Digital Commons Network^™

Preclinical Antibody-Pet Imaging Of Pd-L1, Emma L Brown, Rachel A Deweerd, Abbey Zidel, Patricia M R Pereira

2020-Current year OA Pubs

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade, including antibody therapeutics, has transformed cancer treatment. However, a major challenge in the field relates to selecting patients who are likely to respond to immune checkpoint inhibitors. Indeed, biopsy-based diagnostic tests to determine immune checkpoint protein levels do not accurately capture the inherent spatial and temporal heterogeneity of PD-L1 tumor expression. As a result, not all PD-L1-positive tumors respond to immunotherapies, and some patients with PD-L1-negative tumors have shown clinical benefits. In 2018, a first-in-human study of the clinically-approved anti-PD-L1 antibody Atezolizumab labeled with the positron emitter zirconium-89 validated the ability of positron emission …

The Human Myocardium Harbors A Population Of Naive B-Cells With A Distinctive Gene Expression Signature Conserved Across Species, Kevin C Bermea, Nicolas Kostelecky, Sylvie T Rousseau, Chieh-Yu Lin, Luigi Adamo

2020-Current year OA Pubs

INTRODUCTION: Cardiac immunology studies in murine models have identified a sizeable population of myocardial B-cells and have shown that its modulation represents a promising strategy to develop novel therapies for heart failure. However, scarce data on B-cells in the human heart leaves unclear whether findings in rodents are relevant to human biology.

METHODS: We performed immunohistochemical stains to characterize the amount and distribution of B-cells in human hearts, analyzing both fresh and post-mortem tissue. To gain insight into the biology of human myocardial B-cells we analyzed publicly-available spatial transcriptomics and single-cell sequencing datasets of myocardial and peripheral blood mononuclear cells …

Unauthorized And Unwise: The Lawful Use Requirement In Trademark Law, Robert A. Mikos

Vanderbilt Law Review

For decades, the United States Patent and Trademark Office (“PTO”) has required trademark owners to comply with sundry nontrademark laws governing the sale of their trademarked goods and services. Pursuant to this “lawful use requirement,” the Agency has refused or even cancelled registration of thousands of marks used on everything from Schedule I controlled substances to mislabeled soap. This Article subjects the Agency’s lawful use requirement to long-overdue scrutiny. It suggests that in requiring compliance with other laws for registration, the PTO has lost sight of the one statute it is supposed to administer. In the process, the Agency has …

The Third International Hackathon For Applying Insights Into Large-Scale Genomic Composition To Use Cases In A Wide Range Of Organisms, Kimberly Walker, Divya Kalra, Rebecca Lowdon, Guangyi Chen, David Molik, Daniela C Soto, Fawaz Dabbaghie, Ahmad Al Khleifat, Medhat Mahmoud, Luis F Paulin, Muhammad Sohail Raza, Susanne P Pfeifer, Daniel Paiva Agustinho, Elbay Aliyev, Pavel Avdeyev, Enrico R Barrozo, Sairam Behera, Kimberley Billingsley, Li Chuin Chong, Deepak Choubey, Wouter De Coster, Yilei Fu, Alejandro R Gener, Timothy Hefferon, David Morgan Henke, Wolfram Höps, Anastasia Illarionova, Michael D Jochum, Maria Jose, Rupesh K Kesharwani, Sree Rohit Raj Kolora, Jędrzej Kubica, Priya Lakra, Damaris Lattimer, Chia-Sin Liew, Bai-Wei Lo, Chunhsuan Lo, Anneri Lötter, Sina Majidian, Suresh Kumar Mendem, Rajarshi Mondal, Hiroko Ohmiya, Nasrin Parvin, Carolina Peralta, Chi-Lam Poon, Ramanandan Prabhakaran, Marie Saitou, Aditi Sammi, Philippe Sanio, Nicolae Sapoval, Najeeb Syed, Todd Treangen, Gaojianyong Wang, Tiancheng Xu, Jianzhi Yang, Shangzhe Zhang, Weiyu Zhou, Fritz J Sedlazeck, Ben Busby

Faculty, Staff and Students Publications

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.

Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, …

Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell

Faculty, Staff and Students Publications

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute …

Selectively Targeting Disease-Restricted Secretogranin Iii To Alleviate Choroidal Neovascularization, Liyang Ji, Prabuddha Waduge, Lili Hao, Avinash Kaur, Wencui Wan, Yan Wu, Hong Tian, Jinsong Zhang, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Choroidal neovascularization (CNV), a leading cause of blindness in the elderly, is routinely treated with vascular endothelial growth factor (VEGF) inhibitors that have limited efficacy and potentially adverse side effects. An unmet clinical need is to develop novel therapies against other angiogenic factors for alternative or combination treatment to improve efficacy and safety. We recently described secretogranin III (Scg3) as a disease-selective angiogenic factor, causally linked to diabetic retinopathy and acting independently of the VEGF pathway. An important question is whether such a disease-selective Scg3 pathway contributes to other states of pathological angiogenesis beyond diabetic retinopathy. By applying a novel …

Initial Experiences Using Plasma Rich In Growth Factors To Treat Keratoneuralgia, Margaret Wang, Sowmya Yennam, Stephen Pflugfelder

Faculty, Staff and Students Publications

Keratoneuralgia, a clinical diagnosis of sensitized corneal pain without visible ocular surface damage, generally has minimal response to conventional therapies. Causes include refractive surgery and chronic dry eye. We evaluated the efficacy of Plasma Rich in Growth Factors (PRGF), a novel treatment prepared using a commercially available kit, in patients with keratoneuralgia. A retrospective chart review identified patients who had the clinical diagnosis of keratoneuralgia and were treated with PRGF for at least 3 months from October 2015 to April 2020 at a single academic institution. Both objective eye exam findings and concurrent treatments were obtained at baseline, 3 months, …

Il-17 Producing Lymphocytes Cause Dry Eye And Corneal Disease With Aging In Rxrα Mutant Mouse, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Rodrigo Guimaraes De Souza, Zhiyuan Yu, Stephen C Pflugfelder

Faculty, Staff and Students Publications

PURPOSE: To investigate IL-17 related mechanisms for developing dry eye disease in the Pinkie mouse strain with a loss of function RXRα mutation.

METHODS: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling was performed by single-cell RNA sequencing (scRNA-seq) to compare gene expression in conjunctival immune cells. Conjunctival immune cells were immunophenotyped by flow cytometry and confocal microscopy. The activity of RXRα ligand 9-cis retinoic acid (RA) was evaluated in cultured monocytes and γδ T cells.

RESULTS: Compared to wild type (WT) C57BL/6, Pinkie has increased signs of dry eye disease, including decreased tear …

Spatial Transcriptomics Of The Lacrimal Gland Features Macrophage Activity And Epithelium Metabolism As Key Alterations During Chronic Inflammation, Olivier Mauduit, Vanessa Delcroix, Takeshi Umazume, Cintia S De Paiva, Darlene A Dartt, Helen P Makarenkova

Faculty, Staff and Students Publications

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren’s syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the …

The Autophagic Protein P62 Is A Target Of Reactive Aldehydes In Human And Murine Cholestatic Liver Disease, Colin T Shearn, Aimee L Anderson, Michael W Devereux, David J Orlicky, Cole Michel, Dennis R Petersen, Colin G Miller, Sanjiv Harpavat, Edward E Schmidt, Ronald J Sokol

Faculty, Staff and Students Publications

Inflammatory cholestatic liver diseases, including Primary Sclerosing Cholangitis (PSC), are characterized by periportal inflammation with progression to cirrhosis. The objective of this study was to examine interactions between oxidative stress and autophagy in cholestasis. Using hepatic tissue from male acute cholestatic (bile duct ligated) as well as chronic cholestatic (Mdr2KO) mice, localization of oxidative stress, the antioxidant response and induction of autophagy were analyzed and compared to human PSC liver. Concurrently, the ability of reactive aldehydes to post-translationally modify the autophagosome marker p62 was assessed in PSC liver tissue and in cell culture. Expression of autophagy markers was upregulated in …

