Digital Commons Network^™

Enhancing Adoptive Cell Therapy By Augmenting Fitness And Anti-Tumor Function Of Tumor-Infiltrating Lymphocytes, Parin Shah

Dissertations and Theses (Open Access)

The success of immune checkpoint inhibitors (ICIs) has established the importance of cancer immunotherapy in solid cancers, where it has been adopted as one of the standards of care for advanced melanoma and lung cancer. It is currently being investigated to treat other solid cancers. However, a large fraction of patients do not respond to ICIs and relapse. ICI therapy offers an in vivo approach to activate tumor-specific T cells, albeit in some cases, this modality does not create a sufficiently robust anti-tumor response. Thus, ex vivo approaches employing manipulation of immune cells, such as Adoptive Cell Therapy (ACT) using …

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 …

Early-Learners' Expectations Of And Experience With Ipe: A Multi-Institutional Qualitative Study, Sharon K. Lanning, Karen Pardue, Kathrin Eliot, Amanda Goumas, Ginge Kettenbach, Bernice Mills, Kelly Lockeman, Anthony Breitbach, Tina P. Gunaldo

Center for Interprofessional Education and Collaborative Practice Papers

Background: Multi-institutional qualitative studies are scarce within the interprofessional education (IPE) literature; such a report would provide comprehensive evidence for the application of interprofessional instruction among earlier learners. Objective: This investigation explored students' expectations of and barriers to introductory IPE across four institutions. Design: Qualitative inductive content analysis was utilized to interpret students' narrative responses to assigned pre- and post-survey questions. Setting: Health science schools of four U.S. institutions at Institution A, Institution B, Institution C, and Institution D. Participants: Twenty-two percent (n = 385) of eligible participants completed both pre- and post-surveys. Nursing student participation was greatest (n = …

The Roberts Court, State Courts, And State Constitutions: Judicial Role Shopping, Ariel L. Bendor, Joshua Segev

Journal of Law and Policy

In this Article we reveal a dual dilemma, both material and institutional, that the Supreme Court in its current composition faces when reviewing liberal state court decisions based on the state constitution. The Article further describes substantive and procedural tactics that the Court adopts to address this dilemma, and illustrates the arguments by analyzing a number of recent Supreme Court decisions. The two dilemmas, the combination of which serve as a “power multiplier,” of sorts, have arisen following the last three appointments to the Supreme Court, which resulted in a solid majority of conservative Justices nominated by Republican presidents. One …

Section 230 And The Problem Of Social Cost, Stanley M. Besen, Philip L. Verveer

Journal of Law and Policy

This Article employs, with certain modifications, the framework developed in Ronald Coase’s classic article, “The Problem of Social Cost,” to analyze the current debate over Section 230 of the Communications Decency Act. This provision absolves interactive computer services, also known as platforms, from liability when they disseminate materials that cause “harm” to third parties, “harm” that can take the form of compensable damage of a sort found in ordinary tort cases but also can include broader injuries to social order and cohesion in the form of such things as hate speech and misinformation. The Article begins by pointing out that, …

The Historical Diagnosis Criterion Should Not Apply: Reasonable Accommodations In Standardized Testing For Individuals With A Later Diagnosis Of Adhd, Denise Elliot

Journal of Law and Policy

There is a growing number of adults being diagnosed with ADHD who were not diagnosed in childhood, misdiagnosed, or primarily exhibited symptoms in adulthood. Notably, most of the later diagnoses of ADHD in adults are individuals pursuing some level of higher education. Some of the reasons posited for this increase in ADHD diagnoses in higher education may be attributed to increased workloads, decreased structural and community supports, misdiagnosis in childhood, masking, and racial and socioeconomic factors that overlook subpopulations like children of color, female-presenting, and gender-nonbinary children with ADHD. Unfortunately, testing agencies that administer college entrance exams, graduate school entrance …

On The Outer Reaches Of The Marketplace Of Ideas: The Weaponization Of Title Vi Against Palestinian College Activists, Gavriella Fried

Journal of Law and Policy

On U.S. college campuses, Palestinian rights activists who are critical of Israel risk legal consequences. Title VI of the Civil Rights Act prohibits discrimination on the basis of race, color, or national origin in any program receiving federal funds. Over the past two decades, at least eighteen Title VI complaints have been filed against U.S. colleges and universities, alleging that Palestinian rights activists’ political expression is a form of anti-Semitism. In December 2019, President Trump promulgated Executive Order 13,899, which formally extended Title VI protections to Jews and directed enforcement agencies to investigate allegations of anti-Semitism using guidance that includes …

