Alterations of the CARD15/NOD2 gene and the impact on management and treatment of Crohn's disease patients

The recent identification of the CARD15/NOD2 gene as a susceptibility locus for Crohn's disease represents an important step towards the delineation of the immuno-pathogenesis of inflammatory bowel disease. CARD15 functions as an intracellular receptor for bacterial components and thus represents an important link between inflammatory bowel disease and innate immunity. Three major CARD15/NOD2 gene mutations have been associated with Crohn's disease in Caucasians in several independent studies. Together, they explain about 20% of the genetic susceptibility for Crohn's disease. Genotype-phenotype analyses demonstrated an association of these mutations with ileum-specific disease, an increased incidence of the fibrostenotic phenotype and an earlier age of disease onset. Beside these associations, no other relationship between the CARD15/NOD2 genotype and disease behavior or response to treatment has been detailed so far. Thus, the clinical impact of knowing the patient's genotype is limited at this time. Screening for CARD15 mutations in order to identify high-risk individuals or to introduce an individualized disease management is therefore currently not recommended. Copyright (C) 2003 S. Karger AG, Basel

Analysis of Rayleigh-Plesset dynamics for sonoluminescing bubbles

Recent work on single bubble sonoluminescence (SBSL) has shown that many features of this phenomenon, especially the dependence of SBSL intensity and stability on experimental parameters, can be explained within a hydrodynamic approach. More specifically, many important properties can already be derived from an analysis of bubble wall dynamics. This dynamics is conveniently described by the Rayleigh-Plesset (RP) equation. In this work we derive analytical approximations for RP dynamics and subsequent analytical laws for parameter dependences. These results include (i) an expression for the onset threshold of SL, (ii) an analytical explanation of the transition from diffusively unstable to stable equilibria for the bubble ambient radius (unstable and stable sonoluminescence), and (iii) a detailed understanding of the resonance structure of the RP equation. It is found that the threshold for SL emission is shifted to larger bubble radii and larger driving pressures if surface tension is enlarged, whereas even a considerable change in liquid viscosity leaves this threshold virtually unaltered. As an enhanced viscosity stabilizes the bubbles against surface oscillations, we conclude that the ideal liquid for violently collapsing, surface stable SL bubbles should have small surface tension and large viscosity, although too large viscosity (>40 times the viscosity of water) will again preclude collapses.Comment: 41 pages, 21 eps and ps figures; LaTeX stylefiles replaced because the PostScript file produced at the archive had misplaced and misscaled figure

The Twente turbulent Taylor-Couette (T3C) facility: Strongly turbulent (multiphase) flow between two independently rotating cylinders

A new turbulent Taylor-Couette system consisting of two independently rotating cylinders has been constructed. The gap between the cylinders has a height of 0.927 m, an inner radius of 0.200 m, and a variable outer radius (from 0.279 to 0.220 m). The maximum angular rotation rates of the inner and outer cylinder are 20 and 10 Hz, respectively, resulting in Reynolds numbers up to 3.4 x 10^6 with water as working fluid. With this Taylor-Couette system, the parameter space (Re_i, Re_o, {\eta}) extends to (2.0 x 10^6, {\pm}1.4 x 10^6, 0.716-0.909). The system is equipped with bubble injectors, temperature control, skin-friction drag sensors, and several local sensors for studying turbulent single-phase and two-phase flows. Inner cylinder load cells detect skin-friction drag via torque measurements. The clear acrylic outer cylinder allows the dynamics of the liquid flow and the dispersed phase (bubbles, particles, fibers, etc.) inside the gap to be investigated with specialized local sensors and nonintrusive optical imaging techniques. The system allows study of both Taylor-Couette flow in a high-Reynolds-number regime, and the mechanisms behind skin-friction drag alterations due to bubble injection, polymer injection, and surface hydrophobicity and roughness.Comment: 13 pages, 14 figure

R116C mutation of cationic trypsinogen in a Turkish family with recurrent pancreatitis illustrates genetic microheterogeneity of hereditary pancreatitis

