554 research outputs found

    Global Sourcing of IT Services and Information Security: Prudence before Playing

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    This paper calls for awareness of the risks in global sourcing of IT and IT-enabled services. It calls for appropriate assessment and mitigation of these risks. The authors identify ways in which global sourcing (often called offshoring) increases information security exposures and strategies for managing such risks

    IL-2 limits IL-12 enhanced lymphocyte proliferation during \u3ci\u3eLeishmania amazonensis\u3c/i\u3e infection

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    C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44hiCD4+ T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44hiCD4+ T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4+ T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional Treg cells

    MicroRNAs in bovine milk exosomes are bioavailable in humans but do not elicit a robust pro-inflammatory cytokine response

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    Background: Bovine milk exosomes are studied for their roles as bioactive food compounds and as vehicles for drug delivery. Both lines of investigation converge on immune function, e.g., immune regulation by absorption of microRNAs encapsulated in milk exosomes across species boundaries, and the possibility of exosomes and their cargos triggering an immune response if used in drug delivery. This study assessed the bioavailability of immune-related microRNAs from bovine milk and changes in plasma cytokine concentrations after milk consumption in humans, and the secretion of cytokines by human peripheral blood mononuclear cells (PBMCs) cultured with milk exosomes transfected with immune-relevant microRNAs. Results: Human plasma samples were collected before and at timed intervals after a milk meal and analyzed for concentrations of six immune-relevant microRNAs and nine cytokines. The peak plasma concentrations of miR-15b-5p, miR- 21-5p, miR-106b-5p, and miR-223-3p were 60 ± 9.80% to 162 ± 31.80% higher after milk consumption (Ct values 23 ± 1.2 to 26 ± 1.1 cycles) compared to baseline values (P \u3c 0.05). Plasma concentrations of TNF-alpha were not significantly different before versus after milk consumption; eight other cytokines were below detection limit. PBMCs were collected before and six hours after milk consumption and cultured with or without concanavalin A (ConA). TNF-alpha, IL-1β, IL-6 and IL-10 were detectable in culture media, but concentrations did not depend on milk consumption prior to PBMC isolation (P \u3e 0.05). When PBMC cultures from fasted subjects were supplemented with milk exosomes that had been transfected with immune-relevant microRNAs, the concentrations of IL-1β, IL-6, IL-10 and TNF-alpha were 29 ± 12% to 220 ± 33% higher than controls cultured with non-transfected exosomes (P \u3c 0.05), but cytokine concentrations were not different compared with control exosomes transfected with scrambled microRNA (P \u3e 0.05). Conclusions: MicroRNAs in bovine milk exosomes are bioavailable. Milk exosomes do not elicit an increase of plasma cytokines following oral administration

    IL-2 limits IL-12 enhanced lymphocyte proliferation during \u3ci\u3eLeishmania amazonensis\u3c/i\u3e infection

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    C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44hiCD4+ T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44hiCD4+ T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4+ T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional Treg cells

    Aerodynamic response of turbomachinery blade rows to convecting density distortions

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    Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1997.Includes bibliographical references (leaves 75-76).by Becky E. Ramer.M.S

    The Iowa Homemaker vol.5, no.5

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    Table of Contents What Shall We Teach and Where-withal Shall We Be Clothed? by Marcia E. Turner, page 1 Hand Loom Craft by Thriza Hull, page 2 Autumn Days – Children’s Clothes by Merle Ramer, page 2 Why Not a China Pattern by Alma Riemenschneider, page 3 The 4-H’s of Housekeeping by Dorothy Cook, page 4 With Iowa State Home Economics Association, page 6 Who’s There and Where by Josephine McMullen, page

    Immunomodulatory Role of Urolithin A on Metabolic Diseases

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    Urolithin A (UroA) is a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries, and walnuts. UroA is of growing interest due to its therapeutic potential for various metabolic diseases based on immunomodulatory properties. Recent advances in UroA research suggest that UroA administration attenuates inflammation in various tissues, including the brain, adipose, heart, and liver tissues, leading to the potential delay or prevention of the onset of Alzheimer’s disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In this review, we focus on recent updates of the anti-inflammatory function of UroA and summarize the potential mechanisms by which UroA may help attenuate the onset of diseases in a tissue-specific manner. Therefore, this review aims to shed new insights into UroA as a potent anti-inflammatory molecule to prevent immunometabolic diseases, either by dietary intervention with ellagic acid-rich food or by UroA administration as a new pharmaceutical drug

    Amphiphilic Polyanhydride Nanoparticles Stabilize \u3ci\u3eBacillus anthracis\u3c/i\u3e Protective Antigen

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    Advancements towards an improved vaccine against Bacillus anthracis, the causative agent of anthrax, have focused on formulations composed of the protective antigen (PA) adsorbed to aluminum hydroxide. However, due to the labile nature of PA, antigen stability is a primary concern for vaccine development. Thus, there is a need for a delivery system capable of preserving the immunogenicity of PA through all the steps of vaccine fabrication, storage, and administration. In this work, we demonstrate that biodegradable amphiphilic polyanhydride nanoparticles, which have previously been shown to provide controlled antigen delivery, antigen stability, immune modulation, and protection in a single dose against a pathogenic challenge, can stabilize and release functional PA. These nanoparticles demonstrated polymer hydrophobicity-dependent preservation of the biological function of PA upon encapsulation, storage (over extended times and elevated temperatures), and release. Specifically, fabrication of amphiphilic polyanhydride nanoparticles composed of 1,6-bis(p-carboxyphenoxy)hexane and 1,8-bis(p-carboxyphenoxy)-3,6- dioxaoctane best preserved PA functionality. These studies demonstrate the versatility and superiority of amphiphilic nanoparticles as vaccine delivery vehicles suitable for long-term storage
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