Digital Commons Network^™

The Role Of Fbxl16 In Regulating Erk3 Stability And Cell Migration, Seth Charles Murdock

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Extracellular signal-regulated kinase 3 (ERK3) is a member of the atypical mitogen-activated protein kinase (MAPK) family. While ERK3’s role in promoting cell migration and invasion in multiple types of cancer has been well-documented, its activation and regulation remain poorly understood. Unlike other typical MAPK proteins, whose activation is regulated via the phosphorylation of an upstream kinase, ERK3 is regulated through its abundance, as it is constitutively phosphorylated when present in the cell. While USP20 has been established as a deubiquitinating protein that stabilizes ERK3 by preventing its degradation, both TRIM21 and FBXW7 have been identified as E3 ligases that target …

The Role Of Base Excision Repair In Dna Damage Responses In Human Keratinocytes Exposed To Solar Simulating Uv Radiation, Mobolaji Eniola Alabi

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Ultraviolet (UV) radiation from the sun is the most prominent source of exogenous UV damage to DNA. UV directly causes damage by forming UV photoproducts, including pyrimidine-pyrimidone (6-4) photoproducts ((6-4) PPs), which significantly distort the helical structure of DNA and interfere with transcription and replication processes. The only known repair process of these photoproducts in human cells is nucleotide excision repair (NER). However, a recent study reported an APE1-dependent base excision repair (BER) of a subset of UV photoproducts. The study showed that deletion or inhibition of APE1, PARP1, NTH1, XRCC1, and FEN1 led to a 2-fold increase in sensitivity …

Characterization Of Atr Kinase Function In Quiescent Keratinocytes Exposed To Solar Simulating Uv Radiation, Mohamed Sameer Cholakkathody

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This study examines the role of Ataxia Telangiectasia and Rad3-related kinase in quiescent human keratinocytes exposed to solar-simulated UV radiation (SSL). The ATR inhibitor VE-822 did not significantly affect cell viability in the absence of UV exposure, showing that ATR kinase activity is not essential for quiescent cell survival in the absence of additional genotoxic stress. After SSL exposure, ATR inhibition did not impact acute cell viability but reduced the cells’ long-term ability to proliferate. Western blot analysis demonstrated that VE-822 potently suppressed phosphorylation of ATR target proteins KAP1 and CHK2 in a dose-dependent manner after SSL exposure, confirming strong …

Impacts Of Salinity And Drought On Growth And Carbon Sequestration In Acorus Americanus And Carex Scoparia, Eleora L. Mantle

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From the late 18th century until the 1980s, Ohio lost close to 90% of its wetlands. Despite increased efforts to maintain what is left, many freshwater marshes are still being degraded due to pollutants, such as road salt, and the impacts of climate change. This study sought to understand how both road salt and drought could impact the health and carbon sequestration of two wetland species, Acorus americana and Carex scoparia, to better understand tolerance. To do this, both species were separated into groups and subjected to varying salt concentrations and drought conditions. After 9 weeks of treatment, plants were …

Patient Subset Classification Using Encoded Embeddings And Knowledge Graph Retrieval-Augmented Generation, Benjamin A. Holmes

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The widespread adoption of electronic medical records has created a vast reservoir of clinical data that can be leveraged to better understand how interventions relate to patient outcomes. Much of this information, however, exists as unstructured free-text, posing significant challenges for traditional statistical and machine-learning methods. Solving these challenges would allow the extraction of specific patient subpopulations (clinically relevant cohorts of individuals who share overlapping symptoms, risk factors, or diagnostic criteria), which could be used in precision medicine. Despite this promise, extracting these subpopulations from unstructured medical notes is an ongoing challenge due to the variability of clinical language and …

Vagus Nerve Stimulation Ameliorates Cognitive Impairment Caused By Hypoxia, Birendra Sharma

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Hypoxia disrupts brain function due to the high demand for oxygen, leading to significant cognitive impairments. While vagus nerve stimulation (VNS) has been shown to enhance cognition, its ability to counteract hypoxia-induced deficits remains unclear. In this study, male Sprague–Dawley rats were assigned to sham, hypoxia, or VNS + hypoxia groups, with VNS delivered during hypoxia (8% oxygen) using biphasic pulses (100 μs, 30 Hz, 0.8 mA). Cognitive performance was evaluated using multiple behavioral paradigms, and hippocampal tissue was analyzed for neurotrophin expression through quantitative PCR and immunohistochemistry. Among the behavioral measures, hypoxia specifically impaired performance on the passive avoidance …

