Digital Commons Network^™

Functionalized Dna Nanostructures For Membrane Engineering, Qiancheng Xiong

Yale Graduate School of Arts and Sciences Dissertations

DNA nanotechnology is a powerful tool for constructing precisely designed nanostructures with applications in diverse fields, including synthetic biology, nanomedicine, and biomolecular engineering. This dissertation explores the use of DNA nanotechnology in membrane engineering, focusing on developing DNA endoskeleton-supported membranes and large functionalized DNA-toxin nanopores. The first approach encountered challenges while constructing interlocked DNA nanostructures for endoskeleton-supported membranes. The negative results highlighted the need to optimize the interlocked DNA endoskeleton cage design further to ensure its practical application in templating fully exposed, continuous membranes. The second approach incorporated pneumolysins into DNA-origami channels to create large, functionalized DNA-toxin nanopores. These hybrid …

Copper Complexes For Water Oxidation Electrocatalysis And Strong Bond Activation, Claire C. Cody

Yale Graduate School of Arts and Sciences Dissertations

In order to meet rising global energy and material demands while mitigating negative effects on our climate, renewable energy sources must offer a competitive alternative to fossil fuels. Understanding chemical activation of small molecules such as water can provide a basis for leveraging electrocatalytic reactions using electricity from photovoltaics paired with catalysts for chemical transformations. For an efficient and widely applicable system, catalysts should be robust and use cheap, earth-abundant elements. This thesis investigates Cu-based complexes for electrocatalytic transformations, structural studies, and bond activation. First, we investigate the influence of ligand structure on water oxidation electrocatalysis. In comparison to the …

Optimization And Sequential Decision Making: Implicit Loss Functions And Variance-Aware Reinforcement Learning, Ruitu Xu

Yale Graduate School of Arts and Sciences Dissertations

Machine learning, as a transformative tool, has demonstrated remarkable efficacy across diverse applications. This dissertation delves into a selection of learning algorithms, analyzing their learning dynamics and providing theoretical guarantees on their performance. First, we scrutinize a novel neural network learning paradigm, leveraging a set of random weights that represent more biologically plausible neural connections during the back-propagation training process. Our research establishes a theoretical framework, illustrating both the convergence of the training loss and the mechanism of alignment between the forward-propagated network weights and the randomized backward-propagated weights. Subsequently, we venture into the realm of model-agnostic meta-learning, examining an …

Antiviral Hiv-1 Serinc Restriction Factors Disrupt Virus Membrane Asymmetry, Ziwei Yang

Yale Graduate School of Arts and Sciences Dissertations

The human immunodeficiency virus 1 (HIV-1), which is the causative agent responsible for Acquired Immunodeficiency Syndrome (AIDS), is a retrovirus that primarily infects CD4+ T lymphocytes. When left untreated, HIV replication results in progressive CD4+ T cell loss and leads to a myriad of immunological abnormalities in the host, escalating the risk of infections as well as oncological complications. To combat the progression of HIV-1, host cells have evolved to produce proteins known as restriction factors, which are crucial elements of the innate immune system, to inhibit the HIV-1 infection by disrupting various stages of viral replication. Such factors include …

Statistical Methods In High-Throughput Biomedical Data With Application To Precision Medicine, Yunqing Liu

Yale Graduate School of Arts and Sciences Dissertations

Precision medicine has emerged as a critical approach in healthcare due to its potential to revolutionize patient care. Traditional medical practices often adopt a one-size-fits-all approach, treating patients based on generalized guidelines. However, individuals exhibit significant variations in their genetic makeup, lifestyle factors, and environmental exposures. Precision medicine recognizes and leverages these differences to deliver personalized treatment plans tailored to each patient's unique characteristics. Recent technological advancements have facilitated the generation of high-throughput data, such as single-cell RNA sequencing (scRNA-seq) data, spatial transcriptomics (ST) data, locomotor activity assays measuring behavior, which offers the potential to the development of precision medicine. …

Bacterial Cell Surface Characterization By Phage Display Coupled To High-Throughput Sequencing, Casey Grun