Hereditary pancreatitis is due to heterozygosity for gain-of-function mutations in the cationic trypsinogen gene which result in increased levels of active trypsin within pancreatic acinar cells and autodigestion of the pancreas. The number of disease-causing defects is generally considered to be low. To gain further insight into the molecular basis of this disorder, DNA sequence analysis of all five exons was performed in 109 unrelated patients with idiopathic chronic pancreatitis in order to determine the variability of the underlying mutations. Two German females and one German male were carriers of the most common N291 and R122H mutations (trypsinogen numbering system). In a Turkish proband, an arginine (CGT) to cysteine (TGT) substitution at amino acid position 116 was identified. Family screening demonstrated that the patient had inherited the mutation from his asymptomatic father and that he had transmitted it to both of his children, his daughter being symptomatic since the age of 3 years. In addition, a German male was found to be a heterozygote for a D100H (GAC-->CAC) amino acid replacement. Our data provide evidence for genetic heterogeneity of hereditary pancreatitis. The growing number of cationic trypsinogen mutations is expected to change current mutation screening practices for this disease

Geostrophic convective turbulence: The effect of boundary layers

Rayleigh--B\'enard (RB) convection, the flow in a fluid layer heated from below and cooled from above, is used to analyze the transition to the geostrophic regime of thermal convection. In the geostrophic regime, which is of direct relevance to most geo- and astrophysical flows, the system is strongly rotated while maintaining a sufficiently large thermal driving to generate turbulence. We directly simulate the Navier--Stokes equations for two values of the thermal forcing, i.e. $Ra=10^{10}$ and $Ra=5\cdot10^{10}$, a constant Prandtl number~$Pr=1$, and vary the Ekman number in the range $Ek=1.3\cdot10^{-7}$ to $Ek=2\cdot10^{-6}$ which satisfies both requirements of super-criticality and strong rotation. We focus on the differences between the application of no-slip vs. stress-free boundary conditions on the horizontal plates. The transition is found at roughly the same parameter values for both boundary conditions, i.e. at~$Ek\approx 9\times 10^{-7}$ for~$Ra=1\times 10^{10}$ and at~$Ek\approx 3\times 10^{-7}$ for~$Ra=5\times 10^{10}$. However, the transition is gradual and it does not exactly coincide in~$Ek$ for different flow indicators. In particular, we report the characteristics of the transitions in the heat transfer scaling laws, the boundary-layer thicknesses, the bulk/boundary-layer distribution of dissipations and the mean temperature gradient in the bulk. The flow phenomenology in the geostrophic regime evolves differently for no-slip and stress-free plates. For stress-free conditions the formation of a large-scale barotropic vortex with associated inverse energy cascade is apparent. For no-slip plates, a turbulent state without large-scale coherent structures is found; the absence of large-scale structure formation is reflected in the energy transfer in the sense that the inverse cascade, present for stress-free boundary conditions, vanishes.Comment: Submitted to JF

Bubbly Turbulent Drag Reduction Is a Boundary Layer Effect

In turbulent Taylor-Couette flow, the injection of bubbles reduces the overall drag. On the other hand, rough walls enhance the overall drag. In this work, we inject bubbles into turbulent Taylor-Couette flow with rough walls (with a Reynolds number up to 4×105), finding an enhancement of the dimensionless drag as compared to the case without bubbles. The dimensional drag is unchanged. As in the rough-wall case no smooth boundary layers can develop, the results demonstrate that bubbly drag reduction is a pure boundary layer effec

Boundary layer dynamics at the transition between the classical and the ultimate regime of Taylor-Couette flow

Direct numerical simulations of turbulent Taylor-Couette flow are performed up to inner cylinder Reynolds numbers of {Re_i=10^5} for a radius ratio of {\eta=r_i/r_o=0.714} between the inner and outer cylinder. With increasing {Re_i}, the flow undergoes transitions between three different regimes: (i) a flow dominated by large coherent structures, (ii) an intermediate transitional regime, and (iii) a flow with developed turbulence. In the first regime the large--scale rolls completely drive the meridional flow while in the second one the coherent structures recover only on average. The presence of a mean flow allows for the coexistence of laminar and turbulent boundary layer dynamics. In the third regime the mean flow effects fade away and the flow becomes dominated by plumes. The effect of the local driving on the azimuthal and angular velocity profiles is quantified, in particular we show when and where those profiles develop.Comment: 22 pages, submitted to Po