Utilizing Optimization Tools For Passive Flow Control Passage Loss Reduction In Low-Pressure Turbines, Bryant Robert Duane Burton

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Low-pressure turbines (LPTs) play a crucial role in fuel efficiency and thrust generation of aero-engines. Traditional LPT designs, however, involve multiple stages and numerous blades, resulting in increased weight and manufacturing costs. The challenge of modern- day researchers is to reduce the weight and cost but maintain the high efficiency of LPTs. To address this, one approach is to increase the aerodynamic loading of individual blades, reducing the blade count. However, this can lead to increased secondary losses caused by flow separation, particularly in the endwall regions. This research focuses on optimizing the blade profile at the junction with the …

Distinct Forms Of Myotonia In Pharmacologic And Genetic Mouse Models At Room And Body Temperature, Rola Benammar

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Myotonia congenita (MC) is a genetic disorder caused by loss-of-function mutations in the ClC-1 chloride channel, leading to muscle hyperexcitability and symptoms of transient stiffness and weakness. Work in hyperkalemic periodic paralysis (HKPP), a disorder with overlapping clinical features, has shown that myotonia can arise from two distinct mechanisms: a sustained form and a transient post-stimulus form, which have opposite temperature dependence. In HKPP, sustained myotonia worsens at elevated temperatures, whereas transient myotonia is exacerbated by cooling. This study tested whether these two mechanisms also contribute to myotonia in MC. Ex vivo force recordings were performed in extensor digitorum longus …

Determining The Genetic Population Structure Of The Endangered Scirpus Ancistrochaetus Using Genomic Sequences, Kayci Johnson

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Wetlands are biodiverse ecosystems across the world, and they are being lost at alarming rates due to fragmentation and anthropogenic stressors. Many wetland plants are endangered or threatened due to wetland decreasing numbers. Scirpus ancistrochaetus is an endangered wetland species in the northeastern United States. It is most commonly found in lowlands and forested ecosystems. In this study, I used 105 polymorphic loci obtained from double-digest restriction site associated DNA sequencing (ddRAD-seq), a conservation genetics tool, to determine conservation units, gene flow, kinship, and isolation-by-distance patterns. Discrete populations were identified in New England and the southern part of the species’ …

Screening Of Suppressor Mutants That Confer The Suc22 S239f Mutant Cells Resistance To Hydroxyurea, An Inhibitor Of Ribonucleotide Reductase, Sairam Pasam

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Ribonucleotide reductase (RNR) is a key enzyme for the biosynthesis of dNTPs for DNA replication and repair. It is composed of a large subunit, Cdc22, and a small subunit, Suc22, in the fission yeast S. pombe. We have recently reported a suc22-S239F mutation in the small subunit of RNR, causing replication stress and hypersensitivity to hydroxyurea (HU), an inhibitor of RNR. Interestingly, this mutation does not sensitize the cell to acute treatment with HU, which mainly generates replication stress, suggesting that the mechanism of HU sensitivity in the suc22-S239F mutant remains to be fully understood. To better understand the cell-killing …

Generative Adversarial Networks (Gans) For High-Dimensional Biological Data, Harigovind Harikumar

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This thesis investigates the application of Generative AI models, mainly Generative Adversarial Network (GAN) models to high dimensional and low sample size biological datasets like Motion Sickness, Breast Cancer, Crohn, and Melanoma. We utilized and compared three generative AI frameworks: Vanilla GAN, Wasserstein GAN (WGAN), Locality-Sensitive Hashing GAN (LSH-GAN) and Omics GAN. To address the challenges associated with high-dimensionality and low sample size, which was leading to very poor outputs of biological synthetic samples, we came up with an approach to stop the model when it reaches its saturation level. That is, we printed the loss plots to see where …

Benthic Algal Biomass And Productivity Across Depth Gradients In Lakes Michigan And Erie, Ahmed Ogidan

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Benthic primary production is poorly quantified in the Laurentian Great Lakes relative to phytoplankton-based production. We measured benthic chlorophyll and benthic primary productivity on soft sediments and Dreissena shells along depth gradients in Lakes Erie (2024) and Michigan (2025) during EPA Cooperative Science and Monitoring Initiative cruises. We measured benthic chlorophyll fluorometrically and estimated benthic primary productivity using non-invasive oxygen exchange incubations. We used PAM fluorometry to characterize photosynthetic-irradiance relationships on mussel shells and sediments in Lake Michigan. In Lake Erie, sediment chlorophyll ranged from 20 to 150 mg m⁻², with highest values in the central basin. In Lake Michigan, …

The Role Of Trpm7 In Mouse Development And Immune Cell Function, Jananie Rockwood

