Digital Commons Network^™

Sickle Cell Disease Treatment With Arginine Therapy (Start): Study Protocol For A Phase 3 Randomized Controlled Trial., Chris A Rees, David C. Brousseau, Daniel M Cohen, Anthony Villella, Carlton Dampier, Kathleen Brown, Andrew Campbell, Corrie E Chumpitazi, Gladstone Airewele, Todd Chang, Christopher Denton, Angela Ellison, Alexis Thompson, Fahd Ahmad, Nitya Bakshi, Keli D Coleman, Sara Leibovich, Deborah Leake, Dunia Hatabah, Hagar Wilkinson, Michelle Robinson, T Charles Casper, Elliott Vichinsky, Claudia R Morris

Department of Pediatrics Faculty Papers

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.

METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 …

Molecular Mechanisms Governing The Generation Of Tissue Resident Memory Cd8 T Cells In The Setting Of Cancer, Nikhil Khatwani

Dartmouth College Ph.D Dissertations

Although there has been extensive research on T-cell responses to cancer immunotherapy, the understanding of long-lasting memory in visceral organs remains less well understood. Among these, a population of Trm cells was discovered that reside durably within tumor draining lymph nodes (TDLN) and plays a crucial role in protecting against invading melanoma cells, uncovering a new role for Trm cells at critical metastatic sites. However, little is known about the molecular mechanisms promoting Trm establishment in tissues where cancer can develop and metastasize. Here, employing longitudinal T cell receptor (TCR)-lineage-tracing and single-cell transcriptomics, we find that TDLN contain Teff cells …

Geophysical Investigation Of Permafrost Conditions In A Thermokarst-Prone Area In Fairbanks, Alaska, Abdallah Basiru

Engineering

Permafrost degradation is a significant environmental concern for cold regions, posing risks to communities and infrastructure. The warming of near-surface permafrost leads to diverse topographic variations in the Arctic and sub-Arctic communities. The varying rates of thawing permafrost, influenced by ground ice content, give rise to geologic hazards like thermokarst, which causes ground subsidence. This gradual or sudden subsidence endangers existing infrastructure and economic activities in cold regions. A subsurface 2D Electrical Resistivity Tomography survey was conducted in the West Ridge area of the University of Alaska Fairbanks upper campus to advance our understanding of frozen ground conditions. The objective …

Soil Seed Bank Composition And Spatial Distribution In A Cheatgrass (Bromus Tectorum L.)–Dominated Rangeland In Colorado, Usa, Ryan W. R. Schroeder, Jayne L. Jonas, M. Nikki Grant-Hoffman, Mark W. Paschke

Western North American Naturalist

Invasion by nonnative annual plants that form prolific seed banks, including Bromus tectorum L. (cheatgrass), throughout western North America is a major natural resource concern. Even with known economic and ecological implications, soil seed banks and their potential to impact ecological restoration in arid and semiarid ecosystems are poorly understood. Quantifying the regenerative potential of the soil seed bank—the living seeds in the soil profile and on the soil surface—can help natural resource managers make decisions to increase the likelihood of restoration success. We analyzed the germinable soil seed bank composition and distribution of a rangeland site in western Colorado …

Front Matter, Vol. 83 No. 2

Western North American Naturalist

No abstract provided.

End Matter, Vol. 83 No. 2

Western North American Naturalist

No abstract provided.

Investigating Putative Toxin-Immunity Pairs From A New Class Of Rhs Proteins In Pseudomonas Aeruginosa, Syed Faieq Imam

Master's Theses

Pseudomonas aeruginosa is a gram-negative, opportunistic pathogen that is ubiquitous in nature, especially in human/animal impacted environments. One of the reasons for this is the arsenal of protein systems and toxins that P. aeruginosa utilizes to mold its environment to suit its needs. Recently, we discovered a novel locus in the P. aeruginosa genome, which resembles other loci that are known to mediate interbacterial competition. Our bioinformatic analysis found this locus to be enriched in a rearrangement hotspot (rhs) motif which led us to ad-interim term the three ORFs of the loci as rhsB, rhsC, and rhsI. Furthermore, we have …

