Digital Commons Network^™

Investigating Therapeutic Strategies To Target Metabolic Vulnerabilities Of Nsclc Tumors With Mutant Keap1 Gene, Pranavi Koppula

Dissertations and Theses (Open Access)

The metabolic vulnerability of cancers has long been envisaged as an attractive window to develop novel therapeutic strategies. Metabolic flexibility at the cellular level encompasses the efficient rerouting of anabolic and catabolic pathways in response to varying environmental stimuli to maintain cellular homeostasis and sustain proliferation. The primary objective of this study is to identify metabolic vulnerabilities bestowed by KEAP1/NRF2 signaling axis through SLC7A11. SLC7A11 is a transcriptional target of NRF2, an essential regulator of cellular anti-oxidant response. Under unstressed basal conditions, NRF2 interacts with KEAP1, a tumor suppressor gene and a substrate adaptor protein of the Cullin3-dependent ubiquitin ligase …

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos

Dissertations and Theses (Open Access)

Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …

Modulation Of The Receptor Gating Mechanism And Allosteric Communication In Ionotropic Glutamate Receptors, Nabina Paudyal, Nabina Paudyal

Dissertations and Theses (Open Access)

Ionotropic glutamate receptors (iGluRs) found in mammalian brain are primarily known to mediate excitatory synaptic transmission crucial for learning and memory formation. The family of iGluRs consists of AMPA receptors, NMDA receptors and kainate receptors with each member having distinct physiological role. In the recent years, significant progress has been made in understanding the biophysical, and functional properties of iGluRs. The development of Cryo-EM and X-Ray crystallography techniques have further facilitated in the structural understanding of these receptors. However, the multidomain nature, large size of the protein, complex gating mechanism and inadequate knowledge regarding the conformational dynamics of the receptors …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Cross-Seeding Potential Of Misfolded Amyloid-Beta Strains On Tau Protein: Examining The Puzzle Pieces Of Alzheimer's Disease, Sara Kelley

Dissertations and Theses (Open Access)

Alzheimer’s disease (AD) is a neurodegenerative disorder that will progressively impair cognitive function. AD is the leading source of dementia, and affects one third of the senior citizens in the United States. Aging is the primary risk factor for AD and due to the expected rise in human lifespan worldwide, the occurrence rate of AD diagnosis is projected to increase. This observation is increasingly alarming when considering there is no treatment for reversal or prevention of AD yet.

AD is characterized by gross pathological hallmarks in the brain. These include the extracellular accumulation of misfolded amyloid-beta (Aβ) and the intraneuronal …

Deciphering The Role Of Hsp110 Chaperones In Diseases Of Protein Misfolding, Unekwu M. Yakubu

Dissertations and Theses (Open Access)

Molecular chaperones maintain protein homeostasis (proteostasis) by ensuring the proper folding of polypeptides. Loss of proteostasis has been linked to the onset of numerous neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s disease. Hsp110 is a member of the Hsp70 class of molecular chaperones and acts as a nucleotide exchange factor (NEF) for Hsp70, the preeminent Hsp70-family protein folding chaperone. Hsp110 promotes rapid cycling of ADP for ATP, allowing Hsp70 to properly fold nascent or unfolded polypeptides in iterative cycles. In addition to its NEF activity, Hsp110 possesses an Hsp70-like substrate binding domain (SBD) whose biological roles are undefined. Previous work …

Agonist-Induced Conformational Changes In The Nmda Receptor, Ryan Durham, Ryan Durham

Dissertations and Theses (Open Access)

NMDA receptors are ligand-gated ion channels that mediate a number of physiological and pathological phenomena within the mammalian central nervous system. Under the typical course of activation, these receptors bind to glycine and glutamate molecules and undergo a series of conformational changes that results in the opening of a cation-permeable pore in the neuronal plasma membrane. Various aspects of NMDA receptor function are not fully understood, including the phenomenon of negative cooperativity between the glycine- and glutamate-binding sites of the receptor and the mechanism controlling partial agonism. Past studies utilizing static structural snapshots of the receptor or isolated domains of …

