A new charge-mosaic membrane from a multiblock copolymer.

A charge-mosaic membrane was prepared from a pentablock copolymer of the BABCB type by selectively introducing anion and cation exchange groups into the microseparated phases. The three-layer lamellar structure of the starting pentablock copolymer film was not disturbed by the modifications. The membrane obtained was highly permeable only to sodium chloride in mixed aqueous solutions of sodium chloride and organic species of low molecular weight, such as sucrose. Marked pH-dependent permeabilities were also observed for amino acids.

Development and operation of a Cs-free J-PARC H(-) ion source.

A cesium-free H(-) ion source driven with a LaB(6) filament was developed for the J-PARC. It was operated for the J-PARC linac beam commissioning, which was started on 20 November 2006. Eight runs of 2 or 3 week beam commissioning were done until the end of June 2007. The source was mainly operated with a duty factor of 0.8% (320 micros and 25 Hz) while providing a 5 mA beam typically. Each interval of the runs, precise optimizations, such as the filament position, and so on, are examined. At present, a H(-) beam with a current of 38 mA and a rms normalized emittance of 0.22 pi mm mrad is extracted with a duty factor of 0.8% (320 micros and 25 Hz).

Pre-conditioning procedure suitable for internal-RF-antenna of J-PARC RF-driven H⁻ ion source.

The Japan Proton Accelerator Research Complex (J-PARC) cesiated RF-driven H(-) ion source has been successfully operated for about 1 yr. By the world brightest level beam, the J-PARC design beam power of 1 MW was successfully demonstrated. Although no internal-RF-antenna failure, except for the once caused by an excess cesium due to a misoperation, occurred in the operation, many antennas failed in pre-conditionings for the first hundred days. The antenna failure rate was drastically decreased by using an antenna with coating thicker than a standard value and the pre-conditioning procedure repeating 15 min 25 kW RF-power operation and impurity-gas evacuation a few times, before the full power (50 kW) operation.

Fine-tuning to minimize emittances of J-PARC RF-driven H⁻ ion source.

The Japan Proton Accelerator Research Complex (J-PARC) cesiated RF-driven H(-) ion source has been successfully operated for about one year. By the world's brightest level beam, the J-PARC design beam power of 1 MW was successfully demonstrated. In order to minimize the transverse emittances, the rod-filter-field (RFF) was optimized by changing the triple-gap-lengths of each of pairing five piece rod-filter-magnets. The larger emittance degradation seems to be caused by impurity-gases than the RFF. The smaller beam-hole-diameter of the extraction electrode caused the more than expected improvements on not only the emittances but also the peak beam intensity.

Status of the RF-driven H⁻ ion source for J-PARC linac.

For the upgrade of the Japan Proton Accelerator Research Complex linac beam current, a cesiated RF-driven negative hydrogen ion source was installed during the 2014 summer shutdown period, with subsequent operations commencing on September 29, 2014. The ion source has been successfully operating with a beam current and duty factor of 33 mA and 1.25% (500 µs and 25 Hz), respectively. The result of recent beam operation has demonstrated that the ion source is capable of continuous operation for approximately 1100 h. The spark rate at the beam extractor was observed to be at a frequency of less than once a day, which is an acceptable level for user operation. Although an antenna failure occurred during operation on October 26, 2014, no subsequent serious issues have occurred since then.

Numerical study of plasma generation process and internal antenna heat loadings in J-PARC RF negative ion source.

A numerical model of plasma transport and electromagnetic field in the J-PARC (Japan Proton Accelerator Research Complex) radio frequency ion source has been developed to understand the relation between antenna coil heat loadings and plasma production/transport processes. From the calculation, the local plasma density increase is observed in the region close to the antenna coil. Electrons are magnetized by the magnetic field line with absolute magnetic flux density 30-120 Gauss which leads to high local ionization rate. The results suggest that modification of magnetic configuration can be made to reduce plasma heat flux onto the antenna.

