231 research outputs found

    Evaluation of half wave induction motor drive for use in passenger vehicles

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    Research performed at the University of Missouri-Columbia to devise and design a lower cost inverter induction motor drive for electrical propulsion of passenger vehicles is described. A two phase inverter motor system is recommended. The new design is predicted to provide comparable vehicle performance, improved reliability and a cost advantage for a high production vehicle, decreased total rating of the power semiconductor switches, and a somewhat simpler control hardware compared to the conventional three phase bridge inverter motor drive system. The major disadvantages of the two phase inverter motor drive are that it is larger and more expensive than a three phase machine, the design of snubbers for the power leakage inductances produce higher transient voltages, and the torque pulsations are relatively large because of the necessity to limit the inverter switching frequency to achieve high efficiency

    PO and ID BCG vaccination in humans induce distinct mucosal and systemic immune responses and CD4(+) T cell transcriptomal molecular signatures.

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    Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4(+) memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.Mucosal Immunology advance online publication 30 August 2017; doi:10.1038/mi.2017.67

    Use of Leishmania major parasites expressing a recombinant Trypanosoma cruzi antigen as live vaccines against Chagas disease

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    INTRODUCTION: METHODS: We generated recombinant RESULTS: We demonstrate that mice inoculated with these recombinant TS-expressing DISCUSSION: Altogether, these data indicate tha

    Co-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzi

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    Background: Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. the goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone.Methodology: We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-gamma ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-gamma, TNF-alpha, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-gamma responses and survived a lethal challenge given within the first 3 months following immunization. the addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro restimulation.Conclusion: Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi.National Institutes of HealthFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Millennium Institute for Gene TherapySt Louis Univ, Dept Internal Med, St Louis, MO 63103 USAUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, BrazilSt Louis Univ, Dept Mol Microbiol, St Louis, MO 63103 USAUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, BrazilNational Institutes of Health: RO1 AI040196CNPq: 420067/2005-1Web of Scienc

    Kerr Spinning Particle, Strings, and Superparticle Models

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    A combined model of the Kerr spinning particle and superparticle is considered. The structure of the Kerr geometry is presented in a complex form as being created by a complex source. A natural supergeneralization of this construction is obtained corresponding to a complex "supersource". Peforming a supershift to the Kerr and Kerr-Sen solutions we obtain metrics of supergravity black holes with a nonlinear realization of broken supersymmetry.Comment: minor revision, some grammatical changes and correction of the misprint before eq.(10); 13p., Latex, Talk at the International Seminar "Supersymmetry and quantum field theory" dedicated to the memory of D.V.Volkov, Kharkov, January 199

    Stability of scaling regimes in d2d\geq 2 developed turbulence with weak anisotropy

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    The fully developed turbulence with weak anisotropy is investigated by means of renormalization group approach (RG) and double expansion regularization for dimensions d2d\ge 2. Some modification of the standard minimal substraction scheme has been used to analyze stability of the Kolmogorov scaling regime which is governed by the renormalization group fixed point. This fixed point is unstable at d=2d=2; thus, the infinitesimally weak anisotropy destroyes above scaling regime in two-dimensional space. The restoration of the stability of this fixed point, under transition from d=2d=2 to d=3,d=3, has been demonstrated at borderline dimension 2<dc<3 2<d_c<3. The results are in qualitative agreement with ones obtained recently in the framework of the usual analytical regularization scheme.Comment: 23 pages, 2 figure

    Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

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    © 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

    Clinical Outcomes of Thirteen Patients with Acute Chagas Disease Acquired through Oral Transmission from Two Urban Outbreaks in Northeastern Brazil

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    Chagas disease is caused by a parasitic protozoan transmitted to humans by the contaminated feces of blood-feeding assassin bugs from the Triatominae subfamily. It may also be transmitted from mother to baby during pregnancy, by breastfeeding, blood transfusion or organ transplant. In rare cases, the disease can also be caused by accidental ingestion of contaminated food (sugar cane or açaí juice, drinking water, etc.). Acute Chagas disease often presents itself as a mononucleosis-like syndrome, with symptoms including fever, lymph node enlargement and muscle pain. The mortality rate of acute Chagas disease is high, mainly due to heart failure as a consequence of cardiac fiber lesions. There are few studies describing clinical outcomes and the disease progression of patients who receive therapeutic treatment, especially with regard to cardiac exam findings. In this report, the authors describe clinical findings from two micro-outbreaks occurring in impoverished towns in northeastern Brazil. Prior to receiving treatment, patient mortality rate was 28.6% in one of the outbreaks, and one pregnant woman experienced a spontaneous abortion due to the disease in the other outbreak. Most patients complained of fever, dyspnea, myalgia and periorbital edema. After receiving a two-month course of treatment, clinical symptoms improved and the number of abnormalities in cardiac exams decreased
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