Digital Commons Network^™

The Cx3cl1-Cx3cr1 Chemokine Axis Contributes To Tumor Immune Evasion And Its Blockade Enhances Responses To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri

Dissertations and Theses (Open Access)

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. While CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration, the mechanisms employed by this axis on these cells to mediate immune suppression remain poorly understood. Here, we explore the immune evasion strategies implemented by this axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of mediators to attract …

Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …

Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li

Dissertations and Theses (Open Access)

Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted the transfer of the CAR-cognate-antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their targets, (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen expressing NK cells (NK^TROG+) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

The Diagnostic Odyssey Of Hypermobile Eds Patients: Diagnosis, Clinical Expectations, And Psychosocial Concerns, Madeline Alpar

Dissertations and Theses (Open Access)

Background: Ehlers-Danlos syndrome (EDS) is a highly variable, heritable connective tissue disorder. Hypermobile EDS (hEDS) is the most common subtype of EDS and has no identifiable underlying genetic etiology. Patients with clinical features of hEDS face a long diagnostic odyssey due to lack of genetic testing and wide clinical heterogeneity. Additionally, recent research has shown that genetic institutions limit evaluations for suspected hEDS, adding another barrier to care.

Methods: We developed an online patient survey to explore the diagnostic odyssey of hEDS for those who were diagnosed with or suspicious for hEDS. This survey included sections on demographics, diagnostic information …

Y Chromosome Gene Kdm5d Epigenetically Drives Sex Differences In Colorectal Cancer, Jiexi Li

Dissertations and Theses (Open Access)

Sex exerts a profound impact on cancer incidence, spectrum and outcomes, yet the molecular genetic bases of such sex differences are ill-defined and presumptively ascribed to X-chromosome genes and sex hormones. Such sex differences are particularly prominent in colorectal cancer (CRC) where men experience higher metastases and mortality. A murine CRC model, engineered with an inducible transgene encoding oncogenic mutant KRAS^G12D and conditional null alleles of Apc and Trp53 tumor suppressors (designated iKAP), revealed higher metastases and worse outcomes specifically in males with oncogenic mutant KRAS (KRAS*) CRC. Integrated cross-species molecular and transcriptomic analyses identified Y-chromosome gene histone demethylase …

Bayesian Semi-Mechanistic Dose-Finding Designs For Phase I Oncology Trials, Chao Yang

Dissertations and Theses (Open Access)

Bayesian adaptive designs are getting more popular in research and in practice because they are flexible and efficient in evaluating an experimental drug. In oncology, despite the great advances in novel dose-finding designs, the high failure rates of clinical cancer drug development from phase I to III trials call for further improvements on novel designs, in addition to the need to promote and adopt novel designs in practice. Because anticancer agents often have a narrow therapeutic index, an accurate identification of the maximum tolerated dose (MTD) in a phase I trial is crucial for identifying a tolerable and efficacious dose …

Impact Of Recent Abortion Legislation On Patient Trust In Healthcare Providers, Jasmine Tyson Ms

Dissertations and Theses (Open Access)

Trust is a key aspect of any patient-provider relationship as patients must rely on their healthcare providers (HCPs) to provide appropriate care and guidance, maintain confidentiality, and act in their best interests. Studies suggest that recent changes to abortion legislation have resulted in a loss of the patient-physician relationship, with individuals describing feelings of isolation and fear regarding safety and confidentiality, and many seeking information outside of the medical community. An anonymous survey was distributed among members of abortion support groups and advocacy organizations in the United States to assess how recent changes to abortion legislation may impact patient trust …

Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha

Dissertations and Theses (Open Access)

Human papillomavirus (HPV) is the causative agent of cervical cancer and some cancers of the penis, vulva, vagina, anus, and oropharynx. Current therapies for these cancers include a combination of surgery, radiotherapy, and chemotherapy that often results in permanent, life altering adverse effects. Immunotherapy is partially effective, but with significant recurrence and lower long-term survival. Importantly, there are no few biomarker-selective targeted therapies for these cancers. To address this unmet need, our collaborators conducted a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human …

Public Service Loan Forgiveness? How Improvements To A Student Debt Cancellation Program Can Help To Deliver Gideon's Promise, Jane Fox, Winston Berkman-Breen

Journal of Law and Policy

Student debt is a generational crisis facing forty-five million Americans today. Among those with the highest rates of student loan debt are attorneys and among attorneys, those working in public interest have been hit particularly hard as they carry these same high debt rates yet earn low salaries. While student debt has run roughshod over Americans seeking higher education for almost forty years, another crisis has ravaged Americans who are swept up in the criminal legal system. Mass incarceration and mass policing have sent millions to prisons and jails and separated millions of parents and children through family courts. Often …