Yale Graduate School of Arts and Sciences Dissertations

Antimicrobial resistance is a looming threat that reflects the remarkable capacity of bacteria to adapt and change in response to selective pressures. The versatile pathogen P. aeruginosa is a model case---already intrinsically resistant to many antibiotics, it can establish decades-long chronic infections, during which it evolves to survive antimicrobial treatment and evade host defenses. Many changes occur on its cell surface, a key location for both virulence and antibiotic resistance, but our technologies for studying these adaptive phenotypes are limited. Here we combined phage display with high-throughput DNA sequencing to create a high throughput, highly multiplexed technology for surveying bacterial …

Chromatin Expansion Microscopy Reveals Nanoscale Organization Of Transcription And Chromatin, Mark Pownall

Yale Graduate School of Arts and Sciences Dissertations

Nanoscale chromatin organization regulates gene expression. While chromatin is dramatically reprogrammed during zygotic genome activation (ZGA), the organization of chromatin regulatory factors during this universal process remains unclear. Here, we developed chromatin expansion microscopy (ChromExM) to visualize chromatin, transcription, and transcription factors in vivo. ChromExM of embryos during ZGA revealed how the pioneer factor Nanog interacts with nucleosomes and RNA Polymerase II (Pol II), providing direct visualization of transcriptional elongation as string-like nanostructures. Blocking elongation led to more Pol II particles clustered around Nanog, with Pol II stalled at promoters and Nanog-bound enhancers. This led to a new model termed …

Nutrient Acquisition And Plant-Microbe Interactions In Savanna Trees, Arielle Biro

Yale Graduate School of Arts and Sciences Dissertations

Ecosystem productivity is often constrained by the availability of essential macronutrients. Ecosystem processes that are vital to nutrient acquisition like nutrient cycling and microbial activity are expected to change under global warming, but prediction accuracy in the face of global change is challenging, as prediction requires a thorough mechanistic understanding of how plants acquire nutrients from their environments. These strategies include exploration by roots for resources like nutrients or water, releasing enzymes that decompose organic matter into plant available forms, or forming symbioses with soil bacteria or mycorrhizal fungi, which can have downstream impacts on ecosystem nutrient budgets, nutrient cycling, …

Methods And Complexity In Phage-Bacteria Ecology And Evolution, Michael Blazanin

Yale Graduate School of Arts and Sciences Dissertations

Chapter I:Characterization of microbial growth is of both fundamental and applied interest. Modern platforms can automate collection of high-throughput microbial growth curves, necessitating the development of computational tools to handle and analyze these data to produce insights. However, existing tools are limited. Many use parametric analyses that require mathematical assumptions about the microbial growth characteristics. Those that use non-parametric or model-free analyses often can only quantify a few traits of interest, and none are capable of importing and reshaping all known growth curve data formats. To address this gap, here I present a newly-developed R package: gcplyr. gcplyr can flexibly …

The Role Of Dietary Fats In Driving Atherosclerosis, Zenan Wang

Yale Graduate School of Arts and Sciences Dissertations

Cardiovascular diseases (CVDs) are the number one killer of people worldwide, of which coronary heart disease, which is mainly due to atherosclerosis, is the main contributor to death. Nonetheless, the etiology of atherosclerosis remains poorly understood. It is universally accepted that dietary fat influences atherosclerosis, however, the role of specific fats is not well-understood. Despite the widely-held perception that saturated fats drive atherosclerotic CVDs while monounsaturated fats are protective, there have been numerous studies from human and mice that do not fit with this prevailing narrative. Thus, despite the importance of dietary fats in CVDs, the exact effects remain controversial …

Modifying The Surface Topography Of Pegylated Nanoparticles Based On Bottlebrush Block Copolymer For Drug Delivery Applications, Julian Grundler

Yale Graduate School of Arts and Sciences Dissertations

The clinical translation of nanomedicines has been closely tied to the development ofnovel drug delivery techniques. In particular, nanoparticle formulations promise to improve the pharmacokinetics, selective accumulation at the target site, and intracellular delivery of therapeutics. Extensive research efforts have identified structure-function relationships between nanoparticle physicochemical properties (e.g. size, charge, surface functionalization) and biological fate. However, studying the biological impact of nanoparticle surface topography still remains a challenge due to the limited spatial control of conventional nanoparticle surface coatings based on hydrophilic linear polymers including poly(ethylene glycol) (PEG). In this dissertation, we investigated a novel method to precisely control the …

Computational Study Of The Mechanism Of Attention In Cortical Information Coding, Xiang Wang

Yale Graduate School of Arts and Sciences Dissertations

The animals’ visual perception of natural scenes is influenced by both the external condi-tions of the environment and the internal states. External conditions include the contrast of the stimulus, the crowding of distractors and the complexity of visual features. Internal states include the level of arousal, the deployment of attention, and the goal of behavior. An important and extensively studied internal state is selective attention, which is thought to be critical in solving visual perception problems by increasing the saliency of the attended ob-jects against the background. Electrophysiological studies have indicated attentional modu-lation of single neurons along the hierarchy of …

Multi-Scale Gene Regulation Analysis With Chip-Seq And Beyond, Jiahao Gao

Yale Graduate School of Arts and Sciences Dissertations

Regulation of gene expression is one of the most important and fundamental aspects of biological systems. The intricate regulation could be observed in different aspects, including the variations in individual genes, dynamic interactions between multiple genes, and complicated regulatory relationships between expression and other properties such as methylation level. Therefore, studying gene regulation at all these multiple scales is crucial. Transcription factors (TFs) are a special group of proteins that recognize specific DNA sequences and control gene expression by DNA binding. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) had been developed to identify genome-wide protein–DNA interactions. It has become the standard …

Probing Diverse Biological Systems And Their Hydration Shells By Modeling Chiral Sum Frequency Generation Spectroscopy, Daniel Konstantinovsky

Yale Graduate School of Arts and Sciences Dissertations

All biological processes occur in aqueous solution. Water dictates biomolecular structure, is responsible for a large portion of the free energy of ligand binding, and participates structurally in protein-protein interactions. However, few experimental techniques can probe the biomolecular hydration shell and its diverse environments. Chirality-sensitive vibrational sum frequency generation spectroscopy (chiral SFG) is a powerful technique that probes hydration shell water. The work presented here clarifies the conditions required for a chiral SFG signal to emerge, identifies the water immediately neighboring a biomolecule as the source of the aqueous chiral SFG signal, and investigates the interaction between biomolecules and their …

Outbreak Dynamics Of Emerging Sars-Cov-2 Variants In Human And Animal Populations, Rebecca Lynn Earnest

Yale Graduate School of Arts and Sciences Dissertations

The COVID-19 pandemic is characterized by cycles of SARS-CoV-2 viral variant emergence followed by surges of infections and deaths. In the United States, the most notable variants to date are Alpha (B.1.1.7), Delta (B.1.617.2 and AY.x sub-lineages), and Omicron (BA.1, BA.2, BA.4, BA.5, and various sub-lineages). Pandemic response evolved along with the virus, raising three overarching research questions with each new variant that correspond to the chapters of this dissertation. When a new variant emerges, how is it different from the previously dominant variant(s) in circulation? The set of mutations that define a SARS-CoV-2 variant can affect viral properties such …

Exploiting Dna Repair Deficiencies In Cancer To Develop And Characterize Novel Therapeutics, Sateja Paradkar

Yale Graduate School of Arts and Sciences Dissertations

Genomic instability is one of the hallmarks of cancer, which underlies cancer development and progression. This DNA repair vulnerability presents cancer researchers with a therapeutic opportunity. Targeted therapies designed to overwhelm DNA repair pathways in cancer have proven largely effective as anti-cancer treatments. However, there are currently three major issues with their widespread use in cancer. Firstly, for cancers such as glioblastomas (GBMs), there have been no targeted therapies approved for decades. Secondly, for most targeted therapies there is an incomplete understanding of their precise mechanism of action, which limits their clinical utility. Thirdly, cancers develop resistance to most targeted …

Mechanisms That Control Lipid Synthesis At The Endoplasmic Reticulum And Nuclear Envelope, Jake Williams Carrasquillo Rodriguez

Yale Graduate School of Arts and Sciences Dissertations

The endoplasmic reticulum (ER) is the largest membrane bound organelle in most cells. The ER is made up of distinct structural and functional domains, which include the nuclear envelope (NE) and peripheral ER sheets and tubules. The nuclear envelope surrounds and protects the genome, while the peripheral ER is essential for protein and de novo lipid synthesis. Lipids synthesized at the ER are either retained or shuttled to other membrane bound organelles through membrane contact sites or vesicular trafficking. As such, regulation of ER lipid synthesis is a tightly controlled process carried out by a subset of enzymes that are …

