covariation among residue-specific mutations. Viral progression pathways were inferred using an EM-like algorithm in literature, and we present a normalization method …

Discrete Nondeterministic Modeling Of Biochemical Networks, John R. Jack

Doctoral Dissertations

The ideas expressed in this work pertain to biochemical modeling. We explore our technique, the Nondeterministic Waiting Time algorithm, for modeling molecular signaling cascades. The algorithm is presented with pseudocode along with an explanation of its implementation. The entire source code can be found in the Appendices. This algorithm builds on earlier work from the lab of Dr. Andrei Nun, the advisor for this dissertation. We discuss several important extensions including: (i) a heap with special maintenance functions for sorting reaction waiting times, (ii) a nondeterministic component for handling reaction competition, and (iii) a memory enhancement allowing slower reactions to …

Regulators Of G-Protein Signaling, Rgs13 And Rgs16, Are Associated With Cxcl12-Mediated Cd4+ T Cell Migration, Lijin Xia

Theses and Dissertations

Chemokines are important chemical signals that guide lymphocyte movement within the immune system and promote the organization and functions of germinal centers (GCs) in the secondary lymphoid tissues. Previous studies have shown that GC T cells exhibit high expression of chemokine receptor 4, CXCR4, but that these cells are unable to migrate to the ligand for this receptor, the chemokine CXCL12. This “migratory paralysis” to CXCL12 was found to be correlated with the expression of two Regulators of G-protein Signaling, RGS13 and RGS16 in the GC T cells. The objective of my research was to determine whether RGS13 and RGS16 …

Hiv/Aids Relative Survival And Mean Residual Life Analysis, Xinjian Zhang

Mathematics Theses

HIV/Aids Relative Survival and Mean Residual Life Analysis BY XINJIAN ZHANG Under the Direction of Gengsheng (Jeff) Qin and Ruiguang (Rick) Song ABSTRACT Generalized linear models with Poisson error were applied to investigate HIV/AIDS relative survival. Relative excess risk for death within 3 years after HIV/AIDS diagnosis was significantly higher for non-Hispanic blacks, American Indians and Hispanics compared with Whites. Excess hazard for death was also higher in men injection drug users compared with men who have sex with men (MSM). The relative excess hazard of old HIV/AIDS patients is significantly higher compared with younger patients. When CD4 increased, the …

Structure And Energetics Of Rna - Protein Interactions For Hiv Rreiib Targeting Zinc Finger Proteins., Subrata H. Mishra

Chemistry Dissertations

RNA - protein interactions constitute a vital part of numerous biochemical processes. In the HIV life cycle, the interaction of the viral protein Rev and the Rev Responsive Element (RRE), a part of unspliced HIV RNA, is crucial for the propagation of infectious virions. Intervention of this interaction disrupts the viral life cycle. Rev - RRE interaction initially occurs at a high affinity binding site localized to a relatively small stem loop structure called RREIIB. This binding event has been well characterized by a variety of biochemical, enzymatic and structural studies. Our collaborators have previously demonstrated the efficacy of zinc …

On Modeling Hiv Infection Of Cd4+ T Cells, Amy Comerford

Electronic Theses and Dissertations

We examine an early model for the interaction of HIV with CD4+ T cells in vivo and define possible parameters and effects of said parameters on the model. We then examine a newer, more simplified model for the interaction of HIV with CD4+ T cells that also considers four populations: uninfected T cells, latently infected T cells, actively infected T cells, and free virus. The stability of both the disease free steady state and the endemically infected steady state are examined utilizing standard methods and the Routh-Hurwitz criteria. We show that if N, the number of infectious virions produced per …