BAW-Brief Nr. 3 – April 2012

612-B, Bautechnik, Untersuchungen zu Zwischenhaftungsproblemen bei Korrosionsschutzbeschichtungen für den Stahlhochba

Harmonization of growth hormone measurements with different immunoassays by data adjustment

Background: The aim of our study was to evaluate the between-assay variability of commercially available immunoassays for the measurement of human growth hormone (hGH). In addition, we asked whether the comparability of the diagnosis of childhood onset growth hormone deficiency could be improved by adjusting hGH results by statistical methods, such as linear regression, conversion factors, and quantile transformation. Methods: In archived sera from 312 children and adolescents (age: 17 days-17 years) hGH values between 0.01 and 16.5 ng/mL were determined by using the following immunoassays: AutoDELFIA (PerkinElmer), BC-IRMA (Beckman-Coulter), ELISA (Mediagnost), IMMULITE 2000 (Siemens), iSYS (IDS), Liaison (DiaSorin), UniCel DxI 800 Access (BeckmanCoulter) and "In house"-RIA (Tubingen). Results: The assays differed in median hGH concentrations by as much as 5.44 ng/mL (Immulite), and as little as 2.67 ng/mL (BC-IRMA). The mean difference between assays ranged from 0.35 to 2.71 ng/mL, whereas several samples displayed differences up to 11.4 ng/mL. The best correlation (r=0.992) was found between AutoDELFIA and Liasion, the lowest (r=0.864) was between an in-house RIA and iSYS. The between-assay CV (mean +/- SD) of values within the cut-off range was 24.3%+/- 7.4%, resulting in an assay-dependent diagnosis of growth hormone deficiency (GHD) in more than 27% of patients. Yet, adjustment of this data by linear regression or a conversion factor reduced the CV below 14%, and the ratio of assay-dependent diagnoses below 8%. Using quantile transformation, the CV and ratio were reduced to 11.4% and < 1%, respectively. Conclusions: hGH measurements using different assays vary significantly. Linear regression, conversion factors, or particularly quantile transformation are useful tools to improve comparability in the diagnostic procedure for the confirmation of GHD in childhood and adolescence

The early recognition of environmental impacts

In developing countries problems concerning water quality have agravated during the last decade. While in industrialized countries the traditional and modern types of water pollution (e.g. domestic, industrial, nutrients) occured in over a 100- year period, in developing countries however they have occured within one generation [WHO, 1989]. Short time technical measures have important immediate effects, but for achieving sustainability it is critical to develop tools for long term planning which allow a better understanding of how different strategies affect outcomes and how strategies are sensitive to different levels and types of financing [Bower, 1989]. In industrialized countries the method of Material Flux Analysis (MFA), has been shown to be a suitable instrument for early recognition of environmental problems and evaluation of environmental measures [Baccini and Brunner, 1991]. It has been shown that it is possible to combine data from market research on one hand with data from urban waste management on the other hand to observe the metabolic dynamics of a region [Baccini et al. 1993]. However, this method has not been applied yet in Developing Countries due to the low data availability and the poor data quality. The aim of this paper is to show how the method of MFA was applied to a region in a Developing Country with regard to water resource management

Implications of the E-selectin S128R mutation for drug discovery

The C-type lectin E-selectin mediates the rolling of circulating leukocytes on vascular endothelial cells during the inflammatory process. In numerous studies, the S128R mutation of the E-selectin was associated with cardiovascular and autoimmune diseases. There is evidence that the S128R E-selectin mutation leads to a loss in ligand specificity, thus increasing leukocyte recruitment. Apart from the natural tetrasaccharide ligand sialyl Lewisx (sLex), it has previously been proposed that non-fucosylated carbohydrates also bind to S128R E-selectin. To evaluate the therapeutic potential of the antagonism of the E-selectin mutant, ligand specificity was reinvestigated on a molecular basis. We determined the ligand specificity of wild-type and S128R E-selectin in a target-based competitive assay, a glycan array screen and cell-based binding assays under static and flow conditions. Regarding ligand-specificity, the binding properties of S128R E-selectin were identical to those of wt E-selectin, i.e., no mutant-specific binding of 3′-sialyl-N-acetyllactosamine, heparin, fetuin and K562 cells was observed. Additionally, the binding affinities of glycomimetic E-selectin antagonists were identical for wt and S128R E-selectin. Overall, the previous reports on carbohydrate ligand promiscuity of S128R E-selectin could not be confirme

