20,943 research outputs found

    Modulation of antigen-specific T-cells as immune therapy for chronic infectious diseases and cancer

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    Copyright: © 2014 Li, Symonds, Miao, Sanderson and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.This article has been made available through the Brunel Open Access Publishing Fund.T-cell responses are induced by antigen presenting cells (APC) and signals from the microenvironment. Antigen persistence and inflammatory microenvironments in chronic infections and cancer can induce a tolerant state in T-cells resulting in hyporesponsiveness, loss of effector function, and weak biochemical signaling patterns in response to antigen stimulation. Although the mechanisms of T-cell tolerance induced in chronic infection and cancer may differ from those involved in tolerance to self-antigen, the impaired proliferation and production of IL-2 in response to antigen stimulation are hallmarks of all tolerant T cells. In this review, we will summarize the evidence that the immune responses change from non-self to “self”-like in chronic infection and cancer, and will provide an overview of strategies for re-balancing the immune response of antigen-specific T cells in chronic infection and cancer without affecting the homeostasis of the immune system.Arthritis Research UK and Medical Research Council UK

    Comparison of several author indices for gauging academic productivity

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    Background Many author indices exist to gauge academic productivity. Several of these indices are calculated based upon an author's scholarly publication record, but the measurement methodology to calculate each index varies considerably, and the precise function being used, as well as the end result, is often complex and difficult to assess. Method Two straightforward methods to weigh author productivity from the publication and citation record were evaluated as possible means for providing a clearer assessment of scholarly activity. The author characteristic index (termed c-index) assigns author rank for each publication based upon author position. The characteristic prime (c') -index normalizes author rank from author position, so that the total weight per publication is unity. The top 10 scholars with keyword 'celiac disease' in the Google Scholar database were then assessed using these metrics. Rankings according to total number of publications, h-index, and c- and c'-indices were compared, then tabulated along with total papers included for assessment, and mean values per paper for author position, number of authors, citations, and year of publication. Results The order of the top ten authors with keyword 'celiac disease' varied substantially depending upon whether the h-index, c-index, or c'-index was used as a gauge. The characteristic indices assign credit to authors according to their position in an author list. The affiliated metrics provided a more complete picture of scholarly activity. Conclusions Academic achievement by scholars, based upon quantitative publication characteristics, has recently become of interest for evaluating job candidates, for determining work performance, and for bestowing awards and honors. The characteristic indices as described herein are readily calculated and interpreted, and may improve the assessment of scholarly activity

    DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire

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    The majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire

    The effects of seed inoculation on the rate of garbage composting

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    Enhancement of composting efficiency by seeding specialized inoculum was studied quantitatively by means of general composting parameters, kinetic constant, and maximum degradation rate of compostable substrates. General parameters such as temperature, CO2 and O-2 concentrations, pH, and dry matter decrease were improved by inoculating specialized microorganisms. Seed inoculation increased final percent conversion of garbage to 87.5%, while 72.7% of garbage degraded without inoculation. It was obvious that the seed inoculation could enhance composting rate from the comparison of kinetic constants and maximum degradation rates. The decomposition rates of organic matter in initial stage of inoculated case were 4 to 5 or 1.7 to 2.1 times higher than the values in the case of no inoculation, in terms of kinetic constant and maximum degradation rate, respectively. It was suggested that seed inoculation is applicable to the on-site treatment because it could initiate composting reaction efficiently without initial lag period

    Subterahertz Josephson plasma emission in layered high-T-C superconducting tunnel junctions

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    We investigated the emission of subterahertz frequency electromagnetic radiation from high-TC superconducting c-axis NdBa2Cu3O7−8/PrBa2Cu3O7−8/NdBa2Cu3O7−8 trilayer thin film tunneling junctions when external electric and magnetic fields are applied. The current-voltage characteristics under applied ab-plane magnetic fields H (up 8 T) exhibit well defined steps, Vn, such that eVn -hwp / (2n), where the plasma frequency wp-0.4 THz and n=1,2,3, . . . .. These steps may be interpreted using Josephson plasma dynamics. The applied voltage creates oscillating currents via the Josephson coupling energy EJ (EJ=hIJ /4e, where IJ is the Josephson current and h is Planck’s constant) and the charge energy EC (EC=e2 /2C, where C is the junction capacitance). Thus the Josephson plasma becomes excited by the tunneling current, with some of the energy being emitted as subterahertz frequency radiation. Our results provide a new insight into a solid-state quantum system with considerable potential for new solid-state terahertz emission sources

    Laboratory testing in pharmacies.

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    Point-of-care testing (POCT) is traditionally defined as laboratory diagnostics performed at or near the site where clinical care is delivered. POCT thereby combines sample collection, analysis, and reporting of results into a robust integrated testing structure, with a simple user interface. The availability of reliable devices and consolidated tests for patient screening, diagnosis and monitoring has allowed broad diffusion of POCT to the patient's bedside, physician offices, pharmacies, other healthcare facilities, supermarkets, and even into the patient's home. However, current evidence clearly shows that POCT can be subjective, and might even amplify the traditional problems encountered in the preanalytical, analytical and postanalytical phases of the total testing process. This may especially be seen in inappropriateness of the test request, collection of unsuitable biological materials, inaccurate test performances, larger analytical imprecision, unsuitable report formatting, delayed reporting of critical value, and report recording/retrieval. POCT patient care service in the pharmacy can be regarded as a valuable option for the present and future since it might be beneficial for all parties. However, several economic, clinical and regulatory issues should also be addressed before this opportunity can turn into a real advantage for patients and the entire healthcare system. The most appropriate allocation of POCT within the diagnostic pathway, as well as its adjuvant role in screening, diagnosis and monitoring of diseases should also be clearly established in order to prevent widespread and deregulated implementation

    Organic Scintillator-Fibre Sensors for Proton Therapy Dosimetry: SCSF-3HF and EJ-260

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    In proton therapy, the dose from secondary neutrons to the patient can contribute to side effects and the creation of secondary cancer. A simple and fast detection system to distinguish between dose from protons and neutrons both in pretreatment verification as well as potentially in vivo monitoring is needed to minimize dose from secondary neutrons. Two 3 mm long, 1 mm diameter organic scintillators were tested for candidacy to be used in a proton–neutron discrimination detector. The SCSF-3HF (1500) scintillating fibre (Kuraray Co. Chiyoda-ku, Tokyo, Japan) and EJ-260 plastic scintillator (Eljen Technology, Sweetwater, TX, USA) were irradiated at the TRIUMF Neutron Facility and the Proton Therapy Research Centre. In the proton beam, we compared the raw Bragg peak and spread-out Bragg peak response to the industry standard Markus chamber detector. Both scintillator sensors exhibited quenching at high LET in the Bragg peak, presenting a peak-to-entrance ratio of 2.59 for the EJ-260 and 2.63 for the SCSF-3HF fibre, compared to 3.70 for the Markus chamber. The SCSF-3HF sensor demonstrated 1.3 times the sensitivity to protons and 3 times the sensitivity to neutrons as compared to the EJ-260 sensor. Combined with our equations relating neutron and proton contributions to dose during proton irradiations, and the application of Birks’ quenching correction, these fibres provide valid candidates for inexpensive and replicable proton-neutron discrimination detectors
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