Concurrent TNFRSF1A R92Q and pyrin E230K mutations in a child with multiple sclerosis

We report a 16-year-old female patient with a severe course of multiple sclerosis and concomitant symptoms suggestive of a hereditary autoinflammatory disease. Genetic analyses revealed that she inherited a TNFRSF1A R92Q mutation from her mother and a pyrin E230K mutation from her father. To our knowledge, this is the first report of a patient with severe childhood multiple sclerosis and mutations in two genes which predispose to hereditary autoinflammatory disorders. We speculate that these mutations contribute to early multiple sclerosis manifestation and enhance the inflammatory damage inflicted by the autoimmune response

Caf\'e Latte: Spontaneous layer formation in laterally cooled double diffusive convection

In the preparation of Caf\'e Latte, spectacular layer formation can occur between the expresso shot in a glass of milk and the milk itself. Xue et al. (Nat. Commun., vol. 8, 2017, pp. 1-6) showed that the injection velocity of expresso determines the depth of coffee-milk mixture. After a while when a stable stratification forms in the mixture, the layering process can be modelled as a double diffusive convection system with a stably-stratified coffee-milk mixture cooled from the side. More specifically, we perform (two-dimensional) direct numerical simulations of laterally cooled double diffusive convection for a wide parameter range, where the convective flow is driven by a lateral temperature gradient while stabilized by a vertical concentration gradient. When the thermal driving force dominates over the stabilizing force, the flow behaves like vertical convection in which a large-scale circulation develops. However, with increasing strength of the stabilizing force, a meta-stable layered regime emerges. Initially, several vertically-stacked convection rolls develop, and these well-mixed layers are separated by sharp interfaces with large concentration gradients. The initial thickness of these emerging layers can be estimated by balancing the work exerted by thermal driving and the required potential energy to bring fluid out of its equilibrium position in the stably stratified fluid. In the layered regime, we further observe successive layer merging, and eventually only a single convection roll remains. We elucidate the following merging mechanism: As weakened circulation leads to accumulation of hot fluid adjacent to the hot sidewall, larger buoyancy forces associated with hotter fluid eventually break the layer interface. Then two layers merge into a larger layer, and circulation establishes again within the merged structure.Comment: 10 pages, 4 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

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

Nuclear Saturation with in-Medium Meson Exchange Interactions

We show that the assumption of dropping meson masses together with conventional many-body effects, implemented in the relativistic Dirac-Brueckner formalism, explains nuclear saturation. We use a microscopic model for correlated $2\pi$ exchange and include the standard many-body effects on the in-medium pion propagation, which initially increase the attractive nucleon-nucleon ($NN$) potential with density. For the vector meson exchanges in both the $\pi\pi$ and $NN$ sector, we assume Brown-Rho scaling which---in concert with `chiral' $\pi\pi$ contact interactions---reduces the attraction at higher densities.Comment: 5 pages REVTeX, 2 eps-figures included, submitted to Phys. Rev. Let

Transitions and Probes in Turbulent Helium

Previous analysis of a Paris turbulence experiment \cite{zoc94,tab95} shows a transition at the Taylor Reynolds number \rel \approx 700. Here correlation function data is analyzed which gives further evidence for this transition. It is seen in both the power spectrum and in structure function measurements. Two possible explanations may be offered for this observed transition: that it is intrinsic to the turbulence flow in this closed box experiment or that it is an effect of a change in the flow around the anemometer. We particularly examine a pair of ``probe effects''. The first is a thermal boundary layer which does exist about the probe and does limit the probe response, particularly at high frequencies. Arguments based on simulations of the response and upon observations of dissipation suggests that this effect is only crucial beyond \rel\approx 2000. The second effect is produced by vortex shedding behind the probe. This has been seen to produce a large modification in some of the power spectra for large \rel. It might also complicate the interpretation of the experimental results. However, there seems to be a remaining range of data for \rel < 1300 uncomplicated by these effects, and which are thus suggestive of an intrinsic transition.Comment: uuencoded .ps files. submitted to PRE. 12 figures are sent upon request to jane wang ([email protected]

