Digital Commons Network^™

Potential Role Of A Ruthenium-Based Compound Ru-Im In The Treatment Of Triple Negative Breast Cancer, Rachele Rameau

Dissertations, Theses, and Capstone Projects

Triple negative breast cancer (TNBC) is an aggressive and heterogeneous molecular subtype of breast cancer that has limited available treatments. The organometallic cationic ruthenium derivative Ru-IM was found to be highly water soluble, was differentially toxic for breast cancer cells and tumors, and was involved in the pI3K/AKT/mTOR pathway. However, a full understanding of genetic and epigenetic factors that can be part of regulatory mechanisms of Ru-IM is yet to be determined. Epigenetic assays including DNA methylation, histone acetylation and histone deacetylation were performed with the half inhibitory concentration (IC50) values of Ru-IM. Bisulfite sequencing of untreated and treated MDA-MB-231 …

Advances In Bone And Orthopedics 2025 – 5th Edition, Jean-Philippe Berteau, Laurent Pujo-Menjouet, Hélène Follet, Aurélie Levillain

Publications and Research

This volume brings together selected works from the 2025 Bone and Orthopedics Interdisciplinary Symposium (BONITOS), underscoring our community’s ongoing commitment to advancing research in biomechanics, bone health, and orthopedic science. The symposium unites leading experts from around the world, fostering collaboration and the exchange of ideas across disciplines. Organized in partnership with the French-speaking Society of Biomechanics, the French National Institute of Health and Medical Research (INSERM), the University of Lyon, the College of Staten Island of the City University of New York (CUNY), and the American Association of Physical Therapists (APTA) – Brooklyn Staten Island Chapter, BONITOS 2025 represents …

Fountain, Sadaf Azadehfar

Theses and Dissertations

This thesis investigates the intersections of water, power, identity, and architecture through the lens of colonial and postcolonial landscapes, focusing particularly on Persian gardens and fountain sculptures. Drawing on historical, cultural, and symbolic frameworks, the study explores how water systems embody both practical and spiritual roles, positioning water as a force of control, resistance, and regeneration. Central to this work are analyses of arches and garden designs, which serve as architectural metaphors for cosmic harmony, community gathering, and contested space. Through a combination of visual analysis, historical research, and personal artistic practice—including ceramic sculptures and multimedia installations—this thesis traces the …

Taming Biological Complexity Through The Use Of Symmetries, Luis A. Álvarez-García

Dissertations, Theses, and Capstone Projects

The study of biological systems is, inherently, the study of very complex systems. This is essentially due to the fact that they are made up of numerous, often very complicated, interactions between an extensive number of components. Often necessitating an abundance of quantitative parameters and details for a precise description. The human brain for ex- ample, consisting of ∼ 80 billion neurons with ∼ 800 to 100 trillion connections between them, each of them depending on a large set of parameters. Even simpler examples such as bacterial organisms, such as E. coli and B. subtilis, which we focus on …

Studies Of Oxidopyrylium Ylide Dimers And Their Utility In The Synthesis Of Densely Functionalized Troponoids, Daniel V. Schiavone

Dissertations, Theses, and Capstone Projects

Herein, we describe our efforts to investigate mechanistic considerations of oxidopyrylium ylides and their use in cycloadditions to form complex bicyclic structures and the advancement of these cycloadducts to the synthesis of densely functionalized tropolones. This work also describes applications of tropolones as biologically relevant structures and dynamic fluorophores.

In Chapter 1, we expand upon previous studies done in the Murelli Lab describing the ability of 3-hydroxy-4-pyrone derived oxidopyrylium dimers to revert back to ylides in situ and as result can be used as a clean oxidopyrylium ylide source in accessing oxabicyclic compounds. Intermolecular cycloadditions of these ylides can be …

Racial-Sexual Normativity In/As Narratives Of “The Human”, Jeri Brand

Dissertations, Theses, and Capstone Projects

This thesis synthesizes Sylvia Wynter’s and Judith Butler’s models of identity-formation to analyze discourses of racialization and sex/gender difference in normative scientific theories of “the human.” I argue that eugenicist white supremacism and sex/gender normativity form a single conceptual framework – what I call “the racial-sexual matrix” – throughout these scientific narratives. I then trace an epistemological consistency across 18^th- through 21^st-century scientific literature as evidence for the ongoing legacies of coloniality, white supremacy, and eugenics in current hegemonic sex/gender ontologies. Finally, I contend that the racial-sexual matrix functions as an index of proper humanness not …

