Clinical and functional characterisation of a novel TNFRSF1A c.605T > A/V173D cleavage site mutation associated with tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), cardiovascular complications and excellent response to etanercept treatment.

Objectives: To study the clinical outcome, treatment response, T-cell subsets and functional consequences of a novel tumour necrosis factor (TNF) receptor type 1 (TNFRSF1A) mutation affecting the receptor cleavage site. Methods: Patients with symptoms suggestive of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and 22 healthy controls (HC) were screened for mutations in the TNFRSF1A gene. Soluble TNFRSF1A and inflammatory cytokines were measured by ELISAs. TNFRSF1A shedding was examined by stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol 12-myristate 13-acetate followed by flow cytometric analysis (FACS). Apoptosis of PBMCs was studied by stimulation with TNFa in the presence of cycloheximide and annexin V staining. T cell phenotypes were monitored by FACS. Results: TNFRSF1A sequencing disclosed a novel V173D/ p.Val202Asp substitution encoded by exon 6 in one family, the c.194–14G.A splice variant in another and the R92Q/p.Arg121Gln substitution in two families. Cardiovascular complications (lethal heart attack and peripheral arterial thrombosis) developed in two V173D patients. Subsequent etanercept treatment of the V173D carriers was highly effective over an 18-month follow-up period. Serum TNFRSF1A levels did not differ between TRAPS patients and HC, while TNFRSF1A cleavage from monocytes was significantly reduced in V173D and R92Q patients. TNFa-induced apoptosis of PBMCs and T-cell senescence were comparable between V173D patients and HC. Conclusions: The TNFRSF1A V173D cleavage site mutation may be associated with an increased risk for cardiovascular complications and shows a strong response to etanercept. T-cell senescence does not seem to have a pathogenetic role in affected patients

Solidification of liquid metal drops during impact

Hot liquid metal drops impacting onto a cold substrate solidify during their subsequent spreading. Here we experimentally study the influence of solidification on the outcome of an impact event. Liquid tin drops are impacted onto sapphire substrates of varying temperature. The impact is visualised both from the side and from below, which provides a unique view on the solidification process. During spreading an intriguing pattern of radial ligaments rapidly solidifies from the centre of the drop. This pattern determines the late-time morphology of the splat. A quantitative analysis of the drop spreading and ligament formation is supported by scaling arguments. Finally, a phase diagram for drop bouncing, deposition and splashing as a function of substrate temperature and impact velocity is provided

The evolution of energy in flow driven by rising bubbles

We investigate by direct numerical simulations the flow that rising bubbles cause in an originally quiescent fluid. We employ the Eulerian-Lagrangian method with two-way coupling and periodic boundary conditions. In order to be able to treat up to 288000 bubbles, the following approximations and simplifications had to be introduced: (i) The bubbles were treated as point-particles, thus (ii) disregarding the near-field interactions among them, and (iii) effective force models for the lift and the drag forces were used. In particular, the lift coefficient was assumed to be 1/2, independent of the bubble Reynolds number and the local flow field. The results suggest that large scale motions are generated, owing to an inverse energy cascade from the small to the large scales. However, as the Taylor-Reynolds number is only in the range of 1, the corresponding scaling of the energy spectrum with an exponent of -5/3 cannot develop over a pronounced range. In the long term, the property of local energy transfer, characteristic of real turbulence, is lost and the input of energy equals the viscous dissipation at all scales. Due to the lack of strong vortices the bubbles spread rather uniformly in the flow. The mechanism for uniform spreading is as follows: Rising bubbles induce a velocity field behind them that acts on the following bubbles. Owing to the shear, those bubbles experience a lift force which make them spread to the left or right, thus preventing the formation of vertical bubble clusters and therefore of efficient forcing. Indeed, when the lift is artifically put to zero in the simulations, the flow is forced much more efficiently and a more pronounced energy accumulates at large scales is achieved.Comment: 9 pages, 7 figure

Periodically kicked turbulence

Periodically kicked turbulence is theoretically analyzed within a mean field theory. For large enough kicking strength A and kicking frequency f the Reynolds number grows exponentially and then runs into some saturation. The saturation level can be calculated analytically; different regimes can be observed. For large enough Re we find the saturation level to be proportional to A*f, but intermittency can modify this scaling law. We suggest an experimental realization of periodically kicked turbulence to study the different regimes we theoretically predict and thus to better understand the effect of forcing on fully developed turbulence.Comment: 4 pages, 3 figures. Phys. Rev. E., in pres

Effect of Impurities in Description of Surface Nanobubbles

Surface nanobubbles emerging at solid-liquid interfaces of submerged hydrophobic surfaces show extreme stability and very small (gas-side) contact angles. In a recent study Ducker (W. A. Ducker, Langmuir 25, 8907 (2009).) conjectured that these effects may arise from the presence of impurities at the air-water interface of the nanobubbles. In this paper we present a quantitative analysis of this hypothesis by estimating the dependence of the contact angle and the Laplace pressure on the fraction of impurity coverage at the liquid-gas interface. We first develop a general analytical framework to estimate the effect of impurities (ionic or non-ionic) in lowering the surface tension of a given air-water interface. We then employ this model to show that the (gas-side) contact angle and the Laplace pressure across the nanobubbles indeed decrease considerably with an increase in the fractional coverage of the impurities, though still not sufficiently small to account for the observed surface nanobubble stability. The proposed model also suggests the dependencies of the Laplace pressure and the contact angle on the type of impurity

Mechanisms for Stable Sonoluminescence

A gas bubble trapped in water by an oscillating acoustic field is expected to either shrink or grow on a diffusive timescale, depending on the forcing strength and the bubble size. At high ambient gas concentration this has long been observed in experiments. However, recent sonoluminescence experiments show that in certain circumstances when the ambient gas concentration is low the bubble can be stable for days. This paper presents mechanisms leading to stability which predict parameter dependences in agreement with the sonoluminescence experiments.Comment: 4 pages, 3 figures on request (2 as .ps files

Dynamics of the spontaneous breakdown of superhydrophobicity

Drops deposited on rough and hydrophobic surfaces can stay suspended with gas pockets underneath the liquid, then showing very low hydrodynamic resistance. When this superhydrophobic state breaks down, the subsequent wetting process can show different dynamical properties. A suitable choice of the geometry can make the wetting front propagate in a stepwise manner leading to {\it square-shaped} wetted area: the front propagation is slow and the patterned surface fills by rows through a {\it zipping} mechanism. The multiple time scale scenario of this wetting process is experimentally characterized and compared to numerical simulations.Comment: 7 pages, 5 figure

Spontaneous Breakdown of Superhydrophobicity

In some cases water droplets can completely wet micro-structured superhydrophobic surfaces. The {\it dynamics} of this rapid process is analyzed by ultra-high-speed imaging. Depending on the scales of the micro-structure, the wetting fronts propagate smoothly and circularly or -- more interestingly -- in a {\it stepwise} manner, leading to a growing {\it square-shaped} wetted area: entering a new row perpendicular to the direction of front propagation takes milliseconds, whereas once this has happened, the row itself fills in microseconds ({\it ``zipping''})Comment: Accepted for publication in Physical Review Letter