Mitochondrial Unfolded Protein Response Regulator Atf5 In Mitochondrial Targeted Therapies In Aml, Ran Zhao

Dissertations and Theses (Open Access)

Mitochondrial unfolded protein response (UPR^mt) is an adaptive transcriptional response induced by damaged proteins accumulated in mitochondria. UPR^mt signaling involves induction of mitochondrial specific chaperones and proteases such as HSP60, LonP1 and ClpP, aiding in the restoration of mitochondrial protein pool homeostasis. However, the cell-protective roles of UPR^mt in the context of mitochondrial stress-induced cell death in AML has not been well explored. We demonstrate that AML cells are susceptible to mitochondrial targeted agents such as ONC201, an agonist of the mitochondrial protease ClpP, and gamitrinib, an inhibitor of mitochondrial chaperone TRAP1, however, these agents also …

Atrx Inactivation And Idh1-R132h Drive Preferential Sensitivity To Proton Vs. X-Ray Radiotherapy In Glioma Stem Cells, Ángel Adrián Garcés

Dissertations and Theses (Open Access)

Background: Glioma Stem Cells (GSCs) are self-renewable, treatment resistant cells in the glioma tumor mass known to promote tumor development. In contrast to traditional photon-based radiation therapy (XRT), proton radiation therapy (PRT) may induce more complex DNA damage and therefore might have the potential to eliminate GSCs. Although previous studies have individually linked IDH mutations, specifically IDH1^R132H, and ATRX inactivating mutations to improved patient outcomes and suppressed DNA damage repair compared to their respective wild-types, the mechanisms by which these two genetic alterations interact in GSCs treated with PRT compared to XRT are currently unknown. We hypothesize that …

Cutaneous Melanocytic Tumor With Crtc1::Trim11 Fusion: Review Of The Literature Of A Potentially Novel Entity, Ourania Parra, Konstantinos Linos

Dartmouth Scholarship

“Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion” (CMTCT) is a recently described entity belonging to the family of superficial tumors displaying melanocytic differentiation. Thirteen cases have been reported so far, on the head and neck, extremities, and trunk of adults of all ages (12 cases) and one in an 11-year-old child. Histopathologically, it is a nodular or multilobu-lated tumor composed of spindle and epithelioid cells arranged in nests, fascicles, or bundles that are surrounded by thin collagenous septa. By immunohistochemistry, the tumor shows variable immunoreactivity for S100-protein, SOX10, and MITF, as well as specific melanocytic markers such as MelanA and HMB-45. …

A Close Association Of Freedom From Pain, Migraine-Related Functional Disability, And Other Outcomes: Results Of A Post Hoc Analysis Of Randomized Lasmiditan Studies Samurai And Spartan, Richard B. Lipton, Simin K. Baygani, Stewart J. Tepper, John H. Krege, Raghavendra Vasudeva, Eric M. Pearlman, Paula M. Hauck, Li Shen Loo

Dartmouth Scholarship

Background: While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing. Methods: Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed …

Arabidopsis Thaliana Zinc Accumulation In Leaf Trichomes Is Correlated With Zinc Concentration In Leaves, Felipe K. Ricachenevsky, Tracy Punshon, David E. Salt, Janette P. Fett, Mary Lou Guerinot

Dartmouth Scholarship

Zinc (Zn) is a key micronutrient for plants and animals, and understanding Zn homeostasis in plants can improve both agriculture and human health. While root Zn transporters in plant model species have been characterized in detail, comparatively little is known about shoot processes controlling Zn concentrations and spatial distribution. Previous work showed that Zn hyperaccumulator species such as Arabidopsis halleri accumulate Zn and other metals in leaf trichomes. To date there is no systematic study regarding Zn accumulation in the trichomes of the non-accumulating, genetic model species A. thaliana. Here, we used Synchrotron X-Ray Fluorescence mapping to show that Zn …

Quantifying Planarian Behavior As An Introduction To Object Tracking And Signal Processing, Nicole C. Stowell, T. Goel, Vir Shetty , '22, Jocelyne Noveral, Eva-Maria S. Collins

