Microglia are crucial for the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Here, we show that the E3 ubiquitin ligase Peli1 is abundantly expressed in microglia and serves as a pivotal mediator of microglial activation during the course of EAE induction. Peli1 mediates the induction of chemokines and proinflammatory cytokines in microglia and, thereby, promotes recruitment of T cells into the central nervous system. Peli1-deficient mice are refractory to EAE induction despite their competent production of Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms HHS Public Access

A wave basin experiment has been performed in the MARINTEK laboratories, in one of the largest existing three-dimensional wave tanks in the world. The aim of the experiment is to investigate the effects of directional energy distribution on the statistical properties of surface gravity waves. Different degrees of directionality have been considered, starting from long-crested waves up to directional distributions with a spread of ±30• at the spectral peak. Particular attention is given to the tails of the distribution function of the surface elevation, wave heights and wave crests.Comparison with a simplified model based on second-order theory is reported. The results show that for long-crested, steep and narrow-banded waves, the second-order theory underestimates the probability of occurrence of large waves. As directional effects are included, the departure from second-order theory becomes less accentuated and the surface elevation is characterized by weak deviations from Gaussian statistics.

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We discuss two independent, large scale experiments performed in two wave basins of different dimensions in which the statistics of the surface wave elevation are addressed. Both facilities are equipped with a wave maker capable of generating waves with prescribed frequency and directional properties. The experimental results show that the probability of the formation of large amplitude waves strongly depends on the directional properties of the waves. Sea states characterized by long-crested and steep waves are more likely to be populated by freak waves with respect to those characterized by a large directional spreading. DOI: 10.1103/PhysRevLett.102.114502 PACS numbers: 47.35.Bb, 47.55.NÀ An important task in the study of surface gravity waves is the determination of the probability density function of the surface wave elevation. The knowledge of the probability of the occurrence of large amplitude waves is essential for different engineering purposes such as the prediction of wave forces and structural responses or the design of offshore structures. A deep comprehension of the physical mechanisms of the generation of such waves is also a first step towards the development of an operational methodology for the probabilistic forecast of freak waves. It is well known that surface gravity waves obey nonlinear equations and, to date, a universal tool suitable for deriving the probability distribution function of a nonlinear system has not yet been developed. Fortunately, water waves are on average weakly nonlinear [1,2] and solutions can be generally written as power series, where the small parameter, in the case of deep water waves, is the wave steepness ". Strong departure from Gaussian statistics of the surface elevation can be observed if third order nonlinearities are considered. At such order it has been shown numerically [3] and theoretically [4] that, for long-crested waves, a generalization of the Benjamin-Feir instability [5] (or modulational instability [2]) for random spectra can take place [6]. This instability, that corresponds to a quasiresonant four-wave interaction in Fourier space, results in the formation of large amplitude waves (or rogue waves) [7] which affect the statistical properties of the surface elevation (see, for example, [8]). This is particularly true if the ratio between the wave steepness and the spectral bandwidth, known as the Benjamin-Feir Index (BFI), is large [4]. We mention that rogue waves have also been recently observed in optical systems [9] and in acoustic turbulence in He II [10] where giant waves are observed during an inverse cascade process.We emphasize that in many different fields of physics (plasmas [11,12], nonlinear optics [13,14], chargedparticle beam dynamics [15,16]) the modulational instability plays an important role; under suitable physical conditions a nonlinear Schrödinger equation can be derived and the modulational instability can be analyzed directly with this equation [2]. A major question which has to be addressed (and is the subject of the pre...

We study random surface gravity wave fields and address the formation of large-amplitude waves in a laboratory environment. Experiments are performed in one of the largest wave tank facilities in the world. We present experimental evidence that the tail of the probability density function for wave height strongly depends on the Benjamin-Feir index (BFI)-i.e., the ratio between wave steepness and spectral bandwidth. While for a small BFI the probability density functions obtained experimentally are consistent with the Rayleigh distribution, for a large BFI the Rayleigh distribution clearly underestimates the probability of large events. These results confirm experimentally the fact that large-amplitude waves in random spectra may result from the modulational instability.