Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance.

The identification of associations between interleukin-28B (IL-28B) variants and the spontaneous clearance of hepatitis C virus (HCV) raises the issues of causality and the net contribution of host genetics to the trait. To estimate more precisely the net effect of IL-28B genetic variation on HCV clearance, we optimized genotyping and compared the host contributions in multiple- and single-source cohorts to control for viral and demographic effects. The analysis included individuals with chronic or spontaneously cleared HCV infections from a multiple-source cohort (n = 389) and a single-source cohort (n = 71). We performed detailed genotyping in the coding region of IL-28B and searched for copy number variations to identify the genetic variant or haplotype carrying the strongest association with viral clearance. This analysis was used to compare the effects of IL-28B variation in the two cohorts. Haplotypes characterized by carriage of the major alleles at IL-28B single-nucleotide polymorphisms (SNPs) were highly overrepresented in individuals with spontaneous clearance versus those with chronic HCV infections (66.1% versus 38.6%, P = 6 × 10(-9) ). The odds ratios for clearance were 2.1 [95% confidence interval (CI) = 1.6-3.0] and 3.9 (95% CI = 1.5-10.2) in the multiple- and single-source cohorts, respectively. Protective haplotypes were in perfect linkage (r(2) = 1.0) with a nonsynonymous coding variant (rs8103142). Copy number variants were not detected. We identified IL-28B haplotypes highly predictive of spontaneous HCV clearance. The high linkage disequilibrium between IL-28B SNPs indicates that association studies need to be complemented by functional experiments to identify single causal variants. The point estimate for the genetic effect was higher in the single-source cohort, which was used to effectively control for viral diversity, sex, and coinfections and, therefore, offered a precise estimate of the net host genetic contribution.

Malt1 protease inactivation efficiently dampens immune responses but causes spontaneous autoimmunity.

The protease activity of the paracaspase Malt1 has recently gained interest as a drug target for immunomodulation and the treatment of diffuse large B-cell lymphomas. To address the consequences of Malt1 protease inactivation on the immune response in vivo, we generated knock-in mice expressing a catalytically inactive C472A mutant of Malt1 that conserves its scaffold function. Like Malt1-deficient mice, knock-in mice had strong defects in the activation of lymphocytes, NK and dendritic cells, and the development of B1 and marginal zone B cells and were completely protected against the induction of autoimmune encephalomyelitis. Malt1 inactivation also protected the mice from experimental induction of colitis. However, Malt1 knock-in mice but not Malt1-deficient mice spontaneously developed signs of autoimmune gastritis that correlated with an absence of Treg cells, an accumulation of T cells with an activated phenotype and high serum levels of IgE and IgG1. Thus, removal of the enzymatic activity of Malt1 efficiently dampens the immune response, but favors autoimmunity through impaired Treg development, which could be relevant for therapeutic Malt1-targeting strategies.

Signaling potential gender effect in a spontaneous reporting system : cardiac effects associated with the use of antibiotics

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Propagation characteristics and wavelength tuning of amplified spontaneous emission from dye-doped polymer.

The propagation characteristics of amplified spontaneous emission (ASE) through a rhodamine 6 G-doped polymethyl methacrylate freestanding film waveguide were studied. This was done by shifting the excitation stripe horizontally along a transversely pumped waveguide. By this method, we could tune the ASE wavelength. The maximum tunability thus obtained was ~18 nm with a pump stripe length of 6 mm.

Parity violation in Aharonov-Bohm systems: The spontaneous Hall effect

We show how macroscopic manifestations of P (and T) symmetry breaking can arise in a simple system subject to Aharonov-Bohm interactions. Specifically, we study the conductivity of a gas of charged particles moving through a dilute array of flux tubes. The interaction of the electrons with the flux tubes is taken to be of a purely Aharonov-Bohm type. We find that the system exhibits a nonzero transverse conductivity, i.e., a spontaneous Hall effect. This is in contrast to the fact that the cross sections for both scattering and bremsstrahlung (soft-photon emission) of a single electron from a flux tube are invariant under reflections. We argue that the asymmetry in the conductivity coefficients arises from many-body effects. On the other hand, the transverse conductivity has the same dependence on universal constants that appears in the quantum Hall effect, a result that we relate to the validity of the mean-field approximation.

The importance of causal connections in the comprehension of spontaneous spoken discourse. 'La importancia de las conexiones causales en la comprensi??n de discurso oral espont??neo'

Resumen tomado de la publicaci??n

Spontaneous language measures in monolingual preschool Spanish-speaking children. 'Medidas de evaluación del lenguaje espontáneo en niños hispanohablantes en edad preescolar'.

Resumen en español. Resumen basado en el de la publicación

Spontaneous Meta-Arithmetic as the First Step Toward School Algebra. 'La meta-aritmética espontánea como el primer paso hacia el álgebra escolar'.

Resumen basado en el de la publicación

Spontaneous otoacoustic emissions

This paper reviews spontaneous otoacoustic emissions.

Spontaneous otoacoustic emissions in a chinchilla: audiometric correlates as seen in audiogram microstructure

This paper reviews a study to evaluate the audiogram microstructure of a chinchilla with a documented spontaneous otoacoustic emission.

Application of the Lighthill-Ford theory of spontaneous imbalance to clear-air turbulence forecasting

A new method of clear-air turbulence (CAT) forecasting based on the Lighthill–Ford theory of spontaneous imbalance and emission of inertia–gravity waves has been derived and applied on episodic and seasonal time scales. A scale analysis of this shallow-water theory for midlatitude synoptic-scale flows identifies advection of relative vorticity as the leading-order source term. Examination of leading- and second-order terms elucidates previous, more empirically inspired CAT forecast diagnostics. Application of the Lighthill–Ford theory to the Upper Mississippi and Ohio Valleys CAT outbreak of 9 March 2006 results in good agreement with pilot reports of turbulence. Application of Lighthill–Ford theory to CAT forecasting for the 3 November 2005–26 March 2006 period using 1-h forecasts of the Rapid Update Cycle (RUC) 2 1500 UTC model run leads to superior forecasts compared to the current operational version of the Graphical Turbulence Guidance (GTG1) algorithm, the most skillful operational CAT forecasting method in existence. The results suggest that major improvements in CAT forecasting could result if the methods presented herein become operational.

Spontaneous generation and impact of inertia-gravity waves in a stratified, two-layer shear flow

Inertia-gravity waves exist ubiquitously throughout the stratified parts of the atmosphere and ocean. They are generated by local velocity shears, interactions with topography, and as geostrophic (or spontaneous) adjustment radiation. Relatively little is known about the details of their interaction with the large-scale flow, however. We report on a joint model/laboratory study of a flow in which inertia-gravity waves are generated as spontaneous adjustment radiation by an evolving large-scale mode. We show that their subsequent impact upon the large-scale dynamics is generally small. However, near a potential transition from one large-scale mode to another, in a flow which is simultaneously baroclinically-unstable to more than one mode, the inertia-gravity waves may strongly influence the selection of the mode which actually occurs.