“My Flesh Was Its Own Shield” Eroticism In Aids Activism, Jake Whitney

History Theses, Dissertations, and Student Creative Activity

The most enduring images of the HIV/AIDS crisis are pictures of ACT UP members being arrested and staging die-ins or men huddled together in hospital beds. These images and the historical narrative accompanying them espouse unity, a coming together of the queer community. No one manufactured this unity. Gay men came together to fight AIDS with force stronger than that which had fought back at Stonewall. Although the gay community saw increased unity during the AIDS Pandemic, the benefactors of this unity, the mainstream gay movement, marginalized men practicing radical sex through a rhetoric of anti-eroticism, a negative, rather than …

Pyruvate Anaplerosis Is A Targetable Vulnerability In Persistent Leukaemic Stem Cells, Kevin M Rattigan, Zuzana Brabcova, Daniele Sarnello, Martha M Zarou, Kiron Roy, Ryan Kwan, Lucie De Beauchamp, Amy Dawson, Angela Ianniciello, Ahmed Khalaf, Eric R Kalkman, Mary T Scott, Karen Dunn, David Sumpton, Alison M Michie, Mhairi Copland, Saverio Tardito, Eyal Gottlieb, G Vignir Helgason

Faculty, Staff and Student Publications

Deregulated oxidative metabolism is a hallmark of leukaemia. While tyrosine kinase inhibitors (TKIs) such as imatinib have increased survival of chronic myeloid leukaemia (CML) patients, they fail to eradicate disease-initiating leukemic stem cells (LSCs). Whether TKI-treated CML LSCs remain metabolically deregulated is unknown. Using clinically and physiologically relevant assays, we generate multi-omics datasets that offer unique insight into metabolic adaptation and nutrient fate in patient-derived CML LSCs. We demonstrate that LSCs have increased pyruvate anaplerosis, mediated by increased mitochondrial pyruvate carrier 1/2 (MPC1/2) levels and pyruvate carboxylase (PC) activity, in comparison to normal counterparts. While imatinib reverses BCR::ABL1-mediated LSC metabolic …

Genetic Dissection Of Crossover Mutants Defines Discrete Intermediates In Mouse Meiosis, Tolkappiyan Premkumar, Lakshmi Paniker, Rhea Kang, Mathilde Biot, Ericka Humphrey, Honorine Destain, Isabella Ferranti, Iyinyeoluwa Okulate, Holly Nguyen, Vindhya Kilaru, Melissa Frasca, Parijat Chakraborty, Francesca Cole

Faculty, Staff and Student Publications

Crossovers (COs), the exchange of homolog arms, are required for accurate chromosome segregation during meiosis. Studies in yeast have described the single-end invasion (SEI) intermediate: a stabilized 3' end annealed with the homolog as the first detectible CO precursor. SEIs are thought to differentiate into double Holliday junctions (dHJs) that are resolved by MutLgamma (MLH1/MLH3) into COs. Currently, we lack knowledge of early steps of mammalian CO recombination or how intermediates are differentiated in any organism. Using comprehensive analysis of recombination in thirteen different genetic conditions with varying levels of compromised CO resolution, we infer CO precursors include asymmetric SEI-like …

“Connecting Better And Wider”: A Constructivist Grounded Theory And Situational Analysis Exploration Of Community Resilience In The Anthropocene Among The Transition Network, Deanne M. Boisvert, Caroline Suransky

The Qualitative Report

For decades qualitative researchers have used grounded theory methodologies in their investigations. Although the grounded theory literature is extensive, less well documented are qualitative studies which incorporate complementary grounded theory approaches into their designs; or studies that validate the use of grounded theory strategies for applied research projects. This paper seeks to add to both margins of the grounded theory literature. First, it provides a detailed methodological account of how constructivist grounded theory and grounded theory situational analysis were used in a Ph.D. study exploring how ecologically concerned networks understand community resilience and respond to current and anticipated challenges of …

