Digital Commons Network^™

A Steroid Receptor Coactivator Small Molecule "Stimulator" Attenuates Post-Stroke Ischemic Brain Injury, Lisa K Mcclendon, Roberto L Garcia, Tyler Lazaro, Ariadna Robledo, Viren Vasandani, Zean Aaron Evan Luna, Abhijit S Rao, Aditya Srivatsan, David M Lonard, Clifford C Dacso, Peter Kan, Bert W O'Malley

Faculty, Staff and Students Publications

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion.

Methods: Neurologic impairment and tissue damage responses were evaluated on day …

A Pandemic Instrument Can Start Turning Collective Problems Into Collective Solutions By Governing The Common-Pool Resource Of Antimicrobial Effectiveness, Isaac Weldon, Kathy Liddell, Susan Rogers Van Katwyk, Steven J. Hoffman, Timo Minssen, Kevin Outterson, Stephanie Palmer, A. M. Viens, Jorge Viñuales

Faculty Scholarship

To address the complex challenge of global antimicrobial resistance (AMR), a pandemic treaty should include mechanisms that 1) equitably address the access gap for antimicrobials, diagnostic technologies, and alternative therapies; 2) equitably conserve antimicrobials to sustain effectiveness and access across time and space; 3) equitably finance the investment, discovery, development, and distribution of new technologies; and 4) equitably finance and establish greater upstream and midstream infection prevention measures globally. Biodiversity, climate, and nuclear governance offer lessons for addressing these challenges.

The Nhlbi Study On Long-Term Outcomes After The Multisystem Inflammatory Syndrome In Children (Music): Design And Objectives, Dongngan T Truong, Felicia L Trachtenberg, Gail D Pearson, Audrey Dionne, Matthew D Elias, Kevin Friedman, Kerri H Hayes, Lynn Mahony, Brian W Mccrindle, Matthew E Oster, Victoria Pemberton, Andrew J Powell, Mark W Russell, Lara S Shekerdemian, Mary Beth Son, Michael Taylor, Jane W Newburger

Faculty, Staff and Students Publications

BACKGROUND: The Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood.

METHODS: This multicenter observational cohort study will enroll at least 600 patientsyears, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF)

CONCLUSION: The MUSIC study, with the largest cohort of MIS-C patients and the longest …

The Texas Collaborative Center For Hepatocellular Cancer: Reducing Liver Cancer Mortality In Texas Through Coordination, Collaboration And Advocacy, Ariel C Harrison, Fasiha Kanwal, Sumeet K Asrani, Aaron P Thrift, Chris I Amos, Maria L Jibaja-Weiss, Jane R Montealegre, Jessica P Hwang, Amit G Singal, Hashem B El-Serag

Faculty, Staff and Students Publications

Texas has the highest age-adjusted incidence rate of hepatocellular carcinoma (HCC) in the United States. To address cancer prevention and early detection through research, Cancer Prevention and Research Institute of Texas (CPRIT) has funded the Texas Collaborative Center for Hepatocellular Cancer (TeCH) to facilitate liver cancer research, education and advocacy activities. This paper describes the organizational structure, program measures, the actions completed and future plans of TeCH. This center is comprised of several cores and committees including the Administrative Core, Steering Committee, Data and Biospecimen Core, Scientific Committee, Clinical Network Committee, and the Community Outreach Committee. Each core and committee …

Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell

Faculty, Staff and Students Publications

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute …

Development Of Phage Cocktails To Treate Coli Catheter-Associated Urinary Tract Infection And Associated Biofilms, Belkys C Sanchez, Emmaline R Heckmann, Sabrina I Green, Justin R Clark, Heidi B Kaplan, Robert F Ramig, Casey Hines-Munson, Felicia Skelton, Barbara W Trautner, Anthony W Maresso

Faculty, Staff and Students Publications

High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary E. coli strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized E. coli phage against biofilms in two in vitro CAUTI models. Biofilm viability was …

Privacy Vs. Identity Rights: A Call For The United States To Adopt The United Kingdom’S “Open Id” System For Artificial Reproductive Technology, Rachel L. Emerson

Case Western Reserve Journal of International Law

No abstract provided.

