Leading-edge receptivity for blunt-nose bodies

This research program investigates boundary-layer receptivity in the leading-edge region for bodies with blunt leading edges. Receptivity theory provides the link between the unsteady distrubance environment in the free stream and the initial amplitudes of the instability waves in the boundary layer. This is a critical problem which must be addressed in order to develop more accurate prediction methods for boundary-layer transition. The first phase of this project examines the effects of leading-edge bluntness and aerodynamic loading for low Mach number flows. In the second phase of the project, the investigation is extended to supersonic Mach numbers. Singular perturbation techniques are utilized to develop an asymptotic theory for high Reynolds numbers. In the first year, the asymptotic theory was developed for leading-edge receptivity in low Mach number flows. The case of a parabolic nose is considered. Substantial progress was made on the Navier-Sotkes computations. Analytical solutions for the steady and unsteady potential flow fields were incorporated into the code, greatly expanding the types of free-stream disturbances that can be considered while also significantly reducing the the computational requirements. The time-stepping algorithm was modified so that the potential flow perturbations induced by the unsteady pressure field are directly introduced throughout the computational domain, avoiding an artificial 'numerical diffusion' of these from the outer boundary. In addition, the start-up process was modified by introducing the transient Stokes wave solution into the downstream boundary conditions

Boundary-layer receptivity and laminar-flow airfoil design

Boundary-layer receptivity examines the way in which external disturbances generate instability waves in boundary layers. Receptivity theory is complementary to stability theory, which studies the evolution of disturbances that are already present in the boundary layer. A transition prediction method which combines receptivity with linear stability theory would directly account for the influence of free-stream disturbances and also consider the characteristics of the boundary layer upstream of the neutral stability point. The current e sup N transition prediction methods require empirical correlations for the influence of environmental disturbances, and totally ignore the boundary layer characteristics upstream of the neutral stability point. The regions where boundary-layer receptivity occurs can be separated into two classes, one near the leading edges and the other at the downstream points where the boundary layer undergoes rapid streamwise adjustments. Analyses were developed for both types of regions, and parametric studies which examine the relative importance of different mechanisms were carried out. The work presented here has focused on the low Mach number case. Extensions to high subsonic and supersonic conditions are presently underway

Influence of vane sweep on rotor-stator interaction noise

The influence of vane sweep in rotor-stator interaction noise is investigated. In an analytical approach, the interaction of a convected gust representing the rotor viscous wake, with a cascade of cascade of finite span swept airfoils, representing the stator, is analyzed. The analysis is based on the solution of the exact linearized equations of motion. High frequency convected gusts for which noise generation is concentrated near the leading edge of airfoils is considered. In a preliminary study, the problem of an isolated finite span swept airfoil interacting with a convected gust is analyzed. Results indicate that sweep can substantially reduce the farfield noise levels for a single airfoil. Using the single airfoil model, an approximate solution to the problem of noise radiation from a cascade of finite span swept airfoils interacting with a convected gust is derived. A parametric study of noise generated by gust cascade interaction is carried out to assess the effectiveness of vane sweep in reducing rotor-stator interaction noise. The results show that sweep is beneficial in reducing noise levels. Rotor wake twist or circumferential lean substantially influences the effectiveness of vane sweep. The orientation of vane sweep must be chosen to enhance the natural phase lag caused by wake lean, in which case rather small sweep angles substantially reduce the noise levels

The Plague Virulence Protein YopM Targets the Innate Immune Response by Causing a Global Depletion of NK Cells