Impacts Of Streamflow Variability And Antecedent Conditions On The Magnitude, Timing, And Form Of Watershed Carbon And Nutrient Export From A Coastal Alaskan Watershed, Claire E. Delbecq

Fisheries

The coastal watersheds of Southeast Alaska have diverse hydrologic regimes driven by differences in the contribution of glacial, snow, and rainwater inputs to streamflow. Climate change is set to shift watershed streamflow regimes, which has the potential to impact the source, processing, and export of materials (e.g., organic matter, nutrients, drifting macroinvertebrates) from watersheds to nearshore ecosystems. However, the impact of streamflow variability, such as droughts and floods, on material transport is poorly understood in Southeast Alaska. My study evaluated how streamflow variability impacts the magnitude and composition of materials exported from a predominantly rain-fed watershed in Juneau, Alaska. I …

Environmental Controls On Foraging And Growth Of Juvenile Salmonids In A Southeast Alaska Watershed, Kevin A. Fitzgerald

Fisheries

Small coastal drainages in southeast Alaska (SEAK) support an exceptionally vast and productive region of anadromous fish habitat. However, streamflow patterns within this region are changing. It is expected that hydrologic inputs to streamflow will shift toward increased rain-water contribution, and that extreme high and low water events will become more frequent. Such changes will likely alter the foraging and growth environment of juvenile salmonids throughout this landscape, yet implications of hydrologic change to juvenile salmonid rearing habitats are poorly understood. Moreover, basic questions regarding streamflow impacts on fish foraging and the relative importance of marine-derived resources (MDR) from spawning …

Adult Chinook Salmon Heat Stress And Reproductive Consequences In Southcentral Alaska, Madeline L. Lee

Fisheries

This thesis explores the causes and potential fitness consequences of heat stress on spawning Chinook salmon (Oncorhynchus tshawytscha) in an era of rapid warming in Alaska. Cook Inlet, Southcentral Alaska, accounts for nearly half of the state's total sport, personal use, and subsistence harvest of hatchery-produced Chinook salmon. Southcentral Alaska provides an excellent opportunity to understand the potential for hatcheries to interact with climate warming and increasing habitat alteration with human development. The first objective of this thesis is to improve understanding of the factors associated with heat stress responses among and within Chinook salmon populations in relation to water …

Spatiotemporal Dynamics Of The Marine Invertebrate Community Associated With Amathia Verticillata, Emily Masini Zavacki, Nathalie Reyns Phd, Michel Boudrias Phd, Jeff Crooks Phd

Theses

Non-indigenous species (NIS) are often thought to have negative consequences on ecosystems. However, some NIS are ecosystem engineers, organisms that modify and/or create habitats by changing physical structure (either biogenic or abiotic), such as Amathia verticillata (previously Zoobotryon verticillatum [delle Chiaje, 1822]), a non-indigenous bryozoan with a global distribution. The role of NIS as ecosystem engineers can be complicated due to the mix of impacts that they may have on the ecosystem. Thus, the role of A. verticillata as an ecosystem engineer may shift our understanding about its ecological role on anthropogenic structures, such as docks through an urbanized area, …

Influence Of Freshwater Processes On Juvenile Chinook Salmon Size, Movement, And Outmigration Timing In The Chena River, Alaska, Olivia N. Edwards

Fisheries

Chinook Salmon Oncorhynchus tshawytscha have experienced population declines across their range in recent decades, including Alaska where they are a critical subsistence, commercial, and sport fish species. The Alaska Board of Fisheries has listed Yukon River Chinook salmon as a "stock of yield concern" since 2000 prompting the implementation of escapement goals for key spawning tributaries in 2001. Additionally, research efforts across the basin have increased to better understand potential mechanisms behind these declines and provide information to facilitate management decisions. To help fill a critical data gap in the overall understanding of the fishery, this research investigated various freshwater …

