3,768 research outputs found

    On finite-difference approximations for normalized Bellman equations

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    A class of stochastic optimal control problems involving optimal stopping is considered. Methods of Krylov are adapted to investigate the numerical solutions of the corresponding normalized Bellman equations and to estimate the rate of convergence of finite difference approximations for the optimal reward functions.Comment: 36 pages, ArXiv version updated to the version accepted in Appl. Math. Opti

    Intranasal immunization with pneumococcal polysaccharide conjugate vaccines protects mice against invasive pneumococcal infections.

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    To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldHost defenses against Streptococcus pneumoniae depend largely on opsonophagocytosis mediated by antibodies and complement. Since pneumococcus is a respiratory pathogen, mucosal immune responses may play a significant role in the defense against pneumococcal infections. Thus, mucosal vaccination may be an alternative approach to current immunization strategies, but effective adjuvants are required. Protein antigens induce significant mucosal immunoglobulin A (IgA) and systemic IgG responses when administered intranasally (i. n.) with the glyceride-polysorbate based adjuvant RhinoVax (RV) both in experimental animals and humans. The immunogenicity and efficacy of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 was studied in mice after i.n. immunization with RV. Antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA) and compared to antibody titers induced by parenteral immunization. The PNCs induced significant systemic IgG and IgA antibodies after i.n. immunization only when given with RV and, for serotype 1, serum IgG titers were comparable to titers induced by subcutaneous immunization. In addition, i.n. immunization with PNC-1 in RV elicited detectable mucosal IgA. These results demonstrate that RV is a potent mucosal adjuvant for polysaccharides conjugated to proteins. A majority of the PNC-1-immunized mice were protected against both bacteremia and pneumonia after i.n. challenge with a lethal dose of serotype 1 pneumococci, and protection correlated significantly with the serum IgG titers. Similarly, the survival of mice immunized i.n. with PNC-3 in RV was significantly prolonged. These results indicate that mucosal vaccination with PNC and adjuvants may be an alternative strategy for prevention against pneumococcal infections

    Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections

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    To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldHost defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans

    Plant growth responses to elevated atmospheric CO2 are increased by phosphorus sufficiency but not by arbuscular mycorrhizas

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    Capturing the full growth potential in crops under future elevated CO₂ (eCO₂) concentrations would be facilitated by improved understanding of eCO₂ effects on uptake and use of mineral nutrients. This study investigates interactions of eCO₂, soil phosphorus (P), and arbuscular mycorrhizal (AM) symbiosis in Medicago truncatula and Brachypodium distachyon grown under the same conditions. The focus was on eCO₂ effects on vegetative growth, efficiency in acquisition and use of P, and expression of phosphate transporter (PT) genes. Growth responses to eCO₂ were positive at P sufficiency, but under low-P conditions they ranged from non-significant in M. truncatula to highly significant in B. distachyon Growth of M. truncatula was increased by AM at low P conditions at both CO₂ levels and eCO₂×AM interactions were sparse. Elevated CO₂ had small effects on P acquisition, but enhanced conversion of tissue P into biomass. Expression of PT genes was influenced by eCO₂, but effects were inconsistent across genes and species. The ability of eCO₂ to partly mitigate P limitation-induced growth reductions in B. distachyon was associated with enhanced P use efficiency, and requirements for P fertilizers may not increase in such species in future CO₂-rich climates.Iver Jakobsen, Sally E. Smith, F. Andrew Smith, Stephanie J. Watts-Williams, Signe S. Clausen and Mette Grønlun

    Approximate square-root-time relaxation in glass-forming liquids

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    We present data for the dielectric relaxation of 43 glass-forming organic liquids, showing that the primary (alpha) relaxation is often close to square-root-time relaxation. The better an inverse power-law description of the high-frequency loss applies, the more accurately is square-root-time relaxation obeyed. These findings suggest that square-root-time relaxation is generic to the alpha process, once a common view, but since long believed to be incorrect. Only liquids with very large dielectric losses deviate from this picture by having consistently narrower loss peaks. As a further challenge to the prevailing opinion, we find that liquids with accurate square-root-time relaxation cover a wide range of fragilities
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