956 research outputs found

    A Conjoint Analysis of Site Selection for the U.S. Broiler Industry: Impications for Louisiana (Bulletin #882)

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    The purpose of this study is to analyze broiler industry executives’ decisions on where to locate a broiler complex in the United States. The specific objectives are to identify factors affecting site locations of broiler complexes in the United States and to measure the effects and relative importance of these factors on the broiler complex location decision.https://digitalcommons.lsu.edu/agcenter_bulletins/1013/thumbnail.jp

    A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

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    Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018

    Implantation of a Novel Cryopreserved Viable Osteochondral Allograft for Articular Cartilage Repair in the Knee

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    Restoration and repair of articular cartilage injuries remain a challenge for orthopaedic surgeons. The standard first-line treatment of articular cartilage lesions is marrow stimulation; however, this procedure can often result in the generation of fibrous repair cartilage rather than the biomechanically superior hyaline cartilage. Marrow stimulation is also often limited to smaller lesions, less than 2 cm2. Larger lesions may require implantation of a fresh osteochondal allograft, though a short shelf life, size-matched donor requirements, potential challenges of bone healing, limited availability, and the relatively high price limit the wide use of this therapeutic approach. We present a straightforward, single-stage surgical technique of a novel reparative and restorative approach for articular cartilage repair with the implantation of a cryopreserved viable osteochondral allograft (CVOCA). The CVOCA contains full-thickness articular cartilage and a thin layer of subchondral bone, and maintains the intact native cartilage architecture with viable chondrocytes, growth factors, and extracellular matrix proteins to promote articular cartilage repair. We report the results of a retrospective case series of three patients who presented with articular cartilage lesions more than 2 cm2 and were treated with the CVOCA using the presented surgical technique. Patients were followed up to 2 years after implantation of the CVOCA and all three patients had satisfactory outcomes without adverse events. Controlled randomized studies are suggested for evaluation of CVOCA efficacy, safety, and long-term outcomes

    A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a Combination of Three Monoclonal Antibodies in Neutralization of Botulinum Neurotoxin Serotype A.

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    The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial. However, a triple antibody therapeutic poses unique development and manufacturing challenges. Thus, potentially to streamline development of BoNT antitoxins, we sought to achieve the potency of multiple mAb combinations in a single IgG-based molecule that has a long serum half-life. The design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb) containing the binding sites of each of the three parental BoNT/A mAbs yielded an antibody of nearly equal potency to the combination. The approach taken here could be applied to the design and creation of other multivalent antibodies that could be used for a variety of applications, including toxin elimination

    Revealing the importance of groundwater for potable private water supplies in Wales

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    At least 77,000 people across Wales rely on private water supplies for their drinking water, with 94 % of these supplies dependent on groundwater. Potable private water supplies were mapped to Lower Super Output Area Level, creating the first map of its kind for Wales. Some rural areas report nearly 43 % of properties using private water supplies as their principal source of water. Simplifying the complex geology of Wales into ‘hydrostratigraphic units’ shows that 97 % of private water supplies are sourced from secondary aquifers which have low productivity and storage. Ordovician and Silurian bedrock aquifers and associated Quaternary deposits support nearly 75 % of all private water supplies. The total volume of groundwater abstracted by licensed and unlicensed potable private water supplies across Wales is estimated at 24.6 ML /day. In times of drought many of Wales’ low storage aquifers can experience insufficiency events. During 2018, reports of 132 dry supplies were collated, however we suspect many cases were not reported. In a changing climate with more extreme weather events, and as working from home becomes more common, private water supply users in low-storage and low-permeability aquifers may find themselves at increasing risk of insufficiency events

    A city scale 3D geological model to support ground source heat recovery and storage

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    The Cardiff Urban Geo Observatory was established to characterise, monitor and model groundwater and heat flow in a shallow urban aquifer. Mapping showed that shallow ground groundwater temperatures exceeded 150C, due to effects of the subsurface urban heat island (Farr et al, 2017). A 3D model of the superficial deposits was created to better understand the aquifer dimensions and as a framework for a hydrogeological heat flow model

    A novel method to allow noninvasive, longitudinal imaging of the murine immune system in vivo

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    In vivo imaging has revolutionized understanding of the spatiotemporal complexity that subserves the generation of successful effector and regulatory immune responses. Until now, invasive surgery has been required for microscopic access to lymph nodes (LNs), making repeated imaging of the same animal impractical and potentially affecting lymphocyte behavior. To allow longitudinal in vivo imaging, we conceived the novel approach of transplanting LNs into the mouse ear pinna. Transplanted LNs maintain the structural and cellular organization of conventional secondary lymphoid organs. They participate in lymphocyte recirculation and exhibit the capacity to receive and respond to local antigenic challenge. The same LN could be repeatedly imaged through time without the requirement for surgical exposure, and the dynamic behavior of the cells within the transplanted LN could be characterized. Crucially, the use of blood vessels as fiducial markers also allowed precise re-registration of the same regions for longitudinal imaging. Thus, we provide the first demonstration of a method for repeated, noninvasive, in vivo imaging of lymphocyte behavior

    Human interactions with tropical environments over the last 14,000 years at Iho Eleru, Nigeria

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    The Ihò Eléérú (or Iho Eleru) rock shelter, located in Southwest Nigeria, is the only site from which Pleistocene-age hominin fossils have been recovered in western Africa. Excavations at Iho Eleru revealed regular human occupations ranging from the Later Stone Age (LSA) to the present day. Here, we present chronometric, archaeobotanical, and paleoenvironmental findings, which include the taxonomic, taphonomic, and isotopic analyses of what is the only Pleistocene faunal assemblage documented in western Africa. Our results indicate that the local landscape surrounding Iho Eleru, although situated within a regional open-canopy biome, was forested throughout the past human occupation of the site. At a regional scale, a shift from forest- to savanna-dominated ecotonal environment occurred during a mid-Holocene warm event 6,000 years ago, with a subsequent modern reforestation of the landscape. Locally, no environmental shift was observable, placing Iho Eleru in a persistent forested “island” during the period of occupation

    Establishing an urban geo-observatory to support sustainable development of shallow subsurface heat recovery and storage

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    Low-enthalpy ground source heating and cooling is recognised as one strategy that can contribute towards reducing reliance on traditional, increasingly insecure, CO2-intense thermal power generation, as well as helping to address fuel poverty. Development of this technology is applicable in urban areas where high housing density often coincides with the presence of shallow aquifers. In urban areas groundwater temperatures can be elevated due to the subsurface Urban Heat Island effect. Uptake and development of this technology is often limited by initial investment costs, however, baseline temperature monitoring and characterisation of urban aquifers, conducted in partnership with local authorities, can provide a greater degree of certainty around resource and sustainability that can facilitate better planning, regulation and management of subsurface heat. We present a novel high-density, city-scale groundwater temperature observatory and introduce a 3D geological model aimed at addressing the needs of developers, planners, regulators and policy makers. The Cardiff Geo-Observatory measures temperature in a Quaternary aged sand and gravel aquifer in 61 boreholes and at a pilot shallow open-loop ground source heating system. We show that repurposing existing infrastructure can provide a cost effective method of developing monitoring networks, and make recommendations on establishing similar geo-observatories
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