Characterization Of The Conformational Binding Of N-Methyl Mesoporphyrin Ix With Dna Model Telomeric G-Quadruplex Forming Sequences, Jessica Desamero

Dissertations, Theses, and Capstone Projects

DNA G-quadruplexes are alternative secondary structures formed from guanine rich DNA sequences. G-quadruplexes are found most abundantly at the ends of chromosomes called telomeres, where they can ultimately prevent further tumor growth and progression. Thus, quadruplex interactive agents, or ligands that can bind to and stabilize DNA G-quadruplex structures, are of high interest for their potential chemotherapeutic abilities. One quadruplex interactive agent is the porphyrin N-methyl mesoporphyrin IX (NMM), which has high binding selectivity for quadruplex structures. While the NMM-quadruplex complex in crystallized form has been greatly studied, this complex in solution form is not as well studied. Through circular …

Development Of Chemical Probes For Two Pro-Metastatic Enzymes: Cysteine Cathepsins And Nek2 Kinase, Ashif I. Bhuiyan

Dissertations, Theses, and Capstone Projects

Proteases, specifically cysteine proteases, are crucial for the survival and growth of living organisms. They hydrolyze proteins and use different mechanisms to function. Cysteine proteases are classified into three types: papain, caspase, and picornaviridae. The papain class, with 11 cysteine cathepsins, regulates essential physiological functions, and abnormal expression is linked to various diseases. Our research aims to develop small molecules that inhibit cathepsins B and L to develop probes for functional proteomics.

The centrosome is critical for proper cell division and is regulated by multiple kinases, including Nek2. Nek2 is highly concentrated at the centrosome in vertebrates and plays a …

Separation Of Zr From Complex Matrices For Isotope Harvesting Applications, Jake A. Bence

Dissertations, Theses, and Capstone Projects

Zr isotopes have various applications in nuclear science, such as ⁸⁶Zr and ⁸⁹Zr in nuclear medicine, ⁸⁸Zr as a diagnostic isotope relevant to stockpile stewardship, and the fission product ⁹⁵Zr useful as an s-process branch nucleus for study in astrophysics. To access these isotopes of interest, dedicated production methods and subsequent processing chemistry are required. Direct production routes can be technically challenging and difficult to obtain enough activity to meet demand. The processing chemistry of Zr isotopes is tedious due to the tendency for Zr to hydrolyze in solution without highly acidic conditions or a strong …

Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi

Dissertations, Theses, and Capstone Projects

The role of antibody-based molecular agents for diagnosis and therapy of cancer has expanded significantly over the past decades. However, most of these constructs are synthesized using traditional bioconjugation methods based on the random ligations between the molecular cargo and lysine residues within the protein. These non-specific approaches can create poorly defined conjugates with suboptimal immunoreactivity and in vivo performance while Site-specific approaches to antibody bioconjugation based on ligations between maleimides and free cysteine residues have long stood as attractive alternatives. Yet the inherent instability of the thiol-maleimide linkage has fueled the search for new, more stable thiol-reactive prosthetic groups. …

Ubiquitination Of The Protocadherin-Γa3 Variable Cytoplasmic Domain Modulates Cell-Cell Interaction, Albert Ptashnik, Nicole Lamassa, Aliya Mambetalieva, Emily Schnall, Mike Bucaro, Greg R. Phillips

Publications and Research

The family of ∼60 clustered protocadherins (Pcdhs) are cell adhesion molecules encoded by a genomic locus that regulates expression of distinct combinations of isoforms in individual neurons resulting in what is thought to be a neural surface “barcode” which mediates same-cell interactions of dendrites, as well as interactions with other cells in the environment. Pcdh mediated same-cell dendrite interactions were shown to result in avoidance while interactions between different cells through Pcdhs, such as between neurons and astrocytes, appear to be stable. The cell biological mechanism of the consequences of Pcdh based adhesion is not well understood although various signaling …