An Automated Classifier For Child-Directed Speech From Lena Recordings, Janet Y. Bang, George Kachergis, Adriana Weisleder, Virginia A. Marchman

Faculty Research, Scholarly, and Creative Activity

No abstract provided.

Nav1.1 Is Essential For Proprioceptive Signaling And Motor Behaviors, Cyrrus M. Espino, Cheyanne M. Lewis, Serena Ortiz, Miloni S. Dalal, Snigdha Garlapalli, Kaylee M. Wells, Darik A. O'Neil, Katherine A. Wilkinson, Theanne N. Griffith

Faculty Research, Scholarly, and Creative Activity

The voltage-gated sodium channel (NaV), NaV1.1, is well-studied in the central nervous system; conversely, its contribution to peripheral sensory neuron function is more enigmatic. Here, we identify a new role for NaV1.1 in mammalian proprioception. RNAscope analysis and in vitro patch-clamp recordings in genetically identified mouse proprioceptors show ubiquitous channel expression and significant contributions to intrinsic excitability. Notably, genetic deletion of NaV1.1 in sensory neurons caused profound and visible motor coordination deficits in conditional knockout mice of both sexes, similar to conditional Piezo2-knockout animals, suggesting that this channel is a major contributor to sensory proprioceptive transmission. Ex vivo muscle afferent …

Fake Malware Generation Using Hmm And Gan, Harshit Trehan, Fabio Di Troia

Faculty Research, Scholarly, and Creative Activity

In the past decade, the number of malware attacks have grown considerably and, more importantly, evolved. Many researchers have successfully integrated state-of-the-art machine learning techniques to combat this ever present and rising threat to information security. However, the lack of enough data to appropriately train these machine learning models is one big challenge that is still present. Generative modelling has proven to be very efficient at generating image-like synthesized data that can match the actual data distribution. In this paper, we aim to generate malware samples as opcode sequences and attempt to differentiate them from the real ones with the …

Crowdfunding Non-Fungible Tokens On The Blockchain, Sean Basu, Kimaya Basu, Thomas H. Austin

Faculty Research, Scholarly, and Creative Activity

Non-fungible tokens (NFTs) have been used as a way of rewarding content creators. Artists publish their works on the blockchain as NFTs, which they can then sell. The buyer of an NFT then holds ownership of a unique digital asset, which can be resold in much the same way that real-world art collectors might trade paintings. However, while a deal of effort has been spent on selling works of art on the blockchain, very little attention has been paid to using the blockchain as a means of fundraising to help finance the artist’s work in the first place. Additionally, while …

Blackcurrants: A Nutrient-Rich Source For The Development Of Functional Foods For Improved Athletic Performance, Ali Ali Redha, Shahida Anusha Siddiqui, Reza Zare, Daniele Spadaccini, Silvia Guazzotti, Xi Feng, Nur Alim Bahmid, Yuan Seng Wu, Fathima Zahraa Ozeer, Rotimi E. Aluko

Faculty Research, Scholarly, and Creative Activity

Blackcurrants are nutrient-rich fruits with a significant amount of bioactive compounds including vitamin C and polyphenols, especially anthocyanins. The high phytochemical content of blackcurrants promotes this fruit to become a valuable functional food ingredient with varying health-promoting activities targeting different consumers including athletes. Athletes experience oxidative stress during intense exercise, which can result in inflammation and reduced exercise performance. Antioxidants such as vitamin C and polyphenols can restore the regular oxidative status of the body. Blackcurrant supplementation has shown potential ergogenic activity to improve athlete performance during high-intensity training. Clinical trials have evaluated the effectiveness of blackcurrant supplementation on exercise …

Phenomic And Genetic Controls Of The Drought Stress Response In Sorghum, Melissa A. Lehrer

Graduate Theses, Dissertations, and Problem Reports (ETD)

Drought, one of the most common abiotic stressors, is a result of the precipitation and temperature fluctuations influenced by climate change. As consistent weather patterns are crucial for the maintenance of crop yield, drought threatens food security through its impact on plant growth and development. It is essential to ensure the quality, availability, and affordability of grain-based products in the face of climate change due to expectations of population growth. Therefore, shedding light on the mechanisms associated with drought tolerance is integral to maintaining agricultural production under water-limited conditions. My dissertation work aimed to uncover the morphological, physiological, and genetic …

