HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy.

BACKGROUND: Food allergy is a growing health problem worldwide because of its increasing prevalence, life-threatening potential, and shortage of effective preventive treatments. In an outbreak of wheat allergy in Japan, thousands of patients had allergic reactions to wheat after using soap containing hydrolyzed wheat protein (HWP). OBJECTIVES: The aim of the present study was to investigate genetic variation that can contribute to susceptibility to HWP allergy. METHODS: We conducted a genome-wide association study of HWP allergy in 452 cases and 2700 control subjects using 6.6 million genotyped or imputed single nucleotide polymorphisms. Replication was assessed by genotyping single nucleotide polymorphisms in independent samples comprising 45 patients with HWP allergy and 326 control subjects. RESULTS: Through the genome-wide association study, we identified significant associations with the class II HLA region on 6p21 (P = 2.16 × 10-24 for rs9271588 and P = 2.96 × 10-24 for HLA-DQα1 amino acid position 34) and with the RBFOX1 locus at 16p13 (rs74575857, P = 8.4 × 10-9). The associations were also confirmed in the replication data set. Both amino acid polymorphisms (HLA-DQß1 amino acid positions 13 and 26) located in the P4 binding pockets on the HLA-DQ molecule achieved the genome-wide significance level (P < 5.0 × 10-8). CONCLUSIONS: Our data provide the first demonstration of genetic risk for HWP allergy and show that this genetic risk is mainly represented by multiple combinations of HLA variants.

New soft X-ray beamline BL07LSU at SPring-8.

A new soft X-ray beamline, BL07LSU, has been constructed at SPring-8 to perform advanced soft X-ray spectroscopy for materials science. The beamline is designed to achieve high energy resolution (E/ΔE> 10000) and high photon flux [>10(12) photons s(-1) (0.01% bandwidth)(-1)] in the photon energy range 250-2000 eV with controllable polarization. To realise this state-of-the-art performance, a novel segmented cross undulator was developed and adopted as a light source. The details of the undulator light source and beamline monochromator design are described. The achieved performance of the beamline, such as the photon flux, energy resolution and the state of polarization, is reported.

Prediction of fatigue life of high-heat-load components made of oxygen-free copper by comparing with Glidcop.

Following a successful study on the prediction of fatigue life of high-heat-load components made of Glidcop, the thermal limitation of oxygen-free copper (OFC), which is used more commonly than Glidcop, has been studied. In addition to its general mechanical properties, the low-cycle-fatigue (LCF) and creep properties of OFC were investigated in detail and compared with those of Glidcop. The breaking mode of OFC, which was observed to be completely different from that of Glidcop in a fatigue fracture experiment, clarified the importance of considering the creep-fatigue interaction. An additional LCF test with compressive strain holding was conducted so that the creep-fatigue life diagram for out-of-phase thermal fatigue could be obtained on the basis of the strain-range partitioning method. The life predicted from elasto-plastic creep analysis agreed well with that determined from the void ratio estimated in the fatigue fracture experiment.

Performance upgrade in the JAEA actinide science beamline BL23SU at SPring-8 with a new twin-helical undulator.

The soft X-ray beamline BL23SU at SPring-8 has undergone an upgrade with a twin-helical undulator of in-vacuum type to enhance the experimental capabilities of the endstations. The new light source with a fast helicity-switching operation allows not only the data throughput but also the sensitivity in X-ray magnetic circular dichroism (XMCD) to be improved. The operational performance and potential are described by presenting XMCD results of paramagnetic ß-US(2) measured with a 10 T superconducting magnet.

Extreme ultraviolet free electron laser seeded with high-order harmonic of Ti:sapphire laser.

The 13th harmonic of a Ti:sapphire (Ti:S) laser in the plateau region was injected as a seeding source to a 250-MeV free-electron-laser (FEL) amplifier. When the amplification conditions were fulfilled, strong enhancement of the radiation intensity by a factor of 650 was observed. The random and uncontrollable spikes, which appeared in the spectra of the Self-Amplified Spontaneous Emission (SASE) based FEL radiation without the seeding source, were found to be suppressed drastically to form to a narrow-band, single peak profile at 61.2 nm. The properties of the seeded FEL radiation were well reproduced by numerical simulations. We discuss the future precept of the seeded FEL scheme to the shorter wavelength region.

Universal function for the brilliance of undulator radiation considering the energy spread effect.

Angular and spatial profiles of undulator radiation have been investigated to derive a universal function that evaluates the brilliance of undulator radiation and takes into account the effects of electron beam emittance and energy spread. It has been found that the effects of energy spread on the angular divergence and source size can be expressed by simple analytic expressions, and a universal brilliance function has been derived by convolution with the electron beam distribution functions. Comparisons with numerical results have been carried out to show the validity and applicability of the universal function.