Biology Faculty Works

Answers to mechanistic questions about biological phenomena require fluency in a variety of molecular biology techniques and physical concepts. Here, we present an interdisciplinary approach to introducing undergraduate students to an important problem in the areas of animal behavior and neuroscience—the neuronal control of animal behavior. In this lab module, students explore planarian behavior by quantitative image and data analysis with freely available software and low-cost resources. Planarians are ∼1–2-cm-long aquatic free-living flatworms famous for their regeneration abilities. They are inexpensive and easy to maintain, handle, and perturb, and their fairly large size allows for image acquisition with a webcam, …

Effects Of Nitrogen Management And Cultivar On Strawberry Production Under Disease Pressure, Kamille A. Garcia-Brucher

Master's Theses

Effects of nitrogen management and cultivar on strawberry production under disease pressure

Kamille Garcia-Brucher

California strawberry growers face increasing regulatory pressures to manage nitrogen (N) applications in their production system. Standard practice in the California strawberry industry is to apply a synthetic pre-plant controlled release fertilizer (CRF) to ensure the crop has sufficient N during winter establishment. Some research from the UC Cooperative Extension suggests this practice is not efficient at delivering N to the crop since most of the N is released from CRF before strawberry crop N uptake is significant. Another concern for California strawberry growers is loss …

Practical Wisdom As An Adaptive Algorithm For Leadership: Integrating Eastern And Western Perspectives To Navigate Complexity And Uncertainty, Mai P. Trinh, Elizabeth A. Castillo

Management Faculty Publications

In this paper, we integrate Eastern and Western perspectives of practical wisdom to answer the question, how can practical wisdom transfer across cultural boundaries in a world of increasing interconnection? We describe key properties of practical wisdom in early Western and Eastern schools of thoughts and explain how the concept of practical wisdom in ancient philosophy aligns with modern-day complex system science. We identify seven qualities of complex adaptive systems as a universal pattern that underlies both Eastern and Western perspectives. From these qualities, we develop an integrated conceptual framework of practical wisdom as factors both internal and external to …

Developing Design And Analysis Framework For Hybrid Mechanical-Digital Control Of Soft Robots: From Mechanics-Based Motion Sequencing To Physical Reservoir Computing, Priyanka B. Bhovad

All Dissertations

The recent advances in the field of soft robotics have made autonomous soft robots working in unstructured dynamic environments a close reality. These soft robots can potentially collaborate with humans without causing any harm, they can handle fragile objects safely, perform delicate surgeries inside body, etc. In our research we focus on origami based compliant mechanisms, that can be used as soft robotic skeleton. Origami mechanisms are inherently compliant, lightweight, compact, and possess unique mechanical properties such as– multi-stability, nonlinear dynamics, etc. Researchers have shown that multi-stable mechanisms have applications in motion-sequencing applications. Additionally, the nonlinear dynamic properties of origami …

A Critical Analysis Of The Discourse Of Culturally Responsive Curriculum Within South Carolina’S Secondary U.S. History And Constitution Standards, James L. Goude

All Dissertations

This research study explored the presence of implicit racial bias in South Carolina curriculum policy within its content standards for U.S. history and the Constitution. Curriculum policy discourse flows through the statewide public school system from the legislature, through district offices, and into classrooms. That discourse guides classroom teachers on what the state legislated as essential knowledge of U.S. history. Teachers make instructional choices based on state and district guidance documents that may affect the performance of Black students on South Carolina’s U.S. History and Constitution End-of-Course Exam (USHC-EOC). This study describes the educational policy discourse from macro-documents, meso- documents …

Impact Of Interventions On Student Performance Among Eighth Graders In Algebra 1, Tiffany Osborne

All Dissertations

Educational leaders and practitioners face challenges in South Carolina schools, but through improvement science processes (Bryk, Gomez, Grunow, & LeMahieu, 2015), they can collectively develop solutions which directly address those issues. In this Participatory Action Research (PAR) study, I partnered with participants in ongoing Plan-Do-Study-Act (PDSA) cycles (Bryk, et al., 2015) to improve student outcomes. I triangulated multiple data points and corroborated findings with students’ own perceptions to provide evidence that students can achieve in eighth grade Algebra 1 when given the opportunity to enroll in the course and when afforded appropriate ongoing academic interventions that foster conceptual understanding, self-efficacy, …

