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.

Province of Ontario Patent issued to Cyrus Dean of St. Catharines for a machine for effecting more perfect combustion of fuel in the furnaces of locomotives

Province of Ontario Patent issued to Cyrus Dean of St. Catharines for a machine for effecting more perfect combustion of fuel in the furnaces of locomotives. This patent was listed in the Records Office of the Registrar General of Canada in Lib. JE, folio 361. This patent is accompanied by a 36 cm. x 57 cm. detailed sketch and explanation of the machine. [Samuel D. Woodruff was the assignee of Cyrus Dean in a in a patent for a rotary washing machine in November of 1869 according to The Commissioners of Patents' Journal by the Great Britain Patent Office], March 23, 1870.

Modèles de flammelette en combustion turbulente avec extinction et réallumage : étude asymptotique et numérique, estimation d’erreur a posteriori et modélisation adaptative

On s’intéresse ici aux erreurs de modélisation liées à l’usage de modèles de flammelette sous-maille en combustion turbulente non prémélangée. Le but de cette thèse est de développer une stratégie d’estimation d’erreur a posteriori pour déterminer le meilleur modèle parmi une hiérarchie, à un coût numérique similaire à l’utilisation de ces mêmes modèles. Dans un premier temps, une stratégie faisant appel à un estimateur basé sur les résidus pondérés est développée et testée sur un système d’équations d’advection-diffusion-réaction. Dans un deuxième temps, on teste la méthodologie d’estimation d’erreur sur un autre système d’équations, où des effets d’extinction et de réallumage sont ajoutés. Lorsqu’il n’y a pas d’advection, une analyse asymptotique rigoureuse montre l’existence de plusieurs régimes de combustion déjà observés dans les simulations numériques. Nous obtenons une approximation des paramètres de réallumage et d’extinction avec la courbe en «S», un graphe de la température maximale de la flamme en fonction du nombre de Damköhler, composée de trois branches et d’une double courbure. En ajoutant des effets advectifs, on obtient également une courbe en «S» correspondant aux régimes de combustion déjà identifiés. Nous comparons les erreurs de modélisation liées aux approximations asymptotiques dans les deux régimes stables et établissons une nouvelle hiérarchie des modèles en fonction du régime de combustion. Ces erreurs sont comparées aux estimations données par la stratégie d’estimation d’erreur. Si un seul régime stable de combustion existe, l’estimateur d’erreur l’identifie correctement ; si plus d’un régime est possible, on obtient une fac˛on systématique de choisir un régime. Pour les régimes où plus d’un modèle est approprié, la hiérarchie prédite par l’estimateur est correcte.

Modélisation asymptotique pour la simulation aux grandes échelles de la combustion turbulente prémélangée

Thèse diffusée initialement dans le cadre d'un projet pilote des Presses de l'Université de Montréal/Centre d'édition numérique UdeM (1997-2008) avec l'autorisation de l'auteur.

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