Medicine and Health Sciences Commons^™

Ls301 Fluorescence-Guided Photodynamic Therapy Of Brain Cancer Using Ppix Photosensitizer, Haini Zhang

McKelvey School of Engineering Theses & Dissertations

Incomplete brain tumor removal always causes neurologic deficit, disease recurrence and high mortality. Protoporphyrin IX (PpIX) accumulated in glioma cells with exogenous 5-aminolevulinic acid (5-ALA) serves as contrast agent for fluorescence-guided surgery and as well as acts as a photosensitizer for photodynamic therapy (PDT). However, the accurate tumor delineation using PpIX is limited by autofluorescence and superficial penetration depth. LS301 is a tumor-targeted near-infrared (NIR) contrast agent developed in our lab which allows deeper tumor imaging and avoids autofluorescence. My project aims to investigate whether LS301 can improve PpIX mediated PDT and tumor removal surgery. We have demonstrated co-localization of …

Identification Of Prognostic Cancer Biomarkers Through The Application Of Rna-Seq Technologies And Bioinformatics, Nathan Wong

McKelvey School of Engineering Theses & Dissertations

MicroRNAs (miRNAs) are short single-stranded RNAs that function as the guide sequence of the post-transcriptional regulatory process known as the RNA-induced silencing complex (RISC), which targets mRNA sequences for degradation through complementary binding to the guide miRNA. Changes in miRNA expression have been reported as correlated with numerous biological processes, including embryonic development, cellular differentiation, and disease manifestation. In the latter case, dysregulation has been observed in response to infection by human papillomavirus (HPV), which has also been established as both oncogenic in cervical cancers and oropharyngeal cancers and favorable for overall patient survival after tumor formation. The identification of …

Two-Component Hydrogel As Biomimetic Vitreous Substitutes, Sruthi Santhanam

McKelvey School of Engineering Theses & Dissertations

The vitreous humor of the eye is a biological hydrogel principally composed of fibrillary collagen interspersed with semi-flexible polyelectrolyte, hyaluronic acid (HA). Certain pathological conditions necessitate its removal and replacement. Current vitreous substitutes, such as silicone oils and perfluorocarbons, are hydrophobic, do not resemble the properties of the vitreous, and have known complications. An ideal vitreous substitute should have properties of the natural vitreous, perform its functions, and be biocompatible in the eye. Inspired by the structure and composition of the natural vitreous, we used bio-mimicry to develop an injectable two-component hydrogel. The hydrogel is composed of a fibrillary gellan, …

Development And Validation For A Mobile Speech-In-Noise Audiometric Task, Tommy Peng

McKelvey School of Engineering Theses & Dissertations

Traditional speech-in-noise hearing tests are performed by clinicians with specialized equipment. Furthermore, these tasks often present contextually weak sentences in background babble, which are poor representations of real-world situations. This study proposes a mobile audiometric task, Semantic Auditory Search, which uses the Android platform to bypass the need for specialized equipment and presents multiple tasks of two competing real-world conversations to estimate the user’s speech-in-noise hearing ability. Through linear regression models built from data of seventy-nine subjects, three Semantic Auditory Search metrics have been shown to have statistically significant (p < 0.05) with medium effects sizes for predicting QuickSIN SNR50. The internal consistency of the task was also high, with a Cronbach’s alpha of 0.88 or more across multiple metrics. In conclusion, this preliminary study suggests that Semantic Auditory Search can accurately and reliably perform as an automated speech-in-noise hearing test. It also has tremendous potential for extension into automated tests of cognitive function, as well.

Identification And Characterization Of An Interferon Stimulated Gene That Restricts Alphavirus Infection And Pathogenesis, Subhajit Poddar

Arts & Sciences Electronic Theses and Dissertations

Viral infection of host cells induces the Type I interferon (IFN) response, which is

characterized by the production of hundreds of IFN-stimulated genes (ISGs). Altogether, these

ISGs function to induce an antiviral state, hindering or blocking various steps of the viral

lifecycle. Many individual ISGs have potent and broad antiviral functions. However elimination

of a single ISG does not completely abrogate protection, suggesting that other ISGs, although

moderate or moderate when considered alone, must work cooperatively to provide optimal

antiviral activity.

