Hard X-rays have exceptional properties that are useful in the chemical, elemental and structure analysis of matter. Although single-nanometre resolutions in various hard-X-ray analytical methods are theoretically possible with a focused hard-X-ray beam, fabrication of the focusing optics remains the main hurdle. Aberrations owing to imperfections in the optical system degrade the quality of the focused beam 1 . Here, we describe an in situ wavefront-correction approach to overcome this and demonstrate an X-ray beam focused in one direction to a width of 7 nm at 20 keV. We achieved focal spot improvement of the X-ray nanobeam produced by a laterally graded multilayer mirror 2 . A grazing-incidence deformable mirror 3 was used to restore the wavefront shape. Using this system, ideal focusing conditions are achievable even if hard-X-ray focusing elements do not achieve sufficient performance. It is believed that this will ultimately lead to single-nanometre spatial resolution in X-ray analytical methods.Synchrotron radiation facilities produce high-quality light with wavelengths ranging from the infrared to hard-X-ray regions. The use of hard X-rays with energies higher than several kiloelectronvolts in conjunction with analysis methods such as X-ray diffraction, X-ray fluorescence, X-ray absorption and X-ray photoelectron spectroscopy offers unique advantages for the investigation of the structure, elemental distribution and chemical bonding state of advanced materials and biological samples. In these analytical methods, the resolution, signal strength and contrast must be as high as possible. In this regard, the development of a hard-X-ray focusing device is important for meeting these demands. To focus light, it is necessary to take advantage of its interactions with matter, such as diffraction, reflection and refraction. There are a variety of hard-X-ray focusing optical systems such as mirrors 4 , zone plates 5 , refractive lenses 6 and multilayer Laue lenses 7 . The minimum achievable spot size has been theoretically investigated by many researchers 8-10 , and it has been concluded that sizes below 10 nm are feasible with kiloelectronvolt X-rays. That is, hard-X-ray analytical techniques have the potential for single-nanometre spatial resolution.However, in such discussions, the imperfections of the focusing elements have not been entirely considered. Rayleigh's quarterwavelength rule 1 states that if the wavefront aberration exceeds a quarter of a wavelength, the quality of the retinal image will be significantly impaired. This rule is also applicable to simple light-focusing optical systems. The wavefront error of the focused beam distorts the shape of the intensity profile on the focal plane and spreads the beam. The short wavelength of X-rays demands unprecedented accuracy in the manufacturing of the LETTERS 1.43 nm (r.m.s.) over a 500-nm-square area, which was directly confirmed by atomic force microscopy. A phase shift occurred at the boundary between the X-rays propagating inside and outside the phase ...

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SummaryCells exposed to ER-stress undergo the Unfolded Protein Response (UPR) to avoid apoptosis, but may also activate autophagy. However, the signal for selection of one of these two protective responses is unknown. To clarify the key switch between autophagy and apoptosis, we examined the correlation of UPR-related signals with autophagy and/or apoptosis inductions in HepG2 cells exposed to three ER-stress inducers (NaF, tunicamycin, and thapsigargin) with time, including the effect of small interfering RNA on the cell responses. Thapsigargin-induced ER-stress caused only apoptosis after ∼2 hr with Ire1 phosphorylation, and Grp78, ATF4, and CHOP expressions. On the other hand, NaF- and tunicamycin-induced ER-stress caused only autophagy in the early stage by ∼8 hr with ATF4 expression and without CHOP expression. ATF4-siRNA completely inhibited the autophagy induced by NaF or tunicamycin with suppressed ATF4 protein and mRNA expressions, and also inhibited apoptosis by thapsigargin with suppression of both ATF4 and CHOP. CHOP-siRNA had no effect on autophagy activation by NaF and tunicamycin. On the other hand, CHOP-siRNA activated autophagy in thapsigargin-induced ER-stress with significant ATF4 expression, and suppressed apoptosis with CHOP suppression. These results showed that ATF4 is the key signal for autophagy induced by ER-stress, and that autophagy is switched to apoptosis by subsequent CHOP upregulation, suggesting that the changeover switch between autophagy and apoptosis is located between ATF4 to CHOP in the PERK pathway.