Pathologic Inflammation In Malnutrition Is Driven By Proinflammatory Intestinal Microbiota, Large Intestine Barrier Dysfunction, And Translocation Of Bacterial Lipopolysaccharide, Grace T Patterson, Elvia Y Osorio, Alex Peniche, Sara M Dann, Erika Cordova, Geoffrey A Preidis, Ji Ho Suh, Ichiaki Ito, Omar A Saldarriaga, Michael Loeffelholz, Nadim J Ajami, Bruno L Travi, Peter C Melby

Faculty, Staff and Students Publications

Acute malnutrition, or wasting, is implicated in over half of all deaths in children under five and increases risk of infectious disease. Studies in humans and preclinical models have demonstrated that malnutrition is linked to an immature intestinal microbiota characterized by increased prevalence of Enterobacteriaceae. Observational studies in children with moderate acute malnutrition (MAM) have also observed heightened systemic inflammation and increased circulating bacterial lipopolysaccharides (LPS; endotoxin). However, the mechanisms that underpin the systemic inflammatory state and endotoxemia, and their pathophysiological consequences, remain uncertain. Understanding these pathophysiological mechanisms is necessary to design targeted treatments that will improve the unacceptable rate …

Development Of Phage Cocktails To Treat E Coli Catheter-Associated Urinary Tract Infection And Associated Biofilms, Belkys C Sanchez, Emmaline R Heckmann, Sabrina I Green, Justin R Clark, Heidi B Kaplan, Robert F Ramig, Casey Hines-Munson, Felicia Skelton, Barbara W Trautner, Anthony W Maresso

Faculty, Staff and Students Publications

High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary E. coli strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized E. coli phage against biofilms in two in vitro CAUTI models. Biofilm viability was …

Development Of Phage Cocktails To Treate Coli Catheter-Associated Urinary Tract Infection And Associated Biofilms, Belkys C Sanchez, Emmaline R Heckmann, Sabrina I Green, Justin R Clark, Heidi B Kaplan, Robert F Ramig, Casey Hines-Munson, Felicia Skelton, Barbara W Trautner, Anthony W Maresso

Faculty, Staff and Students Publications

High rates of antimicrobial resistance and formation of biofilms makes treatment of Escherichia coli catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary E. coli strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized E. coli phage against biofilms in two in vitro CAUTI models. Biofilm viability was …

Modified Vaccinia Ankara Expressing Eehv1a Glycoprotein B Elicits Humoral And Cell-Mediated Immune Responses In Mice, Taylor Pursell, Jennifer L Spencer Clinton, Jie Tan, Rongsheng Peng, Paul D Ling

Faculty, Staff and Students Publications

Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease (EEHV-HD) in Asian elephants and is the largest cause of death in captive juvenile Asian elephants in North America and Europe. EEHV-HD also has been documented in captive and wild elephants in their natural range countries. A safe and effective vaccine to prevent lethal EEHV infection would significantly improve conservation efforts for this endangered species. Recent studies from our laboratory suggest that EEHV morbidity and mortality are often associated with primary infection. Therefore, we aim to generate a vaccine, particularly for EEHV1 naïve animals, with the goal of preventing lethal EEHV-HD. …

Functional Studies Of Genetic Variants Associated With Human Diseases In Notch Signaling-Related Genes Using Drosophila, Sheng-An Yang, Jose L Salazar, David Li-Kroeger, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Rare variants in the many genes related to Notch signaling cause diverse Mendelian diseases that affect myriad organ systems. In addition, genome- and exome-wide association studies have linked common and rare variants in Notch-related genes to common diseases and phenotypic traits. Moreover, somatic mutations in these genes have been observed in many types of cancer, some of which are classified as oncogenic and others as tumor suppressive. While functional characterization of some of these variants has been performed through experimental studies, the number of ‘variants of unknown significance’ identified in patients with diverse conditions keeps increasing as high-throughput sequencing technologies …

