Technical investigation on small water leakage incident occurrence in mercury target of J-PARC

Japan Proton Accelerator Research Complex experienced failures of two mercury targets, which were Target #5 and #7, in 2015 when the facility was operating with a proton beam power of 500 kW. The failures involved coolant water leak from the water shroud. In this paper, we investigate the root cause of the Target #5 failure. The results of the visual inspections, mockup tests, and analytical evaluations suggested that the water leak was caused by the possible combination of two incidents. One was the diffusion bonding failure due to the large thermal stress induced by welding of the bolt head during the fabrication process, and the other was the thermal fatigue failure of the seal weld due to the repetitive beam shutdown during beam operation. Though the investigation into the root cause of the Target #7 failure is still going on, these target failures point to the importance of eliminating initial defects and the need to secure the rigidity and stability of welded structures. The next mercury target, Target #8, was fabricated with an improved design and fabrication process to reduce the possibility of similar failures. The beam operation of this mercury target is planned to be started in October 2017.     

Dermatan sulfate enhances the lysis of laser-induced thrombus in vivo

Direct chiral resolution of four major flavanones recovered from post-administrative urine of the traditional Chinese medicines Daisaiko-to and Shosaiko-to was achieved by high-performance liquid chromatography (HPLC) on macroporous silica gel coated with cellulose tris(3,5-dimethylphenylcarbamate), Chiralcel OD. Chromatographic conditions were optimized so as to attain satisfactory enantiomeric resolution of the polysubstituted flavanones. Urinary liquiritigenin and naringenin were considerable mixtures of R and S-enantiomers, while S-enantiomers of dihydrowogonin and dihydrooroxylin A were predominantly excreted. Our chiral HPLC techniques can be applied to pharmacokinetical evaluation of the chiral flavanone enantiomers following oral administration of the herbal medicines.     

A bioassay for serum interferon based on induction of 2''5''-oligoadenylate synthetase activity

BACKGROUND: Patients treated for primary hyperparathyroidism run an increased risk of death. The aim of this study was to analyse several factors that may influence their risk of death. METHODS: General, laboratory, physical and clinical variables, altogether 34 variables, were defined as possible risk factors for death and were studied in a patient series of 845 patients operated on during the period 1953-82. Mean follow-up time was 10.5 years (SD 5.9); 253 patients were deceased at follow-up. Cox's proportional hazard model was used. RESULTS: We found seven variables with independent influence on the risk of death: age, sex, diabetes, cardiovascular disease, glomerular filtration rate, renal tubular concentration capacity and amount of diseased parathyroid tissue. The remaining 27 variables were separately tested, one at a time, using the same method and with the influence of age and sex eliminated. In this test situation, the year of surgery, peak serum calcium, serum creatinine level, body mass index, hypertension, psychiatric symptoms and a history of crisis were all significantly related to the risk of death. The analyses also gave information on the direction and magnitude of the effect of the variables on the risk of death. CONCLUSION: Primary hyperparathyroidism itself is a risk factor for death, but it was concluded that well-preserved renal function at surgery seems to have a protective role. We also found that the greater the amount of diseased parathyroid tissue the lesser the renal function and, furthermore, that hyperparathyroidism of substantial degree or long duration may bring about renal impairment that is not necessarily disclosed by the creatinine value alone.     

Genetic polymorphisms of cytochrome P4502E1 related to the development of alcoholic liver disease

BACKGROUND/AIMS: Because heavy drinkers do not always develop alcoholic liver disease (ALD), genetic factors may be involved. Cytochrome P4502E1 is the main enzyme that oxidizes ethanol in the non-alcohol dehydrogenase pathway. Recently, the presence of genetic polymorphisms of this enzyme was confirmed. In the present study, the genotypes of P4502E1 were analyzed in patients with or without ALD. METHODS: After extraction of DNA from white blood cells, genotypes of P4502E1 were determined by restriction fragment length polymorphisms using two endonucleases. The genotypes were separated into three types: type A, type C (homozygous for the c1 or c2 gene), and type B (heterozygous for both genes). RESULTS: In 50 patients with ALD, the prevalence of type A was 16% and that of the c2 gene was 84%. The genotypes in 10 heavy drinkers without ALD were all type A. In 34 patients with non-alcoholic liver disease and in 88 patients without hepatobiliary disease, the prevalence of type A was 65% and 71%, respectively, indicating a significantly higher prevalence of the c2 gene in ALD. In healthy nonalcoholics, the prevalence of type A was 62%-68%. CONCLUSIONS: These results suggest that polymorphisms of P4502E1 may be related to the development of ALD.     

Development of a colon delivery capsule and the pharmacological activity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in beagle dogs

A peroral dosage form was examined to deliver recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the colon in beagle dogs. A new gelatin capsule with its inside surface coated with ethylcellulose was prepared for this purpose. RhG-CSF was dissolved with propylene glycol and was filled in the capsule. Several kinds of ethylcellulose-gelatin capsules with an ethylcellulose layer of thickness 46 to 221 mm were used. The capsule was filled with propylene glycol solution containing fluorescein as an absorption marker, castor oil derivative and citric acid. The hardness of the capsule was tested after the gelatin layer was dissolved using a hardness tester and was dependent on the thickness of the ethylcellulose layer of the capsule. The time, Tmax, at which plasma fluorescein level reaches its maximum following oral administration of ethylcellulose capsules was used as a parameter for the in-vivo disintegration time of the ethylcellulose capsule into the colon. Capsules of thickness 84 mm with a Tmax of 4-6 h were filled with rhG-CSF solution containing fluorescein and were administered to dogs. After administration, blood samples were collected for 96 h and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The maximum BTL count appeared at 10 h then gradually decreased and returned to its normal level at 48 h. These results suggest the usefulness of ethylcellulose capsules for the delivery of rhG-CSF to the colon and the possibility of a new oral rhG-CSF dosage form has been elucidated.     

Progress in space charge measurement of solid insulating materialsin Japan

The space charge measurement technique may be applied to diagnostic technology for high-voltage machines in the near future. The authors review the progress in the various methods of space charge measurement in Japan     

Wnt signaling from the dorsal neural tube is required for the formation of the medial dermomyotome

Signals originating from tissues surrounding somites are involved in mediolateral and dorsoventral patterning of somites and in the differentiation of the myotome. Wnt-1 and Wnt-3a, which encode members of the Wnt family of cystein-rich secreted signaling molecules, are coexpressed at the dorsal midline of the developing neural tube, an area adjacent to the dorsomedial portion of the somite. Several lines of evidence indicate that Wnt-1 and Wnt-3a have the ability to induce the development of the medial and dorsal portion of somites, as well as to induce myogenesis. To address whether these Wnt signalings are really essential for the development of somites during normal embryogenesis, we investigated the development of somites in mouse embryos lacking both Wnt-1 and Wnt-3a. Here we demonstrate that the medial compartment of the dermomyotome is not formed and the expression of a lateral dermomyotome marker gene, Sim-1, is expanded more medially in the absence of these Wnt signalings. In addition, the expression of a myogenic gene, Myf-5, is decreased at 9.5 days post coitum whereas the level of expression of a number of myogenic genes in the later stage appeared normal. These results indicate that Wnt-1 and Wnt-3a signalings actually regulate the formation of the medial compartment of the dermomyotome and the early part of myogenesis.