Digital Commons Network^™

The Antiregulatory Arsenal, Antidemocratic Can(N)Ons, And The Waters Wars, William W. Buzbee

Georgetown Law Faculty Publications and Other Works

The Clean Water Act has become a centerpiece in an enduring multifront battle against both environmental regulation and federal regulatory power in all of its settings. This Article focuses on the emergence, elements, and linked uses of an antiregulatory arsenal now central to battles over what are federally protected “waters of the United States.” This is the key jurisdictional hook for CWA jurisdiction, and hence, logically, has become the heart of CWA contestation. The multi-decade battle over Waters protections has both drawn on emergent antiregulatory moves and generated new weapons in this increasingly prevalent and powerful antiregulatory arsenal. This array …

Dexmedetomidine As An Adjunct Therapy To Neuraxial Anesthesia In Labor And Delivery, Anthony Nungesser

Doctor of Nursing Practice Projects

In 2011, the Centers for Disease Control (CDC) declared the opioid crisis an epidemic, and in 2017 it was declared a public health emergency. In labor and delivery, neuraxial anesthesia has been used for over a hundred years to provide pain relief for parturients. Although many alternatives have been studied, opioids are the most frequently used local anesthetic adjuvants, and their use in neuraxial blocks has evolved over the last 50 years (Swain et al., 2017). While neuraxial opioids have proven to be an effective adjunct for pain relief, they are associated with undesirable side effects as well as the …

Natural And Artificial Neural Networks: The Chilean Legal Framework, Carlos Amunátegui Perelló

Journal of Civil Law Studies

Neuro-law and neuro-rights are emerging legal fields in the intersection of law, ethics, and technology. The aim of this study is to present the legal and scientific foundations of the matter, highlighting the Chilean regulation model on the problem.

The Constitutional Reshaping Of South Africa's Succession Laws, François Du Toit

Journal of Civil Law Studies

The South African Constitution of 1996 has had a significant im-pact on all the branches of South African law, including its succes-sion laws. The Constitution has transformatively reshaped im-portant aspects of South Africa's succession laws over the past two-and-a-half decades. This Article surveys the reshaping of two such aspects critically, namely (i) the extension of spousal inheritance under the Intestate Succession Act of 1987 and the Wills Act of 1953 as well as the extension of parental inheritance under the former statute; and (ii) the limitation of testamentary freedom. The afore-mentioned developments occurred by and large at the hands of …

Coordination Chemistry Of Uranyl Ions With Surface-Immobilized Peptides: An Xps Study, Esha Mishra, Cody M. Schultz, Rebecca Lai, Peter A. Dowben

Department of Physics and Astronomy: Faculty Publications

The coordination chemistry of uranyl ions with surface immobilized peptides was studied using X-ray photoemission spectroscopy (XPS). All the peptides in the study were modified using a six-carbon alkanethiol as a linker on a gold substrate with methylene blue as the redox label. The X-ray photoemission spectra reveal that each modified peptide interacts differently with the uranyl ion. For all the modified peptides, the XPS spectra were taken in both the absence and presence of the uranium, and their comparison reveals that the interaction depends on the chemical group present in the peptides. The XPS results show that, among all …

A Stealth Health Approach To Dietary Fibre, P. Stephen Baenziger, Katherine Anna Frels, Steve Greenspan, Julie Jones, Alison Lovegrove, Devin J. Rose, Peter Shewry, Rod Wallace

Department of Agronomy and Horticulture: Faculty Publications

Average dietary fibre intakes have increased little in the past twenty years in many countries, including the USA¹ . Multi-million-dollar campaigns promoting fruits, vegetables, whole grains and other foods high in fibre have delivered only small changes in diets² , and consumers have not changed from traditional staples to whole-grain options³ . UK millers report that consumption of whole-wheat bread has actually declined over the past decade (P. Shewry, personal communication). In the US, white flour, which is lower in fibre than whole-wheat flour, accounts for nearly 40% of the fibre intake⁴ . We believe that …

Chemical Elements, Flavor Chemicals, And Nicotine In Unused And Used Electronic Cigarettes Aged 5–10 Years And Effects Of Ph, Monique Williams, Wentai Luo, Kevin J. Mcwhirter, Omeka Ikegbu, Prue Talbot