La Musique Dans Les Cultures Tech. La Synthèse Modulaire En Temps De Covid-19, Eliot Bates

Publications and Research

Depuis 1996, la synthèse modulaire matérielle est passée d’une pratique artisanale de fabrication d’instruments de niche soutenue par un petit nombre de musiciens, à un phénomène transnational, une véritable culture tech. Malgré cet engouement, elle n’a pas donné naissance à de nouveaux genres musicaux populaires, et il n’est pas certain que la « musique », quelle que soit sa définition, soit ce qui rassemble les amateurs de synthèse modulaire. Ce texte a deux objectifs : tout d’abord, il présente les résultats d’une recherche en cours menée en ligne et dans plusieurs pays concernant le rôle des objets technologiques dans la …

Decision Tree And Real Options To Value Agtech Startup Growth, Dylan Kallman

Agribusiness and Applied Economics

Agtech startups face multiple uncertainties and have limited flexibility when it comes to growing their business. Companies that are growing ultimately need to take on new capital. This new capital can be from many different sources like strategic partners, investors, angels, VC, grants, and debt. What source is best for the entrepreneur and what will lead to the highest probability of success or the ideal outcome for shareholders can vary depending on the tradeoffs of each funding round. This paper has developed a model to analyze the returns and risks of alternative funding decisions for a prototypical ag-tech startup. By …

Obesity And Asthma: A Focused Review, Rubabin Tooba, Tianshi David Wu

Faculty, Staff and Students Publications

No abstract provided.

Patterns Of Interdisciplinary Collaboration Resemble Biogeochemical Relationships In The Mcmurdo Dry Valleys, Antarctica: A Historical Social Network Analysis Of Science, 1907–2016, Stephen M. Chignell, Adrian Howkins, Poppie Gullett, Andrew G. Fountain

Geology Faculty Publications and Presentations

Co-authorship networks can provide key insights into the production of scientific knowledge. This is particularly interesting in Antarctica, where most human activity relates to scientific research. Bibliometric studies of Antarctic science have provided a useful understanding of international and interdisciplinary collaboration, yet most research has focused on broad-scale analyses over recent time periods. Here, we take advantage of a ‘Goldilocks’ opportunity in the McMurdo Dry Valleys, an internationally important region of Antarctica and the largest ice-free region on the continent. The McMurdo Dry Valleys have attracted continuous and diverse scientific activity since 1958. It is a geographically confined region with …

A Meta-Analysis Of Studies Addressing The Impact Of Gbh On Human, Animal Health And The Environment, Kodjo Barnor

Agribusiness and Applied Economics

The herbicide glyphosate has been tested and approved by both the FDA and the USDA, as evidenced by many published research papers, i.e., they are deemed safe for humans, animals, and the environment. However, evidence is mounting that glyphosate interferes with many metabolic processes in plants and animals, and glyphosate residues have been detected in both. The factors that influence the outcomes of previous scientific research on the potential adverse effects of GBH on human and animal health and the environment were investigated. Using DAGs and Granger causality tests, the study found that while private and public organizations were more …

A Horor Theory For Introspective Consciousness, Adriana Renero, Richard Brown

Publications and Research

Higher-order theories of consciousness typically account for introspection in terms of one’s higher-order thoughts being conscious, which would require a third-order thought—i.e., a thought about a thought about a mental state. In this work, we offer an alternative account of introspection that builds on the recent Higher-Order Representation of a Representation (HOROR) theory of phenomenal consciousness. According to HOROR theory, phenomenal consciousness consists in having the right kind of higher-order representation. We claim that this theory can be extended to introspection by recognizing that there is a distinctive kind of consciousness—i.e., introspective consciousness—which can be accounted for as the theory …