State Of Delay: Are Outdated Capital Post-Conviction Defense Tactics Undermining Effectiveness And The Attorney-Client Relationship?, Lyle C. May

Journal of Law and Policy

In 2018, death row prisoner Scott Allen was ordered to undergo a psychiatric evaluation to determine whether he was competent enough to fire his appointed attorneys. The competency hearing was not ordered by Scott’s counsel; rather, a superior court judge did so at the behest of an undisclosed third party. The problem was that Scott Allen had no history or symptoms of an intellectual disability or mental illness, nor was either a mitigatory claim in his appeal. The attorney-client conflict was triggered by Scott’s pro se effort to remove counsel after they ignored his lawful instructions to include potentially exculpatory …

Defendants In The Dark: How The Jencks Act Is Incompatible With The Adversarial Legal System, Eli J. Esakoff

Journal of Law and Policy

The Jencks Act is a McCarthy Era law that prohibits compelling the disclosure of any statement made by a government witness in a federal criminal prosecution until after the witness has testified at trial. Passed in 1957 in response to the Supreme Court’s decision in Jencks v. United States, the Act’s life in Congress was “nasty, brutish, and short.” In prosecuting its anti-communist “witch hunts” of the era, the government strove to keep hidden as much of its case against those accused as possible. Against this backdrop of the desire for secrecy, the Supreme Court held that a criminal defendant …

Leave Your Phone At Home: Combatting Data Exploitation In A Post-Dobbs America, Danielle Terracciano

Journal of Law and Policy

This Note comments on the dangers of an under-regulated data privacy sphere and highlights the particularly troubling threats posed to individuals seeking reproductive healthcare. In an ever-digitalizing world, smart phone and device users are subjected to violative data practices, like geofencing and location tracking, without their knowledge or consent. Some data service providers use personal data as a commodity to advance advertising or political objectives. Reproductive healthcare patients are at a heightened risk of exploitation because their personal data may infer or reveal their private healthcare decisions. As the fight for bodily autonomy was upended by the Supreme Court’s decision …

Consumer Reaction To The Use Of Artificial Intelligence Chatbot On Distribution Of General Insurance In Singapore, Lai Hing Tan

Dissertations and Theses Collection (Open Access)

As technology rapidly permeates all aspects of our lives, it is not unusual to question and even challenge the rationale on why certain industries are slower to adapt to the new digital age. Insurance is a business that is under scrutiny given its traditional ways of selling and legacy challenges. Why is technology investment in insurance companies lagging others? One emerging technological disruption is artificial intelligence (AI). It is the science of designing and building intelligent systems that can complete tasks traditionally performed by humans. AI is expected to fundamentally transform today’s marketplace, for businesses and consumers alike. However, because …

Directed Trusts And The Conflict Of Laws, Jeffrey Schoenblum

Vanderbilt Law School Faculty Publications

Directed trusts are an extremely important development in trust law, indeed truly transformative, because they challenge what was presumed to be the "irreducible core" of the trust.' That is, the trustee owes certain nonwaivable fiduciary obligations to the beneficiaries with regard to the management of the trust estate and also with respect to distributions.

The directed trust in its radical format, as found to a greater or lesser degree in Tennessee, Nevada, South Dakota, and Delaware, represents a fundamental assault on this irreducible core of trust law because, with respect to investments and distributions, new actors, known as trust advisers …

Health-Oriented Nonprofit Organizations: The Influence Of Framing And Altruism On Intention To Donate, Abbey Dilatush

Graduate Theses and Dissertations

This study investigated the influence of framing and altruism on individuals' intentions to donate to a health-oriented nonprofit organization. One hundred ninety-three participants were recruited from social media to complete an experiment online. Participants reviewed fundraising messages using either a statistical frame or a narrative frame. Following the presentation of a fundraising message participants completed close-ended self-report scales to evaluate their perceptions of the ad, their intentions to donate, and their personal altruism. Results demonstrated there was a correlation between intention to donate and ad evaluation. Next, there was no relationship between altruism and intention to donate and neither frame …

The Origins And Development Of The Cuban Danzas For The Piano In The Works Of Manuel Saumell, Ignacio Cervantes, Ernesto Lecuona And Gisela Hernandez, Yanet Bermudez Ortiz

Dissertations, 2020-current

This document aims to trace the evolution of the Cuban danza for the piano as seen in the works by Manuel Saumell, Ignacio Cervantes, Ernesto Lecuona, and Gisela Hernandez. The first chapter describes the history and origins of the Cuban danza, ending with Ignacio Cervantes’ compositions. In the following chapters, these composers’ lives and works are contrasted and analyzed in chronological order. Chapter two is dedicated to Manuel Saumell’s compositions, which are framed as the best representative examples of the roots of the Cuban danzas for the piano. Chapter three is centered on Ignacio Cervantes’ compositions and is analyzed …