Reliability Of Trans-Generational Genetic Mark-Recapture For Enumerating Pacific Salmon, Samuel W. Rosenbaum

Fisheries

As Pacific salmon (Oncorhynchus spp.) continue to decline across much of their range, it is imperative to further develop reliable tools to quantify trends in population abundance. Estimating the number of spawning adult Pacific salmon (escapement) is a fundamental but challenging objective for fishery managers. Escapement monitoring of Pacific salmon typically requires intensive sampling across the return migration, often in remote locations, and is subject to changing environmental conditions that can reduce data quality. Alternative methods that increase the efficiency, accuracy, and precision of escapement monitoring are desirable, particularly during times of shrinking budgets for fisheries management. With the advent …

Detection Method Has Independent Prognostic Significance In The Plco Lung Screening Trial, James P Long, Yu Shen

Faculty, Staff and Student Publications

Prognostic models in cancer use patient demographic and tumor characteristics to predict survival and dynamic disease prognosis. Past work in breast cancer has shown that cancer detection method, screen-detected or symptom-detected, has prognostic significance. We investigate this phenomenon in the lung component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial. Patients were randomized to intervention, receiving four annual chest x-rays (CXRs), or to control, receiving usual care. Patients were followed for a total of approximately 13 years. In PLCO, lung cancer detection method has independent prognostic value exceeding that of variables commonly used in lung cancer prognostic models, …

Poplar Borer, Marion Murray, Ryan Davis

All Current Publications

The poplar borer is the most commonly submitted wood borer found in aspens and other poplars in Utah. While large trees are seldom killed by this pest, it can cause the decline of trees, weakening of branches or the bole (which promotes wind breakage), and allows the introduction of pathogens. This fact sheet describes poplar borer life cycle, damage, and control.

Poplar Bud Gall Mite, Marion Murray, Ryan Davis

All Current Publications

The poplar bud gall mite belongs to the eriophyid mite family. These mites are microscopic and about one-fourth the size of a spider mite. Adults are about 0.2 mm in length, reddish, and spindle-shaped. This fact sheet reviews poplar bud gall mite biology and habits, damage, and control.

Cross-Environment Collective Cell Invasion After Mechanical And Hypoxic Priming, Jose Alejandro Almeida

McKelvey School of Engineering Graduate Student Theses & Dissertations

In breast cancer, tumor cells collectively move through microenvironments of varying stiffness and fiber structures. Around primary breast tumors, there are gradients of matrix stiffness that mammary epithelial cells (MECs) must navigate for tumor invasion. In addition, the collagen density of the breast tissue becomes more crosslinked and fibrous. Previous studies of breast tumor invasion capture the effect of either soft or stiff environments, not how cells coming from stiff environments behave in softer 3D collagen matrices. Across stiff and soft regions, we have previously shown a mechanical memory-dependent collective migration of epithelial cells on 2D surfaces. In this work, …

The Rise Of Degrader Drugs, Mingxing Teng, Nathanael S Gray

Faculty, Staff and Students Publications

The cancer genomics revolution has served up a plethora of promising and challenging targets for the drug discovery community. The field of targeted protein degradation (TPD) uses small molecules to reprogram the protein homeostasis system to destroy desired target proteins. In the last decade, remarkable progress has enabled the rational development of degraders for a large number of target proteins, with over 20 molecules targeting more than 12 proteins entering clinical development. While TPD has been fully credentialed by the prior development of immunomodulatory drug (IMiD) class for the treatment of multiple myeloma, the field is poised for a "Gleevec …

An 11,600-Year Reconstruction Of Vegetation Communities, Moisture Availability, And Land Use Changes At Lake Khargal, Northern Mongolia, Joshua A. Barna

Geosciences

The regional response of vegetation to global atmospheric circulation patterns and human influence throughout the Holocene is recorded by environmental proxies in sediment cores from Lake Khargal in northern Mongolia. Pollen, spores, total organic carbon, and grain size analysis indicate that conditions in the watershed were moderately humid at ~11500 cal yr B.P. The vegetation community surrounding Lake Khargal consists of mainly of Artemisia (sage), Poaceae (grass), and Betula (birch) with a modest amount of extra-local Pinus (pine) from nearby boreal forests. Fluctuations in the ratios of these and other taxa show that aridity increased after ~10000 cal yr B.P., …

