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

Fractal dimension crossovers in turbulent passive scalar signals

The fractal dimension $\delta_g^{(1)}$ of turbulent passive scalar signals is calculated from the fluid dynamical equation. $\delta_g^{(1)}$ depends on the scale. For small Prandtl (or Schmidt) number $Pr<10^{-2}$ one gets two ranges, $\delta_g^{(1)}=1$ for small scale r and $\delta_g^{(1)}$=5/3 for large r, both as expected. But for large $Pr> 1$ one gets a third, intermediate range in which the signal is extremely wrinkled and has $\delta_g^{(1)}=2$. In that range the passive scalar structure function $D_\theta(r)$ has a plateau. We calculate the $Pr$-dependence of the crossovers. Comparison with a numerical reduced wave vector set calculation gives good agreement with our predictions.Comment: 7 pages, Revtex, 3 figures (postscript file on request

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

Wind reversals in turbulent Rayleigh-Benard convection

The phenomenon of irregular cessation and subsequent reversal of the large-scale circulation in turbulent Rayleigh-B\'enard convection is theoretically analysed. The force and thermal balance on a single plume detached from the thermal boundary layer yields a set of coupled nonlinear equations, whose dynamics is related to the Lorenz equations. For Prandtl and Rayleigh numbers in the range $10^{-2} \leq \Pr \leq 10^{3}$ and 10^{7} \leq \Ra \leq 10^{12}, the model has the following features: (i) chaotic reversals may be exhibited at Ra $\geq 10^{7}$; (ii) the Reynolds number based on the root mean square velocity scales as \Re_{rms} \sim \Ra^{[0.41 ... 0.47]} (depending on Pr), and as $\Re_{rms} \sim \Pr^{-[0.66 ... 0.76]}$ (depending on Ra); and (iii) the mean reversal frequency follows an effective scaling law \omega / (\nu L^{-2}) \sim \Pr^{-(0.64 \pm 0.01)} \Ra^{0.44 \pm 0.01}. The phase diagram of the model is sketched, and the observed transitions are discussed.Comment: 4 pages, 5 figure

Origin of line tension for a Lennard-Jones nanodroplet

The existence and origin of line tension has remained controversial in literature. To address this issue we compute the shape of Lennard-Jones nanodrops using molecular dynamics and compare them to density functional theory in the approximation of the sharp kink interface. We show that the deviation from Young's law is very small and would correspond to a typical line tension length scale (defined as line tension divided by surface tension) similar to the molecular size and decreasing with Young's angle. We propose an alternative interpretation based on the geometry of the interface at the molecular scale

Formation of surface nanobubbles and universality of their contact angles: A molecular dynamics approach

We study surface nanobubbles using molecular dynamics simulation of ternary (gas, liquid, solid) systems of Lennard-Jones fluids. They form for sufficiently low gas solubility in the liquid, i.e., for large relative gas concentration. For strong enough gas-solid attraction, the surface nanobubble is sitting on a gas layer, which forms in between the liquid and the solid. This gas layer is the reason for the universality of the contact angle, which we calculate from the microscopic parameters. Under the present equilibrium conditions the nanobubbles dissolve within less of a microsecond, consistent with the view that the experimentally found nanobubbles are stabilized by a nonequilibrium mechanism.Comment: 5p,4

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

Apparatus to control and visualize the impact of a high-energy laser pulse on a liquid target

We present an experimental apparatus to control and visualize the response of a liquid target to a laser-induced vaporization. We use a millimeter-sized drop as target and present two liquid-dye solutions that allow a variation of the absorption coefficient of the laser light in the drop by seven orders of magnitude. The excitation source is a Q-switched Nd:YAG laser at its frequency-doubled wavelength emitting nanosecond pulses with energy densities above the local vaporization threshold. The absorption of the laser energy leads to a large-scale liquid motion at timescales that are separated by several orders of magnitude, which we spatiotemporally resolve by a combination of ultra-high-speed and stroboscopic high-resolution imaging in two orthogonal views. Surprisingly, the large-scale liquid motion at upon laser impact is completely controlled by the spatial energy distribution obtained by a precise beam-shaping technique. The apparatus demonstrates the potential for accurate and quantitative studies of laser-matter interactions.Comment: Submitted to Review of Scientific Instrument

Cavitation and bubble collapse in hot asymmetric nuclear matter

The dynamics of embryonic bubbles in overheated, viscous and non-Markovian nuclear matter is studied. It is shown that the memory and the Fermi surface distortions significantly affect the hinderance of bubble collapse and determine a characteristic oscillations of the bubble radius. These oscillations occur due to the additional elastic force induced by the memory integral.Comment: Revtex file (10 pages) and 3 figure