In order to identify and characterize novel ISGs, an attenuated strain of the alphavirus

chikungunya (CHIKV-181/25) was tested against …

Expansion Of Microbial Virology By Impetus Of The Reduction Of Viral Dark Matter, Siddharth Ravindran Krishnamurthy

Arts & Sciences Electronic Theses and Dissertations

Modern metagenomic methods have rapidly accelerated the rate of viral discovery. Currently, to discover a novel virus, deep sequencing reads must align to a known reference virus. While alignment is effective at identifying closely related viruses, highly divergent viruses can often share no discernable sequence alignment with known viruses. Therefore, the accurate classification of viral dark matter – metagenomic sequences that originate from viruses but do not align to any reference virus sequences – is one of the major obstacles in not only discovering novel viruses, but also by extension, comprehensively defining the virome. As viral dark matter results fundamentally …

Participation In Governance And Well-Being In The Yukon Flats, Jessica Charlene Black

Arts & Sciences Electronic Theses and Dissertations

This dissertation explains the relationship between participation in governance and well-being in the Yukon Flats. To garner a deeper understanding of this relationship, definitions of governance and well-being are sought from the participants, thus providing holistic, Indigenous definitions of these concepts. Both formal and informal governance are also explored to understand the important institutions that underpin these larger relationships. Lastly, this dissertation investigates the relationship between participation in traditional hunting, fishing, and gathering and well-being in the Yukon Flats. Qualitative methods, including semi-structured interviews, observations, and photographs are all used to document these relationships. Applied thematic analysis is used due …

Mental Health And Academic Outcomes Among Adolescents In South Korean Orphanages, Hollee Ann Mcginnis

Arts & Sciences Electronic Theses and Dissertations

Research conducted over the past 100 years in Western nations support the adverse effects of orphanages on children’s emotional, developmental, and social well-being as well as economic costs to society (Save the Children UK, 2009; Bakermans-Kranenburg, Van IJzendoorn & Juffer, 2008; Williams & Greenberg, 2010). Globally, the number of orphaned and abandoned children is conservatively estimated to be around 143 million, of whom the majority reside in Asia, followed by Sub-Saharan Africa (UNICEF, UNAIDS, & USAID, 2004). South Korea (hereafter “Korea”) is an exemplary nation for study because it has a well-established child welfare system, including family-based alternatives (domestic and …

Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris

Arts & Sciences Electronic Theses and Dissertations

Here we characterized the initial antigen presenting cells (APCs) within the islet of Langerhans to ascertain their identity and functional role as it pertains to autoimmune diabetes. The activation of the adaptive immune system is induced by the innate immune system, and more specifically APCs. Therefore, it is crucial to identify the APCs that are initiating T1D in order to elucidate the break in tolerance and intervene in order to inhibit progression. We have found that there is a resident macrophage that is present in all strains of mice. This islet macrophage has a distinct transcriptional profile that is unique …

A Study On Factors Affecting Sleep During Pregnancy In Clinical Trials, Zihan Yan

Arts & Sciences Electronic Theses and Dissertations

Regular sleep is required for sensory processing, learning, and brain plasticity. During pregnancy, poor sleep quality and dysregulation of hormones are all associated with increased risk for diseases like postpartum major depression^[1]. Seventy-eight percent of pregnant women experience sleep problems at some point during pregnancy according to the National Sleep Foundation's 1998 Women and Sleep poll_. Chronodisruption is a frequent sleep disturbance experienced by pregnant women that can be primary or due to co-morbid conditions^[2]. For this reason, chronodisruption, which includes insomnia, is currently regarded as one of the most important factors determining pregnancy outcome. …

Flesh And Blood, Clayton Petras

Graduate School of Art Theses

In my work, I look for ways to visualize and document the degenerative mental disease of Parkinson’s and transform it into portrayals of the disease itself, its effects, and those it afflicts. Being a physical breakdown of the body, both popular culture and my own corporal understanding influence my interpretation and representation. This document outlines those influences and their buildup towards a shared understanding of the interests behind the work, as well as implies what the work does through these contexts.

How do we give identity to a disease that is difficult to diagnose or view on medical technology, currently …

Studies On Health, Place, And Education, Kelly Mcclelland Harris

Arts & Sciences Electronic Theses and Dissertations

Good health is positively associated with education outcomes, and likewise higher education-related achievement is positively associated with good health. Similarly, social disadvantage follows a cyclical pattern. It is cumulative; both accruing over the life course and across generations. Moreover, this relationship disproportionately impacts our most vulnerable populations, including both minorities and children living in or near poverty. For example, since the 1990s asthma, the most common chronic illness among youth, has seen the greatest increases in urban environments, and among racial and ethnic minorities in or near poverty. Still, consideration of the interdependence between health, place, and education remains underdeveloped …

