52 research outputs found

    The time variation of dose rate artificially increased by the Fukushima nuclear crisis

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    A car-borne survey for dose rate in air was carried out in March and April 2011 along an expressway passing northwest of the Fukushima Dai-ichi Nuclear Power Station which released radionuclides starting after the Great East Japan Earthquake on March 11, 2011, and in an area closer to the Fukushima NPS which is known to have been strongly affected. Dose rates along the expressway, i.e. relatively far from the power station were higher after than before March 11, in some places by several orders of magnitude, implying that there were some additional releases from Fukushima NPS. The maximum dose rate in air within the high level contamination area was 36 μGy h−1, and the estimated maximum cumulative external dose for evacuees who came from Namie Town to evacuation sites (e.g. Fukushima, Koriyama and Nihonmatsu Cities) was 68 mSv. The evacuation is justified from the viewpoint of radiation protection

    Prediction of the <sup>137</sup>Cs activity concentration in the atmospheric surface layer of the Chernobyl exclusion zone.

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    The time series of the 10-day average Cs-137 volumetric activity concentration in the lower atmosphere measured from 1987 to 1991 in the town of Pripyat, close to the Chernobyl nuclear power plant, was used to construct a model to predict the airborne activity concentration inside the 30-km exclusion zone. For that purpose, individual components of the observed time series were separated by regression analysis and the Group Method of Data Handling. The measured data in Pripyat were divided in two periods. The long-term prediction by the model established using the measured data of the first period, has been validated with the data in the second period with good agreement. The behaviour of the model parameters depending on the length of the periods was also analysed, and the first period of 4.5 y was shown as sufficient for estimating the parameters. Further increase in the length will not significantly enhance the model parameters and the predictive power

    Increased branching and sialylation of N-linked glycans correlate with an improved pharmacokinetic profile for BAY 81&ndash;8973 compared with other full-length rFVIII products

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    John M Teare,1 David S Kates,1 Anita Shah,2 Stephen Garger1 1Biological Development, Bayer US LLC Pharmaceuticals, Berkeley, CA, USA; 2Pharmacokinetics Pharmacodynamics Hematology, Bayer US LLC Pharmaceuticals, Whippany, NJ, USA Background: BAY 81&ndash;8973 (Kovaltry) is an unmodified full-length recombinant factor VIII (rFVIII) for treatment of hemophilia A. The BAY 81&ndash;8973 manufacturing process results in a product of enhanced purity with a consistently high degree of branching and sialylation of N-linked glycans. This study evaluated whether a relationship exists between N-linked glycosylation patterns of BAY 81&ndash;8973 and two other rFVIII (sucrose-formulated rFVIII [rFVIII-FS; Kogenate FS]) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM; Advate) and their pharmacokinetic (PK) characteristics.Materials and methods: N-linked glycans or terminal carbohydrates were enzymatically removed from immobilized BAY 81&ndash;8973, rFVIII-FS, and rAHF-PFM proteins and analyzed using high-performance liquid chromatography to determine the percentage of individual N-linked glycan structures and degree of sialylation of each structure. PK data were available from two separate phase 1 crossover studies in which the PK profile of BAY 81&ndash;8973 was compared with that of rFVIII-FS (n=26) and rAHF-PFM (n=18) in patients with severe hemophilia A who received a single 50 IU/kg dose of each product.Results: BAY 81&ndash;8973 and rFVIII-FS had increased N-linked glycan branching with higher levels of sialylation compared with rAHF-PFM. Levels of trisialylated glycans were 29.0% for BAY 81&ndash;8973 vs 11.5% for rFVIII-FS and 4.8%&ndash;5.5% for rAHF-PFM; tetrasialylated glycans were 12.0% vs 2.8% and 0.6%, respectively. Degree of sialylation was 96% for BAY 81&ndash;8973, 94% for rFVIII-FS, and 78%&ndash;81% for rAHF-PFM. Based on chromogenic assay results from the single-dose phase 1 PK studies, BAY 81&ndash;8973 half-life was 15% longer than that for rFVIII-FS and 16% longer than rAHF-PFM.Conclusion: Increased N-glycan branching and sialylation were seen for BAY 81&ndash;8973 vs rFVIII-FS and rAHF-PFM. Improved PK for BAY 81&ndash;8973 relative to rFVIII-FS and rAHF-PFM as seen in single-dose crossover PK studies might be related to this greater level of branching and sialylation, which can prolong the time BAY 81&ndash;8973 remains in the circulation. Keywords: clearance, glycan structure, glycosylation, half-life &nbsp
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