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Transient receptor melastatin 7 (TRPM7) functions both as an ion channel and a protein kinase. TRPM7 has been implicated in Mg2+ homeostasis, embryogenesis, cardiac automaticity, and immunity. The purpose of this research was to deepen our understanding of TRPM7 channel and kinase functions. To this end, we used two transgenic mouse models: the TRPM7 gain-of-function (GOF) and TRPM7 kinase-dead (KD) mice to address the consequences of increased channel activity and kinase inactivation, respectively. Global deletion of TRPM7 or the kinase domain alone are embryonic lethal, therefore, we used the TRPM7 GOF mouse to investigate germline transmission. We examined embryo development …

Characterization Of An Unknown Mutant C3 With A High Level Of Endogenous Replication Stress In Fission Yeast, Neha Singh

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To maintain genome stability, which is essential for cell proliferation and survival, cells rely on cell cycle checkpoint pathways to deal with perturbed DNA replication or replication stress. The fission yeast Schizosaccharomyces pombe serves as a powerful model organism for studying checkpoint mechanisms because its fundamental cellular processes are highly conserved in higher eukaryotes. During a genetic screening for mutants affecting genome integrity, we identified a novel mutant called C3 that exhibits a unique phenotype. Unlike wild-type cells, where phosphorylation of the checkpoint mediator Mrc1 is typically observed only in response to exogenously induced replication stress, such as the treatment …

Induced Reduction Of N-Glycosylation Leads To Heart Failure, Anthony M. Young

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Cardiovascular disease is the leading cause of death and contributes to the increasing global prevalence of heart failure (HF). N-glycosylation is a common co-/post-translational modification where branching oligosaccharides are bound to the extracellular domain of membrane proteins. This creates a diverse range of glycan structures and requires the coordination of hundreds of regulated genes. Inherited mutations in glycan synthesis frequently present with cardiomyopathies leading to HF with reduced ejection fraction (HFrEF). Additionally, gene expression studies of HFrEF patients have shown altered expression of glycosylation-related genes, including alpha-1,3-mannosyl-glycoproten 2-beta-N acetlyglucosaminyltransferase (Mgat1). This gene encodes N-acetylglucosaminyl transferase 1 (GlcNAcT1) which is required …

The Impact Of Ahr And Hs1.2 Enhancer Genetic Variations On Igh Expression And Antibody Production In Human B Cells, Mili Santosh Bhakta-Yadav

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Antibody production is an essential component of the immune response against pathogens. The immunoglobulin heavy chain (IgH) gene codes for the heavy chain of antibodies. The IgH constant regions Cμ, Cδ, Cγ1-4, Cα1-2, and Cε encode the five major classes of antibodies, i.e., IgM, IgD, IgG1-4, IgA1-2, and IgE, respectively. The transcription of the IgH gene and class switch from IgM to other isotypes is regulated by two 3’ IgH regulatory regions (3’IgHRRs), each of which is a cluster of three enhancer regions (hs3, hs1.2 and hs4). The genetic variations in the hs1.2 enhancer have been identified; a ~53 bp …

Characterizing The Microvesicle Particles From Keratinocytes Stimulated With Multiple Stressors, Muslima Begum

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Many types of environmental and physical stressors act upon the skin and can initiate inflammation, systemic effects, and even damage to internal organs. Recent studies have identified that these harmful events are driven by the release of subcellular microvesicle particles (MVPs), an inflammatory process promoted by the glycerophosphocholines-derived lipid mediator, Platelet-activating Factor (PAF). These harmful effects are driven by the release of MVPs, a process promoted by the inflammatory lipid mediator, PAF. We have previously demonstrated that exposure of human HaCaT keratinocyte and mouse skin to stressors such as thermal burn injury, ultraviolet B (UVB) radiation, and topical photodynamic therapy …

Rejecting The Racialization Of Indianness, Andrea J. Martin

Faculty Scholarship

No abstract provided.

Birth On Mother Earth: Mitigating The Maternal Health Crisis, Jill C. Engle

Faculty Scholarship

Maternal health outcomes in the U.S. are remarkably poor, especially when compared to those in other industrialized countries. For example, our maternal death rate is more than twice that of Canada’s. Women of color in the U.S. suffer maternal morbidity and mortality at rates considerably higher than white women. Indigenous women experience the worst maternal health outcomes of all. Yet, most maternal deaths and injuries are preventable. Furthermore, rates of maternal harm, including death, are lower when midwives and similar birthing attendants are involved. This Article is the first to fully explore the unique skillset of traditional birth attendants (TBAs). …

Risk Analysis Of Radiosurgery For Vestibular Schwannoma: Systematic Review And Comparative Study Of 10-Year Outcomes, Kevin M. Guy, April A. Pace, Derek S. Tsang, Peter G. Volsky

Department of Otolaryngology (ENT) Faculty Publications

Background: Determine the benefit of stereotactic radiosurgery (SRS) compared to no treatment for sporadic vestibular schwannoma (VS) by calculating epidemiologic risk using 10-year data; apply the analysis to VS that have demonstrated linear growth.