Big Dreams And Pyramid Schemes: The Ftc’S Path To Improving Multi-Level Marketing Consumer Protections In Light Of Amg Capital Management And The 2016 Herbalife Settlement, Camille H. Mangiaratti

Journal of Law and Policy

Multi-level marketing, also known as “MLM,” is a type of sales business that relies on both sales to consumers and recruitment of sellers into the company’s tiered commission structure. MLMs are wildly and enduringly popular, especially because they claim to be a flexible and easy source of income for people who need it most. However, almost everyone who joins an MLM will lose money, and many MLMs are illegal pyramid schemes. Millions of Americans are harmed by MLMs every year. Despite this, the government does very little to punish MLMs who lie to prospective participants about their odds of success. …

How Artificial Intelligence Machines Can Legally Become Inventors: An Examination Of And Solution To The Decision On Dabus, Justyn Millamena

Journal of Law and Policy

With proliferation of Artificial Intelligence research and development, it is foreseeable that these machines will invent many new patentable technologies. However, the United States Patent and Trademark Office recently deemed a patent application incomplete for listing an AI machine as the inventor. If the USPTO’s decision is not corrected, the patent system will be in danger because many fraudulent patent applications that list incorrect inventors will be filed. This would drastically change existing and settled inventorship jurisprudence and might endanger the patent protection over such patents. This Note argues that the USPTO’s reasons for not allowing the Artificial Intelligence machine …

Civil Asset Forfeitures: How Prosecutors Can Facilitate Community-Based Criminal Justice Reform, Lane Waples

Journal of Law and Policy

Criminal justice reform is elusive in the United States. Despite evidence that the system is broken, change remains ephemeral at best. This is partially attributable to the fact that most attempts to reform the criminal legal system have occurred through the political process. However, another method of criminal justice reform is to assist communities as they address the root causes of crime. Undergirding this approach is the belief that building stronger communities contributes to less crime and reduces recidivism. After seizing $250 million via prosecutions of financial crimes in 2016, the New York County District Attorney’s Office created a “first-of-its-kind” …

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. …

Methylation-Derived Inflammatory Measures And Lung Cancer Risk And Survival, Naisi Zhao, Mengyuan Ruan, Devin C. Koestler, Jiayun Lu, Lucas A. Salas, Karl T. Kelsey, Elizabeth A. Platz, Dominique S. Michaud

Dartmouth Scholarship

Background: Examining immunity-related DNA methylation alterations in blood could help elucidate the role of the immune response in lung cancer etiology and aid in discovering factors that are key to lung cancer development and progression. In a nested, matched case–control study, we estimated methylation-derived NLR (mdNLR) and quantified DNA methylation levels at loci previously linked with circulating concentrations of C-reactive protein (CRP). We examined associations between these measures and lung cancer risk and survival. Results: Using conditional logistic regression and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell …

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 …

Placental Dna Methylation Signatures Of Maternal Smoking During Pregnancy And Potential Impacts On Fetal Growth, Todd M. Everson, Marta Vives-Usano, Emie Seyve, Andres Cardenas, Marina Lacasaña, Jeffrey M. Craig, Corina Lesseur, Emily R. Baker, Nora Fernandez-Jimenez, Barbara Heude, Patrice Perron, Beatriz Gónzalez-Alzaga, Jane Halliday, Maya A. Deyssenroth, Margaret R. Karagas, Carmen Íñiguez, Luigi Bouchard, Pedro Carmona-Sáez, Yuk J. Loke, Ke Hao

Dartmouth Scholarship

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord …

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 …

Coherently Amplifying Photon Production From Vacuum With A Dense Cloud Of Accelerating Photodetectors, Hui Wang, Miles Blencowe

Dartmouth Scholarship

An accelerating photodetector is predicted to see photons in the electromagnetic vacuum. However, the extreme accelerations required have prevented the direct experimental verification of this quantum vacuum effect. In this work, we consider many accelerating photodetectors that are contained within an electromagnetic cavity. We show that the resulting photon production from the cavity vacuum can be collectively enhanced such as to be measurable. The combined cavity-photodetectors system maps onto a parametrically driven Dicke-type model; when the detector number exceeds a certain critical value, the vacuum photon production undergoes a phase transition from a normal phase to an enhanced superradiant-like, inverted …

A Cluster Randomized Controlled Trial Comparing Virtual Learning Collaborative And Technical Assistance Strategies To Implement An Early Palliative Care Program For Patients With Advanced Cancer And Their Caregivers: A Study Protocol, Lisa Zubkoff, Kathleen Doyle Lyons, J. Nicholas Dionne-Odom, Gregory Hagley, Maria Pisu, Andres Azuero, Marie Flannery, Richard Taylor, Elizabeth Carpenter-Song, Supriya Mohile, Marie Anne Bakitas