The Underreporting And Dismissal Of Sexual Assault Cases Against Women In The United States, Jacey Passmore

Ballard Brief

Sexual assault is a highly prevalent yet rarely addressed issue within the United States. It is considered the most underreported and dismissed crime. There are a plethora of variables contributing to the underreporting and dismissal of sexual assault cases. The most prevalent factor appears to be the various understandings of sexual assault. The United States has no standard definition of rape or consent due to rape myths, victim blaming, disproportionately high perceptions of baseless allegations, and high-profile cases that are unrepresentative of the more common details of sexual assault. Other major contributing factors include knowing the perpetrator, victims’ pre-existing and …

Returning For A Better Life: The Habitus Of Temporary Senegalese Male Migrants, Sophia Margaret Patterson

Sociology and Anthropology Honors Theses

In this thesis, I study the narratives and practices which maintain Senegal’s temporary migration regime. This form of migration functions not as an individual endeavor, but rather as a family and community project which provides its participants—migrants and others—with cultural capital and prestige. I consider how the cultural imaginary of Senegalese male migration encourages young men to migrate in search of masculine social adulthood. I ultimately examine the habitus of temporary Senegalese male migrants in order to understand how their migration projects are oriented towards return to Senegal.

Jinn Discourses In America, Gwen Kaliszewski

Sociology and Anthropology Honors Theses

The scholarly literature shows that jinn are important in the analysis of the formation of Islam in Muslim diasporas in the West. Jinn discourses in America reveal how American Muslims negotiate their religious beliefs in relation to American conceptions of modernity and secularism, as well as highlights competing Islamic epistemologies that result from these negotiations. Imams emphasize the Qur’an and the Sunnah as the only sources of legitimate knowledge, while lay American Muslims and scholars of Islam see personal experience as a way to approach Islam.

There's No Such Thing As Independent Creation, And It's A Good Thing, Too, Christopher Buccafusco

William & Mary Law Review

Independent creation is the foundation of U.S. copyright law. A work is only original and, thus, copyrightable to the extent that it is independently created by its author and not copied from another source. And a work can be deemed infringing only if it is not independently created. Moreover, independent creation provides the grounding for all major theoretical justifications for copyright law. Unfortunately, the doctrine cannot bear the substantial weight that has been foisted upon it. This Article argues that copyright law’s independent creation doctrine rests on a set of discarded psychological assumptions about memory, copying, and creativity. When those …

Monopolizing Digital Commerce, Herbert Hovenkamp

William & Mary Law Review

Section 2 of the Sherman Act condemns firms who “monopolize,” “attempt to monopolize,” or “combine or conspire” to monopolize—all without explanation. Section 2 is the antitrust law’s only provision that reaches entirely unilateral conduct, although it has often been used to reach collaborative conduct as well. In general, § 2 requires greater amounts of individually held market power than do the other antitrust statutes, but it is less categorical about conduct. With one exception, however, the statute reads so broadly that criticisms of the nature that it is outdated cannot be based on faithful readings of the text.

The one …

Which Came First: The Chicken Or The Chick'n? An Fda Amendment Proposal To Reconcile Conflicting Interests In Plant-Based Meat Labeling, Katie Justison

William & Mary Law Review

“The issue is, what is chicken?” As the market for plant-based meats grows, state legislators are left with the question of what the words “chicken” and “burger” mean on food labels. In response to lobbying from the traditional meat industries, states followed suit with the dairy industry and created regulations and restrictions that carve out a meat industry monopoly on meat-related terms. Commercial speech restrictions such as these are guided by the Central Hudson test. Using that test, this Note will argue that while certain state regulations pass constitutional muster, others impose unconstitutional speech restrictions. This Note will draw particularly …

Deep Learning-Based Turkish Spelling Error Detection With A Multi-Class False Positive Reduction Model, Burak Aytan, Cemal Okan Şakar

Turkish Journal of Electrical Engineering and Computer Sciences

Spell checking and correction is an important step in the text normalization process. These tasks are more challenging in agglutinative languages such as Turkish since many words can be derived from the root word by combining many suffixes. In this study, we propose a two-step deep learning-based model for misspelled word detection in the Turkish language. A false positive reduction model is integrated into the system to reduce the false positive predictions originating from the use of foreign words and abbreviations that are commonly used in Internet sharing platforms. For this purpose, we create a multi-class dataset by developing a …

Steps Toward Healing From The Possessive Other: The Vital Role Of Fantastical Literature In Trauma Theory, Rebekah Izard

