72 research outputs found

    Utilization of Lapsi seed stone (choerospondias axillaris) as source of activated charcoal for removal of arsenic

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    People inhabited in Terai region of Nepal use ground water as the main source of drinking water that are contaminated with arsenic at concentration level higher than guide line value set by WHO. The arsenic in the ground water is originated from the dissolution of naturally occurring arsenic containing minerals. Nepal, being a poor country, cannot afford to adopt costly and sophisticated technology to remove arsenic. Adsorptive removal of arsenic utilizing the activated charcoal prepared from the locally available Lapsi (chorespondias axillaris, Roxb) seed stone is presented. Tons of Lapsi seed stones are generated as waste which can be carbonized to activated charcoal. The adsorption capacity for arsenic is quite low for raw charcoal but activation followed by iron impregnation greatly enhances it. The low cost activated charcoal prepared from locally available Lapsi seed stones can be used in community level at point- of- use treatment for arsenic contaminated ground water of Terai region of Nepal

    A long-acting GH receptor antagonist through fusion to GH binding protein.

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    Acromegaly is a human disease of growth hormone (GH) excess with considerable morbidity and increased mortality. Somatostatin analogues are first line medical treatment but the disease remains uncontrolled in up to 40% of patients. GH receptor (GHR) antagonist therapy is more effective but requires frequent high-dose injections. We have developed an alternative technology for generating a long acting potent GHR antagonist through translational fusion of a mutated GH linked to GH binding protein and tested three candidate molecules. All molecules had the amino acid change (G120R), creating a competitive GHR antagonist and we tested the hypothesis that an amino acid change in the GH binding domain (W104A) would increase biological activity. All were antagonists in bioassays. In rats all antagonists had terminal half-lives >20 hours. After subcutaneous administration in rabbits one variant displayed a terminal half-life of 40.5 hours. A single subcutaneous injection of the same variant in rabbits resulted in a 14% fall in IGF-I over 7 days. IN CONCLUSION: we provide proof of concept that a fusion of GHR antagonist to its binding protein generates a long acting GHR antagonist and we confirmed that introducing the W104A amino acid change in the GH binding domain enhances antagonist activity

    Velocity-selective direct frequency-comb spectroscopy of atomic vapors

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    We present an experimental and theoretical investigation of two-photon direct frequency-comb spectroscopy performed through velocity-selective excitation. In particular, we explore the effect of repetition rate on the 5S1/2→5D3/2,5/2\textrm{5S}_{1/2}\rightarrow \textrm{5D}_{3/2, 5/2} two-photon transitions excited in a rubidium atomic vapor cell. The transitions occur via step-wise excitation through the 5P1/2,3/2\textrm{5P}_{1/2, 3/2} states by use of the direct output of an optical frequency comb. Experiments were performed with two different frequency combs, one with a repetition rate of ≈925\approx 925 MHz and one with a repetition rate of ≈250\approx 250 MHz. The experimental spectra are compared to each other and to a theoretical model.Comment: 10 pages, 7 figure

    Immunogenicity, toxicology, pharmacokinetics and pharmacodynamics of growth hormone ligand-receptor fusions A B S T R A C T

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    A fundamental concern for all new biological therapeutics is the possibility of inducing an immune response. We have recently demonstrated that an LR-fusion (ligand-receptor fusion) of growth hormone generates a potent long-acting agonist; however, the immunogenicity and toxicity of these molecules have not been tested. To address these issues, we have designed molecules with low potential as immunogens and undertaken immunogenicity and toxicology studies in Macaca fascicularis and pharmacokinetic and pharmacodynamic studies in rats. Two variants of the LR-fusion, one with a flexible linker (GH-LRv2) and the other without (GH-LRv3), were tested. Comparison was made with native human GH (growth hormone). GH-LRv2 and GHLRv3 demonstrated similar pharmacokinetics in rats, showing reduced clearance compared with native GH and potent agonist activity with respect to body weight gain in a hypophysectomized rat model. In M. fascicularis, a low level of antibodies to GH-LRv2 was found in one sample, but there was no other evidence of any immunogenic response to the other fusion protein. There were no toxic effects and specifically no changes in histology at injection sites after two repeated administrations. The pharmacokinetic profiles in monkeys confirmed long half-lives for both GHLRv2 and GH-LRv3 representing exceptionally delayed clearance over rhGH (recombinant human GH). The results suggest that repeated administration of a GH LR-fusion is safe, non-toxic, and the pharmacokinetic profile suggests that two to three weekly administrations is a potential therapeutic regimen for humans

    The cold regions hydrological modelling platform for hydrological diagnosis and prediction based on process understanding

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    Natural Sciences and Engineering Research Council of Canada, Environment Canada, Indian and Northern Affairs Canada, Yukon Environment, the Forest Resource Improvement Association of Alberta, Alberta Agriculture and Forestry, Alberta Environment, Ducks Unlimited Canada, Water Security Agency of Saskatchewan, Natural Environment Research Council (UK), IPE-CSIC (Spain), Canada Research Chair and Canada Excellence Research Chairs programmes, Canada First Research Excellence Fund’s Global Water Futures programmePeer ReviewedCold regions involve hydrological processes that are not often addressed appropriately in hydrological models. The Cold Regions Hydrological Modelling platform (CRHM) was initially developed in 1998 to assemble and explore the hydrological understanding developed from a series of research basins spanning Canada and international cold regions. Hydrological processes and basin response in cold regions are simulated in a flexible, modular, object-oriented, multiphysics platform. The CRHM platform allows for multiple representations of forcing data interpolation and extrapolation, hydrological model spatial and physical process structures, and parameter values. It is well suited for model falsification, algorithm intercomparison and benchmarking, and has been deployed for basin hydrology diagnosis, prediction, land use change and water quality analysis, climate impact analysis and flood forecasting around the world. This paper describes CRHM’s capabilities, and the insights derived by applying the model in concert with process hydrology research and using the combined information and understanding from research basins to predict hydrological variables, diagnose hydrological change and determine the appropriateness of model structure and parameterisations
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