Immunomodulatory properties of meningococcal outer membrane vesicles.

Neisseria meningitidis (Nm) causes potentially fatal bacterial sepsis and meningitis in susceptible individuals, but induces protective immunity in asymptomatic carriers. Nm naturally sheds outer membrane vesicles (NOMVs) that contain a high proportion of lipopolysaccharide (LPS) and outer membrane proteins. NOMVs are known to induce serum bactericidal antibodies in mice and humans, but their inherent adjuvanticity of humoral responses toward protein and carbohydrate antigens has not been studied in detail. This thesis investigation has determined that NOMVs are potent intraperitoneal and intranasal adjuvants for model T-dependent antigens such as Ovalbumin and T-independent antigens such as dinitrophenol-ficoll. Surprisingly NOMVs had little or no effect on the primary antibody responses towards several clinically relevant capsular polysaccharides from Streptococcus pneumoniae regardless of the route of immunisation. NOMVs induced the proliferation of splenic B cells, and the production of cytokines from splenocytes and bone marrow-derived dendritic cells from not only wild-type but also LPS-hyporesponsive mice which indicates that both LPS and non-LPS components have immunomodulatory properties. Despite the potential of NOMVs inducing proinflammatory responses, preliminary results showed that intranasally applied NOMVs suppressed allergen induced or respiratory syncytial virus-induced airway eosinophilia in mouse models. Together our results provide important insights into the role of NOMVs in inducing protective immunity against meningococcal diseases, and their immunomodulatory properties that could be useful separately or synergistically in adjuvant development or immunotherapy

Vortex lattice stability in the SO(5) model

We study the energetics of superconducting vortices in the SO(5) model for high-$T_c$ materials proposed by Zhang. We show that for a wide range of parameters normally corresponding to type II superconductivity, the free energy per unit flux \FF(m) of a vortex with $m$ flux quanta is a decreasing function of $m$, provided the doping is close to its critical value. This implies that the Abrikosov lattice is unstable, a behaviour typical of type I superconductors. For dopings far from the critical value, \FF(m) can become very flat, indicating a less rigid vortex lattice, which would melt at a lower temperature than expected for a BCS superconductor.Comment: 4 pp, revtex, 5 figure

Discrete Nonholonomic Lagrangian Systems on Lie Groupoids

This paper studies the construction of geometric integrators for nonholonomic systems. We derive the nonholonomic discrete Euler-Lagrange equations in a setting which permits to deduce geometric integrators for continuous nonholonomic systems (reduced or not). The formalism is given in terms of Lie groupoids, specifying a discrete Lagrangian and a constraint submanifold on it. Additionally, it is necessary to fix a vector subbundle of the Lie algebroid associated to the Lie groupoid. We also discuss the existence of nonholonomic evolution operators in terms of the discrete nonholonomic Legendre transformations and in terms of adequate decompositions of the prolongation of the Lie groupoid. The characterization of the reversibility of the evolution operator and the discrete nonholonomic momentum equation are also considered. Finally, we illustrate with several classical examples the wide range of application of the theory (the discrete nonholonomic constrained particle, the Suslov system, the Chaplygin sleigh, the Veselova system, the rolling ball on a rotating table and the two wheeled planar mobile robot).Comment: 45 page

A supergeometric approach to Poisson reduction

This work introduces a unified approach to the reduction of Poisson manifolds using their description by graded symplectic manifolds. This yields a generalization of the classical Poisson reduction by distributions (Marsden-Ratiu reduction). Further it allows one to construct actions of strict Lie 2-groups and to describe the corresponding reductions.Comment: 40 pages. Final version accepted for publicatio

The symmetry of the superconducting order parameter in PuCoGa5_5

The symmetry of the superconducting order parameter in single-crystalline PuCoGa$_5$ ($T_{\rm c} = 18.5$ K) is investigated via zero- and transverse- field muon spin relaxation ($\mu$SR) measurements, probing the possible existence of orbital and/or spin moments (time reversal-symmetry violation TRV) associated with the superconducting phase and the in-plane magnetic-field penetration depth $\lambda(T)$ in the mixed state, respectively. We find no evidence for TRV, and show that the superfluid density, or alternatively, $\Delta\lambda(T) = \lambda(T) - \lambda(0)$, are $\propto T$ for $T/T_{\rm c} \leq 0.5$. Taken together these measurements are consistent with an even-parity (pseudo-spin singlet), d-wave pairing state.Comment: 4 pages, 5 figure