Gamma Protocadherin Synaptic Localization And Intracellular Trafficking Is Consistent With Distinct Adhesive And Anti-Adhesive Roles In Development, Nicole Lamassa

Dissertations, Theses, and Capstone Projects

Clustered protocadherins (Pcdhs) constitute a family of cell adhesion molecules with approximately 60 Pcdh genes clustered in a 1 MB locus on chromosome 5q31 in humans. The Pcdh gene cluster is subdivided into α, β, and γ subclusters which encode related proteins. Individual neurons activate different subsets of Pcdh-α, Pcdh-β and Pcdh-γ genes by epigenetic mechanisms to generate distinct Pcdh adhesive units expressed by each neuron. This is thought to serve as a “surface barcode” for single-cell identity and synaptic recognition in the nervous system. The actual role for Pcdhs in neural development is still relatively unknown and different roles …

The Imaginal Lexicon Of Aging Studies, William Ebenstein

Publications and Research

Aging Studies focuses on the cultural, humanistic and experiential aspects of aging insofar as these are already embedded in literature, art, language and everyday life. The lexicon of this multi-disciplinary field has evolved in response to shifts in cultural attitudes, social roles, and conceptual frameworks. At the same time, many age-related words have links to poetic imagery and ancient myths, and to evocative etymologies that conjure an historical context. The article looks at the ongoing and surprisingly difficult effort to find the right word to call an older person. It reviews the language and literary genres associated with longevity. And, …

Synthetic And Biological Studies On Benzazepine Derivatives As Dopamine Receptor Ligands, Rajan Giri

Dissertations, Theses, and Capstone Projects

Dopamine (DA) receptors, members of the G-protein coupled receptors (GPCRs) family, are divided in two groups based on their transmembrane structural homology domains: D1R-like (D1R, D5R sub-types) and D2R-like DA receptors (D2R, D3R and D4R sub-types). Disturbances in dopaminergic neurotransmission are associated with several CNS disorders. Hence, DA receptor selective ligands have been sought as pharmacological agents to normalize perturbations in the dopaminergic system. Despite several notable efforts, the discovery of highly selective ligands for dopamine receptor sub-types has proved challenging due to close transmembrane structural similarity, especially between DA receptor sub-types within the same group.

The 1-phenylbenzazepine scaffold is …

Mechanistic And Synthetic Studies Of Oxidopyrylium Cycloaddition Reactions, Lauren P. Bejcek

Dissertations, Theses, and Capstone Projects

Cycloaddition chemistry has historically served as a robust route to stereo-rich and highly functionalized cyclic and heterocyclic compounds. Herein we describe our examination of 3-hydroxy-4-pyrone-derived oxidopyrylium cycloadditions in both mechanistic considerations as well as the unique synthetic advancements of their corresponding cycloadducts. Chapter 1 is a literature review where we specifically outline the use of oxidopyrylium cycloadditions in the synthesis of natural products. This includes the mention of previous syntheses prior to 2008, and a more thorough examination of the natural products synthesized from 2008 to present. The work exploits this chemistry as a facile route to highly complex 7-membered …

Antecedents Of Borderline Personality Disorder And Antisocial Personality Disorder: An Examination Of Gene X Environment Interactions, Amy L. Medina

Dissertations, Theses, and Capstone Projects

Current thinking suggests that genotypes associated with impulse-control disorders and negative emotionality, such as monoamine oxidase-a (MAOA), interact with negative early environmental factors like childhood maltreatment and develop into the disorders know as Borderline Personality Disorder (BPD) and Antisocial Personality Disorder (ASPD). Using existing data from a prospective cohort design study of the consequences of child abuse and neglect, participants (N = 896 represent individuals with documented histories of child abuse and neglect and a matched comparison group that were followed up into adulthood and interviewed. A subsample of 631 participants gave permission for DNA extraction and analyses during …

A Peek Inside The Machines Of Bacterial Nucleotide Excision Repair, Thanyalak Kraithong, Silas Hartley, David Jeruzalmi, Danaya Pakotiprapha

Publications and Research

Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). …

Machine Learning Applications For Drug Repurposing, Hansaim Lim

Dissertations, Theses, and Capstone Projects

The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected …

Ecology And Evolution, David J. Lohman

Open Educational Resources

Introduction to the basic principles of ecology and evolutionary biology emphasizing quantitative approaches and hypothesis testing. Scientific reasoning, computer literacy, and writing skills are developed in the laboratory.