Spontaneous luxation of encapsulated intraocular lens onto the retina after a triple procedure of vitrectomy, phacoemulsification, and intraocular lens implantation.

PURPOSE: To report the clinical and histological findings of a luxated intraocular lens (IOL) in the capsular bag. METHODS: Review of a case. RESULTS: Twenty-three months after a triple procedure of vitrectomy, phacoemulsification, and IOL implantation for diabetic vitreous hemorrhage and cataract, the encapsulated IOL spontaneously luxated. Scanning electron microscopy showed sparsely distributed anterior and equatorial zonules, with only a few posterior zonules on the surface of the removed capusular bag. CONCLUSION: The absence of the anterior hyaloid membrane and posterior zonules and contraction of the lens capsule may cause dialysis of the zonules. Therefore, the anterior hyaloid membrane should be left in place in patients at low risk for the development of postoperative proliferation to maintain the long-term stability of the IOL.

Prognostic importance of ophthalmic manifestations in childhood leukaemia.

In order to assess the systemic prognosis of children with leukaemic ocular involvement, 63 of 131 patients admitted to hospital with acute leukaemia were evaluated ophthalmically. A total of 28 of 63 showed ophthalmic involvement and were followed up for up to 84 months. Twenty seven of 28 patients (96.4%) died within 28 months after the onset of ocular involvement and within 83 months after the onset of leukaemia. The 5 year survival rate of patients with ophthalmic manifestations was 21.4% (6/28). This survival rate was significantly lower than that of those who lacked ophthalmic manifestations (16/35: 45.7%, p < 0.05). All of the patients with ophthalmic manifestations had either bone marrow relapse or central nervous system leukaemia. The prognosis was related to risk factors such as central nervous system leukaemia or bone marrow relapse in most cases.

Corneal endothelium in a case of mitochondrial encephalomyopathy (Kearns-Sayre syndrome).

A case of mitochondrial encephalomyopathy (Kearns-Sayre syndrome) with corneal endothelial abnormality is reported. A 22-year-old woman had retinitis pigmentosa, external ophthalmoplegia, complete heart block, ataxia, muscle weakness, dementia, sensorineural hearing loss, and was of short stature. Renal dysfunction, diabetes mellitus, and amenorrhea were also observed. Biopsy revealed decreased cytochrome c oxidase (complex IV) activity in muscle mitochondria. The corneal endothelium examined by specular microscope showed decreased cell density, severe polymegathism, and pleomorphism in both eyes. To our knowledge, this is the first report concerning primary corneal endothelial abnormality in a case with mitochondrial encephalomyopathy. The corneal endothelium is one of the tissues that could be affected by the enzyme deficiency present in this disease.

Interlaboratory validation of the in vitro eye irritation tests for cosmetic ingredients. (3) Evaluation of the haemolysis test.

The haemolysis test using sheep red blood cells (RBC) was evaluated as an alternative method to the Draize rabbit eye irritation test (Draize test) by six to nine laboratories. The participating laboratories performed the test according to the standard operating procedure (SOP). Thirty-eight cosmetic ingredients and isotonic sodium chloride solution were used as test substances in this validation study. The concentrations of the test substances that induced 50% haemolysis (HC(50) value) was obtained to serve as a toxicological index and compared with in vivo Draize scores. HC(50) values were not obtained for coloured or water-insoluble (turbid) substances. Three acids caused denaturation of haemoglobin leaked from RBC and consequently interfered with the determination of the HC(50) value. Interlaboratory reproducibility was relatively good except in the case of water-insoluble substances. The average values of coefficient of variation (CV) was 37%. The correlation coefficient and Spearman's rank correlation between the HC(50) value and maximum average Draize total score (MAS) were -0.631 and 0.641, respectively. The equivalence ratio between the haemolysis test and MAS was 70.0% when MAS 15 was set as the in vivo cut-off point. On the other hand, strong irritants (MAS50) could be correctly classified by this method. These results suggest that the haemolysis test might be applied to cosmetic ingredients as a screening method to distinguish strong irritants that directly affect the cell membrane permeability and do not disturb spectrophotometrical determination of haemoglobin. In order to evaluate the potential for eye irritation of cosmetic ingredients, a combination of haemolysis with other methods based on different mechanism should be employed to improve the predictability.

