Digital Commons Network^™

Diagnostic Brains, Experiential Minds And Metamodernism: Mcewan, Self, And Mccarthy As Case Studies, Mohamed Anis Ferchichi

Open Access Dissertations

In the wake of critical stances encompassing both modernism and postmodernism, we witness a theoretical preoccupation with how recent literary innovations position today's British fiction within the legacy of the novel form. On the one hand, postmodernism disrupted modernism's experiential phenomenology of interiority, subject, and character (what I call an experiential inflexion in critical comprehension of the form). On the other hand, what was declared "the decade of the brain" shifted some narrativization to exteriority, syndromic specifics, and reductive somaticism (what I see as a diagnostic inflexion in critical comprehension of the form). In considering today's British fiction within the …

Elucidating The Mechanisms Of Stress Tolerance In Reef-Building Coral Holobionts, Emma Strand

Open Access Dissertations

Coral reefs worldwide are threatened by climate change effects like increasing ocean warming and ocean acidification. These increased pressures cause a dysbiosis between the coral host, algal endosymbionts, and associated coral microbiome that results in the coral host expelling algal endosymbionts, leaving the coral host with a stark white ‘bleached’ appearance. Without their endosymbionts, coral hosts are forced to sustain themselves energetically with heterotrophy instead of relying on the autotrophic carbon and energy sources that once came from the algal endosymbionts. When this response, termed ‘coral bleaching’, happens reef-wide during an extreme wave of increased ocean temperatures, this is called …

Development Of Localized Drug Delivery Strategies For The Treatment Of Cancers And Infectious Diseases, Weizhou Yue

Open Access Dissertations

Difficult-to-treat human diseases and disorders such as brain cancer and posterior segment eye diseases greatly threaten human health and quality of life. However, the presence of physiological barriers such as the blood-brain barrier (BBB), cornea, and the blood-retinal barrier, renders these organs highly impervious to most therapeutics. As a result, most therapeutics administered systemically have low therapeutic efficacy even with high doses and are often associated with systemic side effects and/or toxicity. Localized drug delivery strategies such as injectables/implants, or locally-acting dosage forms, can circumvent physiological barriers and directly introduce therapeutics to the site of action to improve bioavailability, and …

The Influence Of Nutrient Regime On Diatom Diversity And Diatom Diazotroph Associations, Samantha Patricia Setta

Open Access Dissertations

Phytoplankton are important primary producers at the base of the marine food web. Diatoms are one of the most diverse groups of phytoplankton. Compared to other phytoplankton, diatoms have higher nutrient requirements due to their larger size, and as such, their distribution is limited by nutrients. Because of this, diatoms thrive in high-nutrient ocean regions, such as coastal and high-latitude waters, where the bulk of prior diatom research has occurred. However, diatoms are also found in low-nutrient oligotrophic waters, where they can form blooms and contribute up to 30% of total annual carbon sequestration. Many studies have documented the metabolic …

Pregnancy-Induced Differential Expression Of Sars-Cov-2 And Influenza A Viral Entry Factors In The Lower Respiratory Tract, Tusar Giri, Santosh Panda, Arvind Palanisamy

2020-Current year OA Pubs

Despite differences in the clinical presentation of coronavirus disease-19 and pandemic influenza in pregnancy, fundamental mechanistic insights are currently lacking because of the difficulty in recruiting critically ill pregnant subjects for research studies. Therefore, to better understand host-pathogen interaction during pregnancy, we performed a series of foundational experiments in pregnant rats at term gestation to assess the expression of host entry factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) and genes associated with innate immune response in the lower respiratory tract. We report that pregnancy is characterized by a decrease in host factors mediating …

Expression Of Non-Phosphorylatable S5a-L-Plastin Exerts Phenotypes Distinct From L-Plastin Deficiency During Podosome Formation And Phagocytosis, Xue Lin, Praveen Krishnamoorthy, Emma C Walker, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

No abstract provided.

Treg-Specific Deletion Of The Phosphatase Shp-1 Impairs Control Of Inflammation In Vivo, Qinlei Gu, Kenneth S Tung, Ulrike M Lorenz

2020-Current year OA Pubs

INTRODUCTION: To achieve a healthy and functional immune system, a delicate balance exists between the activation of conventional T cells (Tcon cells) and the suppression by regulatory T cells (Treg). The tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, shapes this 'activation-suppression' balance by modulating Tcon cell resistance to Treg-mediated suppression. Treg cells also express SHP-1, but its role in influencing Treg function is still not fully understood.

