Evaluation of the protective efficacy of reshaped human monoclonal antibody RSHZ19 against respiratory syncytial virus in cotton rats

Reshaped human MAb RSHZ19, which is specific for the surface fusion protein of respiratory syncytial virus (RSV) is in clinical development for the prevention and treatment of RSV-induced disease in human infants. The current studies profile lung virus clearance and evaluate lung histopathology in MAb-treated, RSV-infected cotton rats, a well characterized model of RSV infection. The highest dose of this MAb (10 mg/kg) administered parenterally 24 h before infection decreased subgroup A or B RSV lung titers to below detectable levels (> or = 2.3 log10 reduction), and significantly reduced lung virus titers (> or = 2.0 log10 reduction) when administered 96 h postinfection. Prophylactic administration of 10 mg/kg RSHZ19 was significantly more protective than 1000 mg/kg conventional human immune serum globulin (HSIg), and protective serum-neutralizing titers in MAb-treated animals (1:32, which correlated with approximately 40 micrograms/ml determined by anti-idiotype ELISA) were significantly lower than those reported previously for HSIg or for convalescent human serum (1:200-1:400). MAb concentration in lung lavages was determined by ELISA to be approximately 1% of the serum MAb concentration, but was not detectable by neutralization assay. The degree of lung histopathology in MAb-treated cotton rats was proportional to lung virus titer, and inversely proportional to the RSHZ19 dose administered. There was no evidence of exacerbated disease in the lungs of MAb-treated animals. These studies thus support the potential clinical utility of RSHZ19 MAb in the prevention and treatment of RSV-induced disease in humans.     

Smoke data from the Cone Calorimeter for comparison with the room fire test

Smoke production in the full–scale room fire test ISO 9705 (Commonly referred to as the Room Corner Test) and in the Cone Calorimeter ISO 5660 has been analysed for three sets of building products comprising a total of 28 products. The smoke production may be critical for the fire classification of surface products since some products produce large amounts of smoke in the room fire test even if they do not reach flashover within 20 min. Several smoke parameters in the Cone Calorimeter and the room fire test have been analysed. Good correlations have been obtained when the products are divided into two groups: products with more than 10 min to flashover in the room fire test and those with less than 10 min. These two time categories correspond to the two heat output levels in the room fire test: 100 kW for the first 10 min and then 300 kW up to 20 min. For products with more than 10 min to flashover the average rate of smoke production and the total smoke production seem to be useful parameters for predictions of smoke release in the room fire test. Both parameters have good correlations between data from the Cone Calorimeter and the room fire test. For products with less than 10 min to flashover no parameter seems to give useful predictions. For all products evaluated together, the correlations are not so good, but the same regression lines as for products with more than 10 min might be used as a first rough estimate. In this case the total smoke production in the Cone Calorimeter could be used to estimate the total smoke production in the room fire test for different building products, independent of their estimated time to flashover. It is suggested that the average rate of smoke production and the total smoke production from the Cone Calorimeter is reported in addition to the mass-based specific extinction area. This will be helpful in predicting smoke release in the room fire test and will also make the data on smoke release analogous to those on heat release.     

Rate of heat release by oxygen consumption in an open test arrangement

Equipment has been developed for measuring the rate of heat release from building materials in an open test arrangement. The method is based on an oxygen consumption technique. A vertical sample is placed under an open hood in which the combustion gases and a certain amount of air are collected. The decrease in oxygen concentration and the mass flow of the gases are measured in the exhaust duct. The rate of heat release is then calculated. The equipment has been calibrated with good agreement between input and measured effects. The total response time for the system is 10s. The method has been used for testing building materials at radiation intensities up to 5W Cm^?2. It is able to distinguish between different board materials, and the repeatability is good, The paper describes the equipment, including the weighing of a burning sample and the selection of test condition. Smoke and gas analysis can be added when desirable. Some test results with building materials are also presented.     

Simulation of lung function evolution after heart-lung transplantation using a numerical model

A morphometry-based computational model for expiratory flow in humans was used to study the unusual configuration of the maximum expiratory flow-volume (MEFV) curve associated with alterations in lung function after heart-lung transplantation (HLT). The postoperative MEFV curve showed a peak, followed by a gently sloping plateau over the midvolume range, ending in a knee where the flow suddenly fell, instead of the usual observed uniform decrease in expiratory flow. We have tested several hypotheses about the relationship between the pattern of changes in the configuration of the MEFV curve and pathological changes in the airway mechanics through computer simulations. Principally, effects of lung denervation and airway obstruction, associated with the development of bronchiolitis obliterans in the lung periphery, have been investigated. The calculated curves are similar in appearance to the measured postoperative flow-volume curves and confirm reliability of the earlier hypotheses. We conclude that the plateau-knee configuration of the MEFV curve can result from flow limitation in one of the first airway generations, that this flow limitation coupled with an increase in peripheral airway resistance results in plateau shortening, and that flows exceeding predicted values during the second part of expiration may be produced by lung denervation. Additionally our results demonstrate that airways larger than the transitional and respiratory bronchioles can be involved in pulmonary function deterioration observed in patients affected with obliterative bronchiolitis. Our findings indicate that the computational model, based on a symmetrical dichotomous branching structure of the bronchial tree, along with pathological data, can be employed to evaluate the effects of heterogeneous changes in the lung periphery. Index Terms-Airway mechanics, forced expiration, lung transplantation, mathematical modeling, maximal expiratory flow-volume curve.     