Interlaboratory validation of the in vitro eye irritation tests for cosmetic ingredients. (1) Overview of the validation study and Draize scores for the evaluation of the tests.

A three-step interlaboratory validation of alternative methods to the Draize eye irritation test (Draize test) was conducted by the co-operation of 27 organizations including national research institutes, universities, cosmetic industries, kit suppliers and others. Twelve alternative methods were evaluated using 38 cosmetic ingredients and isotonic sodium chloride solution. Draize tests were conducted according to the OECD guidelines using the same lot of test substances as was evaluated in the alternative tests. Results were as follows. (1) Variation in Draize scores was large near the critical range (maximal average Draize total scores (MAS)=15-50) for the evaluation of cosmetic ingredients. (2) Interlaboratory variation was relatively small for the alternative tests. The mean coefficients of variation (CV%) were less than 50 for all assays except for the hen's egg-chorioallantoic membrane test (HET-CAM), chorioallantoic membrane-trypan blue staining test (CAM-TB) and haemoglobin denaturation test (HD). The CV% of these three methods came into the same range as the other tests when non-irritants were excluded from the data analysis. (3) Results for acids (pH of 10% solution <2.5), alkalis (pH of 10% solution >11.5) and alcohols (lower mono-ol) in cytotoxicity tests clearly deviated from the other samples in the comparison of cytotoxicity with Draize results. (4) Pearson's correlation coefficients (r) between results from cytotoxicity tests using serum and MAS were -0.86 to -0.92 for samples excluding acids, alkalis and alcohols. (5) When the samples were divided into liquids and powders, r of CAM-TB increased from 0.71 for all samples to 0.80 and 0.92, respectively. (6) Spearman's rank correlation coefficients between the results of alternative methods and MAS were relatively high (r>0.8) in the case of HET-CAM and CAM-TB. Those for cytotoxicity tests were high if the data for acids, alkalis and alcohols were excluded (SIRC-CVS: r=0.945, SIRC-NRU: r=0.931, HeLa-MTT: r=0.926, CHL-CVS: r=0.880). Exclusion of data for powdered samples also increased the coefficient of HET-CAM and CAM-TB to 0.831 and 0.863, respectively. These results suggest that no single method can constitute an evaluation system applicable to all types of test substances by itself. However, several methods will be useful for the prediction of eye irritation potential of cosmetic ingredients if they are used with clear understanding of the characteristics of those methods.

Analysis of herpes virus group (DNA) from cerebrospinal fluid in vogt-koyanagi-harada disease.

In order to detect herpes virus group DNA including that of the Epstein-Barr virus (EBV) in patients with Vogt-Koyanagi-Harada disease (VKH), the authors employed the polymerase chain reaction (PCR) procedure using DNA from cerebrospinal fluid (CSF) obtained from patients with VKH. Method. Seven CSF samples were obtained from six definite, active VKH cases and DNA was isolated. DNA fragments containing parts of herpes simplex virus (HSV), herpes zoster virus (VZV), cytomegalo virus (CMV), EBV and human herpes virus type 6 (HHV-6) sequences were amplified by PCR. Results. No DNA fragment corresponding to the DNA sequence of the herpes virus group was detected. Conclusion. Our results suggest that the herpes virus group does not have a close association with the cause of VKH.

In vitro alternatives and phototoxicity testing. I. Evaluation of in vitro phototoxicity assays.