Fall 2023 Gsbms Alumni Connections, New York Medical College

Graduate School of Biomedical Sciences

• Founder's Dinner 2023
• GSBMS Welcomes Incoming Students for the 2023-2024 Academic Year
• Golf Outing Supports Student Scholarships
• GSBMS Hosts Biennial Ph.D. Lab Coat Ceremony
• NYMC and TU Hosts Webinar Series: “Ninety Minutes: The Medical Magazine of the Web”
• NYMC Research: Patric K. Stanton, Ph.D.
• Dr. Sangmi Chung Awarded $7.1 Million in Grants to Support Schizophrenia Research
• NYMC Research | Christopher S. Leonard, Ph.D., and Elizabeth Berry, Ph.D. '23

Bat Occurrence And Diversity In Urban, Suburban, And Rural Locations Around Nashville, Tennessee, Penny Keith, Cassie Tull, Darlene Panvini

Science University Research Symposium (SURS)

As urbanization increases, awareness of the effects of urbanization is crucial for the preservation of wildlife. Many species have adapted to urban areas while others are less successful in locations with a large extent of human impacts, such as noise and light pollution. Bats can be bioindicators for the impact of urbanization on wildlife. During this study, bat echolocation was recorded using an Echo Meter Touch 2 starting around sunset for an hour, once a week, during late September and October 2023. Bat species were confirmed using Kaleidoscope Pro Analysis Software. Environmental variables that could affect the presence of bats …

Equity, Diversity, And Inclusion Annual Report, 2022-2023, Illinois State University

Equity, Diversity, and Inclusion Annual Report

Equity, Diversity, and Inclusion 2022-2023 Annual Report for Illinois State University.

Gold & Blue, Fall 2023, St. Mary's University - San Antonio, Texas

Gold & Blue

This is the Fall 2023 edition of Gold & Blue which is St. Mary's University's official school publication.

Special Operations And International Relations, Caleb Williams

Global Studies Senior Capstone

This paper is an analysis on the impact of special operations on international relations. The Paper provides an analysis of three different case studies involving special operations and describes their impact within the context of those case.

Regional Variation In The Trophic Ecology Of Wahoo (Acanthocybium Solandri) In The Western Atlantic Ocean, Brendan Gough, Alexandra Prouse, Michael A. Dance, R. J.David Wells, Jay R. Rooker

Faculty Publications

Intrinsic tracers, such as stable isotopes of carbon and nitrogen, are common dietary markers that accumulate in the muscle tissue of consumers and can be used to determine the dietary sources and trophic positions of consumers. The aim of this study was to assess regional variation in the trophic ecology of wahoo (Acanthocybium solandri) using bulk stable isotopes. Muscle biopsies of wahoo were collected from four regions in the western Atlantic Ocean: the eastern Gulf of Mexico, western Gulf of Mexico, Northwest Atlantic Ocean, and Caribbean Sea. Muscle tissue δ¹³C and δ¹⁵N values for wahoo ranged …

Editorial: Research Advances Of Modification And Nutrition Properties Of Food Carbohydrates, Volume I, Yanjun Zhang, Jianhua Xie, Bin Li, Srinivas Janaswamy

Dairy Science and Food Science Faculty Publications: 2022 to Present

As a group of essential biopolymers, carbohydrates exist widely in living organisms and play many known and unknown biological roles in life activities via different pathways. Carbohydrates are widely used in foodstuffs, pharmaceuticals, biofuels, and biomaterials, to name a few. Parallelly, a growing understanding and deeper investigation drive the development of natural carbohydrates for novel applications, especially for treating chronic diseases, e.g., hyperlipidemia, obesity, and diabetes. The emerging evidence indicates that carbohydrates are effective for modulating gut microbiota, a vital organ in health and diseases. In addition, modifying carbohydrates alters and/or enhances nutrition properties, further expanding their application potential. Notably, …

Examining How And When Knowledge And Motivation Contribute To Organic Food Purchase Intention Among Individuals With Chronic Diseases: Testing A Moderated Mediation Model, Yam B. Limbu, Christopher Mckinley, P. Ganesan, Tianfu Wang, Junzhou Zhang