METHODS: We generated a Treg-specific SHP-1 deletion model,

RESULTS: We show that SHP-1 modulates Treg suppressive function at different levels. First, at the intracellular signaling level in Treg cells, SHP-1 attenuates …

The In Vivo Study Of Cardiac Mechano-Electric And Mechano-Mechanical Coupling During Heart Development In Zebrafish, Jonathan S Baillie, Alex Gendernalik, Deborah M Garrity, David Bark Jr, T Alexander Quinn

2020-Current year OA Pubs

In the adult heart, acute adaptation of electrical and mechanical activity to changes in mechanical load occurs

Phagocytosis Is A Primary Determinant Of Pulmonary Clearance Of Clinical Klebsiella Pneumoniae Isolates, Rick Van Der Geest, Hongye Fan, Hernán F Peñaloza, William G Bain, Zeyu Xiong, Naina Kohli, Emily Larson, Mara L G Sullivan, Jonathan M Franks, Donna B Stolz, Ryota Ito, Kong Chen, Yohei Doi, Melanie J Harriff, Janet S Lee

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We screened 19 clinical respiratory

RESULTS: The respiratory

CONCLUSION: Altogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical

The Cerebrospinal Fluid Immune Cell Landscape In Animal Models Of Multiple Sclerosis, Gregory F Wu

2020-Current year OA Pubs

The fluid compartment surrounding the central nervous system (CNS) is a unique source of immune cells capable of reflecting the pathophysiology of neurologic diseases. While human clinical and experimental studies often employ cerebrospinal fluid (CSF) analysis, assessment of CSF in animal models of disease are wholly uncommon, particularly in examining the cellular component. Barriers to routine assessment of CSF in animal models of multiple sclerosis (MS) include limited sample volume, blood contamination, and lack of feasible longitudinal approaches. The few studies characterizing CSF immune cells in animal models of MS are largely outdated, but recent work employing transcriptomics have been …

Targeted Aso-Mediated Atp1a2 Knockdown In Astrocytes Reduces Sod1 Aggregation And Accelerates Disease Onset In Mutant Sod1 Mice, Abhirami K. Iyer, Kathleen M. Schoch, Anthony Verbeck, Grant Galasso, Hao Chen, Sarah Smith, Anna Oldenborg, Timothy M. Miller, Celeste M. Karch, Azad Bonni

2020-Current year OA Pubs

Astrocyte-specific ion pump α2-Na+/K+-ATPase plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we test the effect of Atp1a2 mRNA-specific antisense oligonucleotides (ASOs) to induce α2-Na+/K+-ATPase knockdown in the widely used ALS animal model, SOD1*G93A mice. Two ASOs led to efficient Atp1a2 knockdown and significantly reduced SOD1 aggregation in vivo. Although Atp1a2 ASO-treated mice displayed no off-target or systemic toxicity, the ASO-treated mice exhibited an accelerated disease onset and shorter lifespan than control mice. Transcriptomics studies reveal downregulation of genes involved in oxidative response, metabolic pathways, trans-synaptic signaling, and upregulation of genes involved in glutamate receptor …

A Review Of Technological Innovations Leading To Modern Endovascular Brain Aneurysm Treatment, David C Lauzier, Anna L Huguenard, Anja I Srienc, Samuel J Cler, Joshua W Osbun, Arindam R Chatterjee, Ananth K Vellimana, Akash P Kansagra, Colin P Derdeyn, Dewitte T Cross, Christopher J Moran

2020-Current year OA Pubs

Tools and techniques utilized in endovascular brain aneurysm treatment have undergone rapid evolution in recent decades. These technique and device-level innovations have allowed for treatment of highly complex intracranial aneurysms and improved patient outcomes. We review the major innovations within neurointervention that have led to the current state of brain aneurysm treatment.

Rev-Erb Activation As A Novel Pharmacological Approach For Treating Inflammatory Pain, Sangeet Makhija, Joshua D Griffett, Giri Babu Veerakanellore, Thomas P Burris, Bahaa Elgendy, Kristine Griffett

2020-Current year OA Pubs

Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain, one underlying mechanism to the pathogenesis and maintenance of pain conditions is chronic inflammation driven by the NLRP3 inflammasome. Several inflammasome inhibitors are currently under investigation however have the potential to suppress the functioning of the innate immune system, which may cause unwanted affects in patients. Here, we show that the nuclear …

Disease-Causing Mutations In Genes Encoding Transcription Factors Critical For Photoreceptor Development, Chi Sun, Shiming Chen

2020-Current year OA Pubs

Photoreceptor development of the vertebrate visual system is controlled by a complex transcription regulatory network. OTX2 is expressed in the mitotic retinal progenitor cells (RPCs) and controls photoreceptor genesis. CRX that is activated by OTX2 is expressed in photoreceptor precursors after cell cycle exit. NEUROD1 is also present in photoreceptor precursors that are ready to specify into rod and cone photoreceptor subtypes. NRL is required for the rod fate and regulates downstream rod-specific genes including the orphan nuclear receptor NR2E3 which further activates rod-specific genes and simultaneously represses cone-specific genes. Cone subtype specification is also regulated by the interplay of …