Impact Of Haemonchus Contortus On Feed Efficiency And Feeding Behavior Of Katahdin And Suffolk Lambs, Camren L. Maierle

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nutritional impact of internal parasitism, specifically Haemonchus contortus (Hc), is a significant contributor to production losses in small ruminants. Both chronic and subclinical infections generate millions of dollars of losses worldwide. Understanding the nutritional impact of Hc on lamb performance is crucial in determining the additional nutrient requirements of infected individuals. The aim of this study was to evaluate nutritional impact of Hc on infected Katahdin lambs with extensive genetic selection for parasite resistance and susceptible Suffolk lambs. Growth, feeding behavior, and feed efficiency (RFI. F:G) were evaluated during artificial Hc infection. Katahdin ewes from the Virginia …

Investigating The Mitochondrial Protein Mitoneet In C. Elegans Models Of Aging And Alzheimer's Disease, Jacob Ryan Boos

Graduate Theses, Dissertations, and Problem Reports (ETD)

Oxidative stress is an imbalance between reactive oxygen species production and elimination, favoring the former. Reactive oxygen species serve as important signaling molecules for physiological homeostasis. However, when produced in excess, these once important signaling molecules become detrimental, disrupting cellular functions, and ultimately leading to cell death. In aging, reactive oxygen species production is increased, accompanied with reductions in oxidative stress resistance, increasing the risk for developing age-related diseases including cardiovascular disease, cancer, stroke, and neurodegenerative diseases. The outer mitochondrial membrane iron-sulfur cluster containing protein mitoNEET (CISD1; gene CISD1) has shown to be a mediator of mitochondrial function and …

Performance Of Peltier Cooled Technology During Preconcentration Of Volatile Organic Compounds Analyzed By Gas Chromatography-Mass Spectrometry (Gc-Ms) Using Niosh Manual Of Analytical Methods (Nmam) 3900, Elizabeth Ann Fernandez

Graduate Theses, Dissertations, and Problem Reports (ETD)

Using evacuated canisters for whole-air sampling allows for sampling without specific knowledge of the environment and potential analytes. Evacuated canisters are able to tolerate concentrations ranging from parts per trillion (PPT) to parts per million (PPM). The U.S. Environmental Protection Agency (EPA) has used evacuated canisters for years to sample volatile organic compounds (VOCs) from ambient air using their method TO-15 (LeBouf, et al., 2019). The GC-MS system used for the development of NMAM 3900 used liquid nitrogen to cool sorbent traps in the preconcentrator. Liquid nitrogen allows for cooling of specified points below ambient temperature. An alternative to liquid …

Multifunctional Organoboron Compounds And Boralactonate Salts, Randika T. Abeysinghe

Graduate Theses, Dissertations, and Problem Reports (ETD)

Organoboron compounds have gathered an important significance within the chemistry community on account of their wide range of applications in synthesis, catalysis, and medicinal chemistry. Even though the uses of boron compounds in drug discovery have been overlooked until the last several decades, boronic acid containing molecules have garnered increased attention due to the unique chemical properties of the boron center. Boron-functionalized ��-aryl propionic acid non-steroidal anti-inflammatory drug derivatives (bora-NSAIDs) can be accessed via copper(I)-catalyzed alkene boracarboxylation, using CO2 and B2pin2. To explore and expand the current synthetic and future medicinal chemistry applications of these bora-NSAIDs, methods …

Development Of A Thermal Desalination System Using Low Quality Thermal Energy, Takudzwa C. Chipunza

Graduate Theses, Dissertations, and Problem Reports (ETD)

Abstract

Development of a Thermal Desalination System Using Low Quality Thermal Energy

Takudzwa Chipunza

The blowdown water from the cooling tower of the power plant and the produced water from shale gas industry cannot be disposed directly to the environment as they may contain dissolved solids that are harmful to the environment. A detailed physical and chemical process to remove the mineral and organic solids has been developed in West Virginia University. Such a process includes running the blowdown and produced water through a softening tank, activated carbon tank, and a reverse osmosis (RO) system. The RO reject contains a …

Vaping During Pregnancy: Effects On Vascular And Behavioral Outcomes In Offspring, Eiman A. Aboaziza

Graduate Theses, Dissertations, and Problem Reports (ETD)