Chemistry Faculty Publications and Presentations

The concentrations of elements/metals, nicotine, flavor chemicals and acids were compared in the e-liquids of unused and used first-generation electronic cigarettes (ECs) that were stored for 5–10 years. Metal analysis was performed using inductively coupled plasma optical emission spectroscopy; nicotine and flavor chemical analyses were performed using gas chromatography/mass spectroscopy. Of the 22 elements analyzed, 10 (aluminum, chromium, copper, iron, lead, nickel, selenium, silicon, tin, zinc) were often found in the e-liquids. Five elements had the highest average concentrations: copper (1161.6 mg/L), zinc (295.8 mg/L), tin (287.6 mg/L), nickel (71.1 mg/L), and lead (50.3 mg/L). Nicotine concentrations were always lower …

Relationships Among Age, Relative Telomere Length, And Dna Methylation In Pteropus Bats, Erika E. Forest

Masters Theses

Bats are the longest-lived mammalian order relative to body mass, but questions remain about relationships among mechanisms related to aging. Relative telomere length (rTL) decreases with age in most mammals, but the relationship between age and rTL is highly variable among the few bat taxa studied to date. More recently, DNA methylation (DNAm), a type of epigenetic regulation in which methyl groups are added to cytosine-phosphate-guanine (CpG) sites across the genome, has been shown to be highly predictive of age in many species of bats. We examine the relationships among age, rTL, and DNAm in Pteropus pumilus and P. hypomelanus …

Beginning Band: First Steps Instructing Students With Wind Instruments, Christine N. Lovell

Electronic Theses & Dissertations

One of the most important moments in beginning band is when a student first learns how to assemble and hold the instrument. As a band director, it is vital to be precise in explaining each element of this process. If steps are skipped over in this process, bad habits can form quickly and will cause more issues for the director. Instrument assembly and holding the instrument are covered in detail to help young band directors know how to explain this process. Additionally, this will help to find the bad habits quickly so problems do not snowball over time. It is …

Peru: Moving Upstream To Improve Adolescent's Mental Health, Rathmony Van-Ramirez, Rathmony Van-Ramirez

Master's Projects and Capstones

Mental health disorders can emerge at any age, with incidence prevalent in childhood and young adulthood. The cost associated with mental health negatively impacts both personally and economically. The consequences of these impacts are long-lasting and spill over into households and communities. Adolescence is a unique and formative time. Physical, emotional, and social changes, including exposure to poverty, abuse, or violence, can make adolescents vulnerable to mental health problems. Protecting adolescents from adversity, promoting socio-emotional learning and psychological well-being, and ensuring access to mental health care are critical for their health and well-being during adolescence and adulthood (World Health Organization …

Evaluation Of Dam Decommissioning As A Habitat Restoration Method: A Case Study Of California, Carla Lissette Angulo

Master's Projects and Capstones

There have been almost 1,800 dams removed in the United States in the last 100 years. As of 2021, California has a total of 690 dams and has removed 137 dams. The process of removing a dam first undergoes a process called decommissioning. Decommissioning is an assessment of the functional use of the dam and, based on that, a decision on whether a dam will be retained, retrofitted, or removed. In this paper, dams in the US and Asia are reviewed to determine the prioritization of the factors to consider for dam decommissioning and how the cost-benefit analysis can incorporate …

Returning To Life Activities After Hematopoietic Cell Transplantation In Older Adults, Thuy T. Koll

Theses & Dissertations

The prevalence of hematopoietic cell transplant (HCT) among older adults with hematological malignancies has doubled over the last decade and continues to grow. HCT is an intense process that can impact functional status and health-related quality of life. The objective of this thesis is to describe the experience of returning to life activities after HCT in patients 60 years of age and older and the resources required to adapt and cope to limitations in physical, psychological, and cognitive function. Twenty English speaking adults 60 years and older with hematological malignancy three to twelve months post-HCT completed semi-structured interviews. Open-ended questions …

Crispr Technology As An Antiviral In Dsdna And Ssrna Viruses, Cathryn Mayes

Theses & Dissertations

The COVID-19 pandemic highlights the necessity of emergency response and pandemic preparedness, especially for emerging viral threats. Currently, virus-specific vaccines and antivirals are the primary tools to combat viral diseases; however, broad-spectrum antivirals that target more than one virus species could provide additional protection from emerging and re-emerging viral diseases (Andersen et al. 2020; Zhu et al. 2015; Hickman et al. 2022).