Late stage, non-equilibrium dynamics in the dipolar Ising model

Magnetic domain structures are a fascinating area of study with interest deriving both from technological applications and fundamental scientific questions. The nature of the striped magnetic phases observed in ultra-thin films is one such intriguing system. The non-equilibrium dynamics of such systems as they evolve toward equilibrium has only recently become an area of interest and previous work on model systems showed evidence of complex, slow dynamics with glass-like properties as the stripes order mesoscopically. To aid in the characterization of the observed phases and the nature of the transitions observed in model systems we have developed an efficient method for identifying clusters or domains in the spin system, where the clusters are based on the stripe orientation. Thus we are able to track the growth and decay of such clusters of stripes in a Monte Carlo simulation and observe directly the nature of the slow dynamics. We have applied this method to consider the growth and decay of ordered domains after a quench from a saturated magnetic state to temperatures near and well below the critical temperature in the two dimensional dipolar Ising model. We discuss our method of identifying stripe domains or clusters of stripes within this model and present the results of our investigations.Comment: 17 pages, 12 figures, submitted to JMM

Scaling and Universality in the Counterion-Condensation Transition at Charged Cylinders

We address the critical and universal aspects of counterion-condensation transition at a single charged cylinder in both two and three spatial dimensions using numerical and analytical methods. By introducing a novel Monte-Carlo sampling method in logarithmic radial scale, we are able to numerically simulate the critical limit of infinite system size (corresponding to infinite-dilution limit) within tractable equilibration times. The critical exponents are determined for the inverse moments of the counterionic density profile (which play the role of the order parameters and represent the inverse localization length of counterions) both within mean-field theory and within Monte-Carlo simulations. In three dimensions (3D), correlation effects (neglected within mean-field theory) lead to an excessive accumulation of counterions near the charged cylinder below the critical temperature (condensation phase), while surprisingly, the critical region exhibits universal critical exponents in accord with the mean-field theory. In two dimensions (2D), we demonstrate, using both numerical and analytical approaches, that the mean-field theory becomes exact at all temperatures (Manning parameters), when number of counterions tends to infinity. For finite particle number, however, the 2D problem displays a series of peculiar singular points (with diverging heat capacity), which reflect successive de-localization events of individual counterions from the central cylinder. In both 2D and 3D, the heat capacity shows a universal jump at the critical point, and the energy develops a pronounced peak. The asymptotic behavior of the energy peak location is used to locate the critical temperature, which is also found to be universal and in accordance with the mean-field prediction.Comment: 31 pages, 16 figure

E-selectin ligand complexes adopt an extended high-affinity conformation

E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewis(x) (sLe(x)). Efficient leukocyte recruitment under vascular flow conditions depends on an increased lifetime of E-selectin/ligand complexes under tensile force in a so-called catch-bond binding mode. Co-crystal structures of a representative fragment of the extracellular E-selectin region with sLe(x) and a glycomimetic antagonist thereof reveal an extended E-selectin conformation, which is identified as a high-affinity binding state of E-selectin by molecular dynamics simulations. Small-angle X-ray scattering experiments demonstrate a direct link between ligand binding and E-selectin conformational transition under static conditions in solution. This permits tracing a series of concerted structural changes connecting ligand binding to conformational stretching as the structural basis of E-selectin catch-bond-mediated leukocyte recruitment. The detailed molecular view of the binding site paves the way for the design of a new generation of selectin antagonists. This is of special interest, since their therapeutic potential was recently demonstrated with the pan-selectin antagonists GMI-1070 (Rivipansel)

Scaling and Crossover in the Large-N Model for Growth Kinetics

The dependence of the scaling properties of the structure factor on space dimensionality, range of interaction, initial and final conditions, presence or absence of a conservation law is analysed in the framework of the large-N model for growth kinetics. The variety of asymptotic behaviours is quite rich, including standard scaling, multiscaling and a mixture of the two. The different scaling properties obtained as the parameters are varied are controlled by a structure of fixed points with their domains of attraction. Crossovers arising from the competition between distinct fixed points are explicitely obtained. Temperature fluctuations below the critical temperature are not found to be irrelevant when the order parameter is conserved. The model is solved by integration of the equation of motion for the structure factor and by a renormalization group approach.Comment: 48 pages with 6 figures available upon request, plain LaTe