Asymptotic models for the generation of internal waves by a moving ship, and the dead-water phenomenon

This paper deals with the dead-water phenomenon, which occurs when a ship sails in a stratified fluid, and experiences an important drag due to waves below the surface. More generally, we study the generation of internal waves by a disturbance moving at constant speed on top of two layers of fluids of different densities. Starting from the full Euler equations, we present several nonlinear asymptotic models, in the long wave regime. These models are rigorously justified by consistency or convergence results. A careful theoretical and numerical analysis is then provided, in order to predict the behavior of the flow and in which situations the dead-water effect appears.Comment: To appear in Nonlinearit

Pathogen-Induced Proapoptotic Phenotype and High CD95 (Fas) Expression Accompany a Suboptimal CD8+ T-Cell Response: Reversal by Adenoviral Vaccine

MHC class Ia-restricted CD8+ T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8+ T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8+ T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8+ T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8+ T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8+ cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8+ T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination

Antihypertensive efficacy and tolerability of candesartan-hydrochlorothiazide 32/12.5 mg and 32/25 mg in patients not optimally controlled with candesartan monotherapy

Aim. To evaluate the efficacy and tolerability of candesartan cilexetil 32 mg in combination with hydrochlorothiazide (HCT) 12.5 mg or 25 mg in hypertensive patients not optimally controlled with candesartan monotherapy. Patients and methods. A total of 3521 patients with treated or untreated hypertension and sitting diastolic blood pressure (DBP) 90-114 mmHg, entered a single-blind run-in phase with candesartan (16 mg for 2 weeks, followed by 32 mg for 6 weeks). At the end of the run-in phase, 1975 patients who still had DBP 90-114 mmHg were randomized to 8 weeks' double-blind treatment with either candesartan 32 mg (n=654), or candesartan-HCT 32/12.5 mg (n=656), or candesartan-HCT 32/25 mg (n=665). Principal results. At randomization, the mean blood pressure was similar in the three treatment groups (approximately 153/97 mmHg). It was reduced during the double-blind treatment phase by 6.1/5.6 mmHg in the candesartan 32 mg group, by 13.0/8.8 mmHg in the candesartan-HCT 32/12.5 mg group, and by 15.5/10.0 mmHg in the candesartan-HCT 32/25 mg group (p < 0.01 for all between treatment comparisons). All study treatments were generally well tolerated. Conclusion. Candesartan-HCT 32/12.5 mg and candesartan-HCT 32/25 mg are highly effective and provide improved blood pressure reduction and blood pressure control relative to candesartan 32 mg monotherapy, with maintained tolerability, in hypertensive patients whose blood pressure is not optimally controlled with candesartan monotherapy. Furthermore, candesartan-HCT 32/25 mg is more effective than candesartan-HCT 32/12.5 mg in this population