Clustered regulatory interspaced short palindromic repeat (CRISPR)-associated endonucleases have become recently utilized as potential antiviral strategies due to their high specificity, efficacy, and versatility (Najafi et al. 2022). While CRISPR-based antivirals have previously been used to target specific …

Characterization Of Ape1 And Dna G-Quadruplex Interaction In Transcription Regulation And Dna Damage Repair, Suravi Pramanik

Theses & Dissertations

Human AP Endonuclease 1 (APE1) is the primary enzyme in the base excision repair (BER) pathway that repairs apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome. Recently, through genome-wide mapping analysis, we have shown that APE1, as well as its post-translationally modified form, acetylated APE1 (AcAPE1), is enriched in the gene regulatory regions. The APE1/AcAPE1-enriched regions also harbor Guanine (G)-rich sequences that fold into DNA secondary structures called G-quadruplexes (G4s). Our lab has demonstrated a strong genome-wide correlation between the occurrence of G4 structures and the binding of APE1 and AcAPE1. However, it is unknown whether …

Aerosols In Orthodontics: Characterization Of Particle Size And Travel Distance, Donte Jochum-Nesbitt

Theses & Dissertations

Introduction: Aerosol production is a key contributor to occupational risk and disease transmission in the dental clinic. These aerosols can host harmful pathogens, such as SARS-CoV-2. Considering the 2020 pandemic, researchers endeavored to bolster the existing body of literature related to disease transmission via aerosols and droplets to provide better recommendations for infection control. This investigation aims to support that mission by characterizing the risk to orthodontic professionals and patients based on aerosolized particle size and travel distance. Methods: The experimental protocol used in this study was validated through a smaller scale pilot study in 2021. High- and Low-risk orthodontic …

Nanofabrication For Precision Vaccinology, Karen Zagorski

Theses & Dissertations

Vaccines are among the most effective and safe therapeutics known to mankind. Historically the approach to the creation of new vaccines has been dominated by empirical research, trial, and error. This thesis focuses on the more modern, rational approaches to vaccinology based on the current understanding of the inner workings of the immune system. We used nanotechnology for the generation of novel immunogens, addressed several challenges, and characterized the immune responses.

The preparation, characterization, and troubleshooting of several vaccines against dimeric amyloid beta are covered in chapters 4-6. Despite being ultimately unsuccessful, this part provided a deeper understanding of the …

Targeted Therpeutics For Prostate Cancer, Behind The Scenes Of Psma & Cysteine Protease Trapping Mechanism, Alireza Basiri

Theses & Dissertations

In an attempt to increase the residence time of PSMA-targeted theranostics inside the prostate cancer cells and tumors, we designed and prepared a CPTA-PSMATA resembling PSMA-617 by adding a well-known cysteine protease inhibitor (E-64) to the conjugate. Lysosomal proteases, including cysteine, serine, and aspartic families of hydrolytic enzymes, are expressed in high concentrations in the lysosomes and are responsible for the catabolism of proteins inside the cell [165, 278]. We proposed that after successful internalization of the PSMA-targeted conjugates into the cells, they will be conveyed to the endolysosomes. In these endolysosomal compartments, the E-64 moiety will covalently bind to …

A Cell Culture Model To Study Tobacco Associated Oral Cancer Progression And Treatment Resistance, Amanda Busch

Theses & Dissertations

Head and Neck Squamous cell carcinoma is the 6^th most common cancer in the world. Risk factors for HNSCC include alcohol and tobacco consumption, infection with Human Papilloma Virus, and exposure to environmental toxins. Unlike many other cancers, the incidence of HNSCC is growing, yet the treatment options and outcomes have not been significantly improved for decades. An increased understanding of the molecular mechanisms of these cancers is needed for improvement in early diagnosis, enhanced treatment effectiveness, and cancer prevention. 4-nitroquinoline 1-oxide (4NQO) is a well-tested, tobacco mimicking, carcinogen. 4NQO produces similar histological and chemical changes found in human …

Structural And Inhibitory Studies On (I)Two Mycobacterium Tuberculosis Enzymes Essential For Capsular Glucan Biosynthesis And Mrna Degradation: (Ii) Hantann Virus L-Protein Endonuclease Domain, Hettiarachchige Thilina D. Jayasinghe

Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium species that causes Tuberculosis (TB). Understanding the major biosynthetic pathways responsible for cell viability is essential in developing new drugs against Mtb. The first two projects will reflect our approach in identifying inhibitors against Mtb GlgE, Mtb GpsI, and characterization of protein inhibitor interactions using X-ray crystallography.