The Effects Of The Gut Microbiota On The Host Chromatin Landscape, Nicholas Semenkovich

Arts & Sciences Electronic Theses and Dissertations

The human gut microbiota is home to tens of trillions of microbes belonging to all three domains of life. The structure and expressed functions of this community have myriad effects on host physiology, metabolism, and immune function. My studies focused on a facet of host-microbial interactions and mutualism that has not been explored to a significant degree in part because of the absence of suitable tools: namely, if, when, and how the gut microbiota produces durable effects on host biology through its impact on the epigenome. To address this area, I turned to gnotobiotic mice and developed a variety of …

Epigenetic Activation Of The Mouse T Cell Receptor Beta Recombination Center, Jiangyang Zhao

Arts & Sciences Electronic Theses and Dissertations

Lymphocytes are the work horses of adaptive immunity. Compared to the B lymphocyte lineage, early stage progenitors of T lymphocytes maintain considerable potential for differentiation into other hematopoietic lineages. T lineage commitment requires the continuous coordination of transcription factors (TFs) by Notch1 signaling after multi-potent progenitors (MPPs) migrate to thymus. One of the first hall marks of T lineage commitment is expression of the T cell receptor β (TCRβ), which is encoded by the Tcrb locus following its assembly by V(D)J recombination, a somatic shuffling of the genome that joins one V, one D, and one J gene segment. Tcrb …

Vrshape: A Virtual Reality Tool For Shaping Movement Compensation, Matthew Hale Foreman

Arts & Sciences Electronic Theses and Dissertations

The majority of persons living with chronic stroke experience some form of upper extremity motor impairment that affects their functional movement, performance of meaningful activities, and participation in the flow of daily life. Stroke survivors often compensate for these impairments by adapting their movement patterns to incorporate additional degrees of freedom at new joints and body segments. One of the most common compensatory movements is the recruitment of excessive trunk flexion when reaching with the affected upper extremity. Long-term use of these compensations may lead to suboptimal motor recovery and chronic pain or injury due to overuse. Rehabilitation focuses on …

Transitional Care For Older Adults With Dementia: Variation Across Patients And Providers, Patricia Prusaczyk

Arts & Sciences Electronic Theses and Dissertations

Older adults with dementia are particularly vulnerable to negative outcomes and adverse events when they transition between healthcare settings such as being discharged from the hospital. However, little is known about how healthcare providers help patients prepare for a care transition – known as transitional care – among older adults with dementia. Therefore, this study sought to understand the transitional care currently delivered by hospital healthcare providers to older adults with dementia, how it compared to that received by older adults without dementia, and how it varied across different patient and provider characteristics. Guided by key provider/informant interviews and theory, …

Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck

Arts & Sciences Electronic Theses and Dissertations

Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …

The Role Of Bhlhe40 In Autoimmune Neuroinflammation And Mycobacterial Infection, Chih-Chung Lin

Arts & Sciences Electronic Theses and Dissertations

The mammalian immune system is composed of innate and adaptive compartments, which cooperate with each other to maintain homeostasis and protect the host from the invasion by a variety of pathogens. The tight control of immune responses is extremely important for all individuals. Here, we discovered that the transcription factor basic helix-loop-helix family, member e40 (Bhlhe40) is a critical protein that regulates the autoimmune ("against self") and anti-microbial ("against non-self") responses of myeloid cells and T lymphocytes. Multiple sclerosis (MS) is a human neuroinflammatory disease in the central nervous system with an autoimmune etiology. We have reported that Bhlhe40 positively …

Examining The Lumbar Movement Pattern During Functional Activities In People With Low Back Pain, Andrej Vincent Marich

Arts & Sciences Electronic Theses and Dissertations

Low back pain (LBP) is a highly prevalent condition that is often characterized by persistent pain and limitations in the performance of daily functional activities. The repeated use of altered movement patterns during the performance of daily functional activities is proposed to contribute to the development and course of LBP. Specifically, in the case of LBP, the proposed alteration of movement is one in which the lumbar spine moves more readily than other joints that can contribute to the movement. This altered movement pattern is proposed to contribute to accumulation of localized tissue stress, micro- and macro-trauma of lumbar spine …

The Role Of Histidine Rich Protein Ii In Cerebral Malaria, Priya Pal

Arts & Sciences Electronic Theses and Dissertations

Human malaria is caused by five species of Plasmodium. Of these, P. falciparum is the deadliest and is the only species that causes cerebral malaria (CM). CM is a disease of the vascular endothelium characterized by parasite sequestration, increased inflammatory cytokine production, vascular leakage and leukocyte infiltration. A distinguishing feature of P. falciparum infection is the parasite’s production and secretion of histidine-rich protein II (HRPII). HRPII accumulates to high concentrations (up to 100 µg/ml) in serum, which correlates with disease severity. Due to high serum levels of this protein, HRPII has classically been considered a biomarker for P. falciparum infection. …