Bifurcation Diagram for Compartmentalized Granular Gases

The bifurcation diagram for a vibro-fluidized granular gas in N connected compartments is constructed and discussed. At vigorous driving, the uniform distribution (in which the gas is equi-partitioned over the compartments) is stable. But when the driving intensity is decreased this uniform distribution becomes unstable and gives way to a clustered state. For the simplest case, N=2, this transition takes place via a pitchfork bifurcation but for all N>2 the transition involves saddle-node bifurcations. The associated hysteresis becomes more and more pronounced for growing N. In the bifurcation diagram, apart from the uniform and the one-peaked distributions, also a number of multi-peaked solutions occur. These are transient states. Their physical relevance is discussed in the context of a stability analysis.Comment: Phys. Rev. E, in press. Figure quality has been reduced in order to decrease file-siz

Stepwise activation of a class C GPCR begins with millisecond dimer rearrangement

G protein-coupled receptors (GPCRs) are key biological switches that transmit both internal and external stimuli into the cell interior. Among the GPCRs, the "light receptor" rhodopsin has been shown to activate with a rearrangement of the transmembrane (TM) helix bundle within ~1 ms, while all other receptors are thought to become activated within ~50 ms to seconds at saturating concentrations. Here, we investigate synchronous stimulation of a dimeric GPCR, the metabotropic glutamate receptor type 1 (mGluR1), by two entirely different methods: (i) UV light-triggered uncaging of glutamate in intact cells or (ii) piezo-driven solution exchange in outside-out patches. Submillisecond FRET recordings between labels at intracellular receptor sites were used to record conformational changes in the mGluR1. At millimolar ligand concentrations, the initial rearrangement between the mGluR1 subunits occurs at a speed of τ(1) ~ 1-2 ms and requires the occupancy of both binding sites in the mGluR1 dimer. These rapid changes were followed by significantly slower conformational changes in the TM domain (τ(2) ~ 20 ms). Receptor deactivation occurred with time constants of ~40 and ~900 ms for the inter- and intrasubunit conformational changes, respectively. Together, these data show that, at high glutamate concentrations, the initial intersubunit activation of mGluR1 proceeds with millisecond speed, that there is loose coupling between this initial step and activation of the TM domain, and that activation and deactivation follow a cyclic pathway, including-in addition to the inactive and active states-at least two metastable intermediate states

The genome sequence of the grizzled skipper, Pyrgus malvae (Linnaeus, 1758)

This is the final version. Available on open access from F1000 Research via the DOI in this record[version 1; peer review: 2 approved, 1 approved with reservations]Data availability: European Nucleotide Archive: Pyrgus malvae (grizzled skipper). Accession number PRJEB45665; https://identifiers.org/ena.embl/PRJEB45665. The genome sequence is released openly for reuse. The P. malvae genome sequencing initiative is part of the Darwin Tree of Life (DToL) project. All raw sequence data and the assembly have been deposited in INSDC databases. Raw data and assembly accession identifiers are reported in Table 1.We present a genome assembly from an individual male Pyrgus malvae (the grizzled skipper; Arthropoda; Insecta; Lepidoptera; Hesperiidae). The genome sequence is 725 megabases in span. The majority (99.97%) of the assembly is scaffolded into 31 chromosomal pseudomolecules, with the Z sex chromosome assembled

The genome sequence of the marbled white butterfly, Melanargia galathea (Linnaeus, 1758)

This is the final version. Available on open access from F1000 Research via the DOI in this record[version 1; peer review: 1 approved]We present a genome assembly from an individual female Melanargia galathea (the marbled white; Arthropoda; Insecta; Lepidoptera; Nymphalidae). The genome sequence is 606 megabases in span. The majority (99.97%) of the assembly is scaffolded into 25 chromosomal pseudomolecules, with the W and Z sex chromosomes assembled