191 research outputs found

    INEL Spray-forming Research

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    Spray forming is a near-net-shape fabrication technology in which a spray of finely atomized liquid droplets is deposited onto a suitably shaped substrate or mold to produce a coherent solid. The technology offers unique opportunities for simplifying materials processing without sacrificing, and oftentimes substantially improving, product quality. Spray forming can be performed with a wide range of metals and nonmetals, and offers property improvements resulting from rapid solidification (e.g., refined microstructures, extended solid solubilities and reduced segregation). Economic benefits result from process simplification and the elimination of unit operations. Researchers at the Idaho National Engineering Laboratory (INEL) are developing spray-forming technology for producing near-net-shape solids and coatings of a variety of metals, polymers, and composite materials. Results from several spray forming programs are presented to illustrate the range of capabilities of the technique as well as the accompanying technical and economic benefits. Low-carbon steel strip greater than 0.75 mm thick and polymer membranes for gas/gas and liquid/liquid separations that were spray formed are discussed; recent advances in spray forming molds, dies, and other tooling using low-melting-point metals are described

    Near-net-shape manufacturing: Spray-formed metal matrix composites and tooling

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    Spray forming is a materials processing technology in which a bulk liquid metal is converted to a spray of fine droplets and deposited onto a substrate or pattern to form a near-net-shape solid. The technology offers unique opportunities for simplifying materials processing without sacrificing, and oftentimes substantially improving, product quality. Spray forming can be performed with a wide range of metals and nonmetals, and offers property improvements resulting from rapid solidification (e.g. refined microstructures, extended solid solubilities and reduced segregation). Economic benefits result from process simplification and the elimination of unit operations. The Idaho National Engineering Laboratory is developing a unique spray-forming method, the Controlled Aspiration Process (CAP), to produce near-net-shape solids and coatings of metals, polymers, and composite materials. Results from two spray-accompanying technical and economic benefits. These programs involved spray forming aluminum strip reinforced with SiC particulate, and the production of tooling, such as injection molds and dies, using low-melting-point metals

    Controlled, pulsatile release of thermostabilized inactivated polio vaccine from PLGA-based microspheres

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    Many vaccines, such as the inactivated polio vaccine (IPV), must be administered in several doses for full efficacy. Because patient access is a major challenge for vaccination efforts in developing countries, administering multiple doses per patient is impractical in those areas. Single-administration vaccines would greatly improve efforts to vaccinate populations in Third World countries, and the World Health Organization (WHO) Expanded Program for Immunization describes an ideal vaccine as one that is heat-stable, requires only one shot, and is easy to administer. Although already existing technologies, such as microspheres composed of poly(lactic-co-glycolic acid) (PLGA), are able to encapsulate vaccines and release them over an extended period of time up to several weeks, they are not able to maintain antigen stability over the longer time intervals in vivo. Vaccines such as IPV, however, are known to be unstable at elevated temperature, such as the 37°C environment of the body, as well as in the acidic environment of the degrading PLGA microspheres. Please click Additional Files below to see the full abstract

    Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release

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    AbstractVaccines are a critical clinical tool in preventing illness and death due to infectious diseases and are regularly administered to children and adults across the globe. In order to obtain full protection from many vaccines, an individual needs to receive multiple doses over the course of months. However, vaccine administration in developing countries is limited by the difficulty in consistently delivering a second or third dose, and some vaccines, including the inactivated polio vaccine (IPV), must be injected more than once for efficacy. In addition, IPV does not remain stable over time at elevated temperatures, such as those it would encounter over time in the body if it were to be injected as a single-administration vaccine. In this manuscript, we describe microspheres composed of poly(lactic-co-glycolic acid) (PLGA) that can encapsulate IPV along with stabilizing excipients and release immunogenic IPV over the course of several weeks. Additionally, pH-sensitive, cationic dopants such as Eudragit E polymer caused clinically relevant amounts of stable IPV release upon degradation of the PLGA matrix. Specifically, IPV was released in two separate bursts, mimicking the delivery of two boluses approximately one month apart. In one of our top formulations, 1.4, 1.1, and 1.2 doses of the IPV serotype 1, 2, and 3, respectively, were released within the first few days from 50mg of particles. During the delayed, second burst, 0.5, 0.8, and 0.6 doses of each serotype, respectively, were released; thus, 50mg of these particles released approximately two clinical doses spaced a month apart. Immunization of rats with the leading microsphere formulation showed more robust and long-lasting humoral immune response compared to a single bolus injection and was statistically non-inferior from two bolus injections spaced 1 month apart. By minimizing the number of administrations of a vaccine, such as IPV, this technology can serve as a tool to aid in the eradication of polio and other infectious diseases for the improvement of global health

    The role played by cell-substrate interactions in the pathogenesis of osteoclast-mediated peri-implant osteolysis