Methods: PubMed, Google Scholar, Web of Science, and Cochrane Library are systematically reviewed for VS tumor control 10 years after SRS and compared to an historical cohort of untreated VS (primary risk analysis). Subgroups of VS limited by size and observed growth are compared to the untreated cohort (secondary analysis).

Results: Twenty-four studies of 4,079 SRS-treated VS exhibited tumor control in 90.93% (87.0%-100%; SD 4.1%), while …

Categorizing Clinical Response To Mepolizumab For Patients With Chronic Rhinosinusitis With Nasal Polyps: Synapse Trial, Claire Hopkins, Larry Borish, Jared Silver, Peter Howarth, Robert Chan, Priya Dsilva, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

[Introduction] Chronic rhinosinusitis with nasal polyps (CRSwNP) can substantially affect quality of life (QoL), and is often challenging to manage.¹ First-line treatment for the management of CRSwNP involves intranasal corticosteroids, with short courses of systemic corticosteroids (SCS) for exacerbations, and sinus surgery for uncontrolled disease.² Biologics targeting type 2 inflammation (eg, dupilumab, omalizumab, and mepolizumab) have become a treatment option for refractory CRSwNP. With the advent of disease-modifying treatments such as biologics, control, defined as patients reporting no/low-symptom levels, has increasingly become the treatment goal for CRSwNP.³ However, the optimal use of biologics for symptom control in individual patients remains …

Smartphone Based Non Invasive Real Time White Blood Cell Counter Leveraging Blue Light And Static Magnetic Field, Nafi Us Sabbir Sabith, Masud Rabbani, Kazi Shafiul Alam, Sheikh Iqbal Ahamed

Computer Science Faculty Research and Publications

White blood cells (WBCs), also known as leukocytes, are one of the most significant parts of the immune system. They generate antibodies, protect the body from illnesses, and heal wounds. Accurate estimation of WBCs is key for diagnosing cancer, infections, leukemia, lymphoma, and other diseases. However, the widely used Complete Blood Count (CBC) test presents challenges, including prick anxiety, discomfort, and logistical inconvenience to patients. This study introduces a ubiquous White Blood Cell counting system, UbiWhite, a novel smartphone-based, non-invasive system for real-time WBC counting from fingertip videos. Our system uses optical and magnetic techniques to provide accurate WBC counts …

Causal Discovery On The Effect Of Antipsychotic Drugs On Delirium Patients In The Icu Using Large Observational Ehr Dataset, Riddhiman Adib, Md. Osman Gani, Sheikh Iqbal Ahamed, Mohammad Adibuzzaman

Computer Science Faculty Research and Publications

Delirium occurs in about 80% of cases in the Intensive Care Unit (ICU) and is associated with an extended hospital stay, increased mortality, and other complications. Delirium lacks biomarker-based diagnosis and is frequently treated with antipsychotic drugs (APD), despite numerous studies debating its efficacy. Since randomized controlled trials (RCT) are expensive and time-consuming, we approach the research question of estimating the efficacy and safety outcomes of APD in treating delirium through retrospective cohort analysis. We employed the Causal inference framework to explore the underlying causal model for Delirium patient cohort. We focus on building a structural causal model for delirium …

Digital Health Using Data Science, Padmapriya Velupillai Mekandan, Paramita Basak Upama, Masud Rabbani, Amity Ali, Sheikh Iqbal Ahamed

Computer Science Faculty Research and Publications

The digitization of healthcare has led to an unprecedented growth in health-related data, offering new opportunities to transform clinical decision-making, disease prediction, and patient engagement. However, extracting actionable insights from diverse data sources such as electronic health records, wearable devices, and mobile health apps requires a fusion of domain knowledge in healthcare and technical expertise in data science. This paper presents a structured, interdisciplinary framework for digital health that emphasizes practical strategies for data acquisition, preprocessing, feature engineering, machine learning, and ethical data use. The model promotes a holistic understanding of digital health challenges and opportunities, preparing future professionals to …

