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 ...

How a long strand of genomic DNA is compacted into a mitotic chromosome remains one of the basic questions in biology. The nucleosome fibre, in which DNA is wrapped around core histones, has long been assumed to be folded into a 30-nm chromatin fibre and further hierarchical regular structures to form mitotic chromosomes, although the actual existence of these regular structures is controversial. Here, we show that human mitotic HeLa chromosomes are mainly composed of irregularly folded nucleosome fibres rather than 30-nm chromatin fibres. Our comprehensive and quantitative study using cryoelectron microscopy and synchrotron X-ray scattering resolved the long-standing contradictions regarding the existence of 30-nm chromatin structures and detected no regular structure 411 nm. Our finding suggests that the mitotic chromosome consists of irregularly arranged nucleosome fibres, with a fractal nature, which permits a more dynamic and flexible genome organization than would be allowed by static regular structures.

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more important than glomerulopathy in terms of renal dysfunction in diabetic nephropathy [4, 5]. Nonenzymatic modification of proteins by reducing sugars, a process that is also known as Maillard reaction, progress at an extremely accelerated rate under diabetic conditions [6-8]. These early glycation products undergo further complex reaction, such as rearrangement, dehydration, and condensation, to become irreversibly cross-linked, heterogeneous fluorescent derivatives, termed advanced glycation end products (AGEs) [6-8]. There is an accumulating body of evidence that engagement of receptor for AGEs (RAGE) with the ligand AGEs elicits oxidative stress generation and resultantly evokes inflammatory and fibrotic reactions in the kidney cells, thereby causing progressive alteration in renal architecture and loss of renal function associated with tubular injury in diabetes [9-16].

OBJECTIVES To compare the efficacy of two α1‐adrenoceptor antagonists, α1A‐adrenoceptor‐selective tamsulosin hydrochloride and α1D‐adrenoceptor‐selective naftopidil, in the treatment of lower urinary tract symptoms (LUTS) with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS Thirty‐four patients (mean age 72.4 years, sd 4.3, range 66–79) with LUTS (International Prostate Symptom Score, IPSS >8) secondary to BPH were enrolled in a randomized crossover study. Seventeen patients were initially prescribed naftopidil 50 mg for 4 weeks, followed by tamsulosin 0.2 mg for 4 weeks (group A); another 17 were initially prescribed tamsulosin 0.2 mg, followed by naftopidil 50 mg (group B). Patients changed to the alternative treatment after a 1‐week washout period. Efficacy criteria were improvement in LUTS (IPSS), quality of life (QoL), uroflowmetry, and pressure‐flow study (PFS) values based on the treatment with each agent. RESULTS At baseline there were no significant differences between the groups in IPSS, QoL, uroflowmetry values or PFS values, except for the volume at maximum desire to void. After treatment with each agent, the IPSS and QoL were significantly improved and the reduction in bladder outlet obstruction confirmed by PFS. Naftopidil was significantly more effective than tamsulosin in relieving nocturia. The increases from baseline (before treatment) to the endpoint (after treatment with each agent) in the volume at first desire and maximum desire to void were significantly higher with naftopidil than with tamsulosin. Involuntary contractions disappeared in two patients with relief of nocturia with naftopidil, but not with tamsulosin. The decrease in other symptoms of the IPSS, QoL, increase in uroflowmetry values and changes in other PFS values were similar for both agents. CONCLUSIONS The two agents provided similar efficacy in the treatment of LUTS with BPH. However, naftopidil was better than tamsulosin for nocturia. The disappearance of involuntary contraction and the greater increase in first‐desire volume with naftopidil may be associated with the relief of nocturia. The α1D‐adrenoceptor antagonist is effective in alleviating both voiding and storage symptoms. The α1D‐adrenoceptor antagonist may be more effective than the α1A‐adrenoceptor antagonist in LUTS with BPH.