Standing For Rivers, Mountains - And Trees - In The Anthropocene, David Takacs

Faculty Scholarship

In his well-known article, Should Trees Have Standing?—Toward Legal Rights for Natural Objects, Professor Christopher Stone proposed that courts grant nonhuman entities standing as plaintiffs so their interests may directly represented in court. In this Article, I review Stone’s ideas about standing and our relationship with the natural environment and describe the current, burgeoning, widespread trend toward granting not just standing, but legal rights and legal personhood to rivers, mountains, and other natural entities. I analyze the ways in which courts and legislatures in New Zealand, Australia, Colombia, and elsewhere are addressing concerns similar to Stone’s with expansive, even radical …

Dual Federalism, Constitutional Openings, And The Convention On The Rights Of Persons With Disabilities, Benjamin Barsky

Faculty Scholarship

The Convention on the Rights of Persons with Disabilities (“CRPD”) represents a historic achievement for the global disability rights movement. Yet, when the U.S. Senate refused to ratify it on December 4, 2012, its influence on American law and policy seemed doomed. The Founders, after all, had conceived of a constitutional vision where the federal government acts as the ultimate arbiter of questions of international policy. Under this vision of “dual federalism”—which dominated how the legal profession understood U.S. involvement in foreign affairs for over a century—only the federal political branches have the power to make and implement international laws …

Punitive Surveillance, Kate Weisburd

Faculty Scholarship

Budget constraints, bipartisan desire to address mass incarceration, and the COVID-19 crisis in prisons have triggered state and federal officials to seek alternatives to incarceration. As a result, invasive electronic surveillance—such as GPS-equipped ankle monitors, smartphone tracking, and suspicionless searches of electronic devices—is often touted as a humane substitute for incarceration. This type of monitoring, which I term “punitive surveillance,” allows government officials, law enforcement, and for-profit companies to track, record, search, and analyze the location, biometric data, and other meta-data of thousands of people on probation and parole. With virtually no legal oversight or restraint, punitive surveillance deprives people …

Watermarks Of Portland State University’S 1490 Codex, Duane Wiegardt

Extra-Textual Elements

This paper and its accompanying research endeavored to locate, catalog, and identify as fully as possible the watermarks observed throughout Portland State University’s (PSU) 1490 bound codex containing the Fasciculus temporum omnes antiquorum cronicas complectens (FT) and Malleus Maleficarum (MM).

Dozens of watermarks of several categories have been located and cataloged. A listing of the marks found on each leaf of the FT and MM has been constructed for continued use by future researchers. Study of the watermarks also sheds light on the codex’s binding.

Bookbinding And Production In Incunable Age Germany, Brooke Hardy

Provenance and Preservation

Printshops opened all over Germany shortly after 1450 with the invention of the metal moveable type printing press, marking Germany as the center of this new market. Each printer and binder had their own distinct characteristics featured in their works. They each had preferred materials or techniques, or simply had different materials available to them. This paper reviews aspects of incunable bookmaking and bookbinding to provide a broader material context for PSU’s 1490 codex.

Oregon State Rank Assessment For Cascade Torrent Salamander (Rhyacotriton Cascadae), Eleanor P. Gaines

Institute for Natural Resources Publications

Oregon state conservation status assessment for Cascade torrent salamander (Rhyacotriton cascadae) using NatureServe methodology, 2022

Oregon State Rank Assessment For Cope's Giant Salamander (Dicamptodon Copei), Eleanor P. Gaines

Institute for Natural Resources Publications

Oregon state conservation status assessment for Cope's giant salamander (Dicamptodon copei) using NatureServe methodology, 2022.

Evaluating The Use Of Barn Owl Nest Boxes For Rodent Pest Control In Winegrape Vineyards In Napa Valley, Ashley N. Hansen

Cal Poly Humboldt theses and projects

Attracting natural enemies to farms to reduce pests has long been a part of integrated pest management for insects, but knowledge of the impact of raptors on rodents and other vertebrate pests is comparatively sparse. In this study, I compared rodent prey on winegrape vineyards in Napa California with and without occupied barn owl nest boxes. We collected data before the breeding season, when hunting pressure should be light, and again when adult owls were hunting actively to feed their chicks. I used the open-hole method to quantify an index of gopher activity, and Sherman live traps to estimate the …