The enzyme GlgE plays an essential role in the α-glucan biosynthesis pathway in Mtb cells. These α-glucans are one of the major structural units in the Mtb capsule. GlgE catalyzes the elongation of α-glucan by transferring maltose from maltose-1-phosphate (M1P) to the non-reducing end …

Structural And Biochemical Studies Of Three Enzymes Involved In Amino Acid Metabolism To Develop Novel Drugs, Yahani Pankaja Jayasinghe Arachchige

Theses & Dissertations

Intrinsic drug resistance in bacteria predates the clinical use of antibiotics. Additionally, heterogeneous metabolic states and the ability of many bacteria to form biofilms further enhances bacterial survival during infection and exacerbates treatment challenges. This necessitates the identification of novel drugs against new drug targets. These studies focus on the development of compounds targeting enzymes in Mycobacterium tuberculosis (Mtb) and Staphylococcus aureus that avoid intrinsic antibiotic defenses. The Mtb-encoded homoserine transacetylase enzyme (HTA) catalyzes the first step of the methionine biosynthesis pathway that produces methionine and S-adenosyl methionine. These compounds are shown to be essential for both dormant …

The Influence Of Predation Environment On The Sensory Ecology Of Brachyrhaphis Rhabdophora, Alexandra Grace Duffy

Theses and Dissertations

Across the animal kingdom, predation is a ubiquitous and omnipresent selective agent for a variety of traits. I aimed to address gaps in our knowledge pertaining to how predation shapes animal behavior. Many species of fish naturally occur in drainages that differ in the density of predators and exhibit obvious population divergence, making them ideal study organisms to investigate predator-driven behavioral evolution. In Chapter 1, I conducted a systematic review of the literature. The purpose of this review was to determine if predation acted as a stronger or weaker selective agent on particular behavioral traits (e.g., foraging, mating, antipredator etc.) …

Benthic Macroinvertebrate Pre-Assessment Of A Proposed Restoration In The Grand River, Grand Rapids, Mi, Usa, Matthew L. Bain

Masters Theses

River restoration is the dominant field of applied water resources management in the United States. Ecological improvement should be the goal of all river restorations, though many restoration projects fail to produce positive results due to limited scope or inadequate assessment methodologies. Pre-restoration, biotic data is essential for such projects as it can be paired with post-restoration data to gauge ecological outcomes. A major restoration effort is now underway in Michigan's longest river, the Grand River, where it flows through downtown Grand Rapids. The primary restoration measures will occur in-stream at local scale. We conducted a pre- restoration survey for …

Eavesdropping On Animals: Can Bioacoustics Help Save Species?, Zoe Grueskin

Capstones

Around the world, scientists are using sound to study the natural world in a growing field called bioacoustics. Researchers are eavesdropping on frogs and fish, elephants and earthworms, and many hope what they hear can inform and inspire conservation action around the world. From the field’s auspicious beginning with accidentally-recorded whales, to researchers today listening to locations as diverse as the Arctic seafloor and India’s Western Ghats mountain range, this capstone project explores the potential — and limitations — of conservation bioacoustics. Read the story, see photos and listen to audio pieces featuring three bioacousticians and their field recordings here: …

In The U.S., Mena People Are Legally White. But Their Lived Experiences Say Otherwise, Youcef O. Bounab

Capstones

The U.S. Government classifies people whose origins are from the Middle East and North Africa as racially “white.” This is reflected in the decennial census, as well as in other questionnaires and forms, even as many among those groups prefer to have their own categorization. In this feature article, we explore the history of the issue, how individuals from those backgrounds would prefer to identify, and whether their lived experiences in a post-9/11 United States reflect their current categorization.

An Optimized Chromatin Immunoprecipitation Protocol Using Staph-Seq For Analyzing Genome-Wide Protein-Dna Interactions., Fang Tao, Egidy Rhonda, Xi He, John M. Perry, Linheng Li

Manuscripts, Articles, Book Chapters and Other Papers

Genome-wide mapping of transcription factors (TFs) is critical to understand their functions. In chromatin immunoprecipitation (ChIP)-seq assay, it's challenging to study recruitment of low-abundant TFs transiently boud to the genome. Here, we present an optimized protocol using ChIP Next-Gen Seq Sepharose (Staph-seq) to efficiently pull down chromatin complexes. The double size selection promotes sensitive capture of genome-wide protein-DNA associations while eliminating potential Staph A contamination, which is a common problem in protocols using Staph A cells. For complete details on the use and execution of this protocol, please refer to Tao et al. (2020).

How Much Should Or Can Science Impact Theological Formulations? An AshʿArī Perspective On Theology Of Nature, Shoaib Ahmed Malik, Nazif Muhtaroglu

All Works

There have been many developments in the field of science and religion over the past few decades. One such development is referred to as ‘theology of nature’ (ToN), which is the activity of building or revising theological frameworks in light of cont...