Electronic cigarette (e-cig) use is increasing due to aggressive marketing, tempting flavors, and seemingly higher acceptability in the community (lesser perceived social stigma) despite unproven claims of safety. In an alarming trend, pregnant women smokers have turned to novel “modified risk” products, such as e-cigs, in response to heavy marketing of e-cigs as safer alternatives to cigarettes and a tool to help quit smoking. This is despite proven detrimental effects of nicotine on a growing fetus, and scarcity of information regarding toxicity of e-liquid (with and without nicotine) on child development. Moreover, rampant e-cig use among youth (nearly 4 million …

Understanding Vaccine-Induced Memory Responses To Develop The Next Generation Of Pertussis Vaccines, Kelly L. Weaver

Graduate Theses, Dissertations, and Problem Reports (ETD)

Bordetella pertussis is a Gram-negative respiratory pathogen that can infect individuals of all ages and is notably responsible for infant fatalities. Pertussis (whooping cough) is a vaccine-preventable respiratory disease for which vaccines have been available in the United States since the 1940s. Whole cell pertussis vaccines kept incidence of pertussis under 5,000 cases per year, but were associated with reactogenicity issues. Following the introduction of less reactogenic acellular pertussis vaccines in the late 1990s, there have been noteworthy outbreaks of pertussis. For example, in 2012 there were over 50,000 reported cases of pertussis and 20 deaths in the U.S. The …

Student Understanding Of The Definite Integral When Solving Calculus Volume Problems, Krista Bresock

Graduate Theses, Dissertations, and Problem Reports (ETD)

The concept of integration appears in many different scientific fields, and students’ understanding of and ability to use the definite integral in applications is important to success in their STEM (science, technology, engineering, and mathematics) classes. One of the first types of application problems that students encounter is finding the volume of a solid using the definite integral. How students approach these problems and how they use the definite integral to find volumes can have an impact on their future use and understanding of the definite integral.

This study involves a deep and thorough investigation of how ten students understand …

Artificial Intelligence Based Approach For Rapid Material Discovery: From Chemical Synthesis To Quantum Materials, Robert Tempke

Graduate Theses, Dissertations, and Problem Reports (ETD)

With the advent of machine learning (ML) in the field of Materials Science, it has become obvious that trained models are limited by the amount and quality of the data used for training. Where researchers do not have access to the breadth and depth of labeled data that fields like image processing and natural language processing enjoy. In the specific application of materials discovery, there is the issue of continuity in atomistic datasets. Often if one relies on experimental data mined from literature and patents this data is only available for the most favorable of atomistic data. This ultimately leads …

Characterizing Locomotor Disturbance Perception In Young Adults, Daniel James Liss

Graduate Theses, Dissertations, and Problem Reports (ETD)

Falls during walking are a leading cause of injuries across aging. Many of these falls are due to slips and trips. The ability to perceive disturbances to ongoing motion may play an important role in the control of walking balance. However, disturbance perception has been investigated in standing balance, but its role in walking balance due to slip- and trip-like disturbances remains largely unknown. Characterizing locomotor disturbance perception in young adults may lead to a more comprehensive understanding of sensorimotor walking balance control.

This work defined locomotor disturbance perception in response to slip and trip-like disturbances in young adults. We …

Evaluating Potential Soil Amendments And Geomorphic Methods For Mine Land Reclamation, Amanda Rodrigues Silva

Graduate Theses, Dissertations, and Problem Reports (ETD)

The United States has approximately 22% of the world’s coal reserves. Since 1961, the electric power sector has been the major user of coal in the U.S., accounting for 91.9% of the coal consumed in the country in 2021. Sixty-two percent of total U.S. coal production in 2021 was sourced from surface mining, and Wyoming, West Virginia, Pennsylvania, Illinois, and Montana were responsible for 74% of this total production.