Oligosaccharide mimics containing galactose and fucose specifically label tumour cell surfaces and inhibit cell adhesion to fibronectin

With the aim of establishing a versatile and easy synthesis of branched saccharides for biological applications, we used molecular-dynamics simulations to model Lewis(y) to two classes of di- or triantennary saccharide mimetics. One set of mimetics was based on 1,3,5-tris(hydroxymethyl)cyclohexane (TMC) as the core, the other on furan, and both were derivatised with galactose and/or fucose. The TMC-based saccharides were biotinylated, while the furan disaccharides were treated with maleimide-activated biotin in a Diels-Alder fashion to yield oxazatricyclodecanes (OTDs). These were then assayed as cell-surface labels in human colon (SW480 and CaCo-2), liver (PLC), Glia (U333 CG 343) and ovary (SKOV-3) tumour cell lines. Discrete staining patterns were observed in all cells, usually at one or two poles of the cells, particularly with the asymmetric 3-beta-L-fucopyranosyloxymethyl-4-beta-D-galactopyranosyloxymethyl-OTD. Normal SV40-transformed fibroblasts (SV80) showed no staining. Adhesion of the highly metastatic mouse melanoma line B16 F10 to fibronectin was inhibited by 80 % by the TMC-digalactoside and by 30 % by 3,4-bis-(beta-D-galactopyranosyloxymethyl)furan. None of the saccharide mimetics inhibited the adhesion of the less metastatic B16 F1 line. Migration of B16 F10 cells through Matrigel was greatly inhibited by the TMC-digalactoside and weakly inhibited by the TMC-trigalactoside. The saccharide mimetics that had shown the best structural agreements with the terminal saccharides of Lewis(y) in the molecular dynamics simulation were also the most biologically potent compounds; this underlines the predictive nature of molecular dynamics simulations. The use of the non-saccharide cores enabled us to adapt spacer lengths and terminal saccharides to optimise the structures to bind more avidly to cell-surface lectins.     

Regional differences in collagen stable isotope and tissue trace element profiles in populations of long-tailed duck breeding in the Canadian Arctic

Adult long-tailed ducks (Clangula hyemalis) were collected from nine locations across their breeding grounds in northern Canada and measurements of stable isotopes of carbon (delta(13)C), nitrogen (delta(15)N) and sulfur (delta(34)S) in bone collagen were used to investigate if relative use of freshwater habitats such as the Great Lakes (with expected depleted stable isotope profiles) compared with coastal marine environments (with expected enriched stable isotope foodweb profiles) could explain tissue trace element profiles. Contrary to expectation, all three stable isotopes did not covary in our sample, suggesting that mechanisms other than simple freshwater vs. marine isotopic gradients were involved among populations. All three stable isotopes varied significantly with collection location and both delta(15)N and delta(13)C values varied significantly between sexes suggesting that males exploit either a different food base or occur in different geographic areas than females for at least part of the year. The delta(34)S data, in particular, suggested that many of the birds breeding in the western Canadian Arctic probably overwinter in the Great Lakes along with many of the birds breeding in Hudson Bay. Males at the majority of collection locations had higher concentrations of hepatic Hg (1.1-8 microg/g dw), Cu (25-40 mug/g dw), Se (7.3-27 mug/g dw) and renal Cd (33-129 microg/g dw) than females. Concentrations of Hg, Cu and Cd were well below toxicological threshold levels found in the literature. However, hepatic Se concentrations in 64% of the females exceeded 10 mug/g dw and concentrations in 8% of the birds measured exceeded 33 microg/g dw suggesting levels of potential concern.     

Ignitability as proposed by the international standards organization compared with some european fire tests for building panels

Ignitability, one of the new fire test methods for building materials developing within the International Standards Organization is compared with the national fire test methods in Austria, Britain, France, Germany and Scandinavia. Different commercial wood-based panels have been tested, including fire retardant treated panels. The International Standards Organization ignitability test measures the time to ignition at radiation intensities from 1 to 5 Wm ^?2; it seems to be able to distinguish between different materials in an intelligible way. An evaluation of the results of this ignitability test is discussed. One possibility which is proposed here is to calculate the mean time to ignition at different fixed radiation intensities; such a mean value simplifies the evaluation and takes into account all the test data. Agreement with the national fire test methods is rather low, since they partly measure other fire parameters; agreement with the Austrian Schlyter method, which also evaluated ignitability, is somewhat better and agreement between the national fire test methods is relatively good for wood-based panels. This is consistent with earlier experience, which has shown that mainly new types of materials behave differently according to different national test methods.     

Modular process for the flexible synthesis of magnetic beads—Process and product validation

Here we present a modular process for the flexible production of magnetic beads with variable magnetic properties and anion or cation exchanger functionalities. Magnetic beads are used in bio‐separations and downstream processing to remove a valuable substance from e.g., a fermentation broth (Magnetic Fishing). The magnetic beads we are presenting here consist of a composite material, containing nanoscale magnetite and ion exchanger particles which are embedded into a polymer matrix. With this composite concept, anion and cation exchanger properties are available in magnetic beads with different matrix polymers (PVB, PVA, PMMA, and PVAc). The content of magnetite was varied in a range between 0 and 40 wt %, ion exchanger particles between 0 and 60 wt % and the matrix polymer between 20 and 60 wt %. The magnetic bead characteristics, which determine the application properties, are shown. Thermo gravimetrical analyses, FTIR spectra and measurements of the ion exchange capacity prove the different properties in respect to the magnetic beads composition. In an adsorption experiment, it was possible to achieve a maximum capacity of 270 mg/g for β‐galactosidase with PVB‐beads. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009