Cytokine modulation of retinoic acid-inducible gene-I (RIG-I) expression in human epidermal keratinocytes.

BACKGROUND: Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH/D box family proteins and designated as a putative RNA helicase, which plays various roles in gene expression and cellular functions in response to a variety of RNA viruses. OBJECTIVE: The present study was designed to investigate the effects of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha on RIG-I expression in human keratinocytes, and the expression of RIG-I in skin lesions of psoriasis vulgaris, in which IFN-gamma and TNF-alpha are considered to be involved in its pathogenesis. METHODS: The mRNA and protein expression of RIG-I was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Immunohistochemical staining of RIG-I was examined on psoriatic skin section. RESULTS: The levels of RIG-I mRNA and protein were upregulated in HaCaT keratinocytes in the presence of IFN-gamma or TNF-alpha. Immunohistochemically, RIG-I was detected in the cytoplasm of the spinous and basal layers of psoriatic skin. CONCLUSION: Our results suggest that RIG-I might operate not only as a RNA helicase but also as a mediator of the cytokine network in the inflammatory skin diseases, such as psoriasis vulgaris.

Trichoscopic Findings of Erosive Pustular Dermatosis of the Scalp Associated with Gefitinib.

Alopecia associated with epidermal growth factor receptor (EGFR) inhibitor therapy is a rare cutaneous side effect with the potential to progress to scarring alopecia. Thus, dermatologists should make an early diagnosis. We present the case of a 57-year-old Japanese female with scarring alopecia associated with gefitinib, which is an EGFR inhibitor, including trichoscopic findings. The patient treated with gefitinib for non-small cell lung cancer experienced skin rash and hair loss of the scalp. The scalp lesions appeared similar to erosive pustular dermatosis of the scalp. Trichoscopic examination showed follicular keratotic plugging, milky red areas, white patches, hair shaft disorder, tapering hair, and absence of follicular opening. Histological examination showed ruptured hair follicles with a perifollicular infiltration of plasma cells, lymphocytes, and histiocytes. Oral minocycline and topical steroid treatment produced no improvement. With a reduction in the gefitinib dosage, alopecia gradually improved, although scarring remained. We consider these trichoscopic findings and suspect that follicular keratotic plugging might be a finding associated with scarring alopecia due to EGFR inhibitor therapy.

Characterization of retinoic acid-inducible gene-I (RIG-I) expression corresponding to viral infection and UVB in human keratinocytes.

BACKGROUND: Retinoic acid-inducible gene-I (RIG-I) is a cytoplasmic protein that recognizes viral double-stranded RNA to induce the type I interferon (IFN) response. In human keratinocytes, RIG-I is induced by IFN-γ and tumor necrosis factor-α stimulation, and is abundantly expressed in psoriatic keratinocytes of the spinous and basal layers. OBJECTIVE: This study investigated the effects of extraneous stimuli including viral infection and UVB exposure on RIG-I expression in human keratinocytes. METHODS: Human skin keratinocytes (HaCaT cells) were stimulated by polyinosinic-polycytidylic acid (poly(I:C)), which mimics viral infection, and UVB exposure. We assessed the expression of RIG-I and IFN-regulatory factor (IRF)-1 in HaCaT cells by RT-PCR and Western blot analysis. Moreover, we investigated the effect of IRF-1 binding site of RIG-I gene promoter on the regulation of RIG-I expression by luciferase promoter assay and electrophoretic mobility shift assay. RESULTS: Poly(I:C) induced RIG-I expression, while UVB inhibited basal RIG-I expression and the poly(I:C)-induced RIG-I overexpression in HaCaT cells. IRF-1, which binds to a regulatory element located on the RIG-I gene promoter, was required for both inductions of RIG-I expression. IRF-1 expression was enhanced three hours after the poly(I:C) stimulation, consistent with the RIG-I response to poly(I:C), and thereafter was suppressed. Moreover, UVB exposure promptly decreased IRF-1 expression, resulting in decreased IRF-1 protein binding to the RIG-I promoter, and consequently, decreased RIG-I expression. CONCLUSION: Thus, suppression of RIG-I and IRF-1 expression caused by UVB exposure may partly explain the inhibition of skin-based immune responses, leading to viral infection and recrudescence.

Fatigue life prediction for high-heat-load components made of GlidCop by elastic-plastic analysis.