Three in vitro phototoxicity assays -- the photohaemolysis assay, the haemoglobin (Hb) photo-oxidation assay, and the 3T3 cell neutral red uptake phototoxicity (3T3 NRU PT) assay -- were evaluated for use as screening methods in predicting the phototoxicity of test substances. Twenty-seven test substances, including cosmetic ingredients and drugs, were assessed in this study. The phototoxicity predicted in each assay was compared with that in guinea-pigs. In total, nine phototoxic substances used in this study could be detected by some of the in vitro phototoxicity assays. Eleven test substances regarded as non-phototoxic in vivo were predicted as non-phototoxic in the in vitro assays. Of the eight false positives revealed in some of the in vitro assays, five are believed to be photo-allergens. This suggests that in vitro phototoxicity assays might not be able to discriminate clearly between in vivo phototoxicity and in vivo photo-allergy, because the mechanisms in both processes are based on photodynamic reactions. The predictability of the three in vitro assays was comparatively good, but positive predictive values were low. The equivalence values of the photohaemolysis assay, the Hb photo-oxidation assay and the 3T3 NRU PT assay were 81%, 70% and 70%, respectively. From these results, we suggest that the three in vitro phototoxicity assays could be used as screens in predicting phototoxicity.

In Vitro Alternatives and Phototoxicity Testing. II. Effects of Reactive Oxygen Species in In Vitro Phototoxicity Assays.

The effects of reactive oxygen species (including singlet oxygen) in two in vitro phototoxicity assays -- the 3T3 cell neutral red uptake phototoxicity (3T3 NRU PT) assay and the photohaemolysis assay -- were assessed by using scavengers. Fifteen test substances, which had previously been shown to be phototoxic in vitro, were assessed. Eleven of these produced singlet oxygen. The major factor in the photodynamic reaction of bithionol was thought to be a Type I reaction, because bithionol did not produce singlet oxygen and did not react to histidine. Acridine was regarded as a Type II substance, because of the evident effect of histidine as a scavenger. 8-Methoxypsoralen and 5-methoxypsoralen produced singlet oxygen, but their actions were not affected by the scavengers. In this study, we confirmed that reactive oxygen species have great effects in in vitro phototoxicity, and that the 3T3 NRU PT assay can be used to detect effects which are thought to be the direct reaction of an excited photosensitiser to biological substrates (Type III reaction), for example, 8-methoxypsoralen. Therefore, we suggest that photohaemolysis and phototoxicity could be used to evaluate the photodynamic mechanisms of photosensitising chemicals.

[A case of Marshall syndrome with secondary glaucoma due to spontaneous rupture of the lens capsule].

An eight-year-old boy developed acute glaucoma in his left eye. He was diagnosed as having Marshall syndrome because of bilateral cataract, high myopia, saddle nose, hypertelorism, and lack of arthropathy. When seen immediately after the glaucomatous attack, the affected eye showed ruptured anterior and posterior lens capsules and displacement of the lens nucleus into the anterior chamber and vitreous cavity. Lens extraction and vitrectomy induced normalization of intraocular pressure and visual acuity. There are forty cases reported in the world literature and only one cases in Japan. To the best of our knowledge, this is the first case treated successfully by vitreous surgery.

Dependence of beam emittance on plasma electrode temperature and rf-power, and filter-field tuning with center-gapped rod-filter magnets in J-PARC rf-driven H(-) ion source.

The prototype rf-driven H(-) ion-source with a nickel plated oxygen-free-copper (OFC) plasma chamber, which satisfies the Japan Proton Accelerator Research Complex (J-PARC) 2nd stage requirements of a H(-) ion beam current of 60 mA within normalized emittances of 1.5 π mm mrad both horizontally and vertically, a flat top beam duty factor of 1.25% (500 µs × 25 Hz) and a life-time of more than 50 days, was reported at the 3rd international symposium on negative ions, beams, and sources (NIBS2012). The experimental results of the J-PARC ion source with a plasma chamber made of stainless-steel, instead of nickel plated OFC used in the prototype source, are presented in this paper. By comparing these two sources, the following two important results were acquired. One was that the about 20% lower emittance was produced by the rather low plasma electrode (PE) temperature (TPE) of about 120 °C compared with the typically used TPE of about 200 °C to maximize the beam current for the plasma with the abundant cesium (Cs). The other was that by using the rod-filter magnets with a gap at each center and tuning the gap-lengths, the filter-field was optimized and the rf-power necessary to produce the J-PARC required H(-) ion beam current was reduced typically 18%. The lower rf-power also decreases the emittances.