Coal-mining activities expose sulfide minerals in rocks that, when in contact with oxidizing conditions, produce sulfate-rich drainage known as acid mine drainage (AMD). AMD treatment typically involves chemical treatments to raise …

The Burning Bush: Linking Lidar-Derived Shrub Architecture To Flammability, Michelle S. Bester

Graduate Theses, Dissertations, and Problem Reports (ETD)

Light detection and ranging (LiDAR) and terrestrial laser scanning (TLS) sensors are powerful tools for characterizing vegetation structure and for constructing three-dimensional (3D) models of trees, also known as quantitative structural models (QSM). 3D models and structural traits derived from them provide valuable information for biodiversity conservation, forest management, and fire behavior modeling. However, vegetation studies and 3D modeling methodologies often only focus on the forest canopy, with little attention given to understory vegetation. In particular, 3D structural information of shrubs is limited or not included in fire behavior models. Yet, understory vegetation is an important component of forested ecosystems, …

Wetland Mitigation Performance Standards: The Intersection Of Science, Practice, And Policy, Jessica Anne Bryzek

Graduate Theses, Dissertations, and Problem Reports (ETD)

Wetland ecosystem spatial extent and integrity have declined due to conversion to anthropogenic land uses. Wetland mitigation offsets the impact on wetlands encountered during development by restoring a previously degraded wetland or creating new wetlands. This activity creates an ecosystem service market where wetland impacts (debits) are offset by wetland restoration/creation (credits). Mitigation aims to replace functions provided by aquatic resources lost during development. Post-restoration monitoring criteria known as performance standards are used to evaluate and verify restored wetland functionality and regulate mitigation credit release. Therefore, performance standards are vital in ascertaining wetland restoration techniques and mitigation processes. In Chapter …

A Multi-Method Examination Of The Effects Of Students’ Unconscious Biases On Student Evaluations Of Instructors, Brittany M. Kowalski

Graduate Theses, Dissertations, and Problem Reports (ETD)

In this dissertation, I complete three studies to evaluate potential reactions to target role congruity, especially gender role congruity, through an examination of Student Evaluations of Instructors (SEIs). Target role congruity refers to assessments an observer makes of whether or not the various roles a target person fills “fit” with one another. For example, a woman surgeon may be perceived as being in an incongruent role due to the masculine characteristics associated with the occupation and the continued dominance of men in the field. Researchers utilizing congruity theories has shown that both women and men in roles that are incongruent …

Cross-Kingdom Interactions Shape Soil Biogeochemistry In Natural And Agricultural Ecosystems, Jennifer Lynne Kane

Graduate Theses, Dissertations, and Problem Reports (ETD)

Microorganisms influence life on earth in innumerable ways, including in medical, industrial, environmental, and agricultural contexts. Given the increasingly apparent consequences of climate warming, interest in how to better predict and manage Earth’s carbon sinks has never been greater. Soil, the largest terrestrial carbon sink, harbors an incredibly taxonomically and functionally diverse microbial community. These soil-dwelling microbes govern the fate of soil carbon and nutrients by cycling organic matter as they live, grow, and die. It has only been relatively recently that technological advancement has allowed for in-depth surveys of the vast diversity of soil microbes. High throughput analytical capabilities …

A Novel Computational Network Methodology For Discovery Of Biomarkers And Therapeutic Targets, Qing Ye

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer has the second highest cancer incidence rate and the top cancer-related mortality worldwide. An estimate from the American Cancer Society shows that, in 2022, there will be about 236,740 lung cancer cases (117,910 men and 118,830 women) in the US. To date, there are no prognostic/predictive biomarkers to select chemotherapy, immunotherapy, and radiotherapy in individual non-small cell lung cancer (NSCLC) patients. There is an unmet clinical need to identify patients with early-stage NSCLC who are likely to develop recurrence and to predict their therapeutic responses. This dissertation developed a novel computational methodology for modeling molecular gene association networks …

Stationary Solutions And Stability Of Constant Equilibrium Solutions For A Chemotaxis System, Awatif Ramadan Zawali

Graduate Theses, Dissertations, and Problem Reports (ETD)

We consider a one-dimensional Chemotaxis model describing the dynamics of the cell density n, cell velocity u, chemoattractant c1, and chemorepellent c2, respectively. The model is related to angiogenesis in cancer cells. n represents the cell density of the vessel, the chemoattractant c1 is vascular endothelial growth factor (VEGF) and the chemorepellent c2 is the antiangiogenic drug. We study the existence of a nonconstant steady-state solution using the singular perturbation method. We also provide numerical examples of steady-state solutions for the fast system to illustrate the idea. For the dynamical problem in part II, we study the stability of constant …