College of Communication and Media Scholarship and Creative Works

Prior research underscores a need for applying theoretical frameworks to understand the factors influencing diverse populations’ organic food purchase intentions. The objectives of this study are threefold. First, we evaluate the applicability of the information–motivation–behavioral skills model for predicting organic food purchase intention in adults with chronic conditions. Second, we examine the indirect effects of organic food knowledge, attitudes toward organic food purchase, and subjective norms on purchase intention through self-efficacy. Third, we examine whether these indirect effects are moderated by gender and educational attainment. Data were collected from Indian adults with chronic conditions using a self-administered questionnaire. The results …

Effective Entity Augmentation By Querying External Data Sources, Christopher Buss, Jasmin Mousavi, Mikhail Tokarev, Arash Termehchy, David Maier, Stefan Lee

Computer Science Faculty Publications and Presentations

Users often want to augment and enrich entities in their datasets with relevant information from external data sources. As many external sources are accessible only via keyword-search interfaces, a user usually has to manually formulate a keyword query that extract relevant information for each entity. This approach is challenging as many data sources contain numerous tuples, only a small fraction of which may contain entity-relevant information. Furthermore, different datasets may represent the same information in distinct forms and under different terms (e.g., different data source may use different names to refer to the same person). In such cases, it is …

Dynamics And Inhibition Of Abc And Rnd Transporters Associated With Multidrug Resistances In Cancer And Pathogenic Bacteria, Hang Zhao

Biological Sciences Theses and Dissertations

The overexpression of efflux transporters is deemed to be one of the important mechanisms that contribute to Multidrug Resistance (MDR). In this dissertation, three transporters of significance were studied, the Breast Cancer Resistance Protein (BCRP/ABCG2) in a variety of cancer cells, the mtrCDE transporter from Neisseria gonorrhoeae, and the acrAB-tolC transporter from Escherichia coli. It is well known that the overexpression of BCRP in cancer cells results in these cells being resistant to the effects of many chemotherapeutics. This results in multidrug resistance for this cancer because of the fact that BCRP can transport many different types of …

Teaching Phonological Awareness To Children In Early Literacy Acquisition: An Analysis Of A District’S Kindergarten Core Language Arts Curriculum Material, Valerie Jensen

Educational Leadership Theses, Dissertations, and Student Creative Activity

This study explored and analyzed the phonological and phonemic awareness components of a teacher edition of a school district's kindergarten language arts curriculum material. Criteria for this pragmatic content analysis were derived from the research on phonological awareness and the sequence of instruction and intervention (Schuele and Boudreau, 2008). Lessons designated by the publisher as phonological and phonemic awareness in the weekly plan were coded for the type, occurrence, scope, and sequence of phonological and phonemic awareness components, through the 11 instructional units. The phonological and phonemic awareness skills were then coded according to the sequence of phonological instruction and …

The Coastal Monitor: Vol. 10 No. 2, John Tanacredi Ph.D.

The Coastal Monitor

Stephen J. Gould’s prophetic piece, “The Golden Rule: A Proper Scale for Our Environmental Crisis”, noted that, “Patience enjoys a long pedigree of favor”, which he elaborated, “usually involves a deep understanding of the fundamental principle… rarely grasped in daily life – the effects of scale.” Scientists observe changes incessantly, in dimensions and time, from microscopic conditions of cellular biology to the inconceivable distances of galaxies and their influences on Earth.

Tapinarof Cream 1% Once Daily For The Treatment Of Plaque Psoriasis: Case Photography Of Clinical Outcomes From Three Phase 3 Trials, Seemal R. Desai, Linda F. Stein Gold, Michael C. Cameron, Alexandra Golant, G. Michael Lewitt, Matthew J. Bruno, George Martin, Philip M. Brown, David S. Rubenstein, Victoria Butners, Anna M. Tallman

Dermatology Articles

Tapinarof cream 1% (VTAMA(®); Dermavant Sciences, Inc.) is a non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration (FDA) to treat plaque psoriasis in adults and under investigation for the treatment of psoriasis in children down to 2 years of age, and for atopic dermatitis in adults and children down to 2 years of age. The PSOARING phase 3 clinical trial program evaluated tapinarof cream 1% once daily (QD) in adults with mild to severe plaque psoriasis for up to 52 weeks (NCT03956355, NCT03983980, NCT04053387).

Here we present case photography documenting outcomes in the PSOARING …