Defining The Ontogeny And Functions Of Macrophages In Pancreatic Ductal Adenocarcinoma, Yu Zhu

Arts & Sciences Electronic Theses and Dissertations

The immune system plays an essential role in protecting the host organisms against both foreign invaders and self-attacks arisen within the host, such as tumors. Instead of promoting the long-term fitness of the organism, the immune system is often suppressed or hijacked by tumor cells to accelerate the progression of malignancies. Among the key drivers of immune suppression, macrophages are one of the most abundant immune cells present in tumor tissues. High levels of macrophage infiltration in the malignant tissues correlate with negative patient outcome in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), one of the most lethal …

Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan

Undergraduate Research Symposium Posters

Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are found in about 23% of acute myeloid leukemia (AML) samples and about 90% of gliomas. Mutations result in neomorphic function of the IDH enzyme that yields the novel molecule 2-hydroxyglutarate (2HG) instead of alpha-ketoglutarate (aKG). 2HG is known to be associated with hypermethylation of DNA and histones, a phenotype seen in AML. Our lab intends to study the mechanism by which hypermethylation is achieved and how this mechanism relates to the onset of cancer. In this experiment, we utilized a line of H9 stem cells which we had developed. These cells …

Investigating Localization And Activity-Dependent Translation Of Astrocyte Mrna, Rohan Khazanchi

Senior Honors Papers / Undergraduate Theses

Over the past two and a half years, I have studied fundamental aspects of astrocyte biology by investigating the existence and mechanism of astrocyte local translation peripherally around tripartite synapses consisting of pre- and post-synaptic neuron terminals and an associated astrocyte. Astrocytes are critical components of central nervous system synapses (which are predominately tripartite in nature); thus, it is important to consider how astrocyte dysregulation and dysfunction could contribute to the pathogenesis of diseases of synaptic connectivity such as autism spectrum disorders, Alzheimer’s disease, seizure disorders, and more. Overall, my projects involved the development of novel methods to identify astrocyte-specific …

Characterizing The Role Of Cpsa In Mycobacterial Pathogenesis, Amir Hassan

Undergraduate Research Symposium Posters

Mycobacterium tuberculosis infects one-third of the world’s population and causes an estimated 2 million deaths per year, more than any other single bacterial pathogen. The inadequacies of existing tuberculosis therapies demand the discovery of novel agents to treat M. tuberculosis infection, which requires mechanistic insight into the pathways involved in mycobacterial pathogenesis. We identified an unanticipated role of the M. tuberculosis protein CpsA in preventing phago-lysosome fusion by host macrophages, resulting in enhanced intracellular survival of bacteria within the host. Strains of M. tuberculosis lacking cpsA are severely attenuated in both macrophage and mouse models, thus establishing CpsA as a …

Assessment Of Progress Towards Universal Health Coverage For People With Disabilities In Afghanistan: A Multilevel Analysis Of Repeated Cross-Sectional Surveys, Jean Francois Trani, Praveen Kumar, Ellis Ballard, Tarani Chandola

Brown School Faculty Publications

Summary Background Since 2002, Afghanistan has made much effort to achieve universal health coverage. According to the UN Sustainable Development Goal 3, target eight, the provision of quality care to all must include usually underserved groups, including people with disabilities. We investigated whether a decade of international investment in the Afghan health system has brought quality health care to this group. Methods We used data from two representative household surveys, one done in 2005 and one in 2013, in 13 provinces of Afghanistan, that included questions about activity limitations and functioning difficulties, socioeconomic factors, perceived availability of health care, and …

Significance Of The Feminization Of Male Eating Disorders, Rachel Rothman

Undergraduate Research Symposium Posters

Today, many individuals develop eating disorders; however, eating disorders are typically associated with women. In this paper, I declare that male eating disorders are stigmatized due to the feminization of eating disorders. I explain why this stigma exists and how this bias inhibits professionals from conducting objective research on male eating disorders and diagnosing them correctly. I illustrate how the stigma prevents men from recognizing their own unhealthy behaviors and can deter individuals from recognizing eating disorder-related behaviors in other men. Throughout the essay, I provide my own analysis regarding how to combat the stigmatization of eating disorders. By writing …