In Vivo Characterization Of Glutamine Metabolism Identifies Therapeutic Targets In Clear Cell Renal Cell Carcinoma, Akash K Kaushik, Amy Tarangelo, Lindsey K Boroughs, Mukundan Ragavan, Yuanyuan Zhang, Cheng-Yang Wu, Xiangyi Li, Kristen Ahumada, Jui-Chung Chiang, Vanina T Tcheuyap, Faeze Saatchi, Quyen N Do, Cissy Yong, Tracy Rosales, Christina Stevens, Aparna D Rao, Brandon Faubert, Panayotis Pachnis, Lauren G Zacharias, Hieu Vu, Feng Cai, Thomas P Mathews, Giannicola Genovese, Barbara S Slusher, Payal Kapur, Xiankai Sun, Matthew Merritt, James Brugarolas, Ralph J Deberardinis

Faculty, Staff and Student Publications

Targeting metabolic vulnerabilities has been proposed as a therapeutic strategy in renal cell carcinoma (RCC). Here, we analyzed the metabolism of patient-derived xenografts (tumorgrafts) from diverse subtypes of RCC. Tumorgrafts from VHL-mutant clear cell RCC (ccRCC) retained metabolic features of human ccRCC and engaged in oxidative and reductive glutamine metabolism. Genetic silencing of isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 impaired reductive labeling of tricarboxylic acid (TCA) cycle intermediates in vivo and suppressed growth of tumors generated from tumorgraft-derived cells. Glutaminase inhibition reduced the contribution of glutamine to the TCA cycle and resulted in modest suppression of tumorgraft growth. Infusions with …

Processing And Cryopreservation Of Human Ureter Tissues For Single-Cell And Spatial Transcriptomics Assays, Emily E Fink, Surbhi Sona, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Characterizing the cellular heterogeneity of human ureter tissues using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics provides a detailed atlas of cell types, signaling networks, and potential cell-cell cross talk underlying developmental and regenerative pathways. We describe an optimized protocol for generating, cryopreserving, and thawing single-cell suspensions from ureter tissues isolated post-cystectomy for scRNA-seq. In addition, we describe an optimized protocol for cryopreserving human ureter tissues for 10x Genomics Visium spatial gene expression platform. For complete details on the use and execution of this protocol, please refer to Fink et al. (2022).

Isolation, Culture, And Immunophenotypic Analysis Of Bone Marrow Hspcs From Patients With Myelodysplastic Syndromes, Irene Ganan-Gomez, Karen Clise-Dwyer, Simona Colla

Faculty, Staff and Student Publications

Drug testing assays in hematopoietic stem and progenitor cells (HSPCs) are fundamental in biological studies of myelodysplastic syndromes (MDS) but have historically entailed a technical challenge. This protocol allows the efficient isolation of MDS HSPCs from bone marrow mononuclear cell fractions and their culturing with the support of stromal cells for improved maintenance during drug testing. Lastly, specific steps are given to quantify surviving cells and assess changes in the HSPC hierarchies.

For complete details on the use and execution of this protocol, please refer to Ganan-Gomez et al. (2022).

Egfr Is A Master Switch Between Immunosuppressive And Immunoactive Tumor Microenvironment In Inflammatory Breast Cancer, Xiaoping Wang, Takashi Semba, Ganiraju C Manyam, Jing Wang, Shan Shao, Francois Bertucci, Pascal Finetti, Savitri Krishnamurthy, Lan Thi Hanh Phi, Troy Pearson, Steven J Van Laere, Jared K Burks, Evan N Cohen, James M Reuben, Fei Yang, Hu Min, Nicholas Navin, Van Ngu Trinh, Toshiaki Iwase, Harsh Batra, Yichao Shen, Xiang Zhang, Debu Tripathy, Naoto T Ueno

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC), the most aggressive breast cancer subtype, is driven by an immunosuppressive tumor microenvironment (TME). Current treatments for IBC have limited efficacy. In a clinical trial (NCT01036087), an anti-EGFR antibody combined with neoadjuvant chemotherapy produced the highest pathological complete response rate ever reported in patients with IBC having triple-negative receptor status. We determined the molecular and immunological mechanisms behind this superior clinical outcome. Using novel humanized IBC mouse models, we discovered that EGFR-targeted therapy remodels the IBC TME by increasing cytotoxic T cells and reducing immunosuppressive regulatory T cells and M2 macrophages. These changes were due to …