Fibration Symmetries Uncover The Building Blocks Of Biological Networks, Flaviano Morone, Ian Leifer, Hernán A. Makse

Publications and Research

A major ambition of systems science is to uncover the building blocks of any biological network to decipher how cellular function emerges from their interactions. Here, we introduce a graph representation of the information flow in these networks as a set of input trees, one for each node, which contains all pathways along which information can be transmitted in the network. In this representation, we find remarkable symmetries in the input trees that deconstruct the network into functional building blocks called fibers. Nodes in a fiber have isomorphic input trees and thus process equivalent dynamics and synchronize their activity. Each …

Synthesis And Antitumor Activity Of Potentially Tumor Targeting Analogues Of The Tetrahydrofuran Containing Acetogenins, Patricia Gonzalez Periche

Dissertations, Theses, and Capstone Projects

The tetrahydrofuran containing acetogenins (THF-ACGs) are a naturally occurring class of compounds with potent toxicity against a broad range of tumors, including multidrug resistant (MDR) strains. However, the equally high toxicity to normal cells presents a hurdle for their clinical advancement. This study entails synthetic and tumor targeting strategies that are relevant to their therapeutic development.

Chapter 1 presents a review of the synthesis and biological activity of the THF-ACGs. Chapter 2 covers a modular approach for the synthesis of libraries of THF-ACGs. This strategy is illustrated in the synthesis of C-10 epimers of 4-deoxyannonomontacin (4-DAN), one of the more …

Polygenic Risk Score Analysis Revealed Shared Genetic Background In Attention Deficit Hyperactivity Disorder And Narcolepsy, Nagahide Takahashi, Tomoko Nishimura, Taeko Harada, Akemi Okumura, Damee Choi, Toshiki Iwabuchi, Hitoshi Kuwabara, Shu Takagi, Yoko Nomura, Jeffrey H. Newcorn, Nori Takei, Kenji J. Tsuchiya

Publications and Research

Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between …

Adult And Juvenile Rats Differentially Express Mpfc Glua2 Following Traumatic Memory Retrieval, Edgar Rodriguez

Theses and Dissertations

To advance our understanding of how traumatic memories are modulated between adults and juveniles, we characterize the AMPAr subunits, GluA1, GluA2, GluA3 in the mPFC of rodents following traumatic memory retrieval.

GluA2 was differentially expressed in adults but not juveniles rats. There were no changes in GluA1 or GluA3 expression

Adolescent Obesity In The Past Decade: A Systematic Review Of Genetics And Determinants Of Food Choice, Eleanor T. Campbell, Alexis T. Franks, Paule V. Joseph

Publications and Research

Background and purpose: As the incidence of global obesity increases, concerns about adverse health outcomes in adolescents continues to rise. The complexity and expense of this problem require early recognition and specific preventive treatments. Knowledge of genetics and determinants of food choices contributing to adolescent obesity warrants further examination. The primary goal was to appraise the literature from the past decade (2007–2017) on the current state of food choice and genetic determinants of adolescent overweight/obesity in the United States. The secondary goal was to determine trends in the literature and areas for future research.

Methods: A systematic review of research …

Deep Learning Based Medical Image Analysis With Limited Data, Jiaxing Tan

Dissertations, Theses, and Capstone Projects

Deep Learning Methods have shown its great effort in the area of Computer Vision. However, when solving the problems of medical imaging, deep learning’s power is confined by limited data available. We present a series of novel methodologies for solving medical imaging analysis problems with limited Computed tomography (CT) scans available. Our method, based on deep learning, with different strategies, including using Generative Adversar- ial Networks, two-stage training, infusing the expert knowledge, voting based or converting to other space, solves the data set limitation issue for the cur- rent medical imaging problems, specifically cancer detection and diagnosis, and shows very …