Precision Neuromodulation: Promises And Challenges Of Spinal Stimulation For Multi-Modal Rehabilitation, Maria F Bandres, Jefferson L Gomes, Gerson N Moreno Romero, Avery R Twyman, Jacob Graves Mcpherson

2020-Current year OA Pubs

Spinal cord injury results in multiple, simultaneous sensorimotor deficits. These include, but are not limited to, full or partial paralysis of muscles below the lesion, muscle spasms, spasticity, and neuropathic pain. Bowel, bladder, and sexual dysfunction are also prevalent. Yet, the majority of emerging spinal stimulation-based therapies focus on a single issue: locomotor rehabilitation. Despite the enormous potential of these translational advances to transform the lives of people living with spinal cord injury, meaningful recovery in other domains deemed critical priorities remains lacking. Here, we highlight the importance of considering the diverse patterns of neural transmission that underlie clinically similar …

Iron Homeostasis And Post-Hemorrhagic Hydrocephalus: A Review, Shelei Pan, Andrew T Hale, Mackenzie E Lemieux, Dhvanii K Raval, Thomas P Garton, Brooke Sadler, Kelly B Mahaney, Jennifer M Strahle

2020-Current year OA Pubs

Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain …

Glaucoma And Microglia-Induced Neuroinflammation, Makoto Ishikawa, Yukitoshi Izumi, Kota Sato, Taimu Sato, Charles F Zorumski, Hiroshi Kunikata, Toru Nakazawa

2020-Current year OA Pubs

Glaucoma is a multifactorial neurodegenerative disease characterized by a progressive optic neuropathy resulting in visual field defects. Elevated intraocular pressure (IOP) is the greatest risk factor for the development of glaucoma, and IOP reduction therapy is the only treatment currently available. However, there are many cases in which retinal degeneration progresses despite sufficient control of IOP. Therefore, it is important to elucidate the pathophysiology of glaucoma that is resistant to current IOP lowering therapies. Experiments using animal glaucoma models show the relationships between microglial neuroinflammatory responses and damage of retinal ganglion cells (RGCs). Inhibition of neuroinflammatory pathways associated with microglial …

Privacy In Modern American Law And Society, Joanna L. Grossman, Lawrence M. Friedman

Faculty Journal Articles and Book Chapters

No abstract provided.

Development Of Polymeric Nano- And Microparticle-Based Controlled Release Platforms, Ryan Ivone

Open Access Dissertations

The success of the development of drug delivery formulations hinges upon their ability to maintain therapeutic efficacy, while simultaneously aiming to minimize off-site side effects and reduce the dosing burden often faced by patients. Localized formulations deliver therapeutics directly to the disease site and can help circumvent physiological obstacles such as the first pass effect, which remains one of the primary barriers for oral drug delivery. Barriers such as the first pass effect can drastically reduce the overall bioavailability of a formulation, potentially requiring a higher initial dose to remain therapeutically effective. However, many compounds demonstrate dose dependent side effects, …

Flux To Flow: A Clearer View Of Earth’S Water Cycle Via Neural Networks And Satellite Data, Albert Eric Larson

Open Access Dissertations

Earth’s weather and climate changes dynamically, and humans must monitor the evolution of our environment or fail to plan and adapt. Water is our most valuable resource, and as such it is of the utmost importance to have a continuous view of its movements as water cycles over, in, and under land, in the atmosphere, and in the sea. One way that we observe the water cycle is with satellite measurements. Unfortunately, the resolution of these instruments is typically too coarse to visualize many transient phenomena of interest. If their vision is fine enough, the instrument captures only a small …

The (Mis)Formation Of Identity In Joseph Conrad’S Novels: Ideology, Community, And The Self, Youngji Cho

Open Access Dissertations

Joseph Conrad’s Heart of Darkness, Nostromo, and The Secret Agent contain two broad themes: on the one hand, they critically portray the dominant influence of society or societal ideologies on the individual from a socio-political standpoint; on the other hand, they focus on the (dis)illusion of the protagonists regarding their own “ideal” identities from a personal standpoint. Rather than addressing one or the other, as many previous studies of Conrad’s novels have done, this dissertation argues for the intimate continuity between socio-political ideologies and personal identity by finding the point of contact between these two seemingly disparate issues. …

Microfluidic Paper-Based Devices For The Detection Of Chemical And Biological Agents, Hojat Heidaribafroui

Open Access Dissertations

This work was motivated by two needs: to develop low-cost, high-sensitivity, and accurate systems for detecting phosphate in seawater, and to create a platform technology by integrating Bi-Material Cantilever (B-MaC) valves for rapid and affordable biosensors that can be used at home or point-of-care settings to detect pathogens.