Improved Boreal Vegetation Mapping Using Imaging Spectroscopy To Aid Wildfire Management, Interior Alaska, Anushree Badola

Geosciences

Wildfires are a natural and essential part of Alaska ecosystems, but excessive wildfires pose a risk to the ecosystem's health and diversity, as well as to human life and property. To manage wildfires effectively, vegetation/fuel maps play a critical role in identifying high-risk areas and allocating resources for prevention, suppression, and recovery efforts. Furthermore, vegetation/fuel maps are an important input for fire behavior models, along with weather and topography data. By predicting fire behavior, such as spread rate, intensity, and direction, fuel models allow fire managers to make informed decisions about wildfire suppression, management, and prevention. Traditionally used vegetation/fuel maps …

Defining The Roles Of Pyruvate Oxidation, Tca Cycle, And Mannitol Metabolism In Methicillin-Resistant Staphylococcus Aureus Catheter-Associated Urinary Tract Infection, Santosh Paudel, Sarah Guedry, Chloe L P Obernuefemann, Scott J. Hultgren, Jennifer N. Walker, Ritwij Kulkarni

2020-Current year OA Pubs

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of complicated urinary tract infection (UTI) associated with the use of indwelling urinary catheters. Previous reports have revealed host and pathogen effectors critical for MRSA uropathogenesis. Here, we sought to determine the significance of specific metabolic pathways during MRSA UTI. First, we identified four mutants from the Nebraska transposon mutant library in the MRSA JE2 background that grew normally in rich medium but displayed significantly reduced growth in pooled human urine (HU). This prompted us to transduce the uropathogenic MRSA 1369 strain with the transposon mutants in

Teaching Matters: A Guide For Graduate Students (Review), Jamie Zabinsky

Feminist Pedagogy

No abstract provided.

Book Review: Elizabeth Wilson's Gut Feminism, İlkan C. İpekçi̇ Ph.D. Candidate

Feminist Pedagogy

No abstract provided.

Evaluation Of Native Plant Communities On Nebraska Game And Parks Commission State Parks, Robert F. Steinauer

Nebraska Game and Parks Commission: White Papers, Conference Presentations, and Manuscripts

This report evaluates the Native Plant Communities on Nebraska Game and Parks Commission State Parks East Region, also known as Region 3, which includes much of northeast and extreme eastern Nebraska, including portions of the lower Niobrara, Elkhorn and Platte Rivers and nearly the entire east border formed by the Missouri River. Fifteen state-listed threatened and endangered species have been recorded within the boundaries of Region 3 within the last twenty years. Several of these occupy habitats within major river channels.

Surveyed areas which contained habitat for legally protected species include Dead Timber State Recreation Area, Indian Cave State Park, …

A Tale Of Two Fathers: Leadership Between The Estate And The Study House In The Origin Story Of Eliezer Ben Hyrcanus, John Mandsager

Journal of Religious Competition in Antiquity

The coming-of-age tale of R. Eliezer b. Hyrcanus, found in a number of late midrash collections, contains competing ideals of masculine mastery and leadership. Through analysis of the three main characters of the story, R. Eliezer, and his two fathers, Hyrcanus, and his master R. Yoḥanan b. Zakkai across the variants of the story, this article demonstrates that the spaces of the agricultural estate and the study house are idealized in competing ways in rabbinic midrash as spaces for mastery of ideals of masculine identity (success in estate management and excellence in Torah study). In addition, Hyrcanus and R. Yoḥanan …

Ronald E. Mcnair Scholars Program Profiles And Abstracts 2023, Motutama Sipelii

McNair Symposium

This is the complete event program and provides presentation abstracts and biographies of McNair scholars and their mentors.