Diving Into Watershed Science And Education: Blending Science, Storytelling, And Professional Practice In Northern Michigan, Mara Clare Pellerito

Graduate Student Portfolios, Professional Papers, and Capstone Projects

This portfolio expands understanding of the relationship between watershed education and science through storytelling, lived experiences, and research. In northern Michigan, the invasive Myriophyllum spicatum threatens watershed health by forming dense patches that block sunlight, exclude native plants and wildlife, and retain harmful nutrients later released by herbicide treatment. The Lake Leelanau Lake Association has managed this species with preventative and restorative practices since 2020, and this portfolio examines their results through scientific study and practical experience from the summers of 2024 and 25. It also explores how education serves as a stepping stone from childhood curiosity to a lifetime …

Reflections On The Importance Of Critical Theory To Teaching Environmental Law, Sean M. Kammer

South Dakota Law Review

The freedom of students to learn about critical approaches to understanding their world is under sustained political attack. In this time of increasing environmental peril and political dysfunction, Professor Sean M. Kammer reflects upon the importance of critical theory (including Critical Race Theory) to understanding - and ultimately redressing - the related problems of resource scarcity and environmental degradation. While these problems can surely be described in terms of "economic inefficiencies" or "ecological disturbances," as they most often are, they must also be understood (and taught) as problems of colonial exploitation and violence. For example, one cannot understand Justice John …

The State Of Temperate Rainforest In South West England, Thomas Murphy, Katerina Chernyuk, Marcin Roszkowski, Shaun Lewin, Paul Lunt, James Buckley

School of Geography, Earth and Environmental Sciences

Temperate Rainforest is a biome of global significance which is rare and declining, yet supports endemic biodiversity and offers a range of co-benefits including carbon sequestration, natural flood management, climate moderation, and human well-being. The UK hosts a very large proportion of European bioclimatic space suitable for the development of Temperate Rainforest, yet very little of this woodland remains. In SW England, Temperate Rainforest habitat is mostly dominated by oak woodland (NVC communities W11 and W17) and occupies a broad but fragmented distribution across the region. SW temperate rainforest is exposed to a range of current and future threats and …

Near-Infrared Fluorescent Cyanine Probes For Monitoring Nad(P)H Dynamics In Living Cells And Drosophila Larvae, May Waters

Dissertations, Master's Theses and Master's Reports

Nicotinamide adenine dinucleotide (NAD+/NADH) plays a critical role in cellular metabolism, with abnormally elevated NADH levels linked to disrupted metabolic processes and cancer. In this study, we developed near-infrared fluorescent probes to selectively measure NADH concentrations. We present five cyanine-based probes, which were optimized by modifying the connection bridges to fine tune electronics. Two NAD(P)H-biosensing probes consisting of 1,3,3-trimethyl-3H-indolium and 3-quinolinium acceptors, linked by thiophene, A, and 3,4-ethylenedioxythiophene, B, bridges are detailed. They exhibit near-infrared fluorescence at 742.1 nm and 727.2 nm for probes A and B, respectively, and generate absorbance signals at 690.6 nm and 685.9 nm. Probe A …

Sugar Maple (Acer Saccharum Marsh.) Tree-Ring Growth And Carbon Stable Isotope Responses To Nitrogen And Climate, Libbie Ring

Dissertations, Master's Theses and Master's Reports

This dendrochronological and stable carbon isotope study used tree rings from sugar maple (Acer Saccharum Marsh.) collected at long-term nitrogen (N) amended sites throughout Michigan to understand N amendment and deposition, climate, and growth relationships. Climate responses varied by site, however, we found importance in grouping sites by “productivity” which is related to inherent N and soil nutrients. Our results did not detect an overall effect of N amendments on growth during the treatment period. However, data shows N amendments benefiting larger diameter trees, while smaller diameter trees responded more positively without amendments, especially on more productive sites. Results …

Growth, Survival, And Herbivore Browsing Preferences Of Seedlings Planted In Black Ash Stands Of Northern Michigan And Wisconsin, Seth W. Davenport

Dissertations, Master's Theses and Master's Reports

To mitigate the cascading ecosystem impacts of widespread black ash (Fraxinus nigra) mortality due to the invasive emerald ash borer (Agrilus planipennis), forested wetlands can be underplanted with seedlings of alternative species that later repopulate the vacated canopy. This study examined the survival and growth, factors influencing performance, and herbivore browsing preferences of seven non-ash species planted in northern Michigan and Wisconsin. The best performing species were river birch (Betula nigra), silver maple (Acer saccharinum), and swamp white oak (Quercus bicolor). The worst performing species was black spruce (Picea …