A procedure to predict the fatigue fracture life of high-heat-load components made of GlidCop has been successfully established. This method is based upon the Manson-Coffin equation with a cumulative linear damage law. This prediction was achieved by consolidating the results of experiments and analyses, and considered the effects of environment and creep. A low-cycle-fatigue test for GlidCop was conducted so that environment-dependent Delta(t)-N(f) diagrams for any temperature could be prepared. A special test piece was designed to concentrate the strain in a central area locally, resulting in the low-cycle-fatigue fracture. The experiments were carried out by repeatedly irradiating a test piece with an electron beam. The results of the experiment confirmed that the observed fatigue life was within a factor of two when compared with the predicted fatigue life, yet located on the safer side.

Quantitative estimation of thermal contact conductance of a real front-end component at SPring-8 front-ends.

The thermal contact conductance (TCC) of a real front-end component at SPring-8 has been quantitatively estimated by comparing the results of experiments with those of finite-element analyses. In this paper one of the methods of predicting the TCC of a real instrument is presented. A metal filter assembly, which is an indirect-cooling instrument, was selected for the estimation of the TCC. The temperature of the metal filter assembly for the maximum heat load of synchrotron radiation was calculated from the TCC that is expected under normal conditions. This study contributes towards the ongoing research program being conducted to investigate the real thermal limitation of all front-end high-heat-load components.

Magnetic characterization for cryogenic permanent-magnet undulators: a first result.

The cryogenic permanent-magnet undulator (CPMU) is a novel insertion device recently proposed at SPring-8, in which permanent magnets (PMs) are cooled to cryogenic temperatures to improve the magnetic performances, such as remanence and coercivity. A new measurement system for carrying out high-precision magnetic field mapping using a Hall probe has been developed in order to characterize the magnetic field generated by PM arrays at cryogenic temperatures. In this system, alignment of the Hall probe was dynamically performed by means of detecting the variation in its transverse position using optical laser beams introduced into the vacuum chamber. Magnetic measurements of a CPMU prototype were made at different temperatures in order to investigate variations of the magnetic performances owing to temperature. The maximum remanence deduced from the average peak value of the field profile was found to be close to that obtained from a former measurement with a single piece of the same PM material. In addition, the error components in the field profile were found to be insensitive to temperature in terms of the electron trajectory and phase error. This result suggests that the field correction of CPMUs can be performed based on the field profile measured at room temperature, which considerably reduces the task and time necessary for construction of CPMUs.

Degree of circular polarization of soft X-rays emitted from a multi-polarization-mode undulator characterized by means of magnetic circular dichroism measurements.

The degree of circular polarization of soft X-rays emitted from the multi-polarization-mode undulator of BL17SU at SPring-8 has been deduced by means of magnetic circular dichroism in core-level X-ray absorption spectroscopy for a ferrimagnetic Gd-Fe-Co amorphous thin film. The results of reference measurements performed using well characterized undulator radiation of BL25SU at SPring-8 have also been utilized. The degrees of circular polarization were presumed for all the available operational modes and were compared with simple theoretical calculations. It was found that the calculated degrees of circular polarization were validated by the measurements reasonably well and will be useful in further experiments at BL17SU.

Pure-type superconducting permanent-magnet undulator.

A novel synchrotron radiation source is proposed that utilizes bulk-type high-temperature superconductors (HTSCs) as permanent magnets (PMs) by in situ magnetization. Arrays of HTSC blocks magnetized by external magnetic fields are placed below and above the electron path instead of conventional PMs, generating a periodic magnetic field with an offset. Two methods are presented to magnetize the HTSCs and eliminate the field offset, enabling the HTSC arrays to work as a synchrotron radiation source. An analytical formula to calculate the peak field achieved in a device based on this scheme is derived in a two-dimensional form for comparison with synchrotron radiation sources using conventional PMs. Experiments were performed to demonstrate the principle of the proposed scheme and the results have been found to be very promising.

Simple scheme for harmonic suppression by undulator segmentation.

In order to suppress harmonic intensity of undulator radiation, a scheme similar to the detuning technique used in the double-crystal monochromator is investigated and found to be effective only when the number of periods of the undulator is small, once the finite emittance of the electron beam and angular acceptance of the beamline are taken into account. Instead, a simple scheme is proposed for undulators with many periods: the undulator is divided into several segments and the optical phase in between is adjusted to shift the fundamental energy without significantly affecting other harmonics.

Optical switching of X-rays using laser-induced lattice expansion.

The optical switching of X-rays using laser-induced crystal lattice expansion is described. Irradiation of a gallium arsenide (GaAs) crystal using picosecond laser pulses shifts the Bragg angle through the lattice expansion with a response time of a few hundred picoseconds. A single pulse was extracted from the synchrotron radiation pulse train using a double-crystal arrangement of GaAs, in which the two crystals were irradiated by way of two successive laser pulses with an appropriate time delay.