ITERATED QUASI-REVERSIBILITY METHOD APPLIED TO ELLIPTIC AND PARABOLIC DATA COMPLETION PROBLEMS

International audienceWe study the iterated quasi-reversibility method to regularize ill-posed elliptic and parabolic problems: data completion problems for Poisson's and heat equations. We define an abstract setting to treat both equations at once. We demonstrate the convergence of the regularized solution to the exact one, and propose a strategy to deal with noise on the data. We present numerical experiments for both problems: a two-dimensional corrosion detection problem and the one-dimensional heat equation with lateral data. In both cases, the method prove to be efficient even with highly corrupted data

Application of mixed formulations of quasi-reversibility to solve ill-posed problems for heat and wave equations: the 1d case

International audienceIn this paper we address some ill-posed problems involving the heat or the wave equation in one dimension, in particular the backward heat equation and the heat/wave equation with lateral Cauchy data. The main objective is to introduce some variational mixed formulations of quasi-reversibility which enable us to solve these ill-posed problems by using some classical La-grange finite elements. The inverse obstacle problems with initial condition and lateral Cauchy data for heat/wave equation are also considered, by using an elementary level set method combined with the quasi-reversibility method. Some numerical experiments are presented to illustrate the feasibility for our strategy in all those situations. 1. Introduction. The method of quasi-reversibility has now a quite long history since the pioneering book of Latt es and Lions in 1967 [1]. The original idea of these authors was, starting from an ill-posed problem which satisfies the uniqueness property, to introduce a perturbation of such problem involving a small positive parameter ε. This perturbation has essentially two effects. Firstly the perturbation transforms the initial ill-posed problem into a well-posed one for any ε, secondly the solution to such problem converges to the solution (if it exists) to the initial ill-posed problem when ε tends to 0. Generally, the ill-posedness in the initial problem is due to unsuitable boundary conditions. As typical examples of linear ill-posed problems one may think of the backward heat equation, that is the initial condition is replaced by a final condition, or the heat or wave equations with lateral Cauchy data, that is the usual Dirichlet or Neumann boundary condition on the boundary of the domain is replaced by a pair of Dirichlet and Neumann boundary conditions on the same subpart of the boundary, no data being prescribed on the complementary part of the boundary

Transcriptional Analysis of Murine Macrophages Infected with Different Toxoplasma Strains Identifies Novel Regulation of Host Signaling Pathways

Most isolates of Toxoplasma from Europe and North America fall into one of three genetically distinct clonal lineages, the type I, II and III lineages. However, in South America these strains are rarely isolated and instead a great variety of other strains are found. T. gondii strains differ widely in a number of phenotypes in mice, such as virulence, persistence, oral infectivity, migratory capacity, induction of cytokine expression and modulation of host gene expression. The outcome of toxoplasmosis in patients is also variable and we hypothesize that, besides host and environmental factors, the genotype of the parasite strain plays a major role. The molecular basis for these differences in pathogenesis, especially in strains other than the clonal lineages, remains largely unexplored. Macrophages play an essential role in the early immune response against T. gondii and are also the cell type preferentially infected in vivo. To determine if non-canonical Toxoplasma strains have unique interactions with the host cell, we infected murine macrophages with 29 different Toxoplasma strains, representing global diversity, and used RNA-sequencing to determine host and parasite transcriptomes. We identified large differences between strains in the expression level of known parasite effectors and large chromosomal structural variation in some strains. We also identified novel strain-specifically regulated host pathways, including the regulation of the type I interferon response by some atypical strains. IFNβ production by infected cells was associated with parasite killing, independent of interferon gamma activation, and dependent on endosomal Toll-like receptors in macrophages and the cytoplasmic receptor retinoic acid-inducible gene 1 (RIG-I) in fibroblasts.National Institutes of Health (U.S.) (R01-AI080621)New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (Developmental Grant AIO57159)Pew Charitable Trusts (Biomedical Scholars Program)Robert A. Swanson Career Development awardThe Knights Templar Eye Foundation, Inc.Pre-Doctoral Grant in the Biological Sciences (5-T32-GM007287-33)Cleo and Paul Schimmel Foundatio

Why Don’t Philosophers Do Their Intuition Practice?

I bet you don’t practice your philosophical intuitions. What’s your excuse? If you think philosophical training improves the reliability of philosophical intuitions, then practicing intuitions should improve them even further. I argue that philosophers’ reluctance to practice their intuitions highlights a tension in the way that they think about the role of intuitions in philosophy

Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantion in a patient with an underlying immunological deficiency

International audienceIn immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient's HLA-identical brother. Prophylaxis with cotrimoxazole was discontinued a day before the HSCT procedure. Signs of lung infection appeared as early as day 14 post-HSCT. The presence of tachyzoite-like structures on Giemsa-stained bronchoalveolar lavage (BAL) fluid smears suggested toxoplasmosis. Real-time PCR targeted at the T. gondii AF146527 gene revealed extremely high parasite burdens in both blood and BAL fluid. Although immediate introduction of specific treatment resulted in a marked reduction of the parasite load and transient clinical improvement, the patient deteriorated and died of multiple organ failure on day 39 post-HSCT. Direct genotyping of T. gondii DNA from blood and BAL fluid with the PCR-restriction fragment length polymorphism method revealed type II alleles with SAG1, SAG2, and GRA6 markers but alleles of both type I and type II with GRA7. Additional analysis with 15 microsatellite markers showed that the T. gondii DNA was atypical and genetically divergent from that of the clonal type I, II, and III strains. This is the first report of increased clinical severity of toxoplasmosis associated with an atypical strain in the setting of immunosuppression, which emphasizes the need to diagnose and monitor toxoplasmosis by quantitative molecular methods in cases of reactivation risk

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall