Pinedale Glacial History of the Upper Arkansas River Valley: New Moraine Chronologies, Modeling Results and Geologic Mapping

This field trip guidebook chapter outlines the glacial history of the upper Arkansas River valley, Colorado, and builds on a previous GSA field trip to the same area in 2010. The following will be presented: (1) new cosmogenic 10Be exposure ages of moraine boulders from the Pinedale and Bull Lake glaciations (Marine Isotope Stages 2 and 6, respectively) located adjacent to the Twin Lakes Reservoir, (2) numerical modeling of glaciers during the Pinedale glaciation in major tributaries draining into the upper Arkansas River, (3) discharge estimates for glacial-lake outburst floods in the upper Arkansas River valley, and (4) 10Be ages on flood boulders deposited downvalley from the moraine sequences. This research was stimulated by a new geologic map of the Granite 7.5’ quadrangle, in which the mapping of surficial deposits was revised based in part on the interpretation of newly acquired LiDAR data and field investigations. The new 10Be ages of the Pinedale terminal moraine at Twin Lakes average 21.8 ± 0.7 ka (n=14), which adds to nearby Pinedale terminal moraine ages of 23.6 ± 1.4 ka (n=5), 20.5 ± 0.2 ka (n=3) and 16.6 ± 1.0 ka, and downvalley outburst flood terraces that date to 20.9 ± 0.9 ka (n=4) and 19.0 ± 0.6 ka (n=4). This growing chronology leads to improved understanding of the controls and timing of glaciation in the western U.S., the modeling of glacial-lake outburst flooding, and the reconstruction of paleo-temperature through glacier modeling

An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock

BACKGROUND: Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy. METHODS: As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures. RESULTS: The intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B. CONCLUSION: Our results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component. The vaccination method we describe may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product

Impacts of Conventional Agricultural Practices on Aquifer Water Quality: An Overview of the Plains, Georgia Water Quality Study

Proceedings of the 1997 Georgia Water Resources Conference, March 20-22, 1997, Athens, Georgia.Pesticide leaching to groundwater is a potential problem in agricultural production areas of South Georgia where sandy soils predominate. The aquifers in this region are an important resource for South Georgia and North Florida. High soil hydraulic conductivity, coupled with high water-table conditions and high precipitation, can lead to groundwater contamination in the area. A field study near Plains, GA, was initiated in 1988, with the objective of establishing a better understanding of agrichemical transport in this area. Data was collected from 1988 to 1994 on a 0.81 ha research plot. Data indicate under normal climatic conditions nutrient and pesticide transport to groundwater is minimal. However, high precipitation soon after chemical application, combined with a saturated root zone, can lead to groundwater contamination Thus, extreme care must be used to properly manage the application and soil-water regime. Chemical application during periods of excess precipitation and saturated soil-water conditions must be avoided.Sponsored and Organized by: U.S. Geological Survey, Georgia Department of Natural Resources, The University of Georgia, Georgia State University, Georgia Institute of TechnologyThis book was published by the Institute of Ecology, The University of Georgia, Athens, Georgia 30602 with partial funding provided by the U.S. Department of Interior, Geological Survey, through the Georgia Water Research Institutes Authorization Act of 1990 (P.L. 101-397). The views and statements advanced in this publication are solely those of the authors and do not represent official views or policies of the University of Georgia or the U.S. Geological Survey or the conference sponsors

Enhanced immunogenicity following miR-155 incorporation into the influenza A virus genome

Influenza A vaccine efficacy in the elderly is generally poor and so identification of novel molecular adjuvants to improve immunogenicity is important to reduce the overall burden of disease. Short non-coding RNAs, known as microRNAs (miRNAs) are known to regulate gene expression and have the potential to influence immune responses. One such miRNA, miR-155, has been shown to modulate T and B cell development and function. We incorporated miR-155 into the influenza A virus (IAV) genome creating a self-adjuvanting \u27live vaccine\u27 with the ability to modify immunogenicity. Infection of mice with a recombinant influenza virus encoding miR-155 in the NS gene segment altered epitope-specific expansion of influenza-specific CD8(+) T cells and induced significantly higher levels of neutralising antibody

ADAMTS5 is a critical regulator of virus-specific T cell immunity

The extracellular matrix (ECM) provides physical scaffolding for cellular constituents and initiates biochemical and biomechanical cues that are required for physiological activity of living tissues. The ECM enzyme ADAMTS5, a member of the ADAMTS (A Disintegrin-like and Metalloproteinase with Thrombospondin-1 motifs) protein family, cleaves large proteoglycans such as aggrecan, leading to the destruction of cartilage and osteoarthritis. However, its contribution to viral pathogenesis and immunity is currently undefined. Here, we use a combination of in vitro and in vivo models to show that ADAMTS5 enzymatic activity plays a key role in the development of influenza-specific immunity. Influenza virus infection of Adamts5-/- mice resulted in delayed virus clearance, compromised T cell migration and immunity and accumulation of versican, an ADAMTS5 proteoglycan substrate. Our research emphasises the importance of ADAMTS5 expression in the control of influenza virus infection and highlights the potential for development of ADAMTS5-based therapeutic strategies to reduce morbidity and mortality

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy.

Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg- PrkdcscidIL2rgtm1Wjl/Sz (null; NSG) mice were transplanted with human (h)CD34+ hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; non-small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX). Tumor growth curves were similar in HuNSG compared with nonhuman immune-engrafted NSG mice. Treatment with pembrolizumab, which targets programmed cell death protein 1, produced significant growth inhibition in both CDX and PDX tumors in HuNSG but not in NSG mice. Finally, inhibition of tumor growth was dependent on hCD8+ T cells, as demonstrated by antibody-mediated depletion. Thus, tumor-bearing HuNSG mice may represent an important, new model for preclinical immunotherapy research. FASEB J 2018 Mar; 32(3):1537-1549

Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12

PURPOSE: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. PATIENTS AND METHODS: We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life. RESULTS: For the intention-to-treat population, the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, -9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P < .001) and need for hospitalization (P < .001), and preserved quality of life (P = .04). CONCLUSION: For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life

‘It's all the way you look at it, you know’: reading Bill ‘Bojangles’ Robinson's film career

This paper engages with a major paradox in African American tap dancer Bill ‘Bojangles’ Robinson's film image – namely, its concurrent adherences to and contestations of dehumanising racial iconography – to reveal the complex and often ambivalent ways in which identity is staged and enacted. Although Robinson is often understood as an embodiment of popular cultural imagery historically designed to dehumanise African Americans, this paper shows that Robinson's artistry displaces these readings by providing viewing pleasure for black, as much as white, audiences. Robinson's racially segregated scenes in Dixiana (1930) and Hooray for Love (1935) illuminate classical Hollywood's racial codes, whilst also showing how his inclusion within these otherwise all-white films provides grounding for creative and self-reflexive artistry. The films' references to Robinson's stage image and artistry overlap with minstrelsy-derived constructions of ‘blackness’, with the effect that they heighten possible interpretations of his cinematic persona by evading representational conclusion. Ultimately, Robinson's films should be read as sites of representational struggle that help to uncover the slipperiness of performances of African American identities in 1930s Hollywood