Detecting low levels of phosphate in the seawater using an inexpensive sensor is crucial for marine scientists to make informed decisions on where to measure next, compared to the current method of collecting samples and analyzing them ashore. To address these needs, we developed a portable infrared lightbox that can be wirelessly …

Computational Close Reading: A Critique Of Digital Literary Methodology, Damiano Consilvio

Open Access Dissertations

Computational Close Reading intervenes in digital humanities and American literary scholarship to negotiate a significant institutional and disciplinary problem: the devaluation of close reading and interpretation in digital humanities applications to literary studies in favor of more distant modes of reading. To remedy this issue, I pursue a core question meant to bring the literary and the digital into a more perfect confluence, as a demonstration of possibilities meant to run counter to these preconceptions about computational reading: how “close,” if close at all, can digital technologies bring us to the interpretive elements of literary texts? I argue that they …

Small Molecule Inhibiting Microglial Nitric Oxide Release Could Become A Potential Treatment For Neuroinflammation, Philipp Jordan, Amanda Costa, Et Al.

2020-Current year OA Pubs

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or …

Clonal Diversity, Antibiotic Resistance, And Virulence Factor Prevalence Of Community Associated Staphylococcus Aureus In Southeastern Virginia, Katelyn D. Cranmer, Mohan D. Pant, Suzanne Quesnel, Julia A. Sharp

EVMS School of Health Professions Faculty Publications

Staphylococcus aureus is a significant human pathogen with a formidable propensity for antibiotic resistance. Worldwide, it is the leading cause of skin and soft tissue infections (SSTI), septic arthritis, osteomyelitis, and infective endocarditis originating from both community- and healthcare associated settings. Although often grouped by methicillin resistance, both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains are known to cause significant pathologies and injuries. Virulence factors and growing resistance to antibiotics play major roles in the pathogenicity of community-associated strains. In our study, we examined the genetic variability and acquired antibiograms of 122 S. aureus clinical isolates from SSTI, blood, and urinary …

Conserved Gene Signatures Shared Among Mapt Mutations Reveal Defects In Calcium Signaling, Miguel A Minaya, Sidhartha Mahali, Abhirami K Iyer, Abdallah M Eteleeb, Rita Martinez, Guangming Huang, John Budde, Sally Temple, Alissa L Nana, William W Seeley, Salvatore Spina, Lea T Grinberg, Oscar Harari, Celeste M Karch

2020-Current year OA Pubs

No abstract provided.

Unicorn, Hare, Or Tortoise? Using Machine Learning To Predict Working Memory Training Performance, Yi Feng, Anja Pahor, Aaron R Seitz, Dennis L Barbour, Susanne M Jaeggi

2020-Current year OA Pubs

People differ considerably in the extent to which they benefit from working memory (WM) training. Although there is increasing research focusing on individual differences associated with WM training outcomes, we still lack an understanding of which specific individual differences, and in what combination, contribute to inter-individual variations in training trajectories. In the current study, 568 undergraduates completed one of several N-back intervention variants over the course of two weeks. Participants' training trajectories were clustered into three distinct training patterns (high performers, intermediate performers, and low performers). We applied machine-learning algorithms to train a binary tree model to predict individuals' training …

Therapeutic Activity Of Lipoxin A4 In Tio2-Induced Arthritis In Mice: Nf-Κb And Nrf2 In Synovial Fluid Leukocytes And Neuronal Trpv1 Mechanisms, Telma Saraiva-Santos, Tiago H Zaninelli, Felipe A Pinho-Ribeiro, Et Al.

2020-Current year OA Pubs

BACKGROUND: Lipoxin A4 (LXA

METHODS: Mice were stimulated with TiO

RESULTS: LXA

CONCLUSION: LXA

Women's Empowerment And Child Nutrition In A Context Of Shifting Livelihoods In Eastern Oromia, Ethiopia, Karah Mechlowitz, Mark J Manary, Et Al.

2020-Current year OA Pubs

Agriculture, and particularly livestock and animal source foods, has been closely linked to improvements in human nutrition. Production, income, and women's empowerment improve household food security and child nutritional outcomes in interacting ways. Khat production in Eastern Ethiopia is changing the economic and livelihood landscape for communities that have traditionally relied upon small-scale mixed agriculture and livestock production. How this shifting livelihood landscape and the empowerment of women in these communities are affecting nutritional outcomes has not been investigated. Using cross-sectional data collected during formative research for the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) project, we developed models to …

Identification Of Prok2 Gene Polymorphisms As Predictors Of Methamphetamine Use Disorder Risk And Indicators Of Craving Scale In The Chinese Han Population, Zhao Jiang, Tianxiao Zhang, Wei Han, Jing Xiao, Wenpei Zhang, Xiaochen Wang, Jianing Liu, Ying Yang, Congying Yang, Fanglin Guan, Tao Li, John P Rice

2020-Current year OA Pubs

No abstract provided.