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    Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery for aseptic loosening after total joint replacement. Cells were examined for the expression of several markers associated with the osteoclast phenotype using immunohistochemistry, histochemistry, and/or in situ hybridization. CD68 protein, a marker expressed by multiple macrophage lineage cell types, was detected in mononucleated and multinucleated cells associated with polyethylene particles and the bone surface. Cathepsin K and tartrate-resistant acid phosphatase were expressed highly in both mononucleated and multinucleated cells associated with the bone surface. Levels of expression were much lower in cells associated with polyethylene particles. High levels of β(3 )integrin protein were detected in cells in contact with bone. Multinucleated cells associated with polyethylene particles exhibited faint positive staining. Calcitonin receptor mRNA expression was detected solely in multinucleated cells present in resorption lacunae on the bone surface and was absent in cells associated with polyethylene particles. Our findings provide further evidence that cells expressing the full repertoire of osteoclast phenotypic markers are involved in the pathogenesis of peri-implant osteolysis after total joint replacement. They also demonstrate that foreign body giant cells, although believed to be phenotypically and functionally distinct from osteoclasts, express many osteoclast-associated genes and gene products. However, the levels and patterns of expression of these genes in the two cell types differ. We speculate that, in addition to the role of cytokines and growth factors, the substrate with which these cells interact plays a critical role in their differential phenotypic and functional properties

    Deriving economic values for national sheep breeding objectives using a bio-economic model

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    peer-reviewedThe economic value of a trait in a breeding objective can be defined as the value of a unit change in an individual trait, while keeping all other traits constant and are widely used in the development of breeding objectives internationally. The objective of this study was to provide a description of the development of economic values for the pertinent traits included in the Irish national sheep breeding objectives using a whole farm system bio-economic model. A total of fourteen traits of economic importance representing maternal, lambing, production and health characteristics were calculated within a whole farm bio-economic model. The model was parameterised to represent an average Irish flock of 107 ewes with a mean lambing date in early March, stocked at 7.5 ewes per hectare and weaning 1.5 lambs per ewe joined to the ram. The economic values (units in parenthesis) calculated for maternal traits were: €39.76 for number of lambs born (per lamb), €0.12 for ewe mature weight cull value (per kg), −€0.57 for ewe mature weight maintenance value (per kg), −€0.09 for ewe mature weight replacement value (per kg) and −€0.84 for ewe replacement rate (per%). The economic values calculated for lambing traits were: €54.84 for lamb surviving at birth (per lamb), −€0.27 and −€0.30 for direct lambing difficulty in single and multiple-bearing ewes, respectively (per%); the corresponding values for maternal single and multiple lambing difficulty (per%) were −€0.25 and −€0.27, respectively. The calculated economic values for production traits were: −€0.25 for days to slaughter (per day), €3.70 for carcass Conformation (per EUROP grade) and −€0.84 for carcass fat (per fat score). The economic values for health traits were: −€0.24 for ewe lameness (per%), −€0.08 for lamb lameness (per%), −€0.25 for mastitis (per%), −€0.34 for dag score (per dag score) and −€0.08 for faecal egg count (per 50 eggs/g). Within the two Irish breeding objectives, the terminal and replacement breeding objective, the greatest emphasis was placed on production traits across both the terminal (62.56%) and replacement (41.65%) breeding objectives. The maternal and lambing traits accounted for the 34.19% and 23.45% of the emphasis within the replacement breeding objective, respectively. Results from this study will enable the implementation of new economic values within the national terminal and replacement Irish sheep breeding objectives which highlights the traits of importance for increasing overall farm profitability

    Novel pulsatile-release microparticles for single-injection vaccination

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    Many controlled release devices are designed to achieve near zero-order release kinetics, however for some applications, such as vaccination, non-continuous or pulsatile release is desired. Such pulsatile release systems may enable the creation of single-injection vaccines that eliminate the need for subsequent booster immunizations by spontaneously releasing antigen at time points that correspond to normal vaccination regimens. This would be especially important in the developing world where a lack of consistent access to healthcare contributes to approximately 1.5 million vaccine-preventable deaths each year.1 Here we present the fabrication and characterization of biodegradable core-shell microparticles that exhibit pulsatile release kinetics due to their unique structure. These particles are produced using a novel fabrication process that combines soft lithography, picoliter dispensing, optical alignment, and a gentle heat-based sintering step to generate microparticles with a biodegradable polymeric shell surrounding an antigen-filled core. By altering the composition (e.g. copolymer ratio or molecular weight) of the poly(lactic-co-glycolic acid) shell, particles can be tuned to release discrete pulses of a model antigen at times ranging from four days to two months. This fabrication method is also compatible with sensitive biologics, such as the inactivated polio virus, which retains \u3e80% of its antigenicity after encapsulation. Further, because the shell of the particle is physically separated from the core, these particles can be filled with any aqueous vaccine solution without affecting release kinetics and be easily scaled via massively parallel fabrication. As a result, these particles have exciting potential as single-injection vaccines that fully mimic the antigen presentation profile of traditional bolus injections administered over the course of months or years. Please click Additional Files below to see the full abstract
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