Leptonic decay constants f_Ds and f_D in three flavor lattice QCD

We determine the leptonic decay constants in three flavor unquenched lattice QCD. We use O(a^2)-improved staggered light quarks and O(a)-improved charm quarks in the Fermilab heavy quark formalism. Our preliminary results, based upon an analysis at a single lattice spacing, are f_Ds = 263(+5-9)(+/-24) MeV and f_D = 225(+11-13)(+/-21) MeV. In each case, the first reported error is statistical while the is the combined systematic uncertainty.Comment: Talk presented at Lattice2004(heavy), Fermilab, June 21-26, 2004. 3 pages, 2 figure

Comprehensive analysis of blood group antigen binding to classical and El Tor cholera toxin B-pentamers by NMR

Cholera is a diarrheal disease responsible for the deaths of thousands, possibly even hundreds of thousands of people every year, and its impact is predicted to further increase with climate change. It has been known for decades that blood group O individuals suffer more severe symptoms of cholera compared with individuals with other blood groups (A, B and AB). The observed blood group dependence is likely to be caused by the major virulence factor of Vibrio cholerae, the cholera toxin (CT). Here, we investigate the binding of ABH blood group determinants to both classical and El Tor CTB-pentamers using saturation transfer difference NMR and show that all three blood group determinants bind to both toxin variants. Although the details of the interactions differ, we see no large differences between the two toxin genotypes and observe very similar binding constants. We also show that the blood group determinants bind to a site distinct from that of the primary receptor, GM1. Transferred NOESY data confirm that the conformations of the blood group determinants in complex with both toxin variants are similar to those of reported X-ray and solution structures. Taken together, this detailed analysis provides a framework for the interpretation of the epidemiological data linking the severity of cholera infection and an individual's blood group, and brings us one step closer to understanding the molecular basis of cholera blood group dependence

Impurity and interface bound states in dx2−y2+idxyd_{x^2-y^2}+id_{xy} and px+ipyp_x+ip_y superconductors

Motivated by recent discoveries of novel superconductors such as Na$_x$CoO$_2\cdot y$H$_2$O and Sr$_2$RuO$_4$, we analysize features of quasi-particle scattering due to impurities and interfaces for possible gapful $d_{x^2-y^2}+id_{xy}$ and $p_x+ip_y$ Cooper pairing. A bound state appears near a local impurity, and a band of bound states form near an interface. We obtained analytically the bound state energy, and calculated the space and energy dependent local density of states resolvable by high-resolution scanning tunnelling microscopy. For comparison we also sketch results of impurity and surface states if the pairing is nodal p- or d-wave.Comment: 4 pages, 4 figure

Low temperature electronic properties of Sr_2RuO_4 II: Superconductivity

The body centered tetragonal structure of Sr_2RuO_4 gives rise to umklapp scattering enhanced inter-plane pair correlations in the d_{yz} and d_{zx} orbitals. Based on symmetry arguments, Hund's rule coupling, and a bosonized description of the in-plane electron correlations the superconducting order parameter is found to be a orbital-singlet spin-triplet with two spatial components. The spatial anisotropy is 7%. The different components of the order parameter give rise to two-dimensional gapless fluctuations. The phase transition is of third order. The temperature dependence of the pair density, specific heat, NQR, Knight shift, and susceptibility are in agreement with experimental results.Comment: 20 pages REVTEX, 3 figure

Geometric effects on T-breaking in p+ip and d+id superconductors

Superconducting order parameters that change phase around the Fermi surface modify Josephson tunneling behavior, as in the phase-sensitive measurements that confirmed $d$ order in the cuprates. This paper studies Josephson coupling when the individual grains break time-reversal symmetry; the specific cases considered are $p \pm ip$ and $d \pm id$, which may appear in Sr$_2$RuO$_4$ and Na$_x$CoO$_2 \cdot$(H$_2$O)$_y$ respectively. $T$-breaking order parameters lead to frustrating phases when not all grains have the same sign of time-reversal symmetry breaking, and the effects of these frustrating phases depend sensitively on geometry for 2D arrays of coupled grains. These systems can show perfect superconducting order with or without macroscopic $T$-breaking. The honeycomb lattice of superconducting grains has a superconducting phase with no spontaneous breaking of $T$ but instead power-law correlations. The superconducting transition in this case is driven by binding of fractional vortices, and the zero-temperature criticality realizes a generalization of Baxter's three-color model.Comment: 8 page