Yersinia pestis, the etiologic agent of plague, delivers six Yersinia outer proteins (Yops) into host cells upon direct bacterial contact. One of these, YopM, is necessary for virulence in a mouse model of septicemic plague, but its pathogenic function is unknown. We report here the immune processes affected by YopM during infection. To test whether the innate or adaptive immune system is targeted by YopM, C57BL/6 (B6) and B6 SCID mice were infected with either the conditionally virulent Y. pestis KIM5 or a yopM deletion mutant and evaluated for bacterial growth in spleen and liver. Both B6 and SCID mice succumbed to infection with Y. pestis KIM5, whereas both mouse strains survived infection by the YopM(−) mutant. These data showed that YopM counteracts innate defenses present in SCID mice. The YopM(−) strain grew more slowly than the parent Y. pestis during the first 4 days of infection in both mouse strains, indicating an early pathogenic role for YopM. In B6 mice, populations of cells of the immune system were not differentially affected by the two Y. pestis strains, with one major exception: the parent Y. pestis KIM5 but not the YopM(−) mutant caused a significant global decrease in NK cell numbers (blood, spleen, and liver), beginning early in infection. NK cells and macrophages isolated early (day 2) from livers and spleens of mice infected with either Y. pestis strain contained comparable levels of cytokine mRNA: interleukin (IL)-1β, IL-12, IL-15, IL-18, and tumor necrosis factor alpha in macrophages and gamma interferon in NK cells. However, by day 4 postinfection, cells from mice infected with the parent Y. pestis expressed lower levels of these messages, while those from mice infected with the mutant retained strong expression. Significantly, mRNA for the IL-15 receptor α chain was not expressed in NK cells from Y. pestis KIM5-infected mice as early as day 2 postinfection. These findings suggest that YopM interferes with innate immunity by causing depletion of NK cells, possibly by affecting the expression of IL-15 receptor α and IL-15

Mice Naturally Resistant to Yersinia pestis Δpgm Strains Commonly Used in Pathogenicity Studies

We report that females of some substrains of inbred mouse strain 129 are resistant to systemic plague due to conditionally virulent Δpgm strains of Yersinia pestis; however, fully virulent Y. pestis is not attenuated in these mice. Therefore, these mice offer a powerful system in which to map in parallel host resistance traits and opposing bacterial virulence properties for plague

Gr1+ Cells Control Growth of YopM-Negative Yersinia pestis during Systemic Plague▿

YopM, a protein toxin of Yersinia pestis, is necessary for virulence in a mouse model of systemic plague. We previously reported YopM-dependent natural killer (NK) cell depletion from blood and spleen samples of infected mice. However, in this study we found that infection with Y. pestis KIM5 (YopM+) caused depletion of NK cells in the spleen, but not in the liver, and antibody-mediated ablation of NK cells had no effect on bacterial growth. There was no YopM-associated effect on the percentage of dendritic cells (DCs) or polymorphonuclear leukocytes (PMNs) in the early stage of infection; however, there was a YopM-associated effect on PMN integrity and on the influx of monocytes into the spleen. Ablation of Gr1+ cells caused loss of the growth defect of YopM− Y. pestis in both the liver and spleen. In contrast, ablation of macrophages/DCs inhibited growth of both parent and mutant bacteria, accompanied by significantly fewer lesion sites in the liver. These results point toward PMNs and inflammatory monocytes as major cell types that control growth of YopM− Y. pestis. Infection with fully virulent Y. pestis CO92 and a YopM− derivative by intradermal and intranasal routes showed that the absence of YopM significantly increased the 50% lethal dose only in the intradermal model, suggesting a role for YopM in bubonic plague, in which acute inflammation occurs soon after infection

Fetal gene defects precipitate platelet-mediated pregnancy failure in factor V Leiden mothers

We describe a mouse model of fetal loss in factor V Leiden (FvL) mothers in which fetal loss is triggered when the maternal prothrombotic state coincides with fetal gene defects that reduce activation of the protein C anticoagulant pathway within the placenta. Fetal loss is caused by disruption of placental morphogenesis at the stage of labyrinth layer formation and occurs in the absence of overt placental thrombosis, infarction, or perfusion defects. Platelet depletion or elimination of protease-activated receptor 4 (Par4) from the mother allows normal placentation and prevents fetal loss. These findings establish a cause-effect relationship for the observed epidemiologic association between maternal FvL status and fetal loss and identify fetal gene defects as risk modifiers of pregnancy failure in prothrombotic mothers. Pregnancy failure is mediated by Par4-dependent activation of maternal platelets at the fetomaternal interface and likely involves a pathogenic pathway independent of occlusive thrombosis. Our results further demonstrate that the interaction of two given thrombosis risk factors produces markedly disparate consequences on disease manifestation (i.e., thrombosis or pregnancy loss), depending on the vascular bed in which this interaction occurs