Towards Understanding Protein Immobilization Rules Through Site-Specific Covalent Immobilization Of T4 Lysozyme, Maxwell Hilbert

All Dissertations

Soluble enzymes have the unique ability to assist the conversion of complex substrates in fewer steps compared to conventional chemical synthesis; however, when immobilized to a surface, the insoluble enzyme's activity and stability can suffer in its new environment. To improve upon future immobilized enzyme efficacy, a fundamental understanding of the interactions across the enzyme, linker, and surface during covalent, site-specific immobilization that can be detrimental to its activity is required. More specifically, using a well-characterized and model enzyme, T4 lysozyme (T4L), 28 different cysteine attachment points' effects on site-specifically immobilized activity are examined. Different combinations of heterobifunctional amine-to-sulfhydryl crosslinkers …

Time-Lapse Observation Of Sarcomeric Addition In Hypertrophic Models Based On A Tissue Like Cardiomyocyte Culture, Ailin Wei

All Dissertations

Cardiac hypertrophy is the response of the heart to increased mechanical stress exerted on the heart. In a hypertrophic heart, the muscles elongate or/and thicken with cardiomyocytes growing sizes. It is assumed that cardiomyocytes elongate by adding sarcomeres in series; the cardiomyocytes thicken with the addition of sarcomeres in the parallel position.

In this study, a tissue-like culture model was achieved with step-like ICDs. Uniaxial static stretch has been applied to our unique culture model for studying mechanical-load-induced cardiac hypertrophy. Hypertrophic responses of these cardiomyocytes have been confirmed on transcriptional and translational levels in our tissue-like model. The two-photon excitation …

Ecological Outcomes Of Movement Behavior In Brown Pelicans From The South Atlantic Bight, Bradley Wilkinson

All Dissertations

Vagile organisms are expected to display movement behaviors that respond to a wide variety of both intrinsic and extrinsic factors. Identifying drivers of movement is fundamental to understanding the ecology of species, as well as implementing effective conservation measures. Technological advancements have allowed for the collection of fine-scale positional data at rapid temporal scales, which can be a powerful tool for assessing the movement behavior of tracked species and for understanding the potential fitness implications resulting from variations in animal space use. The goal of this dissertation was to identify important drivers of movement behavior and to describe the ecological …

Interventions To Increase Prospective Teacher Candidates' Praxis Ii Content Exam Scores, Takara Hart

All Dissertations

Teacher shortages are a pervasive issue in South Carolina’s public schools. Some prospective teacher candidates have shown obstacles in meeting the minimum required Praxis II Content exam score. The purpose of this qualitative phenomenological study was to explore and develop specific Praxis II Content exam interventions to improve scores for six prospective teacher candidates in South Carolina. All participants were trying to meet the licensure exam requirement for various alternative certification programs. Malcolm Knowles’ Andragogy Adult Learning Theory guided the study as a theoretical framework, and Lev Vygotsky’s Socio-Cultural Constructivism provided the conceptual frame. Descriptive coding and analysis, using Dedoose …

Enabling Dna-Informed Breeding For Disease Resistance In Peach, Wanfang Fu

All Dissertations

DNA-informed breeding is becoming conventional for Rosaceae crops. The advancement of genomic tools and their application in breeding has potential to accelerate the breeding cycle and increase breeding efficiency. The objective of this dissertation was to explore the application of whole genome markers to identify marker-trait associations and potential candidate genes associated with peach disease resistance traits and evaluate the feasibility of applying genomic prediction models in breeding for disease resistance in peach. Two economically important diseases, brown rot and bacterial spot, were explored.

Genome wide association studies (GWAS) were first applied in detecting regions in the peach genome associated …

El Leñador, December 2021, El Leñador Staff

El Leñador Newspaper

El Leñador is an English and Spanish newspaper produced by Humboldt State University students. Our staff cover and provide news to Latinx and other diverse communities on campus and in Humboldt County. We are committed to providing relevant news and expanding the representations and stories told about people of color and other marginalized groups. Our work helps create more social, political and cultural diversity in local media.

El Leñador es un periodico en español y inglés producido por estudiantes de la Universidad Estatal de Humboldt. Nuestro personal cubre y provee noticias a la comunidad Latinx y otras comunidades diversas en …

Comparing Organic And Conventional Yield Responses To Climate Variations, Joost Wilken Meyer

Graduate Theses and Dissertations

This thesis compares the responses of organic yields and conventional yields towards climate variations. To achieve this objective, weather variables such as growing season weather conditions (average temperature, precipitation, cloud cover, relative humidity, drought index), weather anomalies, the occurrence of severe or extreme droughts and excessive rainfalls, are combined with 23 data sets gathered from previous studies that compare organic and conventional yields from the same location and time periods. To narrow the scope, the thesis focuses on soybean, maize, and wheat production in Europe and North America. Study-level fixed-effects models are used to control for any time-invariant factors such …

Crispr Gene Editing Drivers, Barriers And Prospects: A Comparative Study Among Plant Scientists Globally, Adriaan Johannes De Lange

Graduate Theses and Dissertations

The introduction of CRISPR gene editing into food crops has potential to contribute to food security and sustainable food production globally. To date, most scientific studies have focused on consumer perception of CRISPR gene edited foods or the potential benefits and risks of the CRISPR technology and none have focused on the perceptions of plant scientists concerning CRISPR gene editing. This study aimed to explore the investments, functions, barriers, benefits for specific crops and beneficiaries of CRISPR gene editing according to plant scientists, by distributing an online survey in which 1,040 plant scientists active across six continents and in both …

Relative Success Of Native Plants In Curb Cut Rain Gardens, Ana Singh, Rachel Warners, Jonathan Walt, Patrick Jonker, David P. Warners

Faculty and Professional Research

No abstract provided.

Does Bedtime Music Listening Improve Subjective Sleep Quality And Next-Morning Well-Being In Young Adults? A Randomized Cross-Over Trial, Nadyana M. Majeed, Verity Y. Q. Lua, Jun Sen Chong, Zoey Lew, Andree Hartanto

Research Collection School of Social Sciences

Previous research has found that young adults exhibit patterns of poor sleep and that poor sleep is associated with a host of negative psychological consequences. One potential intervention to improve sleep quality is listening to music at bedtime. Although there exist previous works investigating the efficacy of listening to music as a form of sleep aid, these works have been hindered by statistically weak designs, a lack of systematic investigation of critical characteristics of music that may affect its efficacy, and limited generalizability. In light of the limitations in the existing literature, a 15-day randomized cross-over trial was carried out …

Autonomous Feature Detection For Capture Path Planning For Rendezvous And Docking With Non-Cooperative Spacecraft, Trupti Mahendrakar

Theses and Dissertations

With the increasing risk of collisions with space debris and the growing interest in on-orbit servicing, the ability to autonomously capture non-cooperative, tumbling target objects remains an unresolved challenge. This thesis provides an autonomous and artificial intelligence solution to either inspect, avoid, or perform on-orbit spacecraft servicing of an uncooperative resident space object (RSO). The solution is built on the fundamentals of Convolutional Neural Networks (CNN), which is used to classify the four most targeted features of a spacecraft essential for docking and collision avoidance during rendezvous, such as solar panels, antennas, spacecraft bodies, and thrusters. The solution was then …

Assessment And Monitoring Of Deltaic Wetlands And Fluvial Systems: Refining And Validating A Multimetric Index Of Resaca Ecosystem Health, David Lecusay Jr.

Theses and Dissertations

Resacas are ancient distributary channels of the lower Rio Grande River historically serving as floodwater drainage pathways onto the Laguna Madre, Texas. Resacas provide numerous ecosystem services and critical habitat for many species. Mainly influenced by urbanization, integrating a multimetric index for assessing and monitoring resaca ecosystem health is required for adaptive management. The Resaca Health Index (RHI) integrates structural and functional components: (1) nonredundant metrics describing fish communities (Fish Community Index); (2) Trophic State Index derived from Secchi depth; (3) decay constant from riparian vegetation leaf litter decomposing in the water column; and (4) a riparian quality index based …