Dartmouth Scholarship

Background: Virtual Learning Collaboratives (VLC), learning communities focused on a common purpose, are used frequently in healthcare settings to implement best practices. Yet, there is limited research testing the effectiveness of this approach compared to other implementation strategies. This study evaluates the effectiveness of a VLC compared to Technical Assistance (TA) among community oncology practices implementing ENABLE (Educate, Nurture, Advise, Before Life Ends), an evidence-based, early palliative care telehealth, psycho-educational intervention for patients with newly diagnosed advanced cancer and their caregivers. Methods: Using Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) and Proctor’s Implementation Outcomes Frameworks, this two-arm hybrid type-III cluster-randomized controlled …

English As A Foreign Language Preservice Teachers’ Technology Integration In Teaching Speaking Skills: A Study From Indonesia, I Putu Indra Kusuma

Dissertations

The novel coronavirus, namely COVID-19, has drastically forced schools and universities around the globe to implement emergency remote teaching (henceforth, ERT) in online forms. During this ERT, the personal computer, internet-accessible devices, and computer programs have expanded the opportunities of language learners to obtain more authentic materials and learning experiences. Moreover, technology enables students to record and store their speaking performance in digital forms, accommodating a new reform in English language teaching. Very little is known about how English as a foreign language (henceforth, EFL) preservice teachers, especially student teachers, implement technology in teaching speaking skills during their practice teaching. …

How Immigrant English Language Learners Used Internal Fortitude To Utilize Supports And Overcome Obstacles To Graduate From High School, Mark C. Peterson

Dissertations

Immigrants and English Language Learners (ELL) continue to receive attention in the research literature due in part to the continued immigration of families to the U.S. and the continued increasing number of students enrolled in U.S. schools under the ELL designation. The robust influx of immigrant’s school enrollment is reflected in schools across the country as classrooms are transformed from predominantly mono-cultural and mono-lingual environments to multi-cultural and multi-lingual ones. Unfortunately, the national average graduation rate for ELLs is a much lower than native-born students. The economic, social, and mental health ramifications for failing to graduate high school are dramatic; …

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, …

Temporary Penile Urethral Stent Placement Procedure As A Treatment Of Penile Urethral Obstruction In Intact Tom Cats., Houssam Abdelrehim, Reham Elsamanody

Mansoura Veterinary Medical Journal

Objective: The treatment of penile urethral obstruction in Tom Cats with no response to catheterization by placing a temporary urethral stent to avoid going through perineal urethrostomy or preputial urethrostomy. Design:Case Study (April 2015 – June 2021) Animals:14 Intact Tom Cats. Procedures:In the current study, fourteen male cats with obstructed urethras with no response to catheterization were subjected to intervention using a temporary urethral stent. Cases were observed for 10 days postoperative, monitoring blood creatinine level after operations and cases had follow up visits for a year on monthly basis for checkup the subjects’ lifestyle. Results:The procedure was successfully performed, …

Book Review: Intercultural Perspectives On Research Writing, Edited By Pilar Mur-Dueñas And Jolanta Šinkūnienė (Amsterdam/Philadelphia: John Benjamins, 2018), David Sánchez-Jiménez

Publications and Research

No abstract provided.

Kansas Speaks Fall 2021 Statewide Public Opinion Survey, Brett Zollinger Ph.D., Jian Sun Ph.D., Michael Walker M.S., Marisa M. Johnson M.B.A.

Docking Institute of Public Affairs

The 2021 Kansas Speaks fall survey was conducted from December 4 to December 17, 2021. A panel of 523 adult residents of Kansas age 18 and older were surveyed online to assess their attitudes and opinions regarding various issues of interest to Kansas citizens.

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 …

Longleaf Pine Restoration In The South Carolina Sandhills Wiregrass Gap, Jacob W. Murray

All Theses

Longleaf pine restoration has been a topic of great concern and intrigue in the southeast and has taken on new fervor in recent decades as restoration methods continue to develop. Many landowners and forest managers are now pursuing ecological forestry and restoration ecology in great numbers as a new form of land management. However, niche regions can often be overlooked, as is the case with the Carolina Sandhills Wiregrass Gap, an area devoid of wiregrass and one that is on the outskirt regions of the historical longleaf pine range. Field studies were conducted pre- and post-harvest during two growing seasons …

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 …