Dual Inhibition Of Bcl-2/Bcl-Xl And Xpo1 Is Synthetically Lethal In Glioblastoma Model Systems, Enyuan Shang, Yiru Zhang, Chang Shu, Chiaki Tsuge Ishida, Elena Bianchetti, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

XPO1 has recently emerged as a viable treatment target for solid malignancies, including glioblastoma (GBM), the most common primary malignant brain tumor in adults. However, given that tumors become commonly resistant to single treatments, the identification of combination therapies is critical. Therefore, we tested the hypothesis that inhibition of anti-apoptotic Bcl-2 family members and XPO1 are synthetically lethal. To this purpose, two clinically validated drug compounds, the BH3-mimetic, ABT263, and the XPO1 inhibitor, Selinexor, were used in preclinical GBM model systems. Our results show that inhibition of XPO1 reduces cellular viability in glioblastoma cell cultures. Moreover, addition of ABT263 significantly …

Synthesis And Evaluation Of Densely-Functionalized Troponoids, Danielle R. Hirsch

Dissertations, Theses, and Capstone Projects

Herein, we document our efforts to expand the scope of troponoid synthetic methodology towards densely-substituted scaffolds. This body of work has focused primarily on an oxidopyrylium cycloaddition/ring-opening strategy for the synthesis and biochemical evaluation of troponoids for assistance in a variety of medicinal chemistry studies. In Chapter 1, we outline the use of this synthetic strategy in the profiling of a library of synthetic αHTs against an aminoglycoside antibiotic resistance enzyme known as aminoglycoside-2’’-O-nucleotidyltransferase [ANT(2’’)-Ia]. Enzymatic mechanistic insights have been gleaned from an assessment of troponoid/antibiotic synergistic potential. In particular, two synthetic constructs were identified as promising antibiotic adjuvant candidates, …

Directly Light-Regulated Binding Of Rgs-Lov Photoreceptors To Anionic Membrane Phospholipids, Spencer T. Glantz, Erin E. Berlew, Zaynab Jaber, Benjamin S. Schuster, Kevin H. Gardner, Brian Y. Chow

Publications and Research

We report natural light–oxygen–voltage (LOV) photoreceptors with a blue light-switched, high-affinity (KD ∼ 10−7 M), and direct electrostatic interaction with anionic phospholipids. Membrane localization of one such photoreceptor, BcLOV4 from Botrytis cinerea, is directly coupled to its flavin photocycle, and is mediated by a polybasic amphipathic helixinthelinker regionbetween the LOV sensor and its C-terminal domain of unknown function (DUF), as revealed through a combination of bioinformatics, computational protein modeling, structure–function studies, and optogenetic assays in yeast and mammalian cell line expression systems. In model systems, BcLOV4 rapidly translocates from the cytosol to plasma membrane (∼1 second). The reversible electrostatic interaction …

The Economics Of Skin Tone In Nineteenth-Century Maryland, Yuree Kim

Theses and Dissertations

I analyze the effect of subtle differences in skin complexion on heights of free blacks in Maryland during the nineteenth century. I propose that lighter-skinned blacks were taller (indicating better nutrition) than their darker counterparts. I find the hypothesis holds - 15.9% taller for males and 16.5% taller for females.

Catalyzed And Uncatalyzed Modifications Of Nucleosides, Synthesis Of Hippadine, And Deuterated 1,2,3-Triazoles, Hari K. Akula

Dissertations, Theses, and Capstone Projects

The C4 amide carbonyl of O-t-butyldimethylsilyl-protected thymidine, 2’-deoxyuridine, and 3’-azidothymidine (AZT) was activated by reaction with (benzotriazol-1-yloxy)tris(dimethylamino) phosphonium hexafluorophosphate (BOP) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in THF as solvent. This led to the formation of corresponding O⁴-(benzotriazol-1-yl) derivatives, which are reactive intermediates. Substitution at the C4 position was then carried out by reactions with alkyl and aryl amines, and thiols. Typically, reactions were conducted as a two-step, one-pot transformation, and also as a one-step conversion. After examining the reactions, the formation of 1-(4-pyrimidinyl)-1H-benzotriazole-3-oxide derivatives from the pyrimidine nucleosides was identified. However, these too underwent conversion to …