Operation and development status of the J-PARC ion source.

A cesium-free H(-) ion source driven with a LaB6 filament is being operated at the Japan Proton Accelerator Research Complex (J-PARC) without any serious trouble since the restoration from the March 2011 earthquake. The H(-) ion current from the ion source is routinely restricted approximately 19 mA for the lifetime of the filament. In order to increase the beam power at the linac beam operation (January to February 2013), the beam current from the ion source was increased to 22 mA. At this operation, the lifetime of the filament was estimated by the reduction in the filament current. According to the steep reduction in the filament current, the break of the filament was predicted. Although the filament has broken after approximately 10 h from the steep current reduction, the beam operation was restarted approximately 8 h later by the preparation for the exchange of new filament. At the study time for the 3 GeV rapid cycling synchrotron (April 2013), the ion source was operated at approximately 30 mA for 8 days. As a part of the beam current upgrade plan for the J-PARC, the front end test stand consisting of the ion source and the radio frequency quadrupole is under preparation. The RF-driven H(-) ion source developed for the J-PARC 2nd stage requirements will be tested at this test stand.

Development of an H- ion source for Japan Proton Accelerator Research Complex upgrade.

A cesium (Cs) free H(-) ion source driven with a lanthanum hexaboride (LaB(6)) filament was adopted as an ion source for the first stage of the Japan Proton Accelerator Research Complex (J-PARC). At present, the maximum H(-) ion current produced by the ion source is 38 mA, using which J-PARC can produce a proton beam power of 0.6 MW by accelerating it with the 181 MeV linac and the 3 GeV rapid cycling synchrotron. In order to satisfy the beam power of 1 MW required for the second stage of the J-PARC in the near future, we have to increase the ion current to more than 60 mA. Therefore, we have started to develop a Cs-seeded ion source by adding an external Cs-seeding system to a J-PARC test ion source that has a structure similar to that of the J-PARC ion source except for the fact that the plasma chamber is slightly larger. As a result, a H(-) ion current of more than 70 mA was obtained from the ion source using a tungsten filament instead of a LaB(6) filament with a low arc discharge power of 15 kW (100 V, 150 A).

Recent operation status of Japan Proton Accelerator Research Complex H- ion source.

A cesium-free H(-) ion source driven with a LaB(6) filament is being operated at the Japan Proton Accelerator Research Complex for approximately three years without any serious trouble. In the beam commissioning or supply runs, the ion source has been operated in two different modes such as low current mode of 5 mA and high current mode of 30 mA. The total interruption time during the runs due to the ion source failure is approximately 50 h, which correspond to the ion source availability of 99%. After a long-term operation, the surface of the filament and the plasma electrode become discolored with dark partially. The result of surface analysis with field emission scanning electron microscope showed that most of the dark material is formed with boron. At the beam test performed in the interval of the run, we demonstrated that the H(-) current increased by miniaturizing the LaB(6) filament.

A survey of optimal filament shape in a Japan Proton Accelerator Research Complex H- ion source.

Dependence of various shapes of lanthanum hexaboride (LaB(6)) filaments on H(-) ion currents (I_H(-)'s) was examined by using the first Japan Proton Accelerator Research Complex (J-PARC) test ion source. It is almost the same with the J-PARC H(-) ion source (J-PARC-IS) except for the maximum arc current (290 A instead of 400 A). An I_H(-) of 35.2 mA was extracted by using a cylindrical double-spiral LaB(6) filament with a diameter of 29.5 mm and a length of 35.5 mm, which is the same one used in J-PARC-IS. It increased to 43.4 mA with a flat triple-hairpin LaB(6) filament. The I_H(-) is considered to be increased by the enlargement of the high density plasma region near the plasma electrode aperture and the reduction of the LaB(6) filament unemission area located in the high density plasma region.