English (MA) Theses

Fantastical narratives such as fairy tales and magical realist literature utilizes fantastic and intangible spaces to unpack that which is often beyond the limitations imposed on our understanding by reality: the stunting experience of individual and generational traumas. This study aims to contribute to the current literary discourse’s understandings of fantastic literature and its subgenres as a tool for healing from trauma through the application of ontological notions of Selfhood and Otherness supplied by 20th century philosopher, Paul Ricoeur, and the notion of Orientalism by postcolonial scholar, Edward Said. The dialogue generated by these schools of thought provide a space …

Estimating The Functional Consequences Of Intra-Specific Trichome Variation Of Tomato, Solanum Lycopersicum On The Specialist Herbivore, Manduca Sexta, Satinderpal Kaur

Theses and Dissertations

Chapter 1: Plants have a wide array of defenses against herbivores and hence they must confer trade-offs between growth and defense related traits. By using Solanum as a model genus, the major plant defense fitness trade-off hypotheses are reviewed in this chapter along with their assumptions and examples.

Chapter 2: This chapter provides an overview of the enormous intra-specific diversity in trichome morphology in tomato, Solanum lycopersicum. Also, the trichome sub-types are analyzed for the variations in density and dimensions in 10 varieties of tomato by using desktop scanning electron microscope.

Chapter 3: This chapter examines the functional consequences …

Interorganizational Communication: Case Study, Emma Darocha

Comm-entary

The case presented in this study examines coercive power. An eighteen-year-old freshman attending college in a new state found himself longing for a community on campus which led him to decide to join a fraternity. Regrettably, this student did not find this community or brotherhood in this fraternity. As part of the pledging initiation, he was put in an extremely dangerous situation that was overseen by the authority figures of the fraternity. When he tried to drop out of the pledge process, he was coerced by older members to continue it and made to believe that this was something that …

Prevalence, Incidence And Chronicity Of Child Abuse Among Orphaned, Separated, And Street-Connected Children And Adolescents In Western Kenya: What Is The Impact Of Care Environment?, Samuel Ayaya, Allison Delong, Lonnie Embleton, David Ayuku, Edwin Sang, Joseph Hogan, Allan Kamanda, Lukoye Atwoli, Dominic Makori, Mary A. Ott, Caroline Ombok, Paula Braitstein

Internal Medicine, East Africa

Background: The effect of different types of care environment on orphaned and separated children and adolescents’ (OSCA) experiences of abuse in sub-Saharan Africa is uncertain.

Objective: Our two primary objectives were 1) to compare recent child abuse (physical, emotional, and sexual) between OSCA living in institutional environments and those in family-based care; and 2) to understand how recent child abuse among street-connected children and youth compared to these other vulnerable youth populations.

Participants and setting: This project followed a cohort of OSCA in Uasin Gishu County, Kenya (2009–2019). This analysis includes 2393 participants aged 18 years and below, 1017 from …

Prevalence Of Antimicrobial Resistance And Association With Patient Outcomes In A Rural Kenyan Hospital, Ian C. Drobish, Immaculate K. Barasa, George Otieno, Moses Odhiambo Osoo, Solomon K. Thuo, Kaya S. Belknap, Arianna Mclain Shirk, S. Taylor Mcclanahan, Elizabeth Irungu, Felix Riunga

Internal Medicine, East Africa

Data on antimicrobial resistance (AMR) and association with outcomes in resource-variable intensive care units (ICU) are lacking. Data currently available are limited to large, urban centers. We attempted to understand this locally through a dual-purpose, retrospective study. Cohort A consisted of adult and pediatric patients who had blood, urine, or cerebrospinal fluid cultures obtained from 2016 to 2020. A total of 3,013 isolates were used to create the Kijabe Hospital’s first antibiogram. Gram-negative organisms were found to be less than 50% susceptible to third- and fourth-generation cephalosporins, 67% susceptible to piperacillin–tazobactam, 87% susceptible to amikacin, and 93% susceptible to meropenem. …

Substrate Stiffness: A Mechanical Determinant Of Endothelial Phenotype, Sunita Subedi Paudel

Graduate Theses and Dissertations (2019 - present)

Endothelial cells (ECs) adhere to their neighboring cells via adherens and tight junctions, and to the basement membrane via focal adhesions. These structural elements are constantly remodeling i.e., even in a quiescent state, cells are in constant motion. ECs sense the stiffness of the basement membrane, and this stiffness is a physiological signal that control the cellular phenotype. Whereas the normotensive pulmonary circulation has a substrate stiffness that is ~1.25-4 kPa, vascular remodeling in pulmonary arterial hypertension (PAH) increases substrate stiffness to ~30 kPa. The impact that this increase in substrate stiffness has no cell size, shape, and speed was …