BackgroundRecently, we found that Staphylococcus aureus produces extracellular vesicles (EV) that contain pathogenic proteins. Although S. aureus infection has been linked with atopic dermatitis (AD), the identities of the causative agents from S. aureus are controversial. We evaluated whether S. aureus-derived EV are causally related to the pathogenesis of AD.MethodsExtracellular vesicles were isolated by the ultracentrifugation of S. aureus culture media. The EV were applied three times per week to tape-stripped mouse skin. Inflammation and immune dysfunction were evaluated 48 h after the final application in hairless mice. Extracellular vesicles-specific IgE levels were measured by ELISA in AD patients and healthy subjects.ResultsThe in vitro application of S. aureus EV increased the production of pro-inflammatory mediators (IL-6, thymic stromal lymphopoietin, macrophage inflammatory protein-1α, and eotaxin) by dermal fibroblasts. The in vivo application of S. aureus EV after tape stripping caused epidermal thickening with infiltration of the dermis by mast cells and eosinophils in mice. These changes were associated with the enhanced cutaneous production of IL-4, IL-5, IFN-γ, and IL-17. Interestingly, the serum levels of S. aureus EV-specific IgE were significantly increased in AD patients relative to healthy subjects.ConclusionThese results indicate that S. aureus EV induce AD-like inflammation in the skin and that S. aureus-derived EV are a novel diagnostic and therapeutic target for the control of AD.

Although magnesium alloys, as the lightest structural alloys, offer significant potential for automotive applications, their applications remain limited due to their poor formability at room temperature. Since the strategies used for improving formability usually result in a degradation of strength, there are no high strength magnesium alloys showing good formability. Here we report an alloy design concept that can simultaneously provide high strength and good formability. Such designed alloy when subjected to an appropriate processing technique shows a combination of strength and formability that surpasses those of the existing magnesium alloys reported so far. The alloy design concept used in the present study is based on the utilization of alloying elements that can induce precipitation, as well as maximize the segregation of other texture-controlling alloying elements. Such developed alloy is expected to broaden the application of Mg alloy sheets, which are now starting to gain acceptance by automotive industries.

A new physical scheme for femtosecond x-ray lasers, where the upper lasing level (L 23 innershell vacancy level͒ is pumped by x-ray photons and the lower lasing level (M 1 innershell vacancy level͒ is depopulated via a Coster-Kronig radiationless transition, is analyzed for Ca. The transition wavelength is 4.1 nm, which is inside the water window ͑the wavelength range between the K absorption edges of oxygen and carbon͒. The peak spectral brightness of the x-ray laser output at 4.1 nm is predicted to be as large as 5 ϫ10 25 photons/s/͑mm 2 mrad 2 0.1% bandwidth), which is 4 to 5 orders of magnitude brighter than a typical undulator radiation in the similar spectral region. In addition to the high flux, the expected duration of x-ray lasing of ϳ3 fs will be useful for the study of fast dynamics in physical and biological sciences.New regimes of laser matter interaction have opened due to recent advances in the 10 fs range, high-peak-power laser development ͓1-4͔. These lasers are ideal for the generation of femtosecond high-order harmonic radiation in the soft x-ray range ͓5-9͔, and for pumping x-ray lasers based on innershell atomic transitions ͓10-16͔. While the past 15 years have seen significant progress in the x-ray laser research and development, most x-ray lasers operate at lowrepetition rates with pulses in picoseconds or longer. Highrepetition-rate, femtosecond x-ray lasers would be useful for dynamical studies of ultrafast phenomena in nature ͓17͔.Duguay and Rentzepis ͓18͔ first proposed inner-shell x-ray laser schemes in 1967. In their scheme the lower level of the lasing transition was the ground level of the first ion and could not decay. The idea of using an atomic system in which the lower level decays was suggested by Stankevich ͓19͔, elaborated by Arecchi ͓20͔ and Elton ͓21͔, and calculated in detail by Axelrod for K-shell transitions ͓22͔. The technical barrier for the successful realization of these schemes has been the development of a sufficiently fast and energetic x-ray pump source whose time scale is on the order of the lifetime of the keV lasing transitions, i.e., in the 10 fs range ͓10,11,15,22͔. Such pumping sources are now becoming available due to the advent of femtosecond ultrahigh peak-power lasers. Such systems with peak powers of tens to hundreds of terawatt ͑TW͒ have been demonstrated ͓1-4͔ and plans exist for extending peak powers to 1 petawatt at a 20-fs pulse duration. Even with these new lasers, intrinsic problems with the K-shell transition x-ray laser scheme still exist. In particular, electrons produced during photoionization and subsequent Auger decays are energetic enough to collisionally ionize neutral atoms, producing the lower level of the lasing transition and destroying the inversion. If it were possible to create an inner-shell population inversion via atomic processes involving only electrons, the inversion in any photoionization pumped x-ray laser schemes based on the same transitions would be ͑1